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  • Objectives The outcome of American tegumentary leishmaniasis (ATL) may depend on the presence of the Leishmania RNA virus (LRV). This virus may be involved in treatment failure. We aimed to determine whether genetic clusters of LRV1 are involved in this therapeutic outcome. Methods The presence of LRV1 was assessed in 129 L. guyanensis isolates from patients treated with pentamidine in French Guiana. Among the 115 (89%) isolates found to carry LRV1, 96 were successfully genotyped. Patient clinical data were linked to the LRV data. Results The rate of treatment failure for LRV1-positive isolates was 37% (15/41) versus 40% (2/5) among LRV1-negative isolates (p = 0.88). Concerning LRV1 genotypes, two predominant LRV1 groups emerged, groups A (23% (22/96)) and B (70% (67/96)). The treatment failure rate was 37% (3/8) for group A and 45% (9/20) for group B (p = 0.31). Conclusion Neither the presence or genotype of LRV1 in patients with L. guyanensis seemed to correlate with pentamidine treatment failure.Senescence is a cellular response to stress for both dividing and post-mitotic cells. Noteworthy, long-lived post-mitotic cells (collectively named LLPMCs), which can live for decades in the organism, can exhibit a distinct type of cellular aging characterized by a progressive functional decline not associated to an overt senescence phenotype. The age-related drivers of senescence and aging in LLPMCs remain largely unknown. There is evidence that an increased production of reactive oxygen species (ROS) due to dysfunctional mitochondria, coupled with an inherent inability of cellular-degradation mechanisms to remove damaged molecules, is responsible for senescence and aging in LLPMC. Although telomeric DNA shortening, by nature linked to cell division, is generally not considered as a driver of LLPMC aging and senescence, we discuss recent reports revealing the existence of age-related telomere changes in LLPMC. These findings reveal unexpected roles for telomeres in LLPMC function and invite us to consider the hypothesis of a complex telomere clock involved in both dividing and non-dividing cell aging.CD27, a costimulatory molecule on T cells, induces intracellular signals mediating cellular activation, proliferation, effector function, and cell survival on binding to its ligand, CD70. Varlilumab, a novel, first-in-class, agonist immunoglobulin G1 anti-CD27 antibody, mediates antitumor immunity and direct killing of CD27+ tumor cells in animal models. This first-in-human, dose-escalation, and expansion study evaluated varlilumab in patients with hematologic malignancies. Primary objectives were to assess safety and the maximum tolerated and optimal biologic doses of varlilumab. Secondary objectives were to evaluate pharmacokinetics, pharmacodynamics, immunogenicity, and antitumor activity. In a 3 + 3 dose-escalation design, 30 patients with B-cell (n = 25) or T-cell (n = 5) malignancies received varlilumab (0.1, 0.3, 1, 3, or 10 mg/kg IV) as a single dose with a 28-day observation period, followed by weekly dosing (4 doses per cycle, up to 5 cycles, depending on tumor response). In an expansion cohort, 4 additional patients with Hodgkin lymphoma received varlilumab at 0.3 mg/kg every 3 weeks (4 doses per cycle, up to 5 cycles). No dose-limiting toxicities were observed. Treatment-related adverse events, generally grade 1 to 2, included fatigue, decreased appetite, anemia, diarrhea, and headache. Exposure was linear and dose-proportional across dose groups and resulted in increases in proinflammatory cytokines and soluble CD27. One patient with stage IV Hodgkin lymphoma experienced a complete response and remained in remission at >33 months with no further anticancer therapy. These data support further investigation of varlilumab for hematologic malignancies, particularly in combination approaches targeting nonredundant immune regulating pathways. This trial was registered at www.clinicaltrials.gov as #NCT01460134.We investigated the efficacy of tumour necrosis factor (TNF)-α antagonist infliximab on a measure of anhedonia amongst individuals with bipolar I/II depression (ClinicalTrials.gov identifier NCT02363738). Adults (ages 18-65) with bipolar I/II disorder currently experiencing a major depressive episode with a higher probability of inflammatory activity (i.e., meeting one or more of the following inflammatory/metabolic criteria obesity and dyslipidemia/hypertension, daily cigarette smoking, diabetes mellitus, migraine, inflammatory bowel disease, and/or C-reactive protein level of ⩾5 mg/L) were enrolled in a double-blind, 12-week clinical trial of adjunctive infliximab (5 mg/kg) and saline control, which were administered at weeks 0, 2, and 6. The primary outcome measure for the present secondary analysis was change in the Snaith-Hamilton Pleasure Scale (SHAPS) total score between placebo- and infliximab-treated subjects from baseline to weeks 6 and 12. https://www.selleckchem.com/products/pf-04957325.html Plasma concentrations of TNF-α and soluble TNF receptors (sTNFR) 1 and 2 were assessed at weeks 0, 2, 6, and 12. Sixty eligible adults received treatment with infliximab (n=29) or placebo (n=31); 47 subjects completed the study (infliximab n=21, placebo n=26). Overall, infliximab-randomized subjects exhibited significantly larger increases in SHAPS total score, denoting greater reductions in anhedonic symptoms, when compared to placebo-randomized subjects (treatment × time interaction effect χ2=7.15,df=2,p=0.03). Anti-anhedonic efficacy was moderated by baseline plasma levels of TNF-α and sTNFR1, but not by changes in TNF-α or sTNFR1 concentrations. Baseline and changes in sTNFR2 concentrations did not moderate anti-anhedonic efficacy. Infliximab significantly improved a measure of anhedonia relative to placebo in adults with bipolar I/II depression at week 6; intervention efficacy was not sustained 6 weeks after the final infusion.Cholangiocarcinoma (CCA) is a rare but devastating malignancy that presents late, and associated with a high mortality if untreated. CCA is locally aggressive and located in close proximity to vital structures i.e. the portal vein and hepatic artery. A complete extirpation of the tumor including microscopically detectable disease R0 resection offers the best possibility of long-term survival in patients with CCA. As such, the surgical approach to achieve a R0 resection is dictated by the location of the tumor and the presence of underlying liver disease. The present article focuses on the general principles of the multidisciplinary treatment of hilar and intrahepatic CCA.
    Objectives The outcome of American tegumentary leishmaniasis (ATL) may depend on the presence of the Leishmania RNA virus (LRV). This virus may be involved in treatment failure. We aimed to determine whether genetic clusters of LRV1 are involved in this therapeutic outcome. Methods The presence of LRV1 was assessed in 129 L. guyanensis isolates from patients treated with pentamidine in French Guiana. Among the 115 (89%) isolates found to carry LRV1, 96 were successfully genotyped. Patient clinical data were linked to the LRV data. Results The rate of treatment failure for LRV1-positive isolates was 37% (15/41) versus 40% (2/5) among LRV1-negative isolates (p = 0.88). Concerning LRV1 genotypes, two predominant LRV1 groups emerged, groups A (23% (22/96)) and B (70% (67/96)). The treatment failure rate was 37% (3/8) for group A and 45% (9/20) for group B (p = 0.31). Conclusion Neither the presence or genotype of LRV1 in patients with L. guyanensis seemed to correlate with pentamidine treatment failure.Senescence is a cellular response to stress for both dividing and post-mitotic cells. Noteworthy, long-lived post-mitotic cells (collectively named LLPMCs), which can live for decades in the organism, can exhibit a distinct type of cellular aging characterized by a progressive functional decline not associated to an overt senescence phenotype. The age-related drivers of senescence and aging in LLPMCs remain largely unknown. There is evidence that an increased production of reactive oxygen species (ROS) due to dysfunctional mitochondria, coupled with an inherent inability of cellular-degradation mechanisms to remove damaged molecules, is responsible for senescence and aging in LLPMC. Although telomeric DNA shortening, by nature linked to cell division, is generally not considered as a driver of LLPMC aging and senescence, we discuss recent reports revealing the existence of age-related telomere changes in LLPMC. These findings reveal unexpected roles for telomeres in LLPMC function and invite us to consider the hypothesis of a complex telomere clock involved in both dividing and non-dividing cell aging.CD27, a costimulatory molecule on T cells, induces intracellular signals mediating cellular activation, proliferation, effector function, and cell survival on binding to its ligand, CD70. Varlilumab, a novel, first-in-class, agonist immunoglobulin G1 anti-CD27 antibody, mediates antitumor immunity and direct killing of CD27+ tumor cells in animal models. This first-in-human, dose-escalation, and expansion study evaluated varlilumab in patients with hematologic malignancies. Primary objectives were to assess safety and the maximum tolerated and optimal biologic doses of varlilumab. Secondary objectives were to evaluate pharmacokinetics, pharmacodynamics, immunogenicity, and antitumor activity. In a 3 + 3 dose-escalation design, 30 patients with B-cell (n = 25) or T-cell (n = 5) malignancies received varlilumab (0.1, 0.3, 1, 3, or 10 mg/kg IV) as a single dose with a 28-day observation period, followed by weekly dosing (4 doses per cycle, up to 5 cycles, depending on tumor response). In an expansion cohort, 4 additional patients with Hodgkin lymphoma received varlilumab at 0.3 mg/kg every 3 weeks (4 doses per cycle, up to 5 cycles). No dose-limiting toxicities were observed. Treatment-related adverse events, generally grade 1 to 2, included fatigue, decreased appetite, anemia, diarrhea, and headache. Exposure was linear and dose-proportional across dose groups and resulted in increases in proinflammatory cytokines and soluble CD27. One patient with stage IV Hodgkin lymphoma experienced a complete response and remained in remission at >33 months with no further anticancer therapy. These data support further investigation of varlilumab for hematologic malignancies, particularly in combination approaches targeting nonredundant immune regulating pathways. This trial was registered at www.clinicaltrials.gov as #NCT01460134.We investigated the efficacy of tumour necrosis factor (TNF)-α antagonist infliximab on a measure of anhedonia amongst individuals with bipolar I/II depression (ClinicalTrials.gov identifier NCT02363738). Adults (ages 18-65) with bipolar I/II disorder currently experiencing a major depressive episode with a higher probability of inflammatory activity (i.e., meeting one or more of the following inflammatory/metabolic criteria obesity and dyslipidemia/hypertension, daily cigarette smoking, diabetes mellitus, migraine, inflammatory bowel disease, and/or C-reactive protein level of ⩾5 mg/L) were enrolled in a double-blind, 12-week clinical trial of adjunctive infliximab (5 mg/kg) and saline control, which were administered at weeks 0, 2, and 6. The primary outcome measure for the present secondary analysis was change in the Snaith-Hamilton Pleasure Scale (SHAPS) total score between placebo- and infliximab-treated subjects from baseline to weeks 6 and 12. https://www.selleckchem.com/products/pf-04957325.html Plasma concentrations of TNF-α and soluble TNF receptors (sTNFR) 1 and 2 were assessed at weeks 0, 2, 6, and 12. Sixty eligible adults received treatment with infliximab (n=29) or placebo (n=31); 47 subjects completed the study (infliximab n=21, placebo n=26). Overall, infliximab-randomized subjects exhibited significantly larger increases in SHAPS total score, denoting greater reductions in anhedonic symptoms, when compared to placebo-randomized subjects (treatment × time interaction effect χ2=7.15,df=2,p=0.03). Anti-anhedonic efficacy was moderated by baseline plasma levels of TNF-α and sTNFR1, but not by changes in TNF-α or sTNFR1 concentrations. Baseline and changes in sTNFR2 concentrations did not moderate anti-anhedonic efficacy. Infliximab significantly improved a measure of anhedonia relative to placebo in adults with bipolar I/II depression at week 6; intervention efficacy was not sustained 6 weeks after the final infusion.Cholangiocarcinoma (CCA) is a rare but devastating malignancy that presents late, and associated with a high mortality if untreated. CCA is locally aggressive and located in close proximity to vital structures i.e. the portal vein and hepatic artery. A complete extirpation of the tumor including microscopically detectable disease R0 resection offers the best possibility of long-term survival in patients with CCA. As such, the surgical approach to achieve a R0 resection is dictated by the location of the tumor and the presence of underlying liver disease. The present article focuses on the general principles of the multidisciplinary treatment of hilar and intrahepatic CCA.
