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of the upper cervical spinal cord (C2-C3) CONCLUSION This study provides the first evidence of cervical spinal cord atrophy in NMOSD by studying the entire cervical spinal cord. Upper cervical spinal cord atrophy was substantially correlated to clinical disability and seems more involved in the development of clinical disability in NMOSD patients in comparison to the lower cervical spinal cord.The management of diabetes in long-term care (LTC) facilities requires facility staff to perform most self-care activities on the behalf of the residents. A practical model of care to improve diabetes management was developed and implemented at 6 LTC facilities in the Northeast United States between 2009 and 2012. The components of the program included (1) developing an individualized education curriculum and educating LTC interdisciplinary staff; (2) educating patients and caregivers; and (3) developing a clinical care algorithm. Over 500 staff members were educated and achieved competence. There were 1031 residents screened for risk of hypo- or hyperglycemia on admission, and 245 residents (24%) experienced hypoglycemia and 240 residents (23%) experienced hyperglycemia. Hypoglycemia episodes resolved without recurrence in 73%-90% cases because of interventions initiated by LTC staff. The implementation of a practical model of diabetes management in LTC facilities can improve staff education and lead to improved diabetes management.
GOLD 2017 report proposed that the combined COPD assessment should be done according only to symptom burden and exacerbation history in the previous year.
This study aims to investigate the change in the COPD groups after the GOLD 2017 revision and also to discuss the evaluation of group C and D as a single group after the GOLD 2019 report.
The study was designed as a cross-sectional. 251 stable COPD patients admitted to our out-patient clinic; aged ≥40 years, at least one-year diagnosis of COPD and ≥10 pack-year smoking history were consecutively recruited for the study.
In GOLD 2017, a significant difference was found between the distribution of all groups compared to GOLD 2011 (P = 0,001). 31 patients included in group C were reclassified into group A and 37 patients in group D were reclassified into group B. The FEV
values of group A and B patients were significantly low and group C and D patients had had exacerbations in more frequently the previous year in GOLD 2017 compared to GOLD 2011.
After the GOLD 2017 revision, the rate of group C patients decreased even more compared to GOLD 2011 and the group C and D may be considered as a single group in terms of the treatment recommendations with the GOLD 2019 revision. We think that future prospective studies are needed to support this suggestion.
After the GOLD 2017 revision, the rate of group C patients decreased even more compared to GOLD 2011 and the group C and D may be considered as a single group in terms of the treatment recommendations with the GOLD 2019 revision. https://www.selleckchem.com/products/diphenhydramine.html We think that future prospective studies are needed to support this suggestion.Inflammation and the proliferation of vascular smooth muscle cells (VSMCs) are seen to play critical roles in the development of vascular complications induced by diabetes and hyperglycemia. Dihydroartemisinin (DHA) has been identified as a semi-synthetic derivative of artemisinin that exhibits broad protective effects. However, the effect of DHA on high glucose (HG)-induced inflammation and proliferation of VSMCs remains unknown. Therefore, this study aims to show that DHA significantly inhibited the proliferation of VSMCs and that expression of the inflammatory cytokines IL-1β and TNF-α was induced by HG in a dose-dependent manner. Additionally, we were able to determine that KLF15 played a critical role in HG-induced VSMC proliferation and inflammation, confirming its protective effects observed after DHA treatment in the HG-induced inflammatory response of VSMCs. DHA was observed to directly depress the HG-induced expression of miR-376b-3p, which targeted the 3'-UTR of KLF15 and inhibited its expression. These results suggested that DHA plays a protective role in HG-induced VSMC proliferation and associated inflammation by inhibiting the miR-376b-3p/KLF15 axis. Our findings provide new evidence of the mechanisms of DHA and its critical role in treating the pathogenesis of diabetic vascular complications.Here, we report genetically encoded AviTag conjugating system for Channelrhodopsin-2(ChR2) in order to attach various nanostructures to the membrane protein in a cell type specific manner. First, AviTag peptide sequence is cloned to N-terminal site of ChR2 construct and expressed at the membrane of primary-cultured hippocampal neurons via lentiviral transduction. Second, with the help of BirA enzyme and ATP, biotin coated quantum dots (Qdots) and streptavidin (SAv) coated Qdots are successfully bound to AviTag sites at the membrane where ChR2 is located and confirmed by fluorescence imaging. Moreover, we synthesize biotinylated Traptavidin-DNA conjugate probes containing a desthio-biotin that has weaker affinity than a regular biotin, and successfully exchange them with pre-conjugated Biotin-AviTag-ChR2 site at the membrane of neuronal cells which can potentially solve the crosslinking issue of Avidin linked probes. Therefore, we expect the AviTag-ChR2 fusion platform to become a great tool for incorporating various nanostructures at the specific sites of a cellular membrane in order to overcome the limits of optogenetic opsins.In lens, ∼90% of ocular proteins are αβγ-crystallins with concentrations ≥400 mg/ml, which need to remain soluble for the whole life-span and their aggregation leads to cataract. The G18V mutation of human γS-crystallin causes hereditary childhood-onset cortical cataract. Mysteriously, despite being a metabolically-quiescent organ, lens maintains ATP concentrations of 3-7 mM. Very recently, we found that ATP has no significant binding to γS-crystallin as well as no alternation of its conformation. Nevertheless, ATP antagonizes the crowding-induced destabilization of γS-crystallin even at 11, most likely by interacting with the hydration shell. Here by DSF and NMR, we characterized the effect of ATP on binding, conformation, stability of G18V γS-crystallin and its interactions with α-crystallin. The results reveal 1) G18V significantly accelerates the crowding-induced destabilization with Tm of 67 °C reduced to 50.5 °C at 1 mM. 2) Most unexpectedly, G18V almost completely eliminates the antagonizing effect of ATP against the crowding-induced destabilization.
of the upper cervical spinal cord (C2-C3) CONCLUSION This study provides the first evidence of cervical spinal cord atrophy in NMOSD by studying the entire cervical spinal cord. Upper cervical spinal cord atrophy was substantially correlated to clinical disability and seems more involved in the development of clinical disability in NMOSD patients in comparison to the lower cervical spinal cord.The management of diabetes in long-term care (LTC) facilities requires facility staff to perform most self-care activities on the behalf of the residents. A practical model of care to improve diabetes management was developed and implemented at 6 LTC facilities in