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19/12/1992
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Accumulation and propagation of hyperphosphorylated tau (p-tau) is a common neuropathological hallmark associated with neurodegeneration of Alzheimer's disease (AD), frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17), and related tauopathies. Extracellular vesicles, specifically exosomes, have recently been demonstrated to participate in mediating tau propagation in brain. Exosomes produced by human induced pluripotent stem cell (iPSC)-derived neurons expressing mutant Tau (mTau), containing the P301L and V337M Tau mutations of FTDP-17, possess the ability to propagate p-tau pathology after injection into mouse brain. To gain an understanding of the mTau exosome cargo involved in tau pathogenesis, these pathogenic exosomes were analyzed by proteomics and bioinformatics. The data showed that mTau expression dysregulates the exosome proteome to result in (1) proteins uniquely present only in mTau, and not control exosomes, (2) the absence of proteins in mTau exosomes, uniquely present iu exosomes capable of in vivo propagation of p-tau neuropathology in mouse brain. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.Human infantile-onset RNASET2 deficient cystic leukoencephalopathy is a Mendelian mimic of in utero cytomegalovirus brain infection with prenatally developing inflammatory brain lesions. We used a RNASET2 deficient zebrafish model to elucidate the underlying disease mechanisms. Mutant and wildtype zebrafish larvae brain development between 2 and 5 days post fertilisation was examined by confocal live imaging in fluorescent reporter lines of major types of brain cells. In contrast to wild type brains, RNASET2 deficient larvae displayed increased numbers of microglia with altered morphology often containing inclusions of neurons. Furthermore, lysosomes within distinct populations of the myeloid cell lineage including microglia showed increased lysosomal staining. Neurons and oligodendrocyte precursor cells remained unaffected. This study provides first insight into the prenatal onset pathomechanisms of human RNASET2 deficient leukoencephalopathy, linking this inborn lysosomal disease to the innate immune system and other immune-related childhood encephalopathies like Aicardi-Goutieres syndrome (AGS). © 2020. Published by The Company of Biologists Ltd.Previously, we have developed an extramitochondrial assembly system, where mitochondrial targeting signal (MTS) can be removed from a given mitochondrial enzyme, which could be used to characterize the regulatory factors involved in enzyme assembly/disassembly in vivo Here, we demonstrate that addition of exogenous acetaldehyde can quickly induce the supramolecular assembly of MTS-deleted aldehyde dehydrogenase Ald4p in yeast cytoplasm. Also, by using PCR-based modification of the yeast genome, cytoplasmically targeted Ald4p cannot polymerize into long filaments when key functional amino acid residues are substituted, as shown by N192D, S269A, E290K and C324A mutations. This study has confirmed that extramitochondrial assembly could be a powerful external system for studying mitochondrial enzyme assembly, and its regulatory factors outside the mitochondria. In addition, we propose that mitochondrial enzyme assembly/disassembly is coupled to the regulation of a given mitochondrial enzyme activity. © 2020. Published by The Company of Biologists Ltd.The five-protein MuvB core complex is highly conserved in animals. This nuclear complex interacts with RB family tumor suppressor proteins and E2F-DP transcription factors to form DREAM complexes that repress genes that regulate cell cycle progression and cell fate. The MuvB core complex also interacts with proteins Myb family oncoproteins to form the Myb-MuvB complexes that activate many of the same genes. We show that animal-type Myb genes are present in Bilateria, Cnidaria, and Placozoa, the latter including the simplest known animal species. However, bilaterian nematode worms lost their animal-type Myb genes hundreds of millions of years ago. Nevertheless, amino acids in the LIN9 and LIN52 proteins that directly interact with the MuvB-binding domains of human B-Myb and Drosophila Myb are conserved in C. elegans Here we show that, despite greater than 500 million years since their last common ancestor, the Drosophila melanogaster Myb protein can bind to the nematode LIN9-LIN52 proteins in vitro and can cause a synthetic multivulval (synMuv) phenotype in vivo This phenotype is similar to that caused by loss-of-function mutations in C. elegans synMuvB class genes including those that encode homologs of the MuvB core, RB, E2F, and DP. Furthermore, amino acid substitutions in the MuvB-binding domain of Drosophila Myb that disrupt its functions in vitro and in vivo also disrupt these activities in C. elegans We speculate that nematodes and other animals may contain another protein that can bind to LIN9 and LIN52 in order to activate transcription of genes repressed by DREAM complexes. © 2020. Published by The Company of Biologists Ltd.Atherogenic LDL particles are physicochemically and metabolically heterogeneous. Can bioactive lipid cargo differentiate LDL subclasses, and thus potential atherogenicity? What is the effect of statin treatment? Obese, hypertriglyceridemic, hypercholesterolemic males (n=12; Lp(a) less then 10 mg/dL) received pitavastatin calcium (4mg/day) for 180 days in a single-phase, unblinded study. The lipidomic profiles (23 lipid classes) of five LDL subclasses fractionated from baseline and post-statin plasmas were determined by LC-MS. At baseline and on statin treatment, very small dense LDL (LDL5) was preferentially enriched (up to 3-fold) in specific lysophospholipids (lysophosphatidylcholine (LPC); lysophosphatidylinositol (LPI); lyso-platelet activating factor (LPC(O)); 9,0.2 and 0.14 mol/mol apoB respectively; all p less then 0.001 versus LDL1-4), suggesting elevated inflammatory potential per particle. In contrast, lysophosphatidylethanolamine was uniformly distributed among LDL subclasses. Statin treatment markedly reduced absolute plasma concentrations of all LDL subclasses (up to 33.5%), including LPC, LPI and LPC(O) contents (up to -52%), consistent with reduction in cardiovascular risk. Despite such reductions, lipotoxic ceramide load per particle in LDL1-5 (1.5 - 3 mol/mol apoB; 3 - 7 mmol/mol phosphatidylcholine) was either conserved or elevated. https://www.selleckchem.com/products/17-DMAG,Hydrochloride-Salt.html Bioactive lipids may constitute biomarkers for the cardiometabolic risk associated with specific LDL subclasses in atherogenic dyslipidemia at baseline, and with residual risk on statin therapy. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.
Accumulation and propagation of hyperphosphorylated tau (p-tau) is a common neuropathological hallmark associated with neurodegeneration of Alzheimer's disease (AD), frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17), and related tauopathies. Extracellular vesicles, specifically exosomes, have recently been demonstrated to participate in mediating tau propagation in brain. Exosomes produced by human induced pluripotent stem cell (iPSC)-derived neurons expressing mutant Tau (mTau), containing the P301L and V337M Tau mutations of FTDP-17, possess the ability to propagate p-tau pathology after injection into mouse brain. To gain an understanding of the mTau exosome cargo involved in tau pathogenesis, these pathogenic exosomes were analyzed by proteomics and bioinformatics. The data showed that mTau expression dysregulates the exosome proteome to result in (1) proteins uniquely present only in mTau, and not control exosomes, (2) the absence of proteins in mTau exosomes, uniquely present iu exosomes capable of in vivo propagation of p-tau neuropathology in mouse brain. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.Human infantile-onset RNASET2 deficient cystic leukoencephalopathy is a Mendelian mimic of in utero cytomegalovirus brain infection with prenatally developing inflammatory brain lesions. We used a RNASET2 deficient zebrafish model to elucidate the underlying disease mechanisms. Mutant and wildtype zebrafish larvae brain development between 2 and 5 days post fertilisation was examined by confocal live imaging in fluorescent reporter lines of major types of brain cells. In contrast to wild type brains, RNASET2 deficient larvae displayed increased numbers of microglia with altered morphology often containing inclusions of neurons. Furthermore, lysosomes within distinct populations of the myeloid cell lineage including microglia showed increased lysosomal staining. Neurons and oligodendrocyte precursor cells remained unaffected. This study provides first insight into the prenatal onset pathomechanisms of human RNASET2 deficient leukoencephalopathy, linking this inborn lysosomal disease to the innate immune system and other immune-related childhood encephalopathies like Aicardi-Goutieres syndrome (AGS). © 2020. Published by The Company of Biologists Ltd.Previously, we have developed an extramitochondrial assembly system, where mitochondrial targeting signal (MTS) can be removed from a given mitochondrial enzyme, which could be used to characterize the regulatory factors involved in enzyme assembly/disassembly in vivo Here, we demonstrate that addition of exogenous acetaldehyde can quickly induce the supramolecular assembly of MTS-deleted aldehyde dehydrogenase Ald4p in yeast cytoplasm. Also, by using PCR-based modification of the yeast genome, cytoplasmically targeted Ald4p cannot polymerize into long filaments when key functional amino acid residues are substituted, as shown by N192D, S269A, E290K and C324A mutations. This study has confirmed that extramitochondrial assembly could be a powerful external system for studying mitochondrial enzyme assembly, and its regulatory factors outside the mitochondria. In addition, we propose that mitochondrial enzyme assembly/disassembly is coupled to the regulation of a given mitochondrial enzyme activity. © 2020. Published by The Company of Biologists Ltd.The five-protein MuvB core complex is highly conserved in animals. This nuclear complex interacts with RB family tumor suppressor proteins and E2F-DP transcription factors to form DREAM complexes that repress genes that regulate cell cycle progression and cell fate. The MuvB core complex also interacts with proteins Myb family oncoproteins to form the Myb-MuvB complexes that activate many of the same genes. We show that animal-type Myb genes are present in Bilateria, Cnidaria, and Placozoa, the latter including the simplest known animal species. However, bilaterian nematode worms lost their animal-type Myb genes hundreds of millions of years ago. Nevertheless, amino acids in the LIN9 and LIN52 proteins that directly interact with the MuvB-binding domains of human B-Myb and Drosophila Myb are conserved in C. elegans Here we show that, despite greater than 500 million years since their last common ancestor, the Drosophila melanogaster Myb protein can bind to the nematode LIN9-LIN52 proteins in vitro and can cause a synthetic multivulval (synMuv) phenotype in vivo This phenotype is similar to that caused by loss-of-function mutations in C. elegans synMuvB class genes including those that encode homologs of the MuvB core, RB, E2F, and DP. Furthermore, amino acid substitutions in the MuvB-binding domain of Drosophila Myb that disrupt its functions in vitro and in vivo also disrupt these activities in C. elegans We speculate that nematodes and other animals may contain another protein that can bind to LIN9 and LIN52 in order to activate transcription of genes repressed by DREAM complexes. © 2020. Published by The Company of Biologists Ltd.Atherogenic LDL particles are physicochemically and metabolically heterogeneous. Can bioactive lipid cargo differentiate LDL subclasses, and thus potential atherogenicity? What is the effect of statin treatment? Obese, hypertriglyceridemic, hypercholesterolemic males (n=12; Lp(a) less then 10 mg/dL) received pitavastatin calcium (4mg/day) for 180 days in a single-phase, unblinded study. The lipidomic profiles (23 lipid classes) of five LDL subclasses fractionated from baseline and post-statin plasmas were determined by LC-MS. At baseline and on statin treatment, very small dense LDL (LDL5) was preferentially enriched (up to 3-fold) in specific lysophospholipids (lysophosphatidylcholine (LPC); lysophosphatidylinositol (LPI); lyso-platelet activating factor (LPC(O)); 9,0.2 and 0.14 mol/mol apoB respectively; all p less then 0.001 versus LDL1-4), suggesting elevated inflammatory potential per particle. In contrast, lysophosphatidylethanolamine was uniformly distributed among LDL subclasses. Statin treatment markedly reduced absolute plasma concentrations of all LDL subclasses (up to 33.5%), including LPC, LPI and LPC(O) contents (up to -52%), consistent with reduction in cardiovascular risk. Despite such reductions, lipotoxic ceramide load per particle in LDL1-5 (1.5 - 3 mol/mol apoB; 3 - 7 mmol/mol phosphatidylcholine) was either conserved or elevated. https://www.selleckchem.com/products/17-DMAG,Hydrochloride-Salt.html Bioactive lipids may constitute biomarkers for the cardiometabolic risk associated with specific LDL subclasses in atherogenic dyslipidemia at baseline, and with residual risk on statin therapy. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.0 Yorumlar 0 hisse senetleri 15 Views 0 önizlemePlease log in to like, share and comment! -