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  • Intragenic mutations in FGF12 are associated with intractable seizures, developmental regression, intellectual disability, ataxia, hypotonia, and feeding difficulties. FGF12 duplications are rarely reported, but it was suggested that those might have a similar gain-of-function effect and lead to a more or less comparable phenotype. A favorable response to the sodium blocker phenytoin was reported in several cases, both in patients with an intragenic mutation and in patients with a duplication of FGF12. We report three individuals from two families with FGF12 duplications. The duplications are flanked and probably mediated by two long interspersed nuclear elements (LINEs). The duplication cases show phenotypic overlap with the cases with intragenic mutations. Though the onset of epilepsy might be later, after the onset of seizures both groups show developmental stagnation and regression in several cases. This illustrates and further confirms that chromosomal FGF12 duplications and intragenic gain-of-function mutations yield overlapping phenotypes.Ring chromosome 20 syndrome (r(20)) is an ultra-rare disease characterized by drug-refractory epilepsy, cognitive impairment, and behavioral problems. Nonpharmacological treatments alongside antiepileptic drugs early after diagnosis may help reduce seizure frequency and preserve cognition. Ketogenic dietary therapy (KDT) has benefitted children with complex, refractory epilepsies, but its efficacy in r(20) is unknown. We assessed clinical prescription, implementation, and patient experience of KDT in r(20) through online surveys and a workshop. Forty-two patients, families, carers, and 23 healthcare professionals completed the surveys. While nearly all patients were familiar with KDT, only half had tried it. Significant improvement in seizure activity, cognition, and alertness was reported; side effects were typically mild but with one report of increased seizure frequency. A high rate of co-morbidity, older age at presentation, behavioral problems, and cognitive impairment can make implementing KDT in r(20) challenging. In the UK, NHS KDT services are predominantly available to pediatric patients, with very limited adult access. A health economic analysis illustrating reduced acute care costs or improved quality of life may support more widespread KDT implementation. Growing evidence supports KDT as an effective and safe intervention, but further research is needed to understand the mechanisms of r(20) and its interaction with ketosis.Objective Epilepsy is one of the most common neurological disorders . Many individuals continue to have seizures despite medical and surgical treatments, suggesting adjunctive management strategies are required. Promising effects of daily listening to Mozart on reducing seizure frequency in individuals with epilepsy have been demonstrated over the last 20 years, but not in a rigorously controlled manner. In this study, we compared the effect on seizure frequency of daily listening to either Mozart K.448 or a spectrally similar, yet non-rhythmic control piece. We hypothesized that there would be no difference in seizure counts when participants listened to Mozart K.448 vs when they listened to the control piece. Methods We employed a randomized crossover design, in which each participant was exposed to both three months of daily listening to the first six minutes of Sonata for two pianos in D major by Mozart (Mozart K.448; treatment period) and three months of daily listening to phase-scrambled version (control period). There was a three-month baseline and a three-month follow-up period before and after the six-month listening period, respectively. Change in seizure counts obtained from the seizure diaries was considered as the main study outcome. Results Using three methodologies to investigate the existence of the treatment effect (paired t test, estimation statistics and plots, and Cohen's d), our results revealed a reduction in seizure counts during the treatment period, which was not observed for the control period (P-value less then .001). Significance Using a spectrally similar control piece, our study advances previous reports that were limited by a "no music" control condition. Daily listening to Mozart K.448 was associated with reducing seizure frequency in adult individuals with epilepsy. These results suggest that daily Mozart listening may be considered as an adjunctive therapeutic option to reduce seizure burden in individuals with epilepsy.Objective Our study assessed perampanel monotherapy in patients (aged ≥12 years) with focal-onset seizures (FOS) with or without focal to bilateral tonic-clonic seizures (FBTCS) in Japan and South Korea. Methods Study 342 (NCT03201900; FREEDOM) is a single-arm, open-label, Phase III study. Patients initially received perampanel in a 32-week 4-mg/d Treatment Phase (6-week Titration; 26-week Maintenance Periods). If they experienced a seizure during the 4-mg/d Maintenance Period, they could be up-titrated to 8 mg/d across an additional 30-week Treatment Phase (4-week Titration; 26-week Maintenance Periods). Primary endpoint was the seizure-freedom rate during the Maintenance Period (4 mg/d and last evaluated dose [4 or 8 mg/d]). Secondary endpoints included time to first seizure onset and to withdrawal during Maintenance. Treatment-emergent adverse events (TEAEs) were monitored. Results At data cutoff (February 28, 2019), 89 patients with FOS (84 [94.4%] with newly diagnosed epilepsy and 5 [5.6%] with recurrence of epilepsy after a period of remission) had received ≥1 perampanel dose; 16 patients discontinued during the 4-mg/d Titration Period, meaning 73 patients entered the 4-mg/d Maintenance Period and were included in the primary analysis set for efficacy. https://www.selleckchem.com/products/hoipin-8.html Seizure-freedom rate in the 26-week Maintenance Period was 46/73 (63.0%; 95% confidence interval [CI] 50.9-74.0) at 4 mg/d and 54/73 (74.0%; 95% CI 62.4-83.5) at 4 or 8 mg/d. Cumulative probability of seizure-onset and withdrawal rates during Maintenance was 30.8% (95% CI 21.5-43.0) and 23.7% (95% CI 15.4-35.3) at 4 mg/d, and 18.2% (95% CI 11.0-29.3) and 23.3% (95% CI 15.2-34.8) at 4 or 8 mg/d. Perampanel was generally well tolerated, and the most common TEAE was dizziness. Significance Perampanel monotherapy (4 to 8 mg/d) was efficacious and consistent with the known safety profile up to 26 weeks in patients (≥12 years) with primarily newly diagnosed FOS with or without FBTCS.
    Intragenic mutations in FGF12 are associated with intractable seizures, developmental regression, intellectual disability, ataxia, hypotonia, and feeding difficulties. FGF12 duplications are rarely reported, but it was suggested that those might have a similar gain-of-function effect and lead to a more or less comparable phenotype. A favorable response to the sodium blocker phenytoin was reported in several cases, both in patients with an intragenic mutation and in patients with a duplication of FGF12. We report three individuals from two families with FGF12 duplications. The duplications are flanked and probably mediated by two long interspersed nuclear elements (LINEs). The duplication cases show phenotypic overlap with the cases with intragenic mutations. Though the onset of epilepsy might be later, after the onset of seizures both groups show developmental stagnation and regression in several cases. This illustrates and further confirms that chromosomal FGF12 duplications and intragenic gain-of-function mutations yield overlapping phenotypes.Ring chromosome 20 syndrome (r(20)) is an ultra-rare disease characterized by drug-refractory epilepsy, cognitive impairment, and behavioral problems. Nonpharmacological treatments alongside antiepileptic drugs early after diagnosis may help reduce seizure frequency and preserve cognition. Ketogenic dietary therapy (KDT) has benefitted children with complex, refractory epilepsies, but its efficacy in r(20) is unknown. We assessed clinical prescription, implementation, and patient experience of KDT in r(20) through online surveys and a workshop. Forty-two patients, families, carers, and 23 healthcare professionals completed the surveys. While nearly all patients were familiar with KDT, only half had tried it. Significant improvement in seizure activity, cognition, and alertness was reported; side effects were typically mild but with one report of increased seizure frequency. A high rate of co-morbidity, older age at presentation, behavioral problems, and cognitive impairment can make implementing KDT in r(20) challenging. In the UK, NHS KDT services are predominantly available to pediatric patients, with very limited adult access. A health economic analysis illustrating reduced acute care costs or improved quality of life may support more widespread KDT implementation. Growing evidence supports KDT as an effective and safe intervention, but further research is needed to understand the mechanisms of r(20) and its interaction with ketosis.Objective Epilepsy is one of the most common neurological disorders . Many individuals continue to have seizures despite medical and surgical treatments, suggesting adjunctive management strategies are required. Promising effects of daily listening to Mozart on reducing seizure frequency in individuals with epilepsy have been demonstrated over the last 20 years, but not in a rigorously controlled manner. In this study, we compared the effect on seizure frequency of daily listening to either Mozart K.448 or a spectrally similar, yet non-rhythmic control piece. We hypothesized that there would be no difference in seizure counts when participants listened to Mozart K.448 vs when they listened to the control piece. Methods We employed a randomized crossover design, in which each participant was exposed to both three months of daily listening to the first six minutes of Sonata for two pianos in D major by Mozart (Mozart K.448; treatment period) and three months of daily listening to phase-scrambled version (control period). There was a three-month baseline and a three-month follow-up period before and after the six-month listening period, respectively. Change in seizure counts obtained from the seizure diaries was considered as the main study outcome. Results Using three methodologies to investigate the existence of the treatment effect (paired t test, estimation statistics and plots, and Cohen's d), our results revealed a reduction in seizure counts during the treatment period, which was not observed for the control period (P-value less then .001). Significance Using a spectrally similar control piece, our study advances previous reports that were limited by a "no music" control condition. Daily listening to Mozart K.448 was associated with reducing seizure frequency in adult individuals with epilepsy. These results suggest that daily Mozart listening may be considered as an adjunctive therapeutic option to reduce seizure burden in individuals with epilepsy.Objective Our study assessed perampanel monotherapy in patients (aged ≥12 years) with focal-onset seizures (FOS) with or without focal to bilateral tonic-clonic seizures (FBTCS) in Japan and South Korea. Methods Study 342 (NCT03201900; FREEDOM) is a single-arm, open-label, Phase III study. Patients initially received perampanel in a 32-week 4-mg/d Treatment Phase (6-week Titration; 26-week Maintenance Periods). If they experienced a seizure during the 4-mg/d Maintenance Period, they could be up-titrated to 8 mg/d across an additional 30-week Treatment Phase (4-week Titration; 26-week Maintenance Periods). Primary endpoint was the seizure-freedom rate during the Maintenance Period (4 mg/d and last evaluated dose [4 or 8 mg/d]). Secondary endpoints included time to first seizure onset and to withdrawal during Maintenance. Treatment-emergent adverse events (TEAEs) were monitored. Results At data cutoff (February 28, 2019), 89 patients with FOS (84 [94.4%] with newly diagnosed epilepsy and 5 [5.6%] with recurrence of epilepsy after a period of remission) had received ≥1 perampanel dose; 16 patients discontinued during the 4-mg/d Titration Period, meaning 73 patients entered the 4-mg/d Maintenance Period and were included in the primary analysis set for efficacy. https://www.selleckchem.com/products/hoipin-8.html Seizure-freedom rate in the 26-week Maintenance Period was 46/73 (63.0%; 95% confidence interval [CI] 50.9-74.0) at 4 mg/d and 54/73 (74.0%; 95% CI 62.4-83.5) at 4 or 8 mg/d. Cumulative probability of seizure-onset and withdrawal rates during Maintenance was 30.8% (95% CI 21.5-43.0) and 23.7% (95% CI 15.4-35.3) at 4 mg/d, and 18.2% (95% CI 11.0-29.3) and 23.3% (95% CI 15.2-34.8) at 4 or 8 mg/d. Perampanel was generally well tolerated, and the most common TEAE was dizziness. Significance Perampanel monotherapy (4 to 8 mg/d) was efficacious and consistent with the known safety profile up to 26 weeks in patients (≥12 years) with primarily newly diagnosed FOS with or without FBTCS.