Additionally, N-propargylpiperidine 16 is an irreversible and time-dependent inhibitor of MAO-B, while N-benzylpiperidine 10 is reversible. Additionally, compounds 10, 13, 16, and 22 should be able to cross the blood-brain barrier and are not cytotoxic to human neuronal-like SH-SY5Y and liver HepG2 cells. Finally, compounds 10 and 16 also prevent amyloid β1-42 (Aβ1-42)-induced neuronal cell death. https://www.selleckchem.com/products/abc294640.html The neuroprotective effects of compound 16 could be the result of its Aβ1-42 anti-aggregation effects.Long regarded as a disease exclusively found amongst Northern Europeans, Dupuytren's disease was seldom studied amongst Black Africans. Thus, we sought to study the impact of Dupuytren's disease, its etiological, clinical and evolutionary peculiarities on a segment of the Senegalese population. This study analyzed data derived from clinical observations carried out between January 2006 and December 2018. It involved Senegalese subjects with Dupuytren's disease, the patients' history, profession, habitus, clinical findings, therapeutic modalities and disease staging. The population included 20 men and 6 women averaging 63.5 years of age (range 45-77). None of the patients reported a family of Dupuytren's disease. Twelve patients had diabetes, 11 were smokers and 22 were engaged exclusively in manual labor. The condition was bilateral in 14 cases. Tubiana stages N, I, II, III and IV were found in 31, 15, 9, 5 and 6 rays, respectively. Conservative treatment was done in 11 patients. Surgical treatment was carried out in the other 15 patients needle fasciotomy (N=10) including two bilateral involvement and open fasciectomy (N=7). Functional outcomes were satisfactory. Lesions were all stable in the short and medium term. Two patients had progressive lesions on a longer-term basis. Dupuytren's disease is real among Afro-descendants from Senegal even though it is seldom studied. Based on the patients' recollection of Dupuytren's disease in their families, heredity is not yet a proven factor. The early forms are more common, and the lesions remain stable for a long time.We previously reported that interleukin (IL)-6 in the red nucleus (RN) is involved in the maintenance of neuropathic pain induced by spared nerve injury (SNI), and exerts a facilitatory effect via Janus-activated kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) and extracellular signal-regulated kinase (ERK) signal transduction pathways. The present study aimed at investigating the roles of tumor necrosis factor-α (TNF-α) and IL-1β in RN IL-6-mediated maintenance of neuropathic pain and related signal transduction pathways. Being similar to the elevation of RN IL-6 three weeks after SNI, increased protein levels of both TNF-α and IL-1β were also observed in the contralateral RN three weeks after the nerve injury. The upregulations of TNF-α and IL-1β were closely correlative with IL-6 and suppressed by intrarubral injection of a neutralizing antibody against IL-6. Administration of either the JAK2 antagonist AG490 or the ERK antagonist PD98059 to the RN of rats with SNI remarkably increased the paw withdrawal threshold (PWT) and inhibited the up-regulations of local TNF-α and IL-1β. Further experiments indicated that intrarubral injection of exogenous IL-6 in naive rats apparently lowered the PWT of the contralateral hindpaw and boosted the local expressions of TNF-α and IL-1β. Pretreatment with AG490 could block IL-6-induced tactile hypersensitivity and suppress the up-regulations of both TNF-α and IL-1β. However, injection of PD98059 in advance only inhibited the upregulation of IL-1β, but not TNF-α. These findings indicate that RN IL-6 mediates the maintenance of neuropathic pain by inducing the productions of TNF-α and IL-1β. IL-6 induces the expression of TNF-α through the JAK2/STAT3 pathway, and the production of IL-1β through the JAK2/STAT3 and ERK pathways.Objective To evaluate the personal protective equipment (PPE) utilized in common urologic procedures before and during the COVID-19 outbreak in the United States. As elective urologic procedures are being reduced to conserve resources, we sought to quantify the PPE used per case to determine the impact on potentially limited resources needed for protecting healthcare providers treating COVID-19 patients. Methods An IRB approved retrospective analysis of all urologic procedures in March 2019 and March 2020 was performed. Additionally, all urologic procedures performed by vascular interventional radiology (VIR) in May 2019 and March 2020 were included in the analysis. Case length, surgical and operating room staff present and number of articles of PPE were quantified. Articles of PPE were defined as surgical bonnet/hat and mask, and disposable or reusable gown with 1 pair of surgical gloves. Results Four hundred and thirty-seven urologic and VIR procedures were included in the analysis. The mean PPE per case varied significantly between endoscopic and robotic categories. Robotic assisted laparoscopic cystectomy required the most hats and masks (14.5 per case in March 2019) whereas percutaneous nephrostomy tube placement by VIR required the fewest (3.1 in May 2019 and March 2020). Conclusion PPE consumption varied significantly across urologic procedures. Robotic-assisted cases require the most PPE and percutaneous nephrostomy placement by VIR requires the fewest. While PPE shortages are currently being addressed national and internationally, our results provide a baseline benchmark for articles of PPE required should another pandemic or global disaster requiring careful attention to resource allocation occur in the future.The ectoparasitic mite Varroa destructor is the most significant pathological threat to the western honey bee, Apis mellifera, leading to the death of most colonies if left untreated. An alternative approach to chemical treatments is to selectively enhance heritable honey bee traits of resistance or tolerance to the mite through breeding programs, or select for naturally surviving untreated colonies. We conducted a literature review of all studies documenting traits of A. mellifera populations either selectively bred or naturally selected for resistance and tolerance to mite parasitism. This allowed us to conduct an analysis of the diversity, distribution and importance of the traits in different honey bee populations that can survive V. destructor globally. In a second analysis, we investigated the genetic bases of these different phenotypes by comparing 'omics studies (genomics, transcriptomics, and proteomics) of A. mellifera resistance and tolerance to the parasite. Altogether, this review provides a detailed overview of the current state of the research projects and breeding efforts against the most devastating parasite of A.
Additionally, N-propargylpiperidine 16 is an irreversible and time-dependent inhibitor of MAO-B, while N-benzylpiperidine 10 is reversible. Additionally, compounds 10, 13, 16, and 22 should be able to cross the blood-brain barrier and are not cytotoxic to human neuronal-like SH-SY5Y and liver HepG2 cells. Finally, compounds 10 and 16 also prevent amyloid β1-42 (Aβ1-42)-induced neuronal cell death. https://www.selleckchem.com/products/abc294640.html The neuroprotective effects of compound 16 could be the result of its Aβ1-42 anti-aggregation effects.Long regarded as a disease exclusively found amongst Northern Europeans, Dupuytren's disease was seldom studied amongst Black Africans. Thus, we sought to study the impact of Dupuytren's disease, its etiological, clinical and evolutionary peculiarities on a segment of the Senegalese population. This study analyzed data derived from clinical observations carried out between January 2006 and December 2018. It involved Senegalese subjects with Dupuytren's disease, the patients' history, profession, habitus, clinical findings, therapeutic modalities and disease staging. The population included 20 men and 6 women averaging 63.5 years of age (range 45-77). None of the patients reported a family of Dupuytren's disease. Twelve patients had diabetes, 11 were smokers and 22 were engaged exclusively in manual labor. The condition was bilateral in 14 cases. Tubiana stages N, I, II, III and IV were found in 31, 15, 9, 5 and 6 rays, respectively. Conservative treatment was done in 11 patients. Surgical treatment was carried out in the other 15 patients needle fasciotomy (N=10) including two bilateral involvement and open fasciectomy (N=7). Functional outcomes were satisfactory. Lesions were all stable in the short and medium term. Two patients had progressive lesions on a longer-term basis. Dupuytren's disease is real among Afro-descendants from Senegal even though it is seldom studied. Based on the patients' recollection of Dupuytren's disease in their families, heredity is not yet a proven factor. The early forms are more common, and the lesions remain stable for a long time.We previously reported that interleukin (IL)-6 in the red nucleus (RN) is involved in the maintenance of neuropathic pain induced by spared nerve injury (SNI), and exerts a facilitatory effect via Janus-activated kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) and extracellular signal-regulated kinase (ERK) signal transduction pathways. The present study aimed at investigating the roles of tumor necrosis factor-α (TNF-α) and IL-1β in RN IL-6-mediated maintenance of neuropathic pain and related signal transduction pathways. Being similar to the elevation of RN IL-6 three weeks after SNI, increased protein levels of both TNF-α and IL-1β were also observed in the contralateral RN three weeks after the nerve injury. The upregulations of TNF-α and IL-1β were closely correlative with IL-6 and suppressed by intrarubral injection of a neutralizing antibody against IL-6. Administration of either the JAK2 antagonist AG490 or the ERK antagonist PD98059 to the RN of rats with SNI remarkably increased the paw withdrawal threshold (PWT) and inhibited the up-regulations of local TNF-α and IL-1β. Further experiments indicated that intrarubral injection of exogenous IL-6 in naive rats apparently lowered the PWT of the contralateral hindpaw and boosted the local expressions of TNF-α and IL-1β. Pretreatment with AG490 could block IL-6-induced tactile hypersensitivity and suppress the up-regulations of both TNF-α and IL-1β. However, injection of PD98059 in advance only inhibited the upregulation of IL-1β, but not TNF-α. These findings indicate that RN IL-6 mediates the maintenance of neuropathic pain by inducing the productions of TNF-α and IL-1β. IL-6 induces the expression of TNF-α through the JAK2/STAT3 pathway, and the production of IL-1β through the JAK2/STAT3 and ERK pathways.Objective To evaluate the personal protective equipment (PPE) utilized in common urologic procedures before and during the COVID-19 outbreak in the United States. As elective urologic procedures are being reduced to conserve resources, we sought to quantify the PPE used per case to determine the impact on potentially limited resources needed for protecting healthcare providers treating COVID-19 patients. Methods An IRB approved retrospective analysis of all urologic procedures in March 2019 and March 2020 was performed. Additionally, all urologic procedures performed by vascular interventional radiology (VIR) in May 2019 and March 2020 were included in the analysis. Case length, surgical and operating room staff present and number of articles of PPE were quantified. Articles of PPE were defined as surgical bonnet/hat and mask, and disposable or reusable gown with 1 pair of surgical gloves. Results Four hundred and thirty-seven urologic and VIR procedures were included in the analysis. The mean PPE per case varied significantly between endoscopic and robotic categories. Robotic assisted laparoscopic cystectomy required the most hats and masks (14.5 per case in March 2019) whereas percutaneous nephrostomy tube placement by VIR required the fewest (3.1 in May 2019 and March 2020). Conclusion PPE consumption varied significantly across urologic procedures. Robotic-assisted cases require the most PPE and percutaneous nephrostomy placement by VIR requires the fewest. While PPE shortages are currently being addressed national and internationally, our results provide a baseline benchmark for articles of PPE required should another pandemic or global disaster requiring careful attention to resource allocation occur in the future.The ectoparasitic mite Varroa destructor is the most significant pathological threat to the western honey bee, Apis mellifera, leading to the death of most colonies if left untreated. An alternative approach to chemical treatments is to selectively enhance heritable honey bee traits of resistance or tolerance to the mite through breeding programs, or select for naturally surviving untreated colonies. We conducted a literature review of all studies documenting traits of A. mellifera populations either selectively bred or naturally selected for resistance and tolerance to mite parasitism. This allowed us to conduct an analysis of the diversity, distribution and importance of the traits in different honey bee populations that can survive V. destructor globally. In a second analysis, we investigated the genetic bases of these different phenotypes by comparing 'omics studies (genomics, transcriptomics, and proteomics) of A. mellifera resistance and tolerance to the parasite. Altogether, this review provides a detailed overview of the current state of the research projects and breeding efforts against the most devastating parasite of A.0 Yorumlar 0 hisse senetleri 14 Views 0 önizleme -
Acute kidney injury (AKI), once viewed predominantly as a self-limited and reversible condition, is now recognized as a growing problem associated with significant risks of adverse long-term health outcomes. Many cohort studies have established important relationships between AKI and subsequent risks of recurrent AKI, hospital re-admission, morbidity and mortality from cardiovascular disease and cancer, as well as the development of chronic kidney disease and end-stage kidney disease. In both high-income countries (HICs) and low-income or middle-income countries (LMICs), several challenges exist in providing high-quality, patient-centered care following AKI. Despite advances in our understanding about the long-term risks following AKI, large gaps in knowledge remain about effective interventions that can improve the outcomes of patients. Therapies for high blood pressure, glycaemic control (for patients with diabetes), renin-angiotensin inhibition and statins might be important in improving long-term cardiovascular and kidney outcomes after AKI. Novel strategies that incorporate risk stratification approaches, educational interventions and new models of ambulatory care following AKI have been described, and some of these are now being implemented and evaluated in clinical studies in HICs. Care for AKI in LMICs must overcome additional barriers due to limited resources for diagnosis and management.We investigated blood pressure (BP) and heart rate variability and baroreflex sensitivity (BRS) in white-coat, masked and sustained hypertension in untreated patients (n = 645). Normotension and white-coat, masked, and sustained hypertension were defined according to the clinic (cutoff 140/90 mmHg) and 24-h ambulatory (130/80 mmHg) BPs. The Finometer device recorded beat-to-beat finger BP and electrocardiograms in the supine and standing positions for the computation of frequency-domain power-spectral BP and heart rate variability indexes and BRS. In multivariate analysis, BP variability indexes in the supine position differed significantly (P less then 0.0001) for both low-frequency (LF) and high-frequency (HF) components and the LF/HF ratio, with the lowest LF and HF power and highest LF/HF ratio in white-coat hypertension (n = 28), the highest LF and HF power and lowest LF/HF ratio in sustained hypertension (n = 198), and intermediate values in normotension (n = 189) and masked hypertension (n = 230). These differences diminished in the standing position, being significant (P less then 0.0001) only for the LF component variability. The LF/HF ratio in BP in the supine position decreased with advancing age in normotension and sustained hypertension (P ≤ 0.03) but not white-coat or masked hypertension (P ≥ 0.12). For heart rate variability, a significant difference was observed only for the LF component in the supine position (P = 0.0005), which was lowest in white-coat hypertension. BRS in masked and sustained hypertension was significantly (P ≤ 0.0001) lower than that in normotension in both supine and standing positions and decreased with advancing age (P ≤ 0.0001). In conclusion, masked, but not white-coat, hypertension showed similar patterns of, but slightly less severe, changes in BP and heart rate variability and BRS to sustained hypertension.RNA interference (RNAi), a cellular process through which small RNAs target and regulate complementary RNA transcripts, has well-characterized roles in post-transcriptional gene regulation and transposon repression. Recent studies have revealed additional conserved roles for RNAi proteins, such as Argonaute and Dicer, in chromosome function. By guiding chromatin modification, RNAi components promote chromosome segregation during both mitosis and meiosis and regulate chromosomal and genomic dosage response. Small RNAs and the RNAi machinery also participate in the resolution of DNA damage. Interestingly, many of these lesser-studied functions seem to be more strongly conserved across eukaryotes than are well-characterized functions such as the processing of microRNAs. These findings have implications for the evolution of RNAi since the last eukaryotic common ancestor, and they provide a more complete view of the functions of RNAi.An amendment to this paper has been published and can be accessed via a link at the top of the paper.Induced pluripotent stem cells (iPSCs) from patients with genetic disorders are a valuable source for in vitro disease models, which enable drug testing and validation of gene and cell therapies. We generated iPSCs from a severe congenital neutropenia (SCN) patient, who presented with a nonsense mutation in the glucose-6-phosphatase catalytic subunit 3 (G6PC3) gene causing profound defects in granulopoiesis, associated with increased susceptibility of neutrophils to apoptosis. Generated SCN iPSC clones exhibited the capacity to differentiate into hematopoietic cells of the myeloid lineage and we identified two cytokine conditions, i.e., using granulocyte-colony stimulating factor or granulocyte-macrophage colony stimulating factor in combination with interleukin-3, to model the SCN phenotype in vitro. Reduced numbers of granulocytes were produced by SCN iPSCs compared with control iPSCs in both settings, which reflected the phenotype in patients. Interestingly, our model showed increased monocyte/macrophage production from the SCN iPSCs. Most importantly, lentiviral genetic correction of SCN iPSCs with a codon-optimized G6PC3 transgene restored granulopoiesis and reduced apoptosis of in vitro differentiated myeloid cells. Moreover, addition of vitamin B3 clearly induced granulocytic differentiation of SCN iPSCs and increased the number of neutrophils to levels comparable with those obtained from healthy control iPSCs. In summary, we established an iPSC-derived in vitro disease model, which will serve as a tool to test the potency of alternative treatment options for SCN patients, such as small molecules and gene therapeutic vectors.N6-methyladenine (N6-mA) of DNA is an emerging epigenetic mark in mammalian genome. Levels of N6-mA undergo drastic fluctuation during early embryogenesis, indicative of active regulation. Here we show that the 2-oxoglutarate-dependent oxygenase ALKBH1 functions as a nuclear eraser of N6-mA in unpairing regions (e.g., SIDD, Stress-Induced DNA Double Helix Destabilization regions) of mammalian genomes. Enzymatic profiling studies revealed that ALKBH1 prefers bubbled or bulged DNAs as substrate, instead of single-stranded (ss-) or double-stranded (ds-) DNAs. Structural studies of ALKBH1 revealed an unexpected "stretch-out" conformation of its "Flip1" motif, a conserved element that usually bends over catalytic center to facilitate substrate base flipping in other DNA demethylases. Thus, lack of a bending "Flip1" explains the observed preference of ALKBH1 for unpairing substrates, in which the flipped N6-mA is primed for catalysis. https://www.selleckchem.com/products/ri-1.html Co-crystal structural studies of ALKBH1 bound to a 21-mer bulged DNA explained the need of both flanking duplexes and a flipped base for recognition and catalysis.
Acute kidney injury (AKI), once viewed predominantly as a self-limited and reversible condition, is now recognized as a growing problem associated with significant risks of adverse long-term health outcomes. Many cohort studies have established important relationships between AKI and subsequent risks of recurrent AKI, hospital re-admission, morbidity and mortality from cardiovascular disease and cancer, as well as the development of chronic kidney disease and end-stage kidney disease. In both high-income countries (HICs) and low-income or middle-income countries (LMICs), several challenges exist in providing high-quality, patient-centered care following AKI. Despite advances in our understanding about the long-term risks following AKI, large gaps in knowledge remain about effective interventions that can improve the outcomes of patients. Therapies for high blood pressure, glycaemic control (for patients with diabetes), renin-angiotensin inhibition and statins might be important in improving long-term cardiovascular and kidney outcomes after AKI. Novel strategies that incorporate risk stratification approaches, educational interventions and new models of ambulatory care following AKI have been described, and some of these are now being implemented and evaluated in clinical studies in HICs. Care for AKI in LMICs must overcome additional barriers due to limited resources for diagnosis and management.We investigated blood pressure (BP) and heart rate variability and baroreflex sensitivity (BRS) in white-coat, masked and sustained hypertension in untreated patients (n = 645). Normotension and white-coat, masked, and sustained hypertension were defined according to the clinic (cutoff 140/90 mmHg) and 24-h ambulatory (130/80 mmHg) BPs. The Finometer device recorded beat-to-beat finger BP and electrocardiograms in the supine and standing positions for the computation of frequency-domain power-spectral BP and heart rate variability indexes and BRS. In multivariate analysis, BP variability indexes in the supine position differed significantly (P less then 0.0001) for both low-frequency (LF) and high-frequency (HF) components and the LF/HF ratio, with the lowest LF and HF power and highest LF/HF ratio in white-coat hypertension (n = 28), the highest LF and HF power and lowest LF/HF ratio in sustained hypertension (n = 198), and intermediate values in normotension (n = 189) and masked hypertension (n = 230). These differences diminished in the standing position, being significant (P less then 0.0001) only for the LF component variability. The LF/HF ratio in BP in the supine position decreased with advancing age in normotension and sustained hypertension (P ≤ 0.03) but not white-coat or masked hypertension (P ≥ 0.12). For heart rate variability, a significant difference was observed only for the LF component in the supine position (P = 0.0005), which was lowest in white-coat hypertension. BRS in masked and sustained hypertension was significantly (P ≤ 0.0001) lower than that in normotension in both supine and standing positions and decreased with advancing age (P ≤ 0.0001). In conclusion, masked, but not white-coat, hypertension showed similar patterns of, but slightly less severe, changes in BP and heart rate variability and BRS to sustained hypertension.RNA interference (RNAi), a cellular process through which small RNAs target and regulate complementary RNA transcripts, has well-characterized roles in post-transcriptional gene regulation and transposon repression. Recent studies have revealed additional conserved roles for RNAi proteins, such as Argonaute and Dicer, in chromosome function. By guiding chromatin modification, RNAi components promote chromosome segregation during both mitosis and meiosis and regulate chromosomal and genomic dosage response. Small RNAs and the RNAi machinery also participate in the resolution of DNA damage. Interestingly, many of these lesser-studied functions seem to be more strongly conserved across eukaryotes than are well-characterized functions such as the processing of microRNAs. These findings have implications for the evolution of RNAi since the last eukaryotic common ancestor, and they provide a more complete view of the functions of RNAi.An amendment to this paper has been published and can be accessed via a link at the top of the paper.Induced pluripotent stem cells (iPSCs) from patients with genetic disorders are a valuable source for in vitro disease models, which enable drug testing and validation of gene and cell therapies. We generated iPSCs from a severe congenital neutropenia (SCN) patient, who presented with a nonsense mutation in the glucose-6-phosphatase catalytic subunit 3 (G6PC3) gene causing profound defects in granulopoiesis, associated with increased susceptibility of neutrophils to apoptosis. Generated SCN iPSC clones exhibited the capacity to differentiate into hematopoietic cells of the myeloid lineage and we identified two cytokine conditions, i.e., using granulocyte-colony stimulating factor or granulocyte-macrophage colony stimulating factor in combination with interleukin-3, to model the SCN phenotype in vitro. Reduced numbers of granulocytes were produced by SCN iPSCs compared with control iPSCs in both settings, which reflected the phenotype in patients. Interestingly, our model showed increased monocyte/macrophage production from the SCN iPSCs. Most importantly, lentiviral genetic correction of SCN iPSCs with a codon-optimized G6PC3 transgene restored granulopoiesis and reduced apoptosis of in vitro differentiated myeloid cells. Moreover, addition of vitamin B3 clearly induced granulocytic differentiation of SCN iPSCs and increased the number of neutrophils to levels comparable with those obtained from healthy control iPSCs. In summary, we established an iPSC-derived in vitro disease model, which will serve as a tool to test the potency of alternative treatment options for SCN patients, such as small molecules and gene therapeutic vectors.N6-methyladenine (N6-mA) of DNA is an emerging epigenetic mark in mammalian genome. Levels of N6-mA undergo drastic fluctuation during early embryogenesis, indicative of active regulation. Here we show that the 2-oxoglutarate-dependent oxygenase ALKBH1 functions as a nuclear eraser of N6-mA in unpairing regions (e.g., SIDD, Stress-Induced DNA Double Helix Destabilization regions) of mammalian genomes. Enzymatic profiling studies revealed that ALKBH1 prefers bubbled or bulged DNAs as substrate, instead of single-stranded (ss-) or double-stranded (ds-) DNAs. Structural studies of ALKBH1 revealed an unexpected "stretch-out" conformation of its "Flip1" motif, a conserved element that usually bends over catalytic center to facilitate substrate base flipping in other DNA demethylases. Thus, lack of a bending "Flip1" explains the observed preference of ALKBH1 for unpairing substrates, in which the flipped N6-mA is primed for catalysis. https://www.selleckchem.com/products/ri-1.html Co-crystal structural studies of ALKBH1 bound to a 21-mer bulged DNA explained the need of both flanking duplexes and a flipped base for recognition and catalysis.0 Yorumlar 0 hisse senetleri 14 Views 0 önizleme -
INTRODUCTION Transrectal ultrasound of prostate provides better visual for biopsy. Transrectal ultrasound guided prostate biopsy is usually performed in men with an abnormal digital rectal examination, and elevated prostate specific antigen (>4ng/ml) or prostate specific antigen velocity (rate of prostate specific antigen change) i.e., >0.4-0.75ng/ml/year. The aim of the study is to find out the complications of transrectal ultrasound guided prostatic biopsies. METHODS This descriptive cross-sectional study was done among 50 patients who transrectal ultrasound guided prostatic biopsies in a tertiary care hospital, from July 2017 to July 2019 after receiving ethical approval from the Institutional Review Committee of Kathmandu Medical College and teaching hospital. Convenient sampling was done. All patients were informed about the potential benefits and risks of the transrectal ultrasound guided prostate biopsy and patients signed an informed written consent form. Statistical analysis was done by using Statistical Package for Social Sciences version 16. RESULTS Mean prostate specific antigen was 34.571 and mean weight of prostate was 44.6gm. Moderate to severe pain was experienced by 15 (30%), 2 (4%) had hematuria with fever accounting for 3 (6%) patients. All were managed conservatively with no mortality related to the procedure and complication. Three patients was positive for malignancy on re-biopsy. CONCLUSIONS Transrectal ultrasound guided biopsy of prostate is a pioneer experience in Nepal. It has proved to be an useful tool of diagnosis of suspected carcinoma of Prostate. Use of neurovascular block may reduce the pain during the procedure.INTRODUCTION Medical students are more prone to suffer from various physiological and psychological problems but rather than seeking for formal health care, they tend to do informal consultation and often practice self medication. Thus, this study aimed to find out the health seeking behavior of medical students. METHODS This descriptive cross-sectional study was done among first and second year medical students of a teaching hospital from September to November 2019 after taking ethical approval from Institutional Review Committe. Total of 235 students were included in the study and self administered questionnaire was used. Data entry and analysis was done using Statistical Package for Social Sciences version 20.0. RESULTS Among 235 students who participated in the study, 172 (73%) reported having health problems in the last 12 months, and fever and headache were commonly reported by 21 (13%) and 18 (50%) students, respectively. Total of 112 (65%) students visited hospital/clinic for health problems and reason given for not visiting hospital/clinic was 12 (28%) thinking that the problem was minor. University hospital was the most preferred place 189 (80%) during health problem and parents were the first people for consultation 116 (49%). Mean duration of absenteeism was 2.17±4.1 days and 167 (88%) visited hospital more than five times. CONCLUSIONS Health problems were common among students and most of them required multiple hospital visits. Many students seeked for health from hospital/ clinic but informal consultations were also seen.INTRODUCTION Odontophobia or dental fear is a "unique phobia with special psychosomatic components that impact on the dental health of the odontophobia persons". It is well documented that dental fear has a significant impact on dental care utilization behaviors. The objective of this study was to find out the level of dental fear among school children studying in government schools of Dharan, Nepal. METHODS A descriptive cross-sectional study was conducted from March to August 2017 among 215 school going children of Dharan of age group 6 to 15 years. Ethical approval was obtained. Children studying in six different government schools of Dharan were selected using two stage cluster sampling method. The Children's Fear Survey Schedule-Dental Subscale was used to measure dental fear among the study group. Data were entered in Microsoft Excel Sheet 2007 and analyzed in Statistical Package of Social Sciences 11.5. RESULTS This study showed that among the total study population, 96 (44.7%) had high fear, 62 (28.8%) had moderate fear and 57 (26.5%) had low dental fear. Among males, 29 (34.5%) had high fear whereas more than half of the female respondents had high fear. CONCLUSIONS The present study showed that most of the school going children had high fear of dental treatment. So, school health programs should be planned to make the children familiar to dentistry and proper treatment modalities should be provided to make the child comfortable to seek dental care.INTRODUCTION Among patients with Hepatic Encephalopathy, prevalence of Minimal HE varies between 30-50%. Identifying patients with MHE has been shown to improve with medications and delay development of Overt HE, however only limited clinicians screen for MHE in patients due to time consuming neuropsychological and neurophysiological tests. The Number Connection Test is an easy way to evaluate patients to diagnose MHE. The aim of this study is to find out the prevalence of covert hepatic encephalopathy. METHODS The descriptive cross-sectional study was done to find out the prevalence of covert hepatic encephalopathy among patients with chronic liver disease. https://www.selleckchem.com/products/pf-2545920.html To diagnose Covert HE which included MHE as well, NCT was used in Devanagari script. RESULTS The prevalence of covert hepatic encephalopathy is found to be 56 (58.3%) at 90% confidence interval (58.23-58.37%). A total of 96 patients (71.9% male) were diagnosed as HE, with mean age of 49.6+11.8 years. The cause of CLD in 85 (88.5%) of these patients was alcohol, of which 76 (79.2%) consumed locally brewed alcohol. Of these 96 patients with HE, only 40 (41.7%) had overt HE. Among all these, maximum patients had MHE (37.5%). CONCLUSIONS Our study showed that although the prevalence of minimal HE is quite high among cirrhotics, they are usually missed in clinical practice due to absence of symptoms. Active screening with easy-to-administer tests, like Number Connection tests, can help identify patients with minimal HE and hence treat them early.