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  • Objective The aim of this project was to determine revenues and costs over time to assess the sustainability of the Baby Bridge program. Methods The Baby Bridge program was developed to promote timely, consistent and high quality early therapy services for high-risk infants following neonatal intensive care unit (NICU) discharge. Key features of the Baby Bridge program were defined as 1) having the therapist establish rapport with the family while in the NICU, 2) scheduling the first home visit within one week of discharge and continuing weekly visits until other services commence, 3) conducting comprehensive assessments to inform targeted interventions by a skilled, single provider, and 4) using a comprehensive therapeutic approach while collaborating with the NICU medical team and community therapy providers. The Baby Bridge program was implemented with infants hospitalized in an urban Level IV NICU from January 2016 to January 2018. The number of infants enrolled increased gradually over the first several l program income, once scaled up to capacity, would be approximately $16,308. Discussion There were initial losses during phase-in of Baby Bridge programming associated with operating far below capacity, yet the program achieved sustainability within 16 months of implementation. These costs related to implementation do not consider the potential cost reduction due to mitigated health burden for the community and families, particularly due to earlier receipt of therapy services, which is an important area for further inquiry.The (pro)renin receptor ((P)RR) is cleaved to generate soluble (P)RR (s(P)RR), which reflects the status of the tissue renin-angiotensin system. https://www.selleckchem.com/products/sp-600125.html Hemodialysis (HD) patients have a poor prognosis due to the increased prevalence of cardiovascular diseases. The present study aimed to investigate whether serum s(P)RR level is associated with the worsening of cardiac function in HD patients. A total of 258 maintenance HD patients were recruited and serum s(P)RR concentration was measured. Background factors in patients who survived (S group) and patients who died (D group) during the 12-month follow-up period and relationships between serum s(P)RR level and changes in cardiac function during the follow-up period in the S group were investigated. The median serum s(P)RR value at baseline was 29.8 ng/ml. Twenty-four patients died during the follow-up period. Cardiothoracic ratio, human atrial natriuretic peptide (hANP), brain natriuretic peptide (BNP), and E over e-prime were significantly higher in the D group. In the S group, changes in hANP or BNP were significantly greater in the higher serum s(P)RR group than in the lower serum s(P)RR group. High serum s(P)RR level was significantly correlated with changes in BNP, independent of other factors. High serum s(P)RR level was associated with increases in BNP, independent of other risk factors, suggesting that an increased expression of (P)RR may be associated with a progression of heart failure in HD patients and that serum s(P)RR concentration could be used as a biomarker for selecting patients requiring intensive care.Introduction It is increasingly considered important that people make an autonomous and informed decision concerning colorectal cancer (CRC) screening. However, the realisation of autonomy within the concept of informed decision-making might be interpreted too narrowly. Additionally, relatively little is known about what the eligible population believes to be a 'good' screening decision. Therefore, we aimed to explore how the concepts of autonomous and informed decision-making relate to how the eligible CRC screening population makes their decision and when they believe to have made a 'good' screening decision. Methods We conducted 27 semi-structured interviews with the eligible CRC screening population (eighteen CRC screening participants and nine non-participants). The general topics discussed concerned how people made their CRC screening decision, how they experienced making this decision and when they considered they had made a 'good' decision. Results Most interviewees viewed a 'good' CRC screening decisare involved in deciding about CRC screening participation.The surge in the prevalence of drug-resistant bacteria in poultry is a global concern as it may pose an extended threat to humans and animal health. The present study aimed to investigate the colonization proportion of extended-spectrum β-lactamase (ESBL) and carbapenemase-producing Enterobacteriaceae (EPE and CPE, respectively) in the gut of healthy poultry, Gallus gallus domesticus in Kaski district of Western Nepal. Total, 113 pooled rectal swab specimens from 66 private household farms and 47 commercial poultry farms were collected by systematic random sampling from the Kaski district in western Nepal. Out of 113 pooled samples, 19 (28.8%) samples from 66 backyard farms, and 15 (31.9%) from 47 commercial broiler farms were positive for EPE. Of the 38 EPE strains isolated from 34 ESBL positive rectal swabs, 31(81.6%) were identified as Escherichia coli, five as Klebsiella pneumoniae (13.2%), and one each isolate of Enterobacter species and Citrobacter species (2.6%). Based on genotyping, 35/38 examined EPE strains (92.1%) were phylogroup-1 positive, and all these 35 strains (100%) had the CTX-M-15 gene and strains from phylogroup-2, and 9 were of CTX-M-2 and CTX-M-14, respectively. Among 38 ESBL positive isolates, 9 (23.7%) were Ambler class C (Amp C) co-producers, predominant were of DHA, followed by CIT genes. Two (6.5%) E. coli strains of ST131 belonged to clade C, rest 29/31 (93.5%) were non-ST131 E. coli. None of the isolates produced carbapenemase. Twenty isolates (52.6%) were in-vitro biofilm producers. Univariate analysis showed that the odd of ESBL carriage among commercial broilers were 1.160 times (95% CI 0.515, 2.613) higher than organically fed backyard flocks. This is the first study in Nepal, demonstrating the EPE colonization proportion, genotypes, and prevalence of high-risk clone E. coli ST131 among gut flora of healthy poultry. Our data indicated that CTX-M-15 was the most prevalent ESBL enzyme, mainly associated with E. coli belonging to non-ST131clones and the absence of carbapenemases.
    Objective The aim of this project was to determine revenues and costs over time to assess the sustainability of the Baby Bridge program. Methods The Baby Bridge program was developed to promote timely, consistent and high quality early therapy services for high-risk infants following neonatal intensive care unit (NICU) discharge. Key features of the Baby Bridge program were defined as 1) having the therapist establish rapport with the family while in the NICU, 2) scheduling the first home visit within one week of discharge and continuing weekly visits until other services commence, 3) conducting comprehensive assessments to inform targeted interventions by a skilled, single provider, and 4) using a comprehensive therapeutic approach while collaborating with the NICU medical team and community therapy providers. The Baby Bridge program was implemented with infants hospitalized in an urban Level IV NICU from January 2016 to January 2018. The number of infants enrolled increased gradually over the first several l program income, once scaled up to capacity, would be approximately $16,308. Discussion There were initial losses during phase-in of Baby Bridge programming associated with operating far below capacity, yet the program achieved sustainability within 16 months of implementation. These costs related to implementation do not consider the potential cost reduction due to mitigated health burden for the community and families, particularly due to earlier receipt of therapy services, which is an important area for further inquiry.The (pro)renin receptor ((P)RR) is cleaved to generate soluble (P)RR (s(P)RR), which reflects the status of the tissue renin-angiotensin system. https://www.selleckchem.com/products/sp-600125.html Hemodialysis (HD) patients have a poor prognosis due to the increased prevalence of cardiovascular diseases. The present study aimed to investigate whether serum s(P)RR level is associated with the worsening of cardiac function in HD patients. A total of 258 maintenance HD patients were recruited and serum s(P)RR concentration was measured. Background factors in patients who survived (S group) and patients who died (D group) during the 12-month follow-up period and relationships between serum s(P)RR level and changes in cardiac function during the follow-up period in the S group were investigated. The median serum s(P)RR value at baseline was 29.8 ng/ml. Twenty-four patients died during the follow-up period. Cardiothoracic ratio, human atrial natriuretic peptide (hANP), brain natriuretic peptide (BNP), and E over e-prime were significantly higher in the D group. In the S group, changes in hANP or BNP were significantly greater in the higher serum s(P)RR group than in the lower serum s(P)RR group. High serum s(P)RR level was significantly correlated with changes in BNP, independent of other factors. High serum s(P)RR level was associated with increases in BNP, independent of other risk factors, suggesting that an increased expression of (P)RR may be associated with a progression of heart failure in HD patients and that serum s(P)RR concentration could be used as a biomarker for selecting patients requiring intensive care.Introduction It is increasingly considered important that people make an autonomous and informed decision concerning colorectal cancer (CRC) screening. However, the realisation of autonomy within the concept of informed decision-making might be interpreted too narrowly. Additionally, relatively little is known about what the eligible population believes to be a 'good' screening decision. Therefore, we aimed to explore how the concepts of autonomous and informed decision-making relate to how the eligible CRC screening population makes their decision and when they believe to have made a 'good' screening decision. Methods We conducted 27 semi-structured interviews with the eligible CRC screening population (eighteen CRC screening participants and nine non-participants). The general topics discussed concerned how people made their CRC screening decision, how they experienced making this decision and when they considered they had made a 'good' decision. Results Most interviewees viewed a 'good' CRC screening decisare involved in deciding about CRC screening participation.The surge in the prevalence of drug-resistant bacteria in poultry is a global concern as it may pose an extended threat to humans and animal health. The present study aimed to investigate the colonization proportion of extended-spectrum β-lactamase (ESBL) and carbapenemase-producing Enterobacteriaceae (EPE and CPE, respectively) in the gut of healthy poultry, Gallus gallus domesticus in Kaski district of Western Nepal. Total, 113 pooled rectal swab specimens from 66 private household farms and 47 commercial poultry farms were collected by systematic random sampling from the Kaski district in western Nepal. Out of 113 pooled samples, 19 (28.8%) samples from 66 backyard farms, and 15 (31.9%) from 47 commercial broiler farms were positive for EPE. Of the 38 EPE strains isolated from 34 ESBL positive rectal swabs, 31(81.6%) were identified as Escherichia coli, five as Klebsiella pneumoniae (13.2%), and one each isolate of Enterobacter species and Citrobacter species (2.6%). Based on genotyping, 35/38 examined EPE strains (92.1%) were phylogroup-1 positive, and all these 35 strains (100%) had the CTX-M-15 gene and strains from phylogroup-2, and 9 were of CTX-M-2 and CTX-M-14, respectively. Among 38 ESBL positive isolates, 9 (23.7%) were Ambler class C (Amp C) co-producers, predominant were of DHA, followed by CIT genes. Two (6.5%) E. coli strains of ST131 belonged to clade C, rest 29/31 (93.5%) were non-ST131 E. coli. None of the isolates produced carbapenemase. Twenty isolates (52.6%) were in-vitro biofilm producers. Univariate analysis showed that the odd of ESBL carriage among commercial broilers were 1.160 times (95% CI 0.515, 2.613) higher than organically fed backyard flocks. This is the first study in Nepal, demonstrating the EPE colonization proportion, genotypes, and prevalence of high-risk clone E. coli ST131 among gut flora of healthy poultry. Our data indicated that CTX-M-15 was the most prevalent ESBL enzyme, mainly associated with E. coli belonging to non-ST131clones and the absence of carbapenemases.
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  • Ketamine (KET) was originally developed as an anesthetic agent but has also attracted attention for further clinical applications such as medical treatment of depression or pain. The use of KET induces dissociation and emergence delirium. Due to these effects, KET has a high potential for abuse. In order to investigate metabolization of KET or to confirm misuse of KET, highly sensitive analytical methods that cover KET and its metabolites are necessary. A new analytical approach for simultaneous analysis of KET and its metabolites cis-6-hydroxynorketamine (HNK) and norketamine (NK) was established. The compounds were extracted from human blood serum by ultrafiltration and solid phase extraction with subsequent vacuum evaporation. The compounds were analyzed by non-enantioselective ultra-high performance micro-flow liquid chromatography (Waters ACQUITY UPLC® M-Class HSS T3 column, 0.1% formic acid and acetonitrile with 0.1% formic acid, 14 µL/min flow rate) coupled with tandem mass spectrometry in positive scheduled multiple reaction monitoring mode. Validation parameters such as linearity, precision, recovery, accuracy, stability, limit of detection (LOD), and limit of quantification (LOQ) were proven. LOD for KET and NK was 0.08 ng/mL and LOQ were 0.5 ng/mL and 0.6 ng/mL, respectively. For HNK, LOD was 0.1 ng/mL and LOQ 0.8 ng/mL. The method was then successfully applied to quantify KET, HNK, and NK in blood serum samples from subjects who received KET intravenously. A novel method for the simultaneous analysis of KET, NK, and HNK was established. This new method could now be used for clinical trials investigating KET and its metabolites HNK and NK or for forensic analysis in order to confirm KET abuse.In this work, we investigated the interaction of docosahexaenoic acid (DHA) with β-lactoglobulin (β-Lg) using spectroscopic and crystallographic methods. The fluorescence results showed that DHA formed complexes with β-Lg with a binding constant of 4.13 × 104 M-1. The secondary structure of β-Lg was not significantly (p > 0.05) changed after binding with DHA. Dynamic light scattering showed the particle size of β-Lg-DHA complexes was about 5 nm, the same as that of β-Lg alone. The turbidity of DHA in aqueous solution decreased after binding with β-Lg. The crystallographic results showed that DHA was bound at one site in the calyx of β-Lg and that the aliphatic chain was hidden inside the hydrophobic β-barrel while the carboxyl group was located at the calyx entrance. These findings indicate that β-Lg can act as an effective nanocarrier for DHA.This work studied the quantitation of myofibrillar protein isolated from giant squid by three methods (Bradford, biuret, and direct ultraviolet absorbance). The results were examined in relation to compositional size exclusion chromatography, static light scattering, zeta-potential and thermal analysis; comparisons between the apparent vs. the true protein concentration revealed the existence of disk-like nano protein particles (NPP) with a height of 2-3 nm, diameters ranging from several tens nm to 140 nm, and fractal dimensions df of less than 1.3. In order to probe the heterogeneity of NPP particles, their properties were studied under consecutive dilutions the df decreased from 1.265 to 1.087, the zeta-potential increased from -4.55 mV to -1.83 mV, the denaturation temperature reduced from 63.9 °C to 58.6 °C, and the endothermic enthalpy reduced from 0.529 J s-1 to 0.362 J s-1. In addition, ca. 90% protein molecules in solution were aggregated to form NPP.The effects of endogenous proteolysis and oxidation on mechanical properties of sea cucumber (Stichopus japonicus) during thermal processing and storage and their control were investigated. The lactic acid (LA) + tea polyphenols (TP)-treated sea cucumbers showed relatively higher values in texture and rheological indicators than the blank control group after thermal processing. By contrast, the (LA + TP)-treated sea cucumbers also had lower values in water-soluble hydroxyproline, glycosaminoglycans and proteins, trichloroacetic acid-soluble peptide content, and more orderly secondary structure of proteins, indicating that the additives affected the mechanical properties of thermally processed sea cucumbers by preventing the proteolysis of proteins. All texture and rheological indicators of thermally processed sea cucumbers decreased time-dependently during chilled storage. The additives (LA + TP) significantly prevented the progressive deterioration in mechanical properties by retarding the changes in microstructure as well as phase state and distribution of water through preventing protein oxidation.The effect of supercritical fluid extract of tomato pomace (TP) and essential oil of organic peppermint (PM) on pH, color, residual nitrite content, lipid oxidation (TBARS value) and total plate count (TPC) of cooked pork sausages produced with 50 mg/kg of sodium nitrite was investigated. Five batches were produced T1 100 mg/kg of sodium nitrite; T2 50 mg of sodium nitrite; T3 50 mg of sodium nitrite and 0.150 µL/g TP; T4 50 mg of sodium nitrite, 0.075 µL/g TP and 0.075 µL/g PM; T5 50 mg of sodium nitrite and 0.150 µL/g PM. The lowest residual nitrite content and TBARS value were observed in treatment T4. The inclusion of TP increased redness of cooked pork sausages. TPC was the lowest in treatment T5. https://www.selleckchem.com/products/mki-1.html The results of this study showed that the addition of TP and PM enhanced quality of cooked sausages produced with reduced level of sodium nitrite.The objective of this study was to evaluate the chemical composition and fatty acid profile of broilers fed diets containing glycerol monolaurate (GML) in place of antimicrobials. Groups T0 group used as control; T100, T200, and T300 groups received diets supplemented with 100, 200, and 300 mg/kg of GML, respectively. The feed mixture used in the poultry feed during the four phases of the production cycle (days 1 to 7; 8 to 21; 22 to 35; and 36 to 42 of birds age) showed similar levels of protein, lipid and ash, as well as fatty acid profiles. Samples of frozen breasts from chickens slaughtered at 42 days of age were used for chemical gross composition and fatty acid analysis. We observed lower lipid levels in the meat of broilers in the T200 and T300 groups than in the T0 group. Lower lipid peroxidation occurred in the meat of animals that consumed GML in respect to control. Total saturated fatty acid percentage was lower, while total polyunsaturated fatty acid percentage was higher in the meat of broilers fed GML than in the control group.