INTRODUCTION Transrectal ultrasound of prostate provides better visual for biopsy. Transrectal ultrasound guided prostate biopsy is usually performed in men with an abnormal digital rectal examination, and elevated prostate specific antigen (>4ng/ml) or prostate specific antigen velocity (rate of prostate specific antigen change) i.e., >0.4-0.75ng/ml/year. The aim of the study is to find out the complications of transrectal ultrasound guided prostatic biopsies. METHODS This descriptive cross-sectional study was done among 50 patients who transrectal ultrasound guided prostatic biopsies in a tertiary care hospital, from July 2017 to July 2019 after receiving ethical approval from the Institutional Review Committee of Kathmandu Medical College and teaching hospital. Convenient sampling was done. All patients were informed about the potential benefits and risks of the transrectal ultrasound guided prostate biopsy and patients signed an informed written consent form. Statistical analysis was done by using Statistical Package for Social Sciences version 16. RESULTS Mean prostate specific antigen was 34.571 and mean weight of prostate was 44.6gm. Moderate to severe pain was experienced by 15 (30%), 2 (4%) had hematuria with fever accounting for 3 (6%) patients. All were managed conservatively with no mortality related to the procedure and complication. Three patients was positive for malignancy on re-biopsy. CONCLUSIONS Transrectal ultrasound guided biopsy of prostate is a pioneer experience in Nepal. It has proved to be an useful tool of diagnosis of suspected carcinoma of Prostate. Use of neurovascular block may reduce the pain during the procedure.INTRODUCTION Medical students are more prone to suffer from various physiological and psychological problems but rather than seeking for formal health care, they tend to do informal consultation and often practice self medication. Thus, this study aimed to find out the health seeking behavior of medical students. METHODS This descriptive cross-sectional study was done among first and second year medical students of a teaching hospital from September to November 2019 after taking ethical approval from Institutional Review Committe. Total of 235 students were included in the study and self administered questionnaire was used. Data entry and analysis was done using Statistical Package for Social Sciences version 20.0. RESULTS Among 235 students who participated in the study, 172 (73%) reported having health problems in the last 12 months, and fever and headache were commonly reported by 21 (13%) and 18 (50%) students, respectively. Total of 112 (65%) students visited hospital/clinic for health problems and reason given for not visiting hospital/clinic was 12 (28%) thinking that the problem was minor. University hospital was the most preferred place 189 (80%) during health problem and parents were the first people for consultation 116 (49%). Mean duration of absenteeism was 2.17±4.1 days and 167 (88%) visited hospital more than five times. CONCLUSIONS Health problems were common among students and most of them required multiple hospital visits. Many students seeked for health from hospital/ clinic but informal consultations were also seen.INTRODUCTION Odontophobia or dental fear is a "unique phobia with special psychosomatic components that impact on the dental health of the odontophobia persons". It is well documented that dental fear has a significant impact on dental care utilization behaviors. The objective of this study was to find out the level of dental fear among school children studying in government schools of Dharan, Nepal. METHODS A descriptive cross-sectional study was conducted from March to August 2017 among 215 school going children of Dharan of age group 6 to 15 years. Ethical approval was obtained. Children studying in six different government schools of Dharan were selected using two stage cluster sampling method. The Children's Fear Survey Schedule-Dental Subscale was used to measure dental fear among the study group. Data were entered in Microsoft Excel Sheet 2007 and analyzed in Statistical Package of Social Sciences 11.5. RESULTS This study showed that among the total study population, 96 (44.7%) had high fear, 62 (28.8%) had moderate fear and 57 (26.5%) had low dental fear. Among males, 29 (34.5%) had high fear whereas more than half of the female respondents had high fear. CONCLUSIONS The present study showed that most of the school going children had high fear of dental treatment. So, school health programs should be planned to make the children familiar to dentistry and proper treatment modalities should be provided to make the child comfortable to seek dental care.INTRODUCTION Among patients with Hepatic Encephalopathy, prevalence of Minimal HE varies between 30-50%. Identifying patients with MHE has been shown to improve with medications and delay development of Overt HE, however only limited clinicians screen for MHE in patients due to time consuming neuropsychological and neurophysiological tests. The Number Connection Test is an easy way to evaluate patients to diagnose MHE. The aim of this study is to find out the prevalence of covert hepatic encephalopathy. METHODS The descriptive cross-sectional study was done to find out the prevalence of covert hepatic encephalopathy among patients with chronic liver disease. https://www.selleckchem.com/products/pf-2545920.html To diagnose Covert HE which included MHE as well, NCT was used in Devanagari script. RESULTS The prevalence of covert hepatic encephalopathy is found to be 56 (58.3%) at 90% confidence interval (58.23-58.37%). A total of 96 patients (71.9% male) were diagnosed as HE, with mean age of 49.6+11.8 years. The cause of CLD in 85 (88.5%) of these patients was alcohol, of which 76 (79.2%) consumed locally brewed alcohol. Of these 96 patients with HE, only 40 (41.7%) had overt HE. Among all these, maximum patients had MHE (37.5%). CONCLUSIONS Our study showed that although the prevalence of minimal HE is quite high among cirrhotics, they are usually missed in clinical practice due to absence of symptoms. Active screening with easy-to-administer tests, like Number Connection tests, can help identify patients with minimal HE and hence treat them early.0 Yorumlar 0 hisse senetleri 17 Views 0 önizleme -
Lower respiratory tract infections are commonly caused by viruses and cause significant morbidity and mortality among children. Early identification of the pathological agent causing these infections is essential to avoid unnecessary antibiotic use and improve patient management. Multiplex PCR techniques were recently developed to detect multiple viral pathogens using a single PCR reaction. In this study, we identify viral pathogens in children with respiratory infections. We collected 194 nasopharyngeal aspirates from infants (2-24 months old) with lower respiratory tract infections treated at the Vietnam National Children's Hospital between November 2014 and June 2015 and assessed the presence of 16 virus types and subtypes by multiplex PCR using the xTAG Respiratory Viral Panel (RVP) assay. Overall, 73.7% of the samples were positive for at least one virus, and 24.2% corresponded to infections with multiple viruses. The most common viruses were respiratory syncytial virus and enterovirus/rhinovirus. These viruses were more frequent among younger patients (2-5 months old) and caused symptoms similar to those of bronchiolitis and pneumonia. The most common clinical manifestation caused by respiratory tract infection was bronchiolitis. Elevated neutrophils levels were associated with adenovirus infection. Our results showed that the xTAG Respiratory Viral Panel (RVP) can effectively detect multiple viruses causing respiratory infections in children and that the nasopharyngeal aspirates are a good sample choice to detect respiratory viruses in children. Applying this approach in the clinical setting would improve patient management and allow early diagnosis, thus avoiding the unnecessary use of antibiotics. Copyright © 2020 Hien T. Pham et al.Purpose Particulate matter (PM) is increasing every year in Asia. It is not fully understood how the airway is affected when inhaling PM. We investigated the correlation between particulate matter with a diameter of less than 10 μm (PM10) and fractional exhaled nitric oxide (FeNO) to determine whether PM causes airway inflammation. Material and Methods. We analyzed patients who visited our outpatient clinic and tested FeNO from January 2016 to December 2017 at the Korea University Guro Hospital. PM10 data were provided by the government of the Republic of South Korea, and measuring station of PM10 is located 800 meters from the hospital. We analyzed the correlation between PM10 and FeNO by a Pearson correlation analysis and by a multivariate linear regression analysis. To identify the most correlated times, we analyzed the correlation between the FeNO and PM10 daily average from the day of visit to 4 days before visit. Results FeNO positively correlated with PM10 at two days before hospital visit in the Pearson correlation (Pearson correlation coefficient = 0.057; P-value = 0.023) and in the multivariate linear regression analysis (B = 0.051, P-value = 0.026). If the PM10 increased by 100 μg/m3, the FeNO result was expected to rise to 8.3 ppb in healthy people without respiratory disease. Conclusion The positive correlation was found in both healthy people and asthmatic patients. Therefore, PM10 can increase airway inflammation. Copyright © 2020 Juwhan Choi et al.The interrelationship between governmental policies and objectives in primary health care and community pharmacy/pharmacists' strategic plans are of the outmost importance, having significant professional, economic and practical consequences for the future of the pharmacy profession, research, education and health care. Sharing information of the potential and real impact on current and future practice of community pharmacy/pharmacists, be it in product or service, in primary care would benefit many stakeholders. In order to create and focus professional and scientific debate the journal has commissioned key experts to contribute a series of country case studies. https://www.selleckchem.com/products/Cediranib.html The aim of the series is to promulgate and disseminate country-based information on primary health care and community pharmacy/pharmacist. Copyright © Pharmacy Practice.The United Kingdom health and care system is changing dramatically to meet the health challenges of the 21st century. People will increasingly have multiple morbidities. The focus of service delivery is changing from hospital to community, patient to population and curative to preventive. This paper describes the NHS and primary care and community pharmacy in England at the start of 2020, a time of great change. The 10-year vison for the NHS is that everyone gets the best start in life, world class care for major health problems supporting people to age well. It has over 40 mentions of pharmacists and pharmacy. The key aims of the plan are to improve 'out-of-hospital' care, and finally dissolve the historic divide between primary and community health service in England. All of England is covered by integrated care systems and the newly formed primary care networks which will form the foundation of these new systems. Pharmacy is involved at multiple levels. There are 11,569 community pharmacies and most of their total income comes from the NHS (range 68-85%). Around 60% pharmacies are part of multiple chains, with the remaining 40% independents or small chains of less than six outlets. The new five-year community pharmacy contract provides an opportunity to develop community pharmacy and move towards service delivery away from dispensing volume. The new services are described under medicines optimisation, prevention and urgent care. The pharmacy quality scheme is also described. The new deal will help many community pharmacies to plan their future, particularly for those pharmacies who are ready and able to change and work closely with pharmacists and other health professionals in collaboration with Primary Care Networks. There will be specific challenges around dispensing efficiencies, freeing up pharmacists' time, wider use of clinical skills of community pharmacists, community pharmacy viability and consolidations. Copyright © Pharmacy Practice.Background Stroke is a leading cause of death worldwide. The cases of acute ischemic stroke are on the increase in the Asia Pacific, particularly in Malaysia. Various health organizations have recommended guidelines for managing ischemic stroke, but adherence to key performance indicators (KPI) from the guidelines and impact on patient outcomes, particularly mortality, are rarely explored. Objective This study aims to evaluate the impact of adherence to key performance indicators on mortality among patients managed for ischemic stroke. Methods We included all first-ever ischemic stroke patients enrolled in the multiethnic Malaysian National Neurology Registry (NNeuR) - a prospective cohort study and followed-up for six months. Patients' baseline clinical characteristics, risk factors, neurological findings, treatments, KPI and mortality outcome were evaluated. The KPI nonadherence (NAR) and relationship with mortality were evaluated. NAR>25% threshold was considered suboptimal. Results A total of 579 first-ever ischemic stroke patients were included in the final analysis.
Lower respiratory tract infections are commonly caused by viruses and cause significant morbidity and mortality among children. Early identification of the pathological agent causing these infections is essential to avoid unnecessary antibiotic use and improve patient management. Multiplex PCR techniques were recently developed to detect multiple viral pathogens using a single PCR reaction. In this study, we identify viral pathogens in children with respiratory infections. We collected 194 nasopharyngeal aspirates from infants (2-24 months old) with lower respiratory tract infections treated at the Vietnam National Children's Hospital between November 2014 and June 2015 and assessed the presence of 16 virus types and subtypes by multiplex PCR using the xTAG Respiratory Viral Panel (RVP) assay. Overall, 73.7% of the samples were positive for at least one virus, and 24.2% corresponded to infections with multiple viruses. The most common viruses were respiratory syncytial virus and enterovirus/rhinovirus. These viruses were more frequent among younger patients (2-5 months old) and caused symptoms similar to those of bronchiolitis and pneumonia. The most common clinical manifestation caused by respiratory tract infection was bronchiolitis. Elevated neutrophils levels were associated with adenovirus infection. Our results showed that the xTAG Respiratory Viral Panel (RVP) can effectively detect multiple viruses causing respiratory infections in children and that the nasopharyngeal aspirates are a good sample choice to detect respiratory viruses in children. Applying this approach in the clinical setting would improve patient management and allow early diagnosis, thus avoiding the unnecessary use of antibiotics. Copyright © 2020 Hien T. Pham et al.Purpose Particulate matter (PM) is increasing every year in Asia. It is not fully understood how the airway is affected when inhaling PM. We investigated the correlation between particulate matter with a diameter of less than 10 μm (PM10) and fractional exhaled nitric oxide (FeNO) to determine whether PM causes airway inflammation. Material and Methods. We analyzed patients who visited our outpatient clinic and tested FeNO from January 2016 to December 2017 at the Korea University Guro Hospital. PM10 data were provided by the government of the Republic of South Korea, and measuring station of PM10 is located 800 meters from the hospital. We analyzed the correlation between PM10 and FeNO by a Pearson correlation analysis and by a multivariate linear regression analysis. To identify the most correlated times, we analyzed the correlation between the FeNO and PM10 daily average from the day of visit to 4 days before visit. Results FeNO positively correlated with PM10 at two days before hospital visit in the Pearson correlation (Pearson correlation coefficient = 0.057; P-value = 0.023) and in the multivariate linear regression analysis (B = 0.051, P-value = 0.026). If the PM10 increased by 100 μg/m3, the FeNO result was expected to rise to 8.3 ppb in healthy people without respiratory disease. Conclusion The positive correlation was found in both healthy people and asthmatic patients. Therefore, PM10 can increase airway inflammation. Copyright © 2020 Juwhan Choi et al.The interrelationship between governmental policies and objectives in primary health care and community pharmacy/pharmacists' strategic plans are of the outmost importance, having significant professional, economic and practical consequences for the future of the pharmacy profession, research, education and health care. Sharing information of the potential and real impact on current and future practice of community pharmacy/pharmacists, be it in product or service, in primary care would benefit many stakeholders. In order to create and focus professional and scientific debate the journal has commissioned key experts to contribute a series of country case studies. https://www.selleckchem.com/products/Cediranib.html The aim of the series is to promulgate and disseminate country-based information on primary health care and community pharmacy/pharmacist. Copyright © Pharmacy Practice.The United Kingdom health and care system is changing dramatically to meet the health challenges of the 21st century. People will increasingly have multiple morbidities. The focus of service delivery is changing from hospital to community, patient to population and curative to preventive. This paper describes the NHS and primary care and community pharmacy in England at the start of 2020, a time of great change. The 10-year vison for the NHS is that everyone gets the best start in life, world class care for major health problems supporting people to age well. It has over 40 mentions of pharmacists and pharmacy. The key aims of the plan are to improve 'out-of-hospital' care, and finally dissolve the historic divide between primary and community health service in England. All of England is covered by integrated care systems and the newly formed primary care networks which will form the foundation of these new systems. Pharmacy is involved at multiple levels. There are 11,569 community pharmacies and most of their total income comes from the NHS (range 68-85%). Around 60% pharmacies are part of multiple chains, with the remaining 40% independents or small chains of less than six outlets. The new five-year community pharmacy contract provides an opportunity to develop community pharmacy and move towards service delivery away from dispensing volume. The new services are described under medicines optimisation, prevention and urgent care. The pharmacy quality scheme is also described. The new deal will help many community pharmacies to plan their future, particularly for those pharmacies who are ready and able to change and work closely with pharmacists and other health professionals in collaboration with Primary Care Networks. There will be specific challenges around dispensing efficiencies, freeing up pharmacists' time, wider use of clinical skills of community pharmacists, community pharmacy viability and consolidations. Copyright © Pharmacy Practice.Background Stroke is a leading cause of death worldwide. The cases of acute ischemic stroke are on the increase in the Asia Pacific, particularly in Malaysia. Various health organizations have recommended guidelines for managing ischemic stroke, but adherence to key performance indicators (KPI) from the guidelines and impact on patient outcomes, particularly mortality, are rarely explored. Objective This study aims to evaluate the impact of adherence to key performance indicators on mortality among patients managed for ischemic stroke. Methods We included all first-ever ischemic stroke patients enrolled in the multiethnic Malaysian National Neurology Registry (NNeuR) - a prospective cohort study and followed-up for six months. Patients' baseline clinical characteristics, risk factors, neurological findings, treatments, KPI and mortality outcome were evaluated. The KPI nonadherence (NAR) and relationship with mortality were evaluated. NAR>25% threshold was considered suboptimal. Results A total of 579 first-ever ischemic stroke patients were included in the final analysis.0 Yorumlar 0 hisse senetleri 15 Views 0 önizleme -
Integrated Clinic represented the most contaminated attendance area (MRSA - 41.7%, MSSA - 51.2%), the chair arm rest was the most contaminated surface for MRSA (29.7%) and the dental spittoon the most contaminated surface for MSSA (23.5%). Although a low level of contamination was observed, dental clinics, through patients possibly carrying bacteria, may be reservoirs for MRSA and MSSA transmission, and might contribute to potential nosocomial infections. © 2019 The Author(s).The aim of this clinical study was to evaluate and compare the dentoskeletal transverse mandibular arch dimensions following the use of two designs of fixed mandibular expanders using cone beam computed tomography (CBCT). Twenty orthodontic patients, 12 females and 8 males, with mean age of 13.4 ± 0.5 years were selected and randomly divided into two equivalent groups; group A consisted of 10 patients (4 boys, 6 girls) who were treated with modified Williams expander and group B consisted of 10 patients (4 boys, 6 girls) who were treated with a two-arm fixed expander. https://www.selleckchem.com/products/sgc707.html Consistent expansion instructions were given to all patients according to a standardized slow protocol of one quarter turn twice/week for both expanders. Routine orthodontic records as well as mandibular CBCTs were obtained before (T1) and immediately after expansion (T2) to estimate changes in dentoskeletal mandibular transverse dimensions. The data was statistically analyzed and the significance level was set at p ≤ 0.05. Mandibular intercanine, inter-premolar, intermolar widths; and arch perimeter were significantly increased (p ≤ 0.05) following expansion with both fixed expanders. However, the changes in inter-premolar width, intercanine width, and arch perimeter were significantly augmented in two-arm fixed expander group than modified Williams's group. In contrast, their effects on the skeletal mandibular body width were non-significant (p > 0.05). Both expanders yielded significant and equivalent dentoalveolar effects that were more evident with two-arm fixed expander than the William one. Both fixed designs enhanced mandibular transverse dental dimensions; however, they were unsuccessful to create any considerable skeletal effects. © 2019 The Author(s).Background The InBIO Barcoding Initiative (IBI) Diptera 01 dataset contains records of 203 specimens of Diptera. All specimens have been morphologically identified to species level, and belong to 154 species in total. The species represented in this dataset correspond to about 10% of continental Portugal dipteran species diversity. All specimens were collected north of the Tagus river in Portugal. Sampling took place from 2014 to 2018, and specimens are deposited in the IBI collection at CIBIO, Research Center in Biodiversity and Genetic Resources. New information This dataset contributes to the knowledge on the DNA barcodes and distribution of 154 species of Diptera from Portugal and is the first of the planned IBI database public releases, which will make available genetic and distribution data for a series of taxa. All specimens have their DNA barcodes made publicly available in the Barcode of Life Data System (BOLD) online database and the distribution dataset can be freely accessed through the Global Biodiversity Information Facility (GBIF). Sonia A Ferreira, Rui Andrade, Ana R Gonçalves, Pedro Sousa, Joana Paupério, Nuno A Fonseca, Pedro Beja.Changes to the treatment of Coleoptera family-group names published by Bouchard et al. (2011) are given. These include necessary additions and corrections based on ****-appreciated suggestions from our colleagues, as well as our own research. Our ultimate goal is to assemble a complete list of available Coleoptera family-group names published up to the end of 2010 (including information about their spelling, author, year of publication, and type genus). The following 59 available Coleoptera family-group names are based on type genera not included in Bouchard et al. (2011) Prothydrinae Guignot, 1954, Aulonogyrini Ochs, 1953 (Gyrinidae); Pogonostomini Mandl 1954, Merismoderini Wasmann, 1929, †Escheriidae Kolbe, 1880 (Carabidae); Timarchopsinae Wang, Ponomarenko & Zhang, 2010 (Coptoclavidae); Stictocraniini Jakobson, 1914 (Staphylinidae); Cylindrocaulini Zang, 1905, Kaupiolinae Zang, 1905 (Passalidae); Phaeochroinae Kolbe, 1912 (Hybosoridae); Anthypnidae Chalande, 1884 (Glaphyridae); Comophorini Britton, 1957, Cvalid, Heteroscelis Latreille, 1828 and Dysantes Pascoe, 1869 (Tenebrionidae), are determined to be senior homonyms based on bibliographical research. While Dysantes is treated as valid here, Reversal of Precedence (ICZN 1999 Art. 23.9) is used to conserve usage of Anomalipus **érin-Méneville, 1831 over Heteroscelis.The genus Didymocorypha Wood-Mason, 1877 (Eremiaphilidae, Iridinae) has only been recorded in South Asia, including a sole species D. lanceolata (Fabricius). Here, we firstly extend its distribution to China, with description of one new species D. libaii sp. nov. Didymocorypha libaii sp. nov. lives in an area about 3000 meters above sea level on the southern slope of the Himalayas (Tibet in China), one of the highest-altitude inhabited areas of mantis in the Northern Hemisphere. It is also the first recorded Oriental mantis species in which both sexes are wingless. Life history of the new species, necessary illustrations and ecological images are provided. The distribution of the new Didymocorypha species is discussed and mapped. Chao Wu, Chun-Xiang Liu.We present the description of a new genus and species of soldierless termites from South America. Rustitermes boteroi Constantini, Castro & Scheffrahn, gen. et sp. nov. can be identified by the morphology of the enteric valve, with six slightly asymmetric cushions, each one forming a central pouch made of scales smaller than those between the cushions. The new genus features two characteristic rows of thick bristles on the interior margin of the fore tibia, and is supported by COI molecular sequence data. This species is distributed from Tobago to northern Argentina. Daniel Castro, Joice P. Constantini, Rudolf H. Scheffrahn, Tiago F. Carrijo, Eliana M. Cancello.