    Ketamine (KET) was originally developed as an anesthetic agent but has also attracted attention for further clinical applications such as medical treatment of depression or pain. The use of KET induces dissociation and emergence delirium. Due to these effects, KET has a high potential for abuse. In order to investigate metabolization of KET or to confirm misuse of KET, highly sensitive analytical methods that cover KET and its metabolites are necessary. A new analytical approach for simultaneous analysis of KET and its metabolites cis-6-hydroxynorketamine (HNK) and norketamine (NK) was established. The compounds were extracted from human blood serum by ultrafiltration and solid phase extraction with subsequent vacuum evaporation. The compounds were analyzed by non-enantioselective ultra-high performance micro-flow liquid chromatography (Waters ACQUITY UPLC® M-Class HSS T3 column, 0.1% formic acid and acetonitrile with 0.1% formic acid, 14 µL/min flow rate) coupled with tandem mass spectrometry in positive scheduled multiple reaction monitoring mode. Validation parameters such as linearity, precision, recovery, accuracy, stability, limit of detection (LOD), and limit of quantification (LOQ) were proven. LOD for KET and NK was 0.08 ng/mL and LOQ were 0.5 ng/mL and 0.6 ng/mL, respectively. For HNK, LOD was 0.1 ng/mL and LOQ 0.8 ng/mL. The method was then successfully applied to quantify KET, HNK, and NK in blood serum samples from subjects who received KET intravenously. A novel method for the simultaneous analysis of KET, NK, and HNK was established. This new method could now be used for clinical trials investigating KET and its metabolites HNK and NK or for forensic analysis in order to confirm KET abuse.In this work, we investigated the interaction of docosahexaenoic acid (DHA) with β-lactoglobulin (β-Lg) using spectroscopic and crystallographic methods. The fluorescence results showed that DHA formed complexes with β-Lg with a binding constant of 4.13 × 104 M-1. The secondary structure of β-Lg was not significantly (p > 0.05) changed after binding with DHA. Dynamic light scattering showed the particle size of β-Lg-DHA complexes was about 5 nm, the same as that of β-Lg alone. The turbidity of DHA in aqueous solution decreased after binding with β-Lg. The crystallographic results showed that DHA was bound at one site in the calyx of β-Lg and that the aliphatic chain was hidden inside the hydrophobic β-barrel while the carboxyl group was located at the calyx entrance. These findings indicate that β-Lg can act as an effective nanocarrier for DHA.This work studied the quantitation of myofibrillar protein isolated from giant squid by three methods (Bradford, biuret, and direct ultraviolet absorbance). The results were examined in relation to compositional size exclusion chromatography, static light scattering, zeta-potential and thermal analysis; comparisons between the apparent vs. the true protein concentration revealed the existence of disk-like nano protein particles (NPP) with a height of 2-3 nm, diameters ranging from several tens nm to 140 nm, and fractal dimensions df of less than 1.3. In order to probe the heterogeneity of NPP particles, their properties were studied under consecutive dilutions the df decreased from 1.265 to 1.087, the zeta-potential increased from -4.55 mV to -1.83 mV, the denaturation temperature reduced from 63.9 °C to 58.6 °C, and the endothermic enthalpy reduced from 0.529 J s-1 to 0.362 J s-1. In addition, ca. 90% protein molecules in solution were aggregated to form NPP.The effects of endogenous proteolysis and oxidation on mechanical properties of sea cucumber (Stichopus japonicus) during thermal processing and storage and their control were investigated. The lactic acid (LA) + tea polyphenols (TP)-treated sea cucumbers showed relatively higher values in texture and rheological indicators than the blank control group after thermal processing. By contrast, the (LA + TP)-treated sea cucumbers also had lower values in water-soluble hydroxyproline, glycosaminoglycans and proteins, trichloroacetic acid-soluble peptide content, and more orderly secondary structure of proteins, indicating that the additives affected the mechanical properties of thermally processed sea cucumbers by preventing the proteolysis of proteins. All texture and rheological indicators of thermally processed sea cucumbers decreased time-dependently during chilled storage. The additives (LA + TP) significantly prevented the progressive deterioration in mechanical properties by retarding the changes in microstructure as well as phase state and distribution of water through preventing protein oxidation.The effect of supercritical fluid extract of tomato pomace (TP) and essential oil of organic peppermint (PM) on pH, color, residual nitrite content, lipid oxidation (TBARS value) and total plate count (TPC) of cooked pork sausages produced with 50 mg/kg of sodium nitrite was investigated. Five batches were produced T1 100 mg/kg of sodium nitrite; T2 50 mg of sodium nitrite; T3 50 mg of sodium nitrite and 0.150 µL/g TP; T4 50 mg of sodium nitrite, 0.075 µL/g TP and 0.075 µL/g PM; T5 50 mg of sodium nitrite and 0.150 µL/g PM. The lowest residual nitrite content and TBARS value were observed in treatment T4. The inclusion of TP increased redness of cooked pork sausages. TPC was the lowest in treatment T5. https://www.selleckchem.com/products/mki-1.html The results of this study showed that the addition of TP and PM enhanced quality of cooked sausages produced with reduced level of sodium nitrite.The objective of this study was to evaluate the chemical composition and fatty acid profile of broilers fed diets containing glycerol monolaurate (GML) in place of antimicrobials. Groups T0 group used as control; T100, T200, and T300 groups received diets supplemented with 100, 200, and 300 mg/kg of GML, respectively. The feed mixture used in the poultry feed during the four phases of the production cycle (days 1 to 7; 8 to 21; 22 to 35; and 36 to 42 of birds age) showed similar levels of protein, lipid and ash, as well as fatty acid profiles. Samples of frozen breasts from chickens slaughtered at 42 days of age were used for chemical gross composition and fatty acid analysis. We observed lower lipid levels in the meat of broilers in the T200 and T300 groups than in the T0 group. Lower lipid peroxidation occurred in the meat of animals that consumed GML in respect to control. Total saturated fatty acid percentage was lower, while total polyunsaturated fatty acid percentage was higher in the meat of broilers fed GML than in the control group.
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  • Introduction Radiotherapy is an important therapeutic strategy in the management of non-small cell lung cancer (NSCLC). In recent decades, technological implementations and the introduction of image guided radiotherapy (IGRT) have significantly increased the accuracy and tolerability of radiation therapy.Area covered In this review, we provide an overview of technological opportunities and future prospects in NSCLC management.Expert opinion Stereotactic body radiotherapy (SBRT) is now considered the standard approach in patients ineligible for surgery, while in operable cases, it is still under debate. Additionally, in combination with systemic treatment, SBRT is an innovative option for managing oligometastatic patients and features encouraging initial results in clinical outcomes. To date, in inoperable locally advanced NSCLC, the radical dose prescription has not changed (60 Gy in 30 fractions), despite the median overall survival progressively increasing. These results arise from technological improvements in precisely hitting target treatment volumes and organ at risk sparing, which are associated with better treatment qualities. Finally, for the management of NSCLC, proton and carbon ion therapies and the recent development of MR-Linac are new, intriguing technological approaches under investigation.Objectives Different microorganisms contribute in the pregnancy bacteriuria, which resistance microorganisms limited the therapeutic options for the treatment and increasing the related risks to pregnant women and their pregnancy. Based on this, asymptomatic bacteriuria and the use of inappropriate empirical antibiotics are dangerous in the emergence of pregnancy complications and the incidence of drug resistant.Methods A comprehensive systematic search was performed on all international databases including Scopus, PubMed, Web of Science, Medline, Cochrane library during 2000 - June 2019. This meta-analysis, which was registered by a pre-defined protocol in PROSPRO, carried out in accordance with PRISMA guideline. Relevant articles were included in the analysis if reported the susceptibility pattern of antimicrobial resistance related to asymptomatic bacteria in pregnant women with no acute diseases. Overall prevalence and related 95% confidence interval for resistance in different asymptomatic infections were estimated by inverse variance method. The random effect model was used in case of considerable heterogeneity.Results Results of this analysis demonstrated different resistance rate against studied classes of antibiotics. Nitrofurantoin resistance in E. coli, Klebsiella sp, P. aeruginosa, and Staphylococcus aureus isolates were estimated 0.22 (95%CI 0.15-0.30), 0.40 (95%CI 0.26-0.54), 0.81 (95%CI 0.59-0.97), 0.34 (0.11-0.63), respectively. https://www.selleckchem.com/products/hsp27-inhibitor-j2.html Subgroups analysis showed highest resistance in E. coli isolates, in Asia and Africa against Cefotaxime and Ampicillin, respectively.Conclusion In summary, increasing resistance rate in urinary tract infection (UTI)-related agents is a risk factor that endangers both mother and fetus. Health care providers should consider screening as the radical part of infection control strategies. Due to low resistance rate to Nitrofurantoin, this drug can be a good choice for UTI treatment in pregnancies, but it should use with caution.Introduction Dual antiplatelet therapy (DAPT) is required for coronary artery disease treated with drug-eluting stents (DES) implantation. Shortening DAPT duration would be beneficial for patients with high bleeding risk.Areas covered Early healing patterns, especially stent strut coverage, assessed by optical coherence tomography (OCT) as a surrogate of neointima have been investigated to make decisions on whether short DAPT would be a safe alternative. This review evaluates the OCT evidence (i.e. neointimal coverage of stent struts within 3 months) for shortening DAPT duration after DES implantation.Expert commentary Shortening DAPT (i.e. within 3 months) duration after DES implantation might reduce complications including bleeding without increasing stent thrombosis. However, the optimal duration of DAPT after DES implantation is under discussion. Long-term assessment of short DAPT is required for the decision of the new guidelines regarding the recommended duration of DAPT.Background/objectives This study aims to analyze the positive outcomes observed in cardiovascular outcomes trials conducted with sodium-glucose co-transporter inhibitors and determine their statistical and clinical significance.Methods A literature search conducted using the Cochrane library resulted in five citations - randomized controlled trials (RCTs), identified for analysis. Positive cardio-renal outcomes from the five RCTs were analyzed in accordance with a pre-defined strategy which included the hierarchical flow chart, presence of a persuasive p-value (p  less then  0.001), and number needed to treat (NNT) estimation calculated from the absolute risk reduction (ARR) reported.Results Only four instances fulfilled these stringent criteria - reduction of cardiovascular (CV) death with empagliflozin in T2DM patients with established atherosclerotic cardiovascular disease (eASCVD) (p  less then  0.001; NNT 45), reduction in cardiorenal outcomes with canagliflozin in a pooled T2DM population with macroalbuminuria (p  less then  0.00001; NNT 22), as well as reduction in the composite of CV death or hospitalization for heart failure (hHF) (p  less then  0.001; NNT 30) and also reduction in hHF or CV death with dapagliflozin in T2DM with heart failure with reduced ejection fraction (HFrEF) (p  less then  0.001; NNT 21).Conclusions Statistically positive outcome results must be interpreted in the context of associated clinical benefits and not in isolation.Introduction Pharmaceutical research and development (R&D) is costly and only a minority of patients can access innovative medicines due to affordability constraints. Value-added medicines (VAMs) can offer potential benefits at significantly lower R&D costs.Areas covered VAMs may address different health care needs and problems, including off-label use of medicines, poor patient adherence, problems related to polypharmacy, need for home and/or personalized health care services. However, several barriers prevent societies from maximizing the benefits of incremental innovation related to VAMs. Generic manufacturers have limited budget and experience to demonstrate the value of new VAMs. Current market exclusivity options do not efficiently exclude freeridership and do not guarantee a return on investment for VAM innovators. Value propositions of VAMs are limitedly consistent with current HTA frameworks, consequently, incremental innovation is not acknowledged, nor rewarded with differential pricing by payers. Moreover, VAMs are often perceived solely as generic medicines by prescribers.
    Introduction Radiotherapy is an important therapeutic strategy in the management of non-small cell lung cancer (NSCLC). In recent decades, technological implementations and the introduction of image guided radiotherapy (IGRT) have significantly increased the accuracy and tolerability of radiation therapy.Area covered In this review, we provide an overview of technological opportunities and future prospects in NSCLC management.Expert opinion Stereotactic body radiotherapy (SBRT) is now considered the standard approach in patients ineligible for surgery, while in operable cases, it is still under debate. Additionally, in combination with systemic treatment, SBRT is an innovative option for managing oligometastatic patients and features encouraging initial results in clinical outcomes. To date, in inoperable locally advanced NSCLC, the radical dose prescription has not changed (60 Gy in 30 fractions), despite the median overall survival progressively increasing. These results arise from technological improvements in precisely hitting target treatment volumes and organ at risk sparing, which are associated with better treatment qualities. Finally, for the management of NSCLC, proton and carbon ion therapies and the recent development of MR-Linac are new, intriguing technological approaches under investigation.Objectives Different microorganisms contribute in the pregnancy bacteriuria, which resistance microorganisms limited the therapeutic options for the treatment and increasing the related risks to pregnant women and their pregnancy. Based on this, asymptomatic bacteriuria and the use of inappropriate empirical antibiotics are dangerous in the emergence of pregnancy complications and the incidence of drug resistant.Methods A comprehensive systematic search was performed on all international databases including Scopus, PubMed, Web of Science, Medline, Cochrane library during 2000 - June 2019. This meta-analysis, which was registered by a pre-defined protocol in PROSPRO, carried out in accordance with PRISMA guideline. Relevant articles were included in the analysis if reported the susceptibility pattern of antimicrobial resistance related to asymptomatic bacteria in pregnant women with no acute diseases. Overall prevalence and related 95% confidence interval for resistance in different asymptomatic infections were estimated by inverse variance method. The random effect model was used in case of considerable heterogeneity.Results Results of this analysis demonstrated different resistance rate against studied classes of antibiotics. Nitrofurantoin resistance in E. coli, Klebsiella sp, P. aeruginosa, and Staphylococcus aureus isolates were estimated 0.22 (95%CI 0.15-0.30), 0.40 (95%CI 0.26-0.54), 0.81 (95%CI 0.59-0.97), 0.34 (0.11-0.63), respectively. https://www.selleckchem.com/products/hsp27-inhibitor-j2.html Subgroups analysis showed highest resistance in E. coli isolates, in Asia and Africa against Cefotaxime and Ampicillin, respectively.Conclusion In summary, increasing resistance rate in urinary tract infection (UTI)-related agents is a risk factor that endangers both mother and fetus. Health care providers should consider screening as the radical part of infection control strategies. Due to low resistance rate to Nitrofurantoin, this drug can be a good choice for UTI treatment in pregnancies, but it should use with caution.Introduction Dual antiplatelet therapy (DAPT) is required for coronary artery disease treated with drug-eluting stents (DES) implantation. Shortening DAPT duration would be beneficial for patients with high bleeding risk.Areas covered Early healing patterns, especially stent strut coverage, assessed by optical coherence tomography (OCT) as a surrogate of neointima have been investigated to make decisions on whether short DAPT would be a safe alternative. This review evaluates the OCT evidence (i.e. neointimal coverage of stent struts within 3 months) for shortening DAPT duration after DES implantation.Expert commentary Shortening DAPT (i.e. within 3 months) duration after DES implantation might reduce complications including bleeding without increasing stent thrombosis. However, the optimal duration of DAPT after DES implantation is under discussion. Long-term assessment of short DAPT is required for the decision of the new guidelines regarding the recommended duration of DAPT.Background/objectives This study aims to analyze the positive outcomes observed in cardiovascular outcomes trials conducted with sodium-glucose co-transporter inhibitors and determine their statistical and clinical significance.Methods A literature search conducted using the Cochrane library resulted in five citations - randomized controlled trials (RCTs), identified for analysis. Positive cardio-renal outcomes from the five RCTs were analyzed in accordance with a pre-defined strategy which included the hierarchical flow chart, presence of a persuasive p-value (p  less then  0.001), and number needed to treat (NNT) estimation calculated from the absolute risk reduction (ARR) reported.Results Only four instances fulfilled these stringent criteria - reduction of cardiovascular (CV) death with empagliflozin in T2DM patients with established atherosclerotic cardiovascular disease (eASCVD) (p  less then  0.001; NNT 45), reduction in cardiorenal outcomes with canagliflozin in a pooled T2DM population with macroalbuminuria (p  less then  0.00001; NNT 22), as well as reduction in the composite of CV death or hospitalization for heart failure (hHF) (p  less then  0.001; NNT 30) and also reduction in hHF or CV death with dapagliflozin in T2DM with heart failure with reduced ejection fraction (HFrEF) (p  less then  0.001; NNT 21).Conclusions Statistically positive outcome results must be interpreted in the context of associated clinical benefits and not in isolation.Introduction Pharmaceutical research and development (R&D) is costly and only a minority of patients can access innovative medicines due to affordability constraints. Value-added medicines (VAMs) can offer potential benefits at significantly lower R&D costs.Areas covered VAMs may address different health care needs and problems, including off-label use of medicines, poor patient adherence, problems related to polypharmacy, need for home and/or personalized health care services. However, several barriers prevent societies from maximizing the benefits of incremental innovation related to VAMs. Generic manufacturers have limited budget and experience to demonstrate the value of new VAMs. Current market exclusivity options do not efficiently exclude freeridership and do not guarantee a return on investment for VAM innovators. Value propositions of VAMs are limitedly consistent with current HTA frameworks, consequently, incremental innovation is not acknowledged, nor rewarded with differential pricing by payers. Moreover, VAMs are often perceived solely as generic medicines by prescribers.
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  • Background Hypertension is the most common chronic disease and is the leading cause of morbidity and mortality. Its screening, diagnosis, and management depend heavily on accurate blood pressure (BP) measurement. It is recommended that the diagnosis of hypertension should be confirmed or corroborated by out-of-office BP values, measured using ambulatory BP monitoring (ABPM) and home BP monitoring (HBPM). When office BP is used, automated office BP (AOBP) measurement method, which automatically provides an average of 3-5 BP readings, should be preferred. This study aimed to describe the BP measurement methods commonly used by doctors in primary care in Hong Kong, to screen, diagnose, and manage hypertensive patients. Methods In this cross-sectional survey, all doctors registered in the Hong Kong "Primary Care Directory" were mailed a questionnaire, asking their preferred BP-measuring methods to screen, diagnose, and manage hypertensive patients. Furthermore, we also elicited information on the usual number of d manage hypertension, highlighting a marked underutilisation of AOBP and out-of-office BP measuring techniques, especially that of ABPM. Further studies are indicated to understand the underlying reasons and to minimise the gap between real-life clinical practice and those recommended, based on scientific advances. Trial registration Clinicaltrial.gov; ref. no. NCT03926897.Background HIV/AIDS is one of the most serious problems in many parts of the world, and is a high priority for health managers and decision-makers. The aim of the qualitative part of this study will be to develop a mobile SMS (short messaging services) counselling intervention to prevent HIV/AIDS, while the quantitative part will be to test the effectiveness of a mobile SMS counselling intervention to improve the knowledge, attitude, and practices of patients concerning the prevention of HIV/AIDS. Method A mixed methods approach will be used. Qualitative part Design focus group discussions (FGDs) will be conducted. Setting Hospital/NGOs in Terengganu, Malaysia. Participants Three FGDs will be conducted with male and female HIV/AIDS patients, and one group of local community leaders. One FGD will be conducted for each group. Three in-depth interviews (IDIs) will be conducted with patients who had HIV/AIDS, of which one will be female. Quantitative part Design a cluster randomized clinical trial with 384 HIV/AIDS patients in Terengganu, Malaysia. Intervention Mobile SMS counselling intervention for patients concerning the prevention of HIV/AIDS. Results The main outcomes of this study will be the differences in knowledge, attitude, and practices of patients concerning the prevention of HIV/AIDS between the baseline and immediate follow-up after the intervention, and after 3 months. Conclusions The mobile based SMS counselling intervention developed will be effective in improving the knowledge, attitude, and practices of patients concerning HIV/AIDS prevention in Terengganu, Malaysia. Trial registration Thai Clinical Trials Registry, TCTR20200212001; 7/02/2020.Background DL-3-n-butylphthalide (NBP) was demonstrated to increase the cerebral blood flow (CBF) in the animal models, but there are no clinic studies to verify this. We aimed to explore the effect of NBP on improving cerebral hypoperfusion caused by cerebral large-vessel stenosis. Methods In this single-center, randomized, double-blind, placebo-controlled study, 120 patients with severe carotid atherosclerotic stenosis and cerebral hypoperfusion in the ipsilateral middle cerebral artery (MCA) were included and randomly assigned into NBP or placebo group as 11 radio. Patients in NBP or placebo group received 200 mg or 20 mg of NBP capsules three times daily for four weeks respectively. Single photon emission computed tomography (SPECT) was used to assess regional CBF (rCBF) in four regions of interest (ROIs) corresponding to MCA before and 12 weeks after the treatment. After therapy, the rCBF change for every ROI and the whole CBF change in MCA territory for every patient were classified into amelioration, s2019- Retrospectively registered (http//www.chictr.org.cn/index.aspx).Background People with migration background and dementia are a vulnerable group. Providing care for this group is a public health challenge in Europe. An increasing number of countries are issuing national dementia plans, but a systematic overview of national dementia plans of European countries focusing on care for people with migration background is lacking. This study aims to illustrate how European countries identify the dementia-related needs of people with migration background and whether there are specific healthcare services for them at the national level. Methods A qualitative analysis of national dementia plans of the EU and EFTA (European Free Trade Association) countries was carried out. Using the discourse analysis model according to Rainer Keller (2011), documents were systematically screened for their relation to migration via keyword and context analysis. The content of the migration-related sections was analyzed using the methods of paraphrasing, memos, comments, and open coding. https://www.selleckchem.com/products/pi4kiiibeta-in-10.html Results Twenparability at the European level, a common definition of migration is needed. Further studies should include country-specific problems related to dementia and migration.Background The provision of epidural analgesia during labor is ideally a shared decision between the woman and her health care provider. However, immigrant characteristics such as maternal birthplace could affect decision-making and thus access to pain relief. We aimed to assess disparities in the provision of epidural analgesia in planned vaginal birth according to maternal region of birth. Methods We performed a nation-wide register study of 842,496 live-born singleton deliveries in Norway between 2000 and 2015. Maternal birthplace was categorized according to the Global Burden of Disease framework. The provision of epidural analgesia was compared in regression models stratified by parity and mode of delivery. Results Compared to native-born women, primiparous women from Latin America/Caribbean countries with an instrumental vaginal delivery were most likely to be provided epidural analgesia (OR 2.12, 95%CI 1.69-2.66), whilst multiparous women from Sub-Saharan Africa with a spontaneous vaginal delivery were least likely to be provided epidural analgesia (OR 0.