Integrated Clinic represented the most contaminated attendance area (MRSA - 41.7%, MSSA - 51.2%), the chair arm rest was the most contaminated surface for MRSA (29.7%) and the dental spittoon the most contaminated surface for MSSA (23.5%). Although a low level of contamination was observed, dental clinics, through patients possibly carrying bacteria, may be reservoirs for MRSA and MSSA transmission, and might contribute to potential nosocomial infections. © 2019 The Author(s).The aim of this clinical study was to evaluate and compare the dentoskeletal transverse mandibular arch dimensions following the use of two designs of fixed mandibular expanders using cone beam computed tomography (CBCT). Twenty orthodontic patients, 12 females and 8 males, with mean age of 13.4 ± 0.5 years were selected and randomly divided into two equivalent groups; group A consisted of 10 patients (4 boys, 6 girls) who were treated with modified Williams expander and group B consisted of 10 patients (4 boys, 6 girls) who were treated with a two-arm fixed expander. https://www.selleckchem.com/products/sgc707.html Consistent expansion instructions were given to all patients according to a standardized slow protocol of one quarter turn twice/week for both expanders. Routine orthodontic records as well as mandibular CBCTs were obtained before (T1) and immediately after expansion (T2) to estimate changes in dentoskeletal mandibular transverse dimensions. The data was statistically analyzed and the significance level was set at p ≤ 0.05. Mandibular intercanine, inter-premolar, intermolar widths; and arch perimeter were significantly increased (p ≤ 0.05) following expansion with both fixed expanders. However, the changes in inter-premolar width, intercanine width, and arch perimeter were significantly augmented in two-arm fixed expander group than modified Williams's group. In contrast, their effects on the skeletal mandibular body width were non-significant (p > 0.05). Both expanders yielded significant and equivalent dentoalveolar effects that were more evident with two-arm fixed expander than the William one. Both fixed designs enhanced mandibular transverse dental dimensions; however, they were unsuccessful to create any considerable skeletal effects. © 2019 The Author(s).Background The InBIO Barcoding Initiative (IBI) Diptera 01 dataset contains records of 203 specimens of Diptera. All specimens have been morphologically identified to species level, and belong to 154 species in total. The species represented in this dataset correspond to about 10% of continental Portugal dipteran species diversity. All specimens were collected north of the Tagus river in Portugal. Sampling took place from 2014 to 2018, and specimens are deposited in the IBI collection at CIBIO, Research Center in Biodiversity and Genetic Resources. New information This dataset contributes to the knowledge on the DNA barcodes and distribution of 154 species of Diptera from Portugal and is the first of the planned IBI database public releases, which will make available genetic and distribution data for a series of taxa. All specimens have their DNA barcodes made publicly available in the Barcode of Life Data System (BOLD) online database and the distribution dataset can be freely accessed through the Global Biodiversity Information Facility (GBIF). Sonia A Ferreira, Rui Andrade, Ana R Gonçalves, Pedro Sousa, Joana Paupério, Nuno A Fonseca, Pedro Beja.Changes to the treatment of Coleoptera family-group names published by Bouchard et al. (2011) are given. These include necessary additions and corrections based on much-appreciated suggestions from our colleagues, as well as our own research. Our ultimate goal is to assemble a complete list of available Coleoptera family-group names published up to the end of 2010 (including information about their spelling, author, year of publication, and type genus). The following 59 available Coleoptera family-group names are based on type genera not included in Bouchard et al. (2011) Prothydrinae Guignot, 1954, Aulonogyrini Ochs, 1953 (Gyrinidae); Pogonostomini Mandl 1954, Merismoderini Wasmann, 1929, †Escheriidae Kolbe, 1880 (Carabidae); Timarchopsinae Wang, Ponomarenko & Zhang, 2010 (Coptoclavidae); Stictocraniini Jakobson, 1914 (Staphylinidae); Cylindrocaulini Zang, 1905, Kaupiolinae Zang, 1905 (Passalidae); Phaeochroinae Kolbe, 1912 (Hybosoridae); Anthypnidae Chalande, 1884 (Glaphyridae); Comophorini Britton, 1957, Cvalid, Heteroscelis Latreille, 1828 and Dysantes Pascoe, 1869 (Tenebrionidae), are determined to be senior homonyms based on bibliographical research. While Dysantes is treated as valid here, Reversal of Precedence (ICZN 1999 Art. 23.9) is used to conserve usage of Anomalipus Guérin-Méneville, 1831 over Heteroscelis.The genus Didymocorypha Wood-Mason, 1877 (Eremiaphilidae, Iridinae) has only been recorded in South Asia, including a sole species D. lanceolata (Fabricius). Here, we firstly extend its distribution to China, with description of one new species D. libaii sp. nov. Didymocorypha libaii sp. nov. lives in an area about 3000 meters above sea level on the southern slope of the Himalayas (Tibet in China), one of the highest-altitude inhabited areas of mantis in the Northern Hemisphere. It is also the first recorded Oriental mantis species in which both sexes are wingless. Life history of the new species, necessary illustrations and ecological images are provided. The distribution of the new Didymocorypha species is discussed and mapped. Chao Wu, Chun-Xiang Liu.We present the description of a new genus and species of soldierless termites from South America. Rustitermes boteroi Constantini, Castro & Scheffrahn, gen. et sp. nov. can be identified by the morphology of the enteric valve, with six slightly asymmetric cushions, each one forming a central pouch made of scales smaller than those between the cushions. The new genus features two characteristic rows of thick bristles on the interior margin of the fore tibia, and is supported by COI molecular sequence data. This species is distributed from Tobago to northern Argentina. Daniel Castro, Joice P. Constantini, Rudolf H. Scheffrahn, Tiago F. Carrijo, Eliana M. Cancello.0 Yorumlar 0 hisse senetleri 18 Views 0 önizleme -
An amendment to this paper has been published and can be accessed via a link at the top of the paper.Accurate prediction of disease risk based on the genetic make-up of an individual is essential for effective prevention and personalized treatment. https://www.selleckchem.com/products/Cediranib.html Nevertheless, to date, individual genetic variants from genome-wide association studies have achieved only moderate prediction of disease risk. The aggregation of genetic variants under a polygenic model shows promising improvements in prediction accuracies. Increasingly, electronic health records (EHRs) are being linked to patient genetic data in biobanks, which provides new opportunities for developing and applying polygenic risk scores in the clinic, to systematically examine and evaluate patient susceptibilities to disease. However, the heterogeneous nature of EHR data brings forth many practical challenges along every step of designing and implementing risk prediction strategies. In this Review, we present the unique considerations for using genotype and phenotype data from biobank-linked EHRs for polygenic risk prediction.The increase in superconducting transition temperature (TC) of Sn nanostructures in comparison to bulk, was studied. Changes in the phonon density of states (PDOS) of the weakly coupled superconductor Sn were analyzed and correlated with the increase in TC measured by magnetometry. The PDOS of all nanostructured samples shows a slightly increased number of low-energy phonon modes and a strong decrease in the number of high-energy phonon modes in comparison to the bulk Sn PDOS. The phonon densities of states, which were determined previously using nuclear resonant inelastic X-ray scattering, were used to calculate the superconducting transition temperature using the Allen-Dynes-McMillan (ADMM) formalism. Both the calculated as well as the experimentally determined values of TC show an increase compared to the bulk superconducting transition temperature. The good agreement between these values indicates that phonon softening has a major influence on the superconducting transition temperature of Sn nanostructures. The influence of electron confinement effects appears to be minor in these systems.BACKGROUND Oropharyngeal cancer (OPC) exhibits diverse immunological properties; however, their implications for immunotherapy are unknown. METHODS We analysed 37 surgically resected and nine recurrent or metastatic anti-programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1)-treated OPC tumours. OPCs were classified into immune-rich (IR), mesenchymal (MS) and xenobiotic (XB) subtypes based on RNA-sequencing data. RESULTS All IR type tumours were human papillomavirus (HPV) positive, most XB types were HPV negative, and MS types showed mixed HPV status. The IR type showed an enriched T cell exhaustion signature with PD-1+ CD8+ T cells and type I macrophages infiltrating the tumour nest on multiplex immunohistochemistry. The MS type showed an exclusion of CD8+ T cells from the tumour nest and high MS and tumour growth factor-β signatures. The XB type showed scant CD8+ T cell infiltration and focal CD73 expression. The IR type was associated with a favourable response signature during anti-PD-1/PD-L1 therapy and showed a high APOBEC mutation signature, whereas the MS and XB types showed resistance signature upregulation. Among anti-PD-1/PD-L1-treated OPC patients, the IR type showed a favourable clinical response (3/4 patients), whereas the XB type showed early progression (3/3 patients). CONCLUSION Our analysis classified OPCs into three subtypes with distinct immune microenvironments that are potentially related to the response to anti-PD-1/PD-L1 therapy.Cognitive impairment is an increasingly recognized major cause of chronic disability and is commonly found in patients with chronic kidney disease (CKD). Knowledge of the relationship between kidney dysfunction and impaired cognition may improve our understanding of other forms of cognitive dysfunction. Patients with CKD are at an increased risk (compared with the general population) of both dementia and its prodrome, mild cognitive impairment (MCI), which are characterized by deficits in executive functions, memory and attention. Brain imaging in patients with CKD has revealed damage to white matter in the prefrontal cortex and, in animal models, in the subcortical monoaminergic and cholinergic systems, accompanied by widespread macrovascular and microvascular damage. Unfortunately, current interventions that target cardiovascular risk factors (such as anti-hypertensive drugs, anti-platelet agents and statins) seem to have little or no effect on CKD-associated MCI, suggesting that the accumulation of uraemic neurotoxins may be more important than disturbed haemodynamic factors or lipid metabolism in MCI pathogenesis. Experimental models show that the brain monoaminergic system is susceptible to uraemic neurotoxins and that this system is responsible for the altered sleep pattern commonly observed in patients with CKD. Neural progenitor cells and the glymphatic system, which are important in Alzheimer disease pathogenesis, may also be involved in CKD-associated MCI. More detailed study of CKD-associated MCI is needed to fully understand its clinical relevance, underlying pathophysiology, possible means of early diagnosis and prevention, and whether there may be novel approaches and potential therapies with wider application to this and other forms of cognitive decline.Tumours reprogram host physiology, metabolism and immune responses during cancer progression. The release of soluble factors, exosomes and metabolites from tumours leads to systemic changes in distant organs, where cancer cells metastasize and grow. These tumour-derived circulating factors also profoundly impact tissues that are rarely inhabited by metastatic cancer cells such as skeletal muscle and adipose tissue. In fact, the majority of patients with metastatic cancer develop a debilitating muscle-wasting syndrome, known as cachexia, that is associated with decreased tolerance to antineoplastic therapy, poor prognosis and accelerated death, with no approved treatments. In this Perspective, we discuss the development of cachexia in the context of metastatic progression. We briefly discuss how circulating factors either directly or indirectly promote cachexia development and examine how signals from the metastatic process can trigger and amplify this process. Finally, we highlight promising therapeutic opportunities for targeting cachexia in the context of metastatic cancers.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.Accurate prediction of disease risk based on the genetic make-up of an individual is essential for effective prevention and personalized treatment. https://www.selleckchem.com/products/Cediranib.html Nevertheless, to date, individual genetic variants from genome-wide association studies have achieved only moderate prediction of disease risk. The aggregation of genetic variants under a polygenic model shows promising improvements in prediction accuracies. Increasingly, electronic health records (EHRs) are being linked to patient genetic data in biobanks, which provides new opportunities for developing and applying polygenic risk scores in the clinic, to systematically examine and evaluate patient susceptibilities to disease. However, the heterogeneous nature of EHR data brings forth many practical challenges along every step of designing and implementing risk prediction strategies. In this Review, we present the unique considerations for using genotype and phenotype data from biobank-linked EHRs for polygenic risk prediction.The increase in superconducting transition temperature (TC) of Sn nanostructures in comparison to bulk, was studied. Changes in the phonon density of states (PDOS) of the weakly coupled superconductor Sn were analyzed and correlated with the increase in TC measured by magnetometry. The PDOS of all nanostructured samples shows a slightly increased number of low-energy phonon modes and a strong decrease in the number of high-energy phonon modes in comparison to the bulk Sn PDOS. The phonon densities of states, which were determined previously using nuclear resonant inelastic X-ray scattering, were used to calculate the superconducting transition temperature using the Allen-Dynes-McMillan (ADMM) formalism. Both the calculated as well as the experimentally determined values of TC show an increase compared to the bulk superconducting transition temperature. The good agreement between these values indicates that phonon softening has a major influence on the superconducting transition temperature of Sn nanostructures. The influence of electron confinement effects appears to be minor in these systems.BACKGROUND Oropharyngeal cancer (OPC) exhibits diverse immunological properties; however, their implications for immunotherapy are unknown. METHODS We analysed 37 surgically resected and nine recurrent or metastatic anti-programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1)-treated OPC tumours. OPCs were classified into immune-rich (IR), mesenchymal (MS) and xenobiotic (XB) subtypes based on RNA-sequencing data. RESULTS All IR type tumours were human papillomavirus (HPV) positive, most XB types were HPV negative, and MS types showed mixed HPV status. The IR type showed an enriched T cell exhaustion signature with PD-1+ CD8+ T cells and type I macrophages infiltrating the tumour nest on multiplex immunohistochemistry. The MS type showed an exclusion of CD8+ T cells from the tumour nest and high MS and tumour growth factor-β signatures. The XB type showed scant CD8+ T cell infiltration and focal CD73 expression. The IR type was associated with a favourable response signature during anti-PD-1/PD-L1 therapy and showed a high APOBEC mutation signature, whereas the MS and XB types showed resistance signature upregulation. Among anti-PD-1/PD-L1-treated OPC patients, the IR type showed a favourable clinical response (3/4 patients), whereas the XB type showed early progression (3/3 patients). CONCLUSION Our analysis classified OPCs into three subtypes with distinct immune microenvironments that are potentially related to the response to anti-PD-1/PD-L1 therapy.Cognitive impairment is an increasingly recognized major cause of chronic disability and is commonly found in patients with chronic kidney disease (CKD). Knowledge of the relationship between kidney dysfunction and impaired cognition may improve our understanding of other forms of cognitive dysfunction. Patients with CKD are at an increased risk (compared with the general population) of both dementia and its prodrome, mild cognitive impairment (MCI), which are characterized by deficits in executive functions, memory and attention. Brain imaging in patients with CKD has revealed damage to white matter in the prefrontal cortex and, in animal models, in the subcortical monoaminergic and cholinergic systems, accompanied by widespread macrovascular and microvascular damage. Unfortunately, current interventions that target cardiovascular risk factors (such as anti-hypertensive drugs, anti-platelet agents and statins) seem to have little or no effect on CKD-associated MCI, suggesting that the accumulation of uraemic neurotoxins may be more important than disturbed haemodynamic factors or lipid metabolism in MCI pathogenesis. Experimental models show that the brain monoaminergic system is susceptible to uraemic neurotoxins and that this system is responsible for the altered sleep pattern commonly observed in patients with CKD. Neural progenitor cells and the glymphatic system, which are important in Alzheimer disease pathogenesis, may also be involved in CKD-associated MCI. More detailed study of CKD-associated MCI is needed to fully understand its clinical relevance, underlying pathophysiology, possible means of early diagnosis and prevention, and whether there may be novel approaches and potential therapies with wider application to this and other forms of cognitive decline.Tumours reprogram host physiology, metabolism and immune responses during cancer progression. The release of soluble factors, exosomes and metabolites from tumours leads to systemic changes in distant organs, where cancer cells metastasize and grow. These tumour-derived circulating factors also profoundly impact tissues that are rarely inhabited by metastatic cancer cells such as skeletal muscle and adipose tissue. In fact, the majority of patients with metastatic cancer develop a debilitating muscle-wasting syndrome, known as cachexia, that is associated with decreased tolerance to antineoplastic therapy, poor prognosis and accelerated death, with no approved treatments. In this Perspective, we discuss the development of cachexia in the context of metastatic progression. We briefly discuss how circulating factors either directly or indirectly promote cachexia development and examine how signals from the metastatic process can trigger and amplify this process. Finally, we highlight promising therapeutic opportunities for targeting cachexia in the context of metastatic cancers.0 Yorumlar 0 hisse senetleri 16 Views 0 önizleme -
0052), lower A G ratios (P = 0.0037), and lower α-globulin levels (P = 0.0073), while their γ-globulin levels were significantly higher (P = 0.0004). In the same comparison, clinically healthy arenavirus-positive boas showed only significantly lower α-globulin (P = 0.0124) and higher γ-globulin levels (P = 0.0394). The results of the present study indicate that reptarenavirus infection may influence plasma protein fractions in boa constrictors.There is an unmet need for specific diagnostics of immune perturbations and inflammation in beluga whale (Delphinapterus leucas) clinical care. Quantitative real-time polymerase chain reaction (qPCR) has been used to measure immunomediator gene transcription in beluga whales. The study hypothesis was that a qPCR-based immunomediator assay would supplement routine clinical data with specific and sensitive information on immune status. Two beluga whale clinical cases provided an opportunity to test this hypothesis a whale with a skin laceration and a whale with gastrointestinal inflammation. Mitogen-stimulated immunomediator gene transcription (MSIGT) was compared between the cases and healthy contact whales. In both case studies, mitogens increased transcription of IL1B, PTGS2 (Cox-2), TNF, HIF1A, and IL2 but decreased IL10 transcription in peripheral blood mononuclear cells (PBMC) from the abnormal whale over the control. Correlations were identified between most immunomediators tested and one or more standard blood clinical values. Considering all 15 immunomediators tested, the whale with gastrointestinal inflammation had a more unique MSIGT signature than the whale with a laceration. These results support further elucidation of beluga whale PBMC cytokine profiles for use as immune biomarkers.Gastrointestinal (GI) pathology is common in elasmobranchs; however, information regarding normal GI transit time and the effect of therapeutics on GI motility is lacking. The objective of this study was to determine baseline gastric emptying and GI transit times in cownose rays (Rhinoptera bonasus) and whitespotted bamboo sharks (Chiloscyllium plagiosum) via radiographic barium sulfate contrast studies. Additionally, a pilot study was undertaken to determine the effect of metoclopramide on GI transit time in whitespotted bamboo sharks. Eight cownose rays and eight whitespotted bamboo sharks were administered a 98% w/w barium sulfate suspension at 8 ml/kg via orogastric tube. Post-contrast radiographs were obtained at 2 min, 3, 6, 12, and 23 hr for rays; and 2 min, 3, 6, 9, 12, 16, 25, 30, 36, and every 12 hr until complete gastric emptying occurred for sharks. https://www.selleckchem.com/products/scriptaid.html In cownose rays, the mean and standard error were established for time of initial spiral colon filling (3.4 ± 0.4 hr), complete spiral colon opacification (12 ± 0 hr), initial spiral colon emptying (21.6 ± 1.4 hr), and complete gastric emptying (23 ± 0 hr). In bamboo sharks, the mean and standard error were established for time of initial spiral colon filling (5.3 ± 0.5 hr), complete spiral colon opacification (12.4 ± 1.3 hr), initial spiral colon emptying (22.5 ± 2.7 hr), and complete gastric emptying (39.9 ± 3.3 hr). Cownose rays had a significantly shorter time to spiral colon filling and complete gastric emptying compared with bamboo sharks (P less then 0.05). Whitespotted bamboo sharks (n = 8) were administered metoclopramide (0.4 mg/kg orally once daily for 10 days) and the barium series was repeated. Complete gastric emptying time was significantly shorter in treated sharks compared with control (P less then 0.05), suggesting that metoclopramide may be a useful therapeutic for GI motility disorders in elasmobranchs.Pronghorn (Antilocapra americana) are native to western North America and are found in 24 Association of Zoos and Aquariums (AZA)-accredited institutions. Acute-phase proteins (APP) are a broad class of proteins that are stimulated in response to inflammation and have been shown to be a sensitive measure of inflammation in equids and ruminants. In this study, blood samples from clinically normal free-ranging and captive populations of pronghorn were analyzed using assays for protein electrophoresis (EPH) and APP, including serum amyloid A (SAA) and haptoglobin (HP), to develop preliminary ranges to gauge potential differences between these populations. Additional samples were taken from clinically abnormal captive pronghorn with facial abscesses. By EPH measurements, albumin globulin ratio mean and SE were significantly different (P less then 0.05) with 1.02 (0.08) for captive populations and 1.91 (0.05) for free-ranging populations. Total protein mean and SE were significantly different (P less then 0.05) for captive and free-ranging populations, respectively 5.6 (0.3) g/dl and 6.9 (0.1) g/dl. Mean and SD of SAA for captive pronghorn were 1.4 (3.2) mg/L, and were significantly different from the free-ranging population, which was below the limits of detection for (P less then 0.05). There was no difference in HP levels between these groups. In a case study of a pronghorn with facial abscesses, elevated levels of HP, but not SAA, suggested that HP maybe useful in certain disease states. Future studies should explore the use of these biomarkers as tools to monitor general health, prognosis, and subclinical disease.Cardiac disease has been recognized as a major cause of death in captive nonhuman primates, which necessitates diagnostic (imaging) techniques to screen for and diagnose preclinical and clinical stages of possible cardiac conditions. Echocardiography is currently the most commonly used diagnostic tool for evaluation of cardiac anatomy and function. Complete with thoracic radiography and blood levels of two cardiac biomarkers, N-terminal probrain natriuretic peptide (NT-proBNP) and cardiac troponin T (cTnT), it gives an extensive examination of the cardiorespiratory system. The purpose of this cross-sectional cohort study is to describe normal thoracic anatomy using thoracic radiography, and to provide normal values for echocardiographic measurements in 20 ring-tailed lemurs (Lemur catta). Additionally, cardiac biomarkers were determined. Three radiographic projections of the thoracic cavity and a complete transthoracic echocardiography were performed in 20 clinically healthy ring-tailed lemurs during their annual health examinations.
0052), lower A G ratios (P = 0.0037), and lower α-globulin levels (P = 0.0073), while their γ-globulin levels were significantly higher (P = 0.0004). In the same comparison, clinically healthy arenavirus-positive boas showed only significantly lower α-globulin (P = 0.0124) and higher γ-globulin levels (P = 0.0394). The results of the present study indicate that reptarenavirus infection may influence plasma protein fractions in boa constrictors.There is an unmet need for specific diagnostics of immune perturbations and inflammation in beluga whale (Delphinapterus leucas) clinical care. Quantitative real-time polymerase chain reaction (qPCR) has been used to measure immunomediator gene transcription in beluga whales. The study hypothesis was that a qPCR-based immunomediator assay would supplement routine clinical data with specific and sensitive information on immune status. Two beluga whale clinical cases provided an opportunity to test this hypothesis a whale with a skin laceration and a whale with gastrointestinal inflammation. Mitogen-stimulated immunomediator gene transcription (MSIGT) was compared between the cases and healthy contact whales. In both case studies, mitogens increased transcription of IL1B, PTGS2 (Cox-2), TNF, HIF1A, and IL2 but decreased IL10 transcription in peripheral blood mononuclear cells (PBMC) from the abnormal whale over the control. Correlations were identified between most immunomediators tested and one or more standard blood clinical values. Considering all 15 immunomediators tested, the whale with gastrointestinal inflammation had a more unique MSIGT signature than the whale with a laceration. These results support further elucidation of beluga whale PBMC cytokine profiles for use as immune biomarkers.Gastrointestinal (GI) pathology is common in elasmobranchs; however, information regarding normal GI transit time and the effect of therapeutics on GI motility is lacking. The objective of this study was to determine baseline gastric emptying and GI transit times in cownose rays (Rhinoptera bonasus) and whitespotted bamboo sharks (Chiloscyllium plagiosum) via radiographic barium sulfate contrast studies. Additionally, a pilot study was undertaken to determine the effect of metoclopramide on GI transit time in whitespotted bamboo sharks. Eight cownose rays and eight whitespotted bamboo sharks were administered a 98% w/w barium sulfate suspension at 8 ml/kg via orogastric tube. Post-contrast radiographs were obtained at 2 min, 3, 6, 12, and 23 hr for rays; and 2 min, 3, 6, 9, 12, 16, 25, 30, 36, and every 12 hr until complete gastric emptying occurred for sharks. https://www.selleckchem.com/products/scriptaid.html In cownose rays, the mean and standard error were established for time of initial spiral colon filling (3.4 ± 0.4 hr), complete spiral colon opacification (12 ± 0 hr), initial spiral colon emptying (21.6 ± 1.4 hr), and complete gastric emptying (23 ± 0 hr). In bamboo sharks, the mean and standard error were established for time of initial spiral colon filling (5.3 ± 0.5 hr), complete spiral colon opacification (12.4 ± 1.3 hr), initial spiral colon emptying (22.5 ± 2.7 hr), and complete gastric emptying (39.9 ± 3.3 hr). Cownose rays had a significantly shorter time to spiral colon filling and complete gastric emptying compared with bamboo sharks (P less then 0.05). Whitespotted bamboo sharks (n = 8) were administered metoclopramide (0.4 mg/kg orally once daily for 10 days) and the barium series was repeated. Complete gastric emptying time was significantly shorter in treated sharks compared with control (P less then 0.05), suggesting that metoclopramide may be a useful therapeutic for GI motility disorders in elasmobranchs.Pronghorn (Antilocapra americana) are native to western North America and are found in 24 Association of Zoos and Aquariums (AZA)-accredited institutions. Acute-phase proteins (APP) are a broad class of proteins that are stimulated in response to inflammation and have been shown to be a sensitive measure of inflammation in equids and ruminants. In this study, blood samples from clinically normal free-ranging and