    Background Hypertension is the most common chronic disease and is the leading cause of morbidity and mortality. Its screening, diagnosis, and management depend heavily on accurate blood pressure (BP) measurement. It is recommended that the diagnosis of hypertension should be confirmed or corroborated by out-of-office BP values, measured using ambulatory BP monitoring (ABPM) and home BP monitoring (HBPM). When office BP is used, automated office BP (AOBP) measurement method, which automatically provides an average of 3-5 BP readings, should be preferred. This study aimed to describe the BP measurement methods commonly used by doctors in primary care in Hong Kong, to screen, diagnose, and manage hypertensive patients. Methods In this cross-sectional survey, all doctors registered in the Hong Kong "Primary Care Directory" were mailed a questionnaire, asking their preferred BP-measuring methods to screen, diagnose, and manage hypertensive patients. Furthermore, we also elicited information on the usual number of d manage hypertension, highlighting a marked underutilisation of AOBP and out-of-office BP measuring techniques, especially that of ABPM. Further studies are indicated to understand the underlying reasons and to minimise the gap between real-life clinical practice and those recommended, based on scientific advances. Trial registration Clinicaltrial.gov; ref. no. NCT03926897.Background HIV/AIDS is one of the most serious problems in many parts of the world, and is a high priority for health managers and decision-makers. The aim of the qualitative part of this study will be to develop a mobile SMS (short messaging services) counselling intervention to prevent HIV/AIDS, while the quantitative part will be to test the effectiveness of a mobile SMS counselling intervention to improve the knowledge, attitude, and practices of patients concerning the prevention of HIV/AIDS. Method A mixed methods approach will be used. Qualitative part Design focus group discussions (FGDs) will be conducted. Setting Hospital/NGOs in Terengganu, Malaysia. Participants Three FGDs will be conducted with male and female HIV/AIDS patients, and one group of local community leaders. One FGD will be conducted for each group. Three in-depth interviews (IDIs) will be conducted with patients who had HIV/AIDS, of which one will be female. Quantitative part Design a cluster randomized clinical trial with 384 HIV/AIDS patients in Terengganu, Malaysia. Intervention Mobile SMS counselling intervention for patients concerning the prevention of HIV/AIDS. Results The main outcomes of this study will be the differences in knowledge, attitude, and practices of patients concerning the prevention of HIV/AIDS between the baseline and immediate follow-up after the intervention, and after 3 months. Conclusions The mobile based SMS counselling intervention developed will be effective in improving the knowledge, attitude, and practices of patients concerning HIV/AIDS prevention in Terengganu, Malaysia. Trial registration Thai Clinical Trials Registry, TCTR20200212001; 7/02/2020.Background DL-3-n-butylphthalide (NBP) was demonstrated to increase the cerebral blood flow (CBF) in the animal models, but there are no clinic studies to verify this. We aimed to explore the effect of NBP on improving cerebral hypoperfusion caused by cerebral large-vessel stenosis. Methods In this single-center, randomized, double-blind, placebo-controlled study, 120 patients with severe carotid atherosclerotic stenosis and cerebral hypoperfusion in the ipsilateral middle cerebral artery (MCA) were included and randomly assigned into NBP or placebo group as 11 radio. Patients in NBP or placebo group received 200 mg or 20 mg of NBP capsules three times daily for four weeks respectively. Single photon emission computed tomography (SPECT) was used to assess regional CBF (rCBF) in four regions of interest (ROIs) corresponding to MCA before and 12 weeks after the treatment. After therapy, the rCBF change for every ROI and the whole CBF change in MCA territory for every patient were classified into amelioration, s2019- Retrospectively registered (http//www.chictr.org.cn/index.aspx).Background People with migration background and dementia are a vulnerable group. Providing care for this group is a public health challenge in Europe. An increasing number of countries are issuing national dementia plans, but a systematic overview of national dementia plans of European countries focusing on care for people with migration background is lacking. This study aims to illustrate how European countries identify the dementia-related needs of people with migration background and whether there are specific healthcare services for them at the national level. Methods A qualitative analysis of national dementia plans of the EU and EFTA (European Free Trade Association) countries was carried out. Using the discourse analysis model according to Rainer Keller (2011), documents were systematically screened for their relation to migration via keyword and context analysis. The content of the migration-related sections was analyzed using the methods of paraphrasing, memos, comments, and open coding. https://www.selleckchem.com/products/pi4kiiibeta-in-10.html Results Twenparability at the European level, a common definition of migration is needed. Further studies should include country-specific problems related to dementia and migration.Background The provision of epidural analgesia during labor is ideally a shared decision between the woman and her health care provider. However, immigrant characteristics such as maternal birthplace could affect decision-making and thus access to pain relief. We aimed to assess disparities in the provision of epidural analgesia in planned vaginal birth according to maternal region of birth. Methods We performed a nation-wide register study of 842,496 live-born singleton deliveries in Norway between 2000 and 2015. Maternal birthplace was categorized according to the Global Burden of Disease framework. The provision of epidural analgesia was compared in regression models stratified by parity and mode of delivery. Results Compared to native-born women, primiparous women from Latin America/Caribbean countries with an instrumental vaginal delivery were most likely to be provided epidural analgesia (OR 2.12, 95%CI 1.69-2.66), whilst multiparous women from Sub-Saharan Africa with a spontaneous vaginal delivery were least likely to be provided epidural analgesia (OR 0.
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  • Retinal diseases, such as age-related macular degeneration (AMD), are the leading cause of blindness in the elderly population. Since no known cures are currently present, it is crucial to diagnose the condition in its early stages so that disease progression is monitored. https://www.selleckchem.com/products/ono-ae3-208.html Recent advances show that the mechanical elasticity of the posterior eye changes with the onset of AMD. In this work, we present a quantitative method of mapping the mechanical elasticity of the posterior eye using confocal shear wave acoustic radiation force optical coherence elastography (SW-ARF-OCE). This technique has been developed and validated with both an ex-vivo porcine tissue model and a customized in-vivo rabbit model, which both showed the quantified elasticity variations between different layers. This study verifies the feasibility of using this technology for the quantification and diagnosis of retinal diseases from the in-vivo posterior eye.In this work, we investigate two-dimensional arrays of High-T C superconducting quantum interference devices (SQUIDs) for optimization of their electrical transport characteristics. Specifically, we look at devices with different electrode configurations in between the series segments to gain insight into how the array spacing, in the direction of the bias current, affects the voltage magnetic field characteristics. Our results suggest that for spacing dimensions greater than the penetration depth interactions are minimal. Furthermore, comparisons of voltage field characteristics reveal higher modulation voltages and narrower peaks with as the numbers of SQUIDs in the parallel direction increases from 1 to 6. For larger numbers of SQUIDs in parallel greater than 6 little change is observed. These results suggest a pathway to SQUID array scaling for very large numbers of SQUIDs within in a small area.The purpose of this study was to identify the vessels feeding the FPL to reduce the FPL tendon ruptures related to VLP surgery. The dissections identified the FPL, radial artery (RA) and anterior interosseous artery (AIA). The mean number of branches of the RA and AIA to the FPL was 2.0 and 4.0, respectively. The distance from volar prominence of the radius to the most distal branch of the RA and AIA was 43 mm and 57 mm, respectively. The most distal branch would be frequently injured during VLP surgery because of its proximity to the surgical field. © 2020 Professor P K Surendran Memorial Education Foundation. Published by Elsevier B.V. All rights reserved.Aims To assess whether the degree of radiological retraction and chronicity of distal biceps tendon ruptures are related to the ability to reattach the tendon and long-term functional outcomes. Methods Analysis of consecutive patients undergoing surgery for distal biceps tendon ruptures by a single surgeon. Measurements regarding the site and degree of tendon retraction in relation to anatomical landmarks following rupture were correlated with intraoperative findings. Postoperative functional outcomes were assessed in cases with >12 months follow-up. Results 24 cases of distal biceps tendon ruptures treated surgically were identified. Mean tendon retraction was 6.0 cm (range 1.2-9.5) from the radial tuberosity. 22 cases were reattached successfully. 2 required ligament augmentation/bridging using a synthetic ligament. In 2 cases the tendon could not be reattached due to poor quality of the tendon stump. Ability to reattach the tendon was unrelated to degree of radiological retraction or chronicity of rupture. Degree of retraction was not related to rupture chronicity. All reattachments healed with no re-rupture at follow-up with no substantial motion loss. In 17 cases >12months follow-up the DASH and OES were not related to retraction or chronicity of rupture. Conclusions Radiological retraction and chronicity are not related to the ability to reattach distal biceps tendon ruptures or their clinical outcomes, hence should not discourage surgical exploration and attempted reattachment. Substantial tendon retractions can occur acutely and reattachment in considerable flexion did not produce any significant motion loss. Some cases will need augmentation or gap bridging and augmentation devices need to be available at surgery. Level of evidence Level IV Retrospective Study Defined. © 2019 Professor P K Surendran Memorial Education Foundation. Published by Elsevier B.V. All rights reserved.Purpose Determine the impact of self-citation on external funding for orthopedic fellowship directors. Methods The San Francisco Match's website identified directors encompassing 8 subspecialties. The Scopus database identified the number of publications, citations, and h-index for each director. H-index was assessed with/without self-citation. Results Mean publications, citations, self-citation rate, and h-index for the 446 directors were 71.2, 1816, 3.86%, and 18.3, respectively. Excluding self-citations reduces mean h-index to 18.0; and h-index changed by ≤ 1 integer in 95% of directors. Conclusions Self-citation has minimal impact among fellowship directors and should not be adjusted for when considering external funding.The purpose of this study is to assess the role of bioskills in orthopaedic and neurosurgical resident education. A survey of the utilization and perceived efficacy of bioskills was submitted to Lumbar Spine Research Society (LSRS) members. 36/104 surgeons responded, including 25 orthopaedic, 7 neurosurgical, and 4 integrated respondents. 63% of orthopaedic and 83% of neurosurgery faculty, reported using bioskills. When asked if completion of bioskills modules would encourage advancing trainees' participation (1-10 scale, 10 greatly increase), neurosurgical faculty reported 4.00 versus orthopaedics 6.43. Although orthopaedic faculty perceive greater efficacy of bioskills, the clinical impact of this difference remains uncertain. © 2020 Professor P K Surendran Memorial Education Foundation. Published by Elsevier B.V. All rights reserved.Purpose We performed a systematic review of the studies including clinical/functional outcomes and complications of bone grafting for glenoid defects in reverse total shoulder arthroplasty (RTSA). Methods The PubMed and Cochrane databases were searched for relevant papers. Results Thirteen articles were included. The mean clinical/functional subjective scores significantly improved postoperatively. The implant revision rate for primary and revision RTSA was 3.1% and 21.1% respectively. The reoperation rate was 3.5% and 24.4% respectively. Conclusions There was moderate evidence that bone grafting is effective for glenoid defects in primary RTSA. Further high-quality research is required about revision RTSA for moderate-to-severe glenoid defects. © 2019 Professor P K Surendran Memorial Education Foundation. Published by Elsevier B.V. All rights reserved.
    Retinal diseases, such as age-related macular degeneration (AMD), are the leading cause of blindness in the elderly population. Since no known cures are currently present, it is crucial to diagnose the condition in its early stages so that disease progression is monitored. https://www.selleckchem.com/products/ono-ae3-208.html Recent advances show that the mechanical elasticity of the posterior eye changes with the onset of AMD. In this work, we present a quantitative method of mapping the mechanical elasticity of the posterior eye using confocal shear wave acoustic radiation force optical coherence elastography (SW-ARF-OCE). This technique has been developed and validated with both an ex-vivo porcine tissue model and a customized in-vivo rabbit model, which both showed the quantified elasticity variations between different layers. This study verifies the feasibility of using this technology for the quantification and diagnosis of retinal diseases from the in-vivo posterior eye.In this work, we investigate two-dimensional arrays of High-T C superconducting quantum interference devices (SQUIDs) for optimization of their electrical transport characteristics. Specifically, we look at devices with different electrode configurations in between the series segments to gain insight into how the array spacing, in the direction of the bias current, affects the voltage magnetic field characteristics. Our results suggest that for spacing dimensions greater than the penetration depth interactions are minimal. Furthermore, comparisons of voltage field characteristics reveal higher modulation voltages and narrower peaks with as the numbers of SQUIDs in the parallel direction increases from 1 to 6. For larger numbers of SQUIDs in parallel greater than 6 little change is observed. These results suggest a pathway to SQUID array scaling for very large numbers of SQUIDs within in a small area.The purpose of this study was to identify the vessels feeding the FPL to reduce the FPL tendon ruptures related to VLP surgery. The dissections identified the FPL, radial artery (RA) and anterior interosseous artery (AIA). The mean number of branches of the RA and AIA to the FPL was 2.0 and 4.0, respectively. The distance from volar prominence of the radius to the most distal branch of the RA and AIA was 43 mm and 57 mm, respectively. The most distal branch would be frequently injured during VLP surgery because of its proximity to the surgical field. © 2020 Professor P K Surendran Memorial Education Foundation. Published by Elsevier B.V. All rights reserved.Aims To assess whether the degree of radiological retraction and chronicity of distal biceps tendon ruptures are related to the ability to reattach the tendon and long-term functional outcomes. Methods Analysis of consecutive patients undergoing surgery for distal biceps tendon ruptures by a single surgeon. Measurements regarding the site and degree of tendon retraction in relation to anatomical landmarks following rupture were correlated with intraoperative findings. Postoperative functional outcomes were assessed in cases with >12 months follow-up. Results 24 cases of distal biceps tendon ruptures treated surgically were identified. Mean tendon retraction was 6.0 cm (range 1.2-9.5) from the radial tuberosity. 22 cases were reattached successfully. 2 required ligament augmentation/bridging using a synthetic ligament. In 2 cases the tendon could not be reattached due to poor quality of the tendon stump. Ability to reattach the tendon was unrelated to degree of radiological retraction or chronicity of rupture. Degree of retraction was not related to rupture chronicity. All reattachments healed with no re-rupture at follow-up with no substantial motion loss. In 17 cases >12months follow-up the DASH and OES were not related to retraction or chronicity of rupture. Conclusions Radiological retraction and chronicity are not related to the ability to reattach distal biceps tendon ruptures or their clinical outcomes, hence should not discourage surgical exploration and attempted reattachment. Substantial tendon retractions can occur acutely and reattachment in considerable flexion did not produce any significant motion loss. Some cases will need augmentation or gap bridging and augmentation devices need to be available at surgery. Level of evidence Level IV Retrospective Study Defined. © 2019 Professor P K Surendran Memorial Education Foundation. Published by Elsevier B.V. All rights reserved.Purpose Determine the impact of self-citation on external funding for orthopedic fellowship directors. Methods The San Francisco Match's website identified directors encompassing 8 subspecialties. The Scopus database identified the number of publications, citations, and h-index for each director. H-index was assessed with/without self-citation. Results Mean publications, citations, self-citation rate, and h-index for the 446 directors were 71.2, 1816, 3.86%, and 18.3, respectively. Excluding self-citations reduces mean h-index to 18.0; and h-index changed by ≤ 1 integer in 95% of directors. Conclusions Self-citation has minimal impact among fellowship directors and should not be adjusted for when considering external funding.The purpose of this study is to assess the role of bioskills in orthopaedic and neurosurgical resident education. A survey of the utilization and perceived efficacy of bioskills was submitted to Lumbar Spine Research Society (LSRS) members. 36/104 surgeons responded, including 25 orthopaedic, 7 neurosurgical, and 4 integrated respondents. 63% of orthopaedic and 83% of neurosurgery faculty, reported using bioskills. When asked if completion of bioskills modules would encourage advancing trainees' participation (1-10 scale, 10 greatly increase), neurosurgical faculty reported 4.00 versus orthopaedics 6.43. Although orthopaedic faculty perceive greater efficacy of bioskills, the clinical impact of this difference remains uncertain. © 2020 Professor P K Surendran Memorial Education Foundation. Published by Elsevier B.V. All rights reserved.Purpose We performed a systematic review of the studies including clinical/functional outcomes and complications of bone grafting for glenoid defects in reverse total shoulder arthroplasty (RTSA). Methods The PubMed and Cochrane databases were searched for relevant papers. Results Thirteen articles were included. The mean clinical/functional subjective scores significantly improved postoperatively. The implant revision rate for primary and revision RTSA was 3.1% and 21.1% respectively. The reoperation rate was 3.5% and 24.4% respectively. Conclusions There was moderate evidence that bone grafting is effective for glenoid defects in primary RTSA. Further high-quality research is required about revision RTSA for moderate-to-severe glenoid defects. © 2019 Professor P K Surendran Memorial Education Foundation. Published by Elsevier B.V. All rights reserved.
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  • We conclude that APC/CTE plays a key role in regulating plant architecture by mediating the signaling cross talks between ABA and GA. © 2020 American Society of Plant Biologists. https://www.selleckchem.com/products/recilisib.html All rights reserved.Copy number variations (CNVs) greatly contribute to intraspecies genetic polymorphism and phenotypic diversity. Recent analyses of sequencing data for >1000 accessions of Arabidopsis thaliana were focused on small variations and did not include CNVs. Here, we performed a genome-wide analysis and identified large indels (50-499 bp) and CNVs (500 bp and larger) present in these accessions. The CNVs fully overlap with 18.3% of protein-coding genes, with enrichment for evolutionarily young genes and genes involved in stress and defense. By combined analysis of both genes and transposable elements affected by CNVs, we revealed that the variation statuses of genes and TEs are tightly linked and jointly contribute to the unequal distribution of these elements in the genome. We also determined the gene copy numbers in a set of 1,060 accessions, and we experimentally validated the accuracy of our predictions by multiplex ligation-dependent probe amplification assays. We then successfully used the CNVs as markers in an analysis of population structure and migration patterns. Additionally, we examined the impact of gene dosage variation triggered by a CNV spanning the SEC10 gene on SEC10 expression, both at the transcript and protein levels. The provided catalog of CNVs, CNV-overlapping genes and their genotypes in a top model dicot will stimulate the exploration of the genetic bases of phenotypic variation. © 2020 American Society of Plant Biologists. All rights reserved.The septo-hippocampal cholinergic system is critical for hippocampal learning and memory. However, a quantitative description of the in vivo firing patterns and physiological function of medial septal (MS) cholinergic neurons is still missing. In this study, we combined optogenetics with multi-channel in vivo recording and recorded MS cholinergic neurons' firings in freely behaving male **** for 5.5 - 72 hours. We found that their firing activities were highly correlated with hippocampal theta states. MS cholinergic neurons were highly active during theta-dominant epochs, such as active exploration (AE) and rapid eye movement (REM) sleep, but almost silent during non-theta epochs, such as slow wave sleep (SWS). Interestingly, optogenetic activation of these MS cholinergic neurons during SWS suppressed CA1 ripple oscillations. This suppression could be rescued by muscarinic M2 or M4 receptor antagonists. These results suggest an important physiological function of MS cholinergic neurons maintaining high hippocampal acetylcholine (ACh) level by persistent firing during theta epochs, consequently suppressing ripples and allowing theta oscillations to dominate.Significance StatementThe major source of acetylcholine in the hippocampus comes from the medial septum. Early experiments found that lesions to the MS result in the disappearance of hippocampal theta oscillation, which leads to the speculation of the septo-hippocampal cholinergic projection contributing to theta oscillation. In this paper, by long-term recording of MS cholinergic neurons, we found that they do show theta-state-related firing pattern. However, optogenetically activating these neurons shows little effect on theta rhythm in the hippocampus. Instead, we found that activating MS cholinergic neurons during SWS could suppress hippocampal ripple oscillations. This suppression is mediated by muscarinic M2 and M4 receptors. Copyright © 2020 Ma et al.The action potential (AP) waveform controls the opening of voltage-gated calcium channels and contributes to the driving force for calcium ion flux that triggers neurotransmission at presynaptic nerve terminals. Although the frog neuromuscular junction (NMJ) has long been a model synapse for the study of neurotransmission, its presynaptic AP waveform has never been directly studied, and thus the AP waveform shape and propagation through this long presynaptic nerve terminal are unknown. Using a fast voltage-sensitive dye, we have imaged the AP waveform from the presynaptic terminal of male and female frog NMJs and shown that the AP is very brief in duration and actively propagated down the entire length of the terminal. Furthermore, based on measured AP waveforms at different regions along the length of the nerve terminal, we show that the terminal is divided into three distinct electrical regions A beginning region immediately after the last node of Ranvier where the AP is broadest, a middle region with a relh et al.The Drosophila nervous system is ensheathed by a layer of outer glial cells, the perineurial glia, and a specialized extracellular matrix, the neural lamella. The function of perineurial glial cells and how they interact with the extracellular matrix is just beginning to be elucidated. Integrin-based focal adhesion complexes link the glial membrane to the extracellular matrix, but little is known about integrin's regulators in the glia. The transmembrane Ig domain protein Basigin/CD147/EMMPRIN is highly expressed in the perineurial glia surrounding the Drosophila larval nervous system. Here we show that Basigin associates with integrin at the focal adhesions in order to uphold the structure of the glia-extracellular matrix sheath. Knock down of Basigin in perineurial glia using RNAi results in significant shortening of the ventral nerve cord, compression of the glia and extracellular matrix in the peripheral nerves, and reduction in larval locomotion. We determined that Basigin is expressed in close proximityroper ensheathment of the central and peripheral nervous systems. Loss of Bsg in the glia results in an overall compression of the nervous system due to integrin dysregulation, which causes locomotor defects in the animals. This underlies the importance of glia-matrix communication for structural and functional support of the nervous system. Copyright © 2020 Hunter et al.Synaptic dysfunction provoking dysregulated cortical neural circuits is currently hypothesized as a key pathophysiological process underlying clinical manifestations in Alzheimer's disease and related neurodegenerative tauopathies. Here, we conducted positron emission tomography (PET) along with postmortem assays to investigate time-course changes of excitatory and inhibitory synaptic constituents in an rTg4510 mouse model of tauopathy, which develops tau pathologies leading to noticeable brain atrophy at 5-6 months of age. Both male and female **** were analyzed in this study. We observed that radiosignals derived from [11C]flumazenil, a tracer for benzodiazepine receptor, in rTg4510 **** were significantly lower than the levels in non-transgenic littermates at 2-3 months of age. In contrast, retentions of (E)-[11C]ABP688, a tracer for mGluR5, were unaltered relative to controls at 2 months of age but then gradually declined with aging in parallel with progressive brain atrophy. Biochemical and immunohistochemical assessment of postmortem brain tissues demonstrated that inhibitory but not excitatory synaptic constituents selectively diminished without overt loss of somas of GABAergic interneurons in the neocortex and hippocampus of rTg4510 **** at 2 months of age, which was concurrent with enhanced immunoreactivity of cFos, a well-characterized immediate early gene, suggesting that impaired inhibitory neurotransmission may cause hyperexcitability of cortical circuits.
    We conclude that APC/CTE plays a key role in regulating plant architecture by mediating the signaling cross talks between ABA and GA. © 2020 American Society of Plant Biologists. https://www.selleckchem.com/products/recilisib.html All rights reserved.Copy number variations (CNVs) greatly contribute to intraspecies genetic polymorphism and phenotypic diversity. Recent analyses of sequencing data for >1000 accessions of Arabidopsis thaliana were focused on small variations and did not include CNVs. Here, we performed a genome-wide analysis and identified large indels (50-499 bp) and CNVs (500 bp and larger) present in these accessions. The CNVs fully overlap with 18.3% of protein-coding genes, with enrichment for evolutionarily young genes and genes involved in stress and defense. By combined analysis of both genes and transposable elements affected by CNVs, we revealed that the variation statuses of genes and TEs are tightly linked and jointly contribute to the unequal distribution of these elements in the genome. We also determined the gene copy numbers in a set of 1,060 accessions, and we experimentally validated the accuracy of our predictions by multiplex ligation-dependent probe amplification assays. We then successfully used the CNVs as markers in an analysis of population structure and migration patterns. Additionally, we examined the impact of gene dosage variation triggered by a CNV spanning the SEC10 gene on SEC10 expression, both at the transcript and protein levels. The provided catalog of CNVs, CNV-overlapping genes and their genotypes in a top model dicot will stimulate the exploration of the genetic bases of phenotypic variation. © 2020 American Society of Plant Biologists. All rights reserved.The septo-hippocampal cholinergic system is critical for hippocampal learning and memory. However, a quantitative description of the in vivo firing patterns and physiological function of medial septal (MS) cholinergic neurons is still missing. In this study, we combined optogenetics with multi-channel in vivo recording and recorded MS cholinergic neurons' firings in freely behaving male mice for 5.5 - 72 hours. We found that their firing activities were highly correlated with hippocampal theta states. MS cholinergic neurons were highly active during theta-dominant epochs, such as active exploration (AE) and rapid eye movement (REM) sleep, but almost silent during non-theta epochs, such as slow wave sleep (SWS). Interestingly, optogenetic activation of these MS cholinergic neurons during SWS suppressed CA1 ripple oscillations. This suppression could be rescued by muscarinic M2 or M4 receptor antagonists. These results suggest an important physiological function of MS cholinergic neurons maintaining high hippocampal acetylcholine (ACh) level by persistent firing during theta epochs, consequently suppressing ripples and allowing theta oscillations to dominate.Significance StatementThe major source of acetylcholine in the hippocampus comes from the medial septum. Early experiments found that lesions to the MS result in the disappearance of hippocampal theta oscillation, which leads to the speculation of the septo-hippocampal cholinergic projection contributing to theta oscillation. In this paper, by long-term recording of MS cholinergic neurons, we found that they do show theta-state-related firing pattern. However, optogenetically activating these neurons shows little effect on theta rhythm in the hippocampus. Instead, we found that activating MS cholinergic neurons during SWS could suppress hippocampal ripple oscillations. This suppression is mediated by muscarinic M2 and M4 receptors. Copyright © 2020 Ma et al.The action potential (AP) waveform controls the opening of voltage-gated calcium channels and contributes to the driving force for calcium ion flux that triggers neurotransmission at presynaptic nerve terminals. Although the frog neuromuscular junction (NMJ) has long been a model synapse for the study of neurotransmission, its presynaptic AP waveform has never been directly studied, and thus the AP waveform shape and propagation through this long presynaptic nerve terminal are unknown. Using a fast voltage-sensitive dye, we have imaged the AP waveform from the presynaptic terminal of male and female frog NMJs and shown that the AP is very brief in duration and actively propagated down the entire length of the terminal. Furthermore, based on measured AP waveforms at different regions along the length of the nerve terminal, we show that the terminal is divided into three distinct electrical regions A beginning region immediately after the last node of Ranvier where the AP is broadest, a middle region with a relh et al.The Drosophila nervous system is ensheathed by a layer of outer glial cells, the perineurial glia, and a specialized extracellular matrix, the neural lamella. The function of perineurial glial cells and how they interact with the extracellular matrix is just beginning to be elucidated. Integrin-based focal adhesion complexes link the glial membrane to the extracellular matrix, but little is known about integrin's regulators in the glia. The transmembrane Ig domain protein Basigin/CD147/EMMPRIN is highly expressed in the perineurial glia surrounding the Drosophila larval nervous system. Here we show that Basigin associates with integrin at the focal adhesions in order to uphold the structure of the glia-extracellular matrix sheath. Knock down of Basigin in perineurial glia using RNAi results in significant shortening of the ventral nerve cord, compression of the glia and extracellular matrix in the peripheral nerves, and reduction in larval locomotion. We determined that Basigin is expressed in close proximityroper ensheathment of the central and peripheral nervous systems. Loss of Bsg in the glia results in an overall compression of the nervous system due to integrin dysregulation, which causes locomotor defects in the animals. This underlies the importance of glia-matrix communication for structural and functional support of the nervous system. Copyright © 2020 Hunter et al.Synaptic dysfunction provoking dysregulated cortical neural circuits is currently hypothesized as a key pathophysiological process underlying clinical manifestations in Alzheimer's disease and related neurodegenerative tauopathies. Here, we conducted positron emission tomography (PET) along with postmortem assays to investigate time-course changes of excitatory and inhibitory synaptic constituents in an rTg4510 mouse model of tauopathy, which develops tau pathologies leading to noticeable brain atrophy at 5-6 months of age. Both male and female mice were analyzed in this study. We observed that radiosignals derived from [11C]flumazenil, a tracer for benzodiazepine receptor, in rTg4510 mice were significantly lower than the levels in non-transgenic littermates at 2-3 months of age. In contrast, retentions of (E)-[11C]ABP688, a tracer for mGluR5, were unaltered relative to controls at 2 months of age but then gradually declined with aging in parallel with progressive brain atrophy. Biochemical and immunohistochemical assessment of postmortem brain tissues demonstrated that inhibitory but not excitatory synaptic constituents selectively diminished without overt loss of somas of GABAergic interneurons in the neocortex and hippocampus of rTg4510 mice at 2 months of age, which was concurrent with enhanced immunoreactivity of cFos, a well-characterized immediate early gene, suggesting that impaired inhibitory neurotransmission may cause hyperexcitability of cortical circuits.