captive populations of pronghorn were analyzed using assays for protein electrophoresis (EPH) and APP, including serum amyloid A (SAA) and haptoglobin (HP), to develop preliminary ranges to gauge potential differences between these populations. Additional samples were taken from clinically abnormal captive pronghorn with facial abscesses. By EPH measurements, albumin globulin ratio mean and SE were significantly different (P less then 0.05) with 1.02 (0.08) for captive populations and 1.91 (0.05) for free-ranging populations. Total protein mean and SE were significantly different (P less then 0.05) for captive and free-ranging populations, respectively 5.6 (0.3) g/dl and 6.9 (0.1) g/dl. Mean and SD of SAA for captive pronghorn were 1.4 (3.2) mg/L, and were significantly different from the free-ranging population, which was below the limits of detection for (P less then 0.05). There was no difference in HP levels between these groups. In a case study of a pronghorn with facial abscesses, elevated levels of HP, but not SAA, suggested that HP maybe useful in certain disease states. Future studies should explore the use of these biomarkers as tools to monitor general health, prognosis, and subclinical disease.Cardiac disease has been recognized as a major cause of death in captive nonhuman primates, which necessitates diagnostic (imaging) techniques to screen for and diagnose preclinical and clinical stages of possible cardiac conditions. Echocardiography is currently the most commonly used diagnostic tool for evaluation of cardiac anatomy and function. Complete with thoracic radiography and blood levels of two cardiac biomarkers, N-terminal probrain natriuretic peptide (NT-proBNP) and cardiac troponin T (cTnT), it gives an extensive examination of the cardiorespiratory system. The purpose of this cross-sectional cohort study is to describe normal thoracic anatomy using thoracic radiography, and to provide normal values for echocardiographic measurements in 20 ring-tailed lemurs (Lemur catta). Additionally, cardiac biomarkers were determined. Three radiographic projections of the thoracic cavity and a complete transthoracic echocardiography were performed in 20 clinically healthy ring-tailed lemurs during their annual health examinations.0 Yorumlar 0 hisse senetleri 19 Views 0 önizleme -
The mean gestational age at the time of presentation was 26.5 weeks. Caesarean sections were performed in three women prior to the neurosurgical procedure, while the pregnancies were maintained in the six other patients. Eight infants who were healthy at birth had an unremarkable development. CONCLUSION Surgery for spinal emergencies in pregnancy can be performed safely according to individual treatment plans developed by an interdisciplinary team taking into account the expectant mother`s decision. Maintenance of pregnancy is possible and feasible in the majority of patients. BACKGROUND Diabetes mellitus (DM) is regarded to be associated with poor postoperative outcomes and increased morbidity following surgeries. Some previous studies have addressed the close association between DM and those leading to reoperations, whereas others objected this opinion. This study aimed to evaluate the long-term effect of DM on lumbar spinal surgery using data from a nationwide sample cohort. METHODS A population-based cohort comprised one million people, which is a 2.1% representative sample of the Korean population. The present study included adult patients with lumbar degenerative diseases, such as lumbar spinal stenosis and spondylolisthesis, who underwent their first lumbar surgery in 2006. The cumulative incidence function for reoperation was calculated and multivariate analysis were performed to define correlation between reoperation and independent factors, RESULTS A total of 2,020 patients were enrolled and followed up for 10 years. Non-diabetic patients, DM without complication (DwoC), and DM with complication (DwC) accounted for 79.5%, 9.36%, and 11.14% of all patients, respectively. Reoperation incidence stratified by DM was 12.7% for nondiabetic patients; 22.2% for DwoC; and 20.0% for DwC in 10 years of follow-up. During the same period, death, a competing event of reoperation, occurred 7.8% of the time in nondiabetic patients; 13.2% in DwoC; and 20.9% in DwC. CONCLUSION DM increased 1.65 times the overall cumulative incidences of reoperation after lumbar spinal surgeries for 10 years of follow-up. The reoperation incidences for DwC may be lower than that for DwoC because of a high incidence of death as a competing event of reoperation. BACKGROUND Intracranial bronchogenic cysts(IBCs) are extremely rare. To our knowledge, this is the first report of ** in which lesions involve the middle and posterior cranial fossa as well as the infratemporal fossa. CASE DESCRIPTION We present the case of a 38-year-old woman who suffered from a cranial nerve dysfunction for 2 years. Magnetic resonance imaging(MRI) showed that there were skull base communication lesions across the middle and posterior fossa. The patient was operated on through an infratemporal fossa approach. The final diagnosis was ** after histopathological examination and immunohistochemical verification. The patient's neurological dysfunction was partially ameliorated at the half-year follow-up. CONCLUSIONS IBCs are rare.However,it should be considered in the differential diagnosis for those cystic lesions with edge enhancement or extracranial extension. OBJECTIVE CT reduction in favor of rapid sequence MRI to decrease pediatric radiation exposure has varied across institutions. We aim to understand national trends in CT and rapid sequence MRI usage, as well as identify variables affecting imaging practices and obstacles to CT reduction. METHODS Retrospective review of deidentified discharge data for children with hydrocephalus and TBI in the Healthcare Cost and Utilization Project's Kid's Inpatient Database (KID) in 2000, 2003, 2006, 2009, 2012, and 2016. MRI without contrast and CT use were extracted using ICD9 and ICD10 codes. Hospital region and age cohorts were extracted and used to categorize data. Chi square tests and logistic regression were used for analysis. https://www.selleckchem.com/products/wnk-in-11.html RESULTS Hospitalization utilizing CT use decreased (p less then 0.05) and those using MRI increased (p less then 0.05) overall in both diagnosis groups throughout the years analyzed. However, there was significant regional variation in imaging. The Northeast had higher CT rates (p less then 0.05) and the South had lower CT rates in hydrocephalus and TBI patients (p less then 0.05). No regional variation was found for TBI patients receiving MRIs. CONCLUSIONS Nationwide, the average number of discharges after hospitalizations involving CT use in hydrocephalus and TBI patients has decreased, while those involving MRI use as an alternative imaging modality has increased. Despite successful overall CT reduction, significant regional variation exists within this trend showing inconsistent reduction of CT use. BACKGROUND Hemifacial spasm (HFS) is a debilitating disorder characterized by intermittent involuntary movement of muscles innervated by the facial nerve. HFS is caused by neurovascular compression along the facial nerve root exit zone and can be treated by microvascular decompression (MVD). OBJECTIVE Determine rates and predictors of spasm freedom after MVD for HFS. METHODS A literature search using key terms "microvascular decompression" and "hemifacial spasm" was done. The primary outcome variable was spasm freedom at last follow up. Analysis was completed to evaluate for variables associated with spasm free outcome. RESULTS A total of 39 studies including 6249 patients were analyzed. Overall spasm freedom rate was 90.5% (5652/6249) at a follow up of 1.25 ± 0.04 years. There was no significant relationship between spasm freedom vs. persistent spasm and age at surgery, timing of follow up, gender, disease duration, side of disease, or vessel type. Spasm freedom was more likely after an initial surgery vs. a redo MVD (OR 4.16, 95% CI 1.99 to 8.68; p 90% at 1 year follow up in 6249 patients from 39 studies included in this report. A significant predictor of long-term spasm freedom at 1 year was an initial MVD as compared to repeat MVD. The majority of published manuscripts on MVD for HFS are heterogeneous single-institutional retrospective studies, as such, a large-scale meta-analysis reporting outcome rates and evaluating significant predictors of spasm freedom provides utility in the absence of randomized controlled studies.
The mean gestational age at the time of presentation was 26.5 weeks. Caesarean sections were performed in three women prior to the neurosurgical procedure, while the pregnancies were maintained in the six other patients. Eight infants who were healthy at birth had an unremarkable development. CONCLUSION Surgery for spinal emergencies in pregnancy can be performed safely according to individual treatment plans developed by an interdisciplinary team taking into account the expectant mother`s decision. Maintenance of pregnancy is possible and feasible in the majority of patients. BACKGROUND Diabetes mellitus (DM) is regarded to be associated with poor postoperative outcomes and increased morbidity following surgeries. Some previous studies have addressed the close association between DM and those leading to reoperations, whereas others objected this opinion. This study aimed to evaluate the long-term effect of DM on lumbar spinal surgery using data from a nationwide sample cohort. METHODS A population-based cohort comprised one million people, which is a 2.1% representative sample of the Korean population. The present study included adult patients with lumbar degenerative diseases, such as lumbar spinal stenosis and spondylolisthesis, who underwent their first lumbar surgery in 2006. The cumulative incidence function for reoperation was calculated and multivariate analysis were performed to define correlation between reoperation and independent factors, RESULTS A total of 2,020 patients were enrolled and followed up for 10 years. Non-diabetic patients, DM without complication (DwoC), and DM with complication (DwC) accounted for 79.5%, 9.36%, and 11.14% of all patients, respectively. Reoperation incidence stratified by DM was 12.7% for nondiabetic patients; 22.2% for DwoC; and 20.0% for DwC in 10 years of follow-up. During the same period, death, a competing event of reoperation, occurred 7.8% of the time in nondiabetic patients; 13.2% in DwoC; and 20.9% in DwC. CONCLUSION DM increased 1.65 times the overall cumulative incidences of reoperation after lumbar spinal surgeries for 10 years of follow-up. The reoperation incidences for DwC may be lower than that for DwoC because of a high incidence of death as a competing event of reoperation. BACKGROUND Intracranial bronchogenic cysts(IBCs) are extremely rare. To our knowledge, this is the first report of BC in which lesions involve the middle and posterior cranial fossa as well as the infratemporal fossa. CASE DESCRIPTION We present the case of a 38-year-old woman who suffered from a cranial nerve dysfunction for 2 years. Magnetic resonance imaging(MRI) showed that there were skull base communication lesions across the middle and posterior fossa. The patient was operated on through an infratemporal fossa approach. The final diagnosis was BC after histopathological examination and immunohistochemical verification. The patient's neurological dysfunction was partially ameliorated at the half-year follow-up. CONCLUSIONS IBCs are rare.However,it should be considered in the differential diagnosis for those cystic lesions with edge enhancement or extracranial extension. OBJECTIVE CT reduction in favor of rapid sequence MRI to decrease pediatric radiation exposure has varied across institutions. We aim to understand national trends in CT and rapid sequence MRI usage, as well as identify variables affecting imaging practices and obstacles to CT reduction. METHODS Retrospective review of deidentified discharge data for children with hydrocephalus and TBI in the Healthcare Cost and Utilization Project's Kid's Inpatient Database (KID) in 2000, 2003, 2006, 2009, 2012, and 2016. MRI without contrast and CT use were extracted using ICD9 and ICD10 codes. Hospital region and age cohorts were extracted and used to categorize data. Chi square tests and logistic regression were used for analysis. https://www.selleckchem.com/products/wnk-in-11.html RESULTS Hospitalization utilizing CT use decreased (p less then 0.05) and those using MRI increased (p less then 0.05) overall in both diagnosis groups throughout the years analyzed. However, there was significant regional variation in imaging. The Northeast had higher CT rates (p less then 0.05) and the South had lower CT rates in hydrocephalus and TBI patients (p less then 0.05). No regional variation was found for TBI patients receiving MRIs. CONCLUSIONS Nationwide, the average number of discharges after hospitalizations involving CT use in hydrocephalus and TBI patients has decreased, while those involving MRI use as an alternative imaging modality has increased. Despite successful overall CT reduction, significant regional variation exists within this trend showing inconsistent reduction of CT use. BACKGROUND Hemifacial spasm (HFS) is a debilitating disorder characterized by intermittent involuntary movement of muscles innervated by the facial nerve. HFS is caused by neurovascular compression along the facial nerve root exit zone and can be treated by microvascular decompression (MVD). OBJECTIVE Determine rates and predictors of spasm freedom after MVD for HFS. METHODS A literature search using key terms "microvascular decompression" and "hemifacial spasm" was done. The primary outcome variable was spasm freedom at last follow up. Analysis was completed to evaluate for variables associated with spasm free outcome. RESULTS A total of 39 studies including 6249 patients were analyzed. Overall spasm freedom rate was 90.5% (5652/6249) at a follow up of 1.25 ± 0.04 years. There was no significant relationship between spasm freedom vs. persistent spasm and age at surgery, timing of follow up, gender, disease duration, side of disease, or vessel type. Spasm freedom was more likely after an initial surgery vs. a redo MVD (OR 4.16, 95% CI 1.99 to 8.68; p 90% at 1 year follow up in 6249 patients from 39 studies included in this report. A significant predictor of long-term spasm freedom at 1 year was an initial MVD as compared to repeat MVD. The majority of published manuscripts on MVD for HFS are heterogeneous single-institutional retrospective studies, as such, a large-scale meta-analysis reporting outcome rates and evaluating significant predictors of spasm freedom provides utility in the absence of randomized controlled studies.0 Yorumlar 0 hisse senetleri 43 Views 0 önizleme
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