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  • The expression of IL-6 was significantly raised in cases compared to controls (P = 0.018). IL-8 and IL-10 were also raised in cases, compared to controls (P = 0.284 and P = 0.018). An increased plasma TNF-α was observed in cases (1.36-fold and P = 0.289). The mRNA expression of IFN-γ was also increased in cases compared to controls (0.87-fold). However, the plasma level of IFN-γ was higher in the non-influenza controls compared to cases. Conclusions The study revealed a differential cytokine profile during influenza virus infection in the population, which may influence disease severity. An extended study on host immune response may provide better insights for the use of cytokine antagonists in therapeutic treatments among severe cases of influenza virus infection.Aims Cervical cancer is one of the leading causes of cancer among women, worldwide. HIV-positive women tend to have persistent infection and infection with multiple human papillomavirus (HPV) types. There is a need for affordable HPV DNA tests as viable alternatives to the existing costly commercial assays. The aim of the study was to establish PGMY-CHUV reverse hybridization assay as a cost-effective tool for HPV genotyping. Study design This was a prospective study conducted in a tertiary care centre from March 2011 to July 2012. Subjects and methods Fifty cervical brush samples from HIV-infected women and 43 WHO reference samples were tested by both the CHUV assay and linear array (LA). Results The CHUV assay in comparison to the LA showed a sensitivity of 91%, specificity of 52% and a moderate agreement for all samples that were compared. However, most high-risk HPV types were identified amongst the clinical samples, and the entire range of genotypes in the WHO reference panel was detected. Statistical analysis The accuracy indices such as sensitivity, specificity, positive predictive value and negative predictive value were calculated. The level of agreement (kappa value) between the two assays was also calculated. Conclusion The CHUV assay had an acceptable sensitivity, but it lacked specificity for HPV detection. Despite the lower rates of detection of multiple infections from clinical samples, better results were obtained with the WHO reference samples and the ability of the assay to identify the entire range of genotypes suggests that it can be an efficient tool for genotyping.Introduction Over the past four decades, there has been an increase in the number of fatal opportunistic invasive trichosporonosis cases especially in immunocompromised hosts. Objective The objective of the study is to evaluate the epidemiological, clinical details and antifungal susceptibility pattern of the patients with Trichosporon infections. Materials and methods Twenty-four clinical isolates of Trichosporon species isolated from blood, samples, pleural fluid and nail were included in this study, over a period of 12 years (2005-2016) in a tertiary hospital in North India. The isolates were characterised phenotypically and few representative isolates were sequenced also. The minimum inhibitory concentration (MIC) was determined as per Clinical and Laboratory Standards Institute, 2012. Results Trichosporon spp. from blood culture (57.78%), nail (37.5%) and pleural fluid (4.17%). On phenotypic tests, 79.16% of the isolates were Trichosporon asahii, followed by Trichosporon dermatis (8.33%), Trichosporon jarable outcomes.Background A single-stage implant revision for failed fixation of proximal femoral fractures is performed only when there is no evidence of infection. Else, a two-staged revision is preferred - where the definitive revision surgery is done a few months after the implant exit. This study aims to audit the safety and incidence of culture positivity in single-stage revisions. Materials and methods Forty one of 284 patients that presented over the last 12 years for implant exchange of the hip, had a single stage revision surgery for failed fixation of a fracture of the hip, as there was no obvious evidence of infection at the time of implant exit. Results Micro-organisms were grown in 51% of the 41 hips. https://www.selleckchem.com/products/dl-thiorphan.html 76% were gram positive, of which 63% were Coagulase negative staphylococci (CoNS). 50% of CoNS and 75% of S. aureus were resistant to oxacillin, but susceptible to Vancomycin. Of the gram negative organisms, 2 (Enterobacter sp) were resistant to carbapenam, while others were susceptible. Preoperative ESR and CRP, individually, had low specificity - 50% for ESR >30mm at 1 hour and 62% for CRP>10. The combined use of ESR > 30mm and CRP>10 increased the specificity to 90%. 12% of the patients had immediate postoperative complications that required a wash out in theatre. The long term clinical follow up of these patients is limited. Conclusion This study suggests that implant exit and simultaneous arthroplasty for failed fracture fixation should be done with caution due to the high possibility of infection. It may be prudent to opt for a 2 stage revision.Introduction It was also known that the IncP-1 plasmids are ubiquitous in environmental bacteria and those reside in soil, sewage, marine sediments and in manure. The blaNDMis associated with resistance determinants along with various mobile elements such as plasmid, insertion sequences and transposons, which facilitates its horizontal dissemination. These plasmids, if tracked, can be a starting point for the control of infection due to multidrug-resistant pathogens. The aim of the study was to investigate that IncP-type plasmids carrying blaNDMis adapted in different hosts. Materials and methods Thirteen of the isolates were harbouring IncP-type plasmid and they all were Escherichia coli isolated from hospitalised patients of Silchar Medical College and Hospital, India. The isolates were checked for susceptibility test, and the stability was assessed by a serial passage. These isolates were further subjected to transcriptional analysis of NDM gene as well as plasmid copy number alteration. Results The study isolates were highly stable, and the resistance gene (blaNDM) was retained within isolates till 55th subsequent serial passages. Plasmid copy number alteration was random in isolates when exposed to carbapenem antibiotics, whereas increasing trend in transcriptional expression was observed with the increase in imipenem concentration. Conclusion This study was able to underscore the presence of IncP plasmid that was harbouring blaNDMand was maintained within diverse host. The finding also highlights the adaptation of the broad-host-range plasmid that responds in terms of transcriptional expression under antibiotic exposure.
    The expression of IL-6 was significantly raised in cases compared to controls (P = 0.018). IL-8 and IL-10 were also raised in cases, compared to controls (P = 0.284 and P = 0.018). An increased plasma TNF-α was observed in cases (1.36-fold and P = 0.289). The mRNA expression of IFN-γ was also increased in cases compared to controls (0.87-fold). However, the plasma level of IFN-γ was higher in the non-influenza controls compared to cases. Conclusions The study revealed a differential cytokine profile during influenza virus infection in the population, which may influence disease severity. An extended study on host immune response may provide better insights for the use of cytokine antagonists in therapeutic treatments among severe cases of influenza virus infection.Aims Cervical cancer is one of the leading causes of cancer among women, worldwide. HIV-positive women tend to have persistent infection and infection with multiple human papillomavirus (HPV) types. There is a need for affordable HPV DNA tests as viable alternatives to the existing costly commercial assays. The aim of the study was to establish PGMY-CHUV reverse hybridization assay as a cost-effective tool for HPV genotyping. Study design This was a prospective study conducted in a tertiary care centre from March 2011 to July 2012. Subjects and methods Fifty cervical brush samples from HIV-infected women and 43 WHO reference samples were tested by both the CHUV assay and linear array (LA). Results The CHUV assay in comparison to the LA showed a sensitivity of 91%, specificity of 52% and a moderate agreement for all samples that were compared. However, most high-risk HPV types were identified amongst the clinical samples, and the entire range of genotypes in the WHO reference panel was detected. Statistical analysis The accuracy indices such as sensitivity, specificity, positive predictive value and negative predictive value were calculated. The level of agreement (kappa value) between the two assays was also calculated. Conclusion The CHUV assay had an acceptable sensitivity, but it lacked specificity for HPV detection. Despite the lower rates of detection of multiple infections from clinical samples, better results were obtained with the WHO reference samples and the ability of the assay to identify the entire range of genotypes suggests that it can be an efficient tool for genotyping.Introduction Over the past four decades, there has been an increase in the number of fatal opportunistic invasive trichosporonosis cases especially in immunocompromised hosts. Objective The objective of the study is to evaluate the epidemiological, clinical details and antifungal susceptibility pattern of the patients with Trichosporon infections. Materials and methods Twenty-four clinical isolates of Trichosporon species isolated from blood, samples, pleural fluid and nail were included in this study, over a period of 12 years (2005-2016) in a tertiary hospital in North India. The isolates were characterised phenotypically and few representative isolates were sequenced also. The minimum inhibitory concentration (MIC) was determined as per Clinical and Laboratory Standards Institute, 2012. Results Trichosporon spp. from blood culture (57.78%), nail (37.5%) and pleural fluid (4.17%). On phenotypic tests, 79.16% of the isolates were Trichosporon asahii, followed by Trichosporon dermatis (8.33%), Trichosporon jarable outcomes.Background A single-stage implant revision for failed fixation of proximal femoral fractures is performed only when there is no evidence of infection. Else, a two-staged revision is preferred - where the definitive revision surgery is done a few months after the implant exit. This study aims to audit the safety and incidence of culture positivity in single-stage revisions. Materials and methods Forty one of 284 patients that presented over the last 12 years for implant exchange of the hip, had a single stage revision surgery for failed fixation of a fracture of the hip, as there was no obvious evidence of infection at the time of implant exit. Results Micro-organisms were grown in 51% of the 41 hips. https://www.selleckchem.com/products/dl-thiorphan.html 76% were gram positive, of which 63% were Coagulase negative staphylococci (CoNS). 50% of CoNS and 75% of S. aureus were resistant to oxacillin, but susceptible to Vancomycin. Of the gram negative organisms, 2 (Enterobacter sp) were resistant to carbapenam, while others were susceptible. Preoperative ESR and CRP, individually, had low specificity - 50% for ESR >30mm at 1 hour and 62% for CRP>10. The combined use of ESR > 30mm and CRP>10 increased the specificity to 90%. 12% of the patients had immediate postoperative complications that required a wash out in theatre. The long term clinical follow up of these patients is limited. Conclusion This study suggests that implant exit and simultaneous arthroplasty for failed fracture fixation should be done with caution due to the high possibility of infection. It may be prudent to opt for a 2 stage revision.Introduction It was also known that the IncP-1 plasmids are ubiquitous in environmental bacteria and those reside in soil, sewage, marine sediments and in manure. The blaNDMis associated with resistance determinants along with various mobile elements such as plasmid, insertion sequences and transposons, which facilitates its horizontal dissemination. These plasmids, if tracked, can be a starting point for the control of infection due to multidrug-resistant pathogens. The aim of the study was to investigate that IncP-type plasmids carrying blaNDMis adapted in different hosts. Materials and methods Thirteen of the isolates were harbouring IncP-type plasmid and they all were Escherichia coli isolated from hospitalised patients of Silchar Medical College and Hospital, India. The isolates were checked for susceptibility test, and the stability was assessed by a serial passage. These isolates were further subjected to transcriptional analysis of NDM gene as well as plasmid copy number alteration. Results The study isolates were highly stable, and the resistance gene (blaNDM) was retained within isolates till 55th subsequent serial passages. Plasmid copy number alteration was random in isolates when exposed to carbapenem antibiotics, whereas increasing trend in transcriptional expression was observed with the increase in imipenem concentration. Conclusion This study was able to underscore the presence of IncP plasmid that was harbouring blaNDMand was maintained within diverse host. The finding also highlights the adaptation of the broad-host-range plasmid that responds in terms of transcriptional expression under antibiotic exposure.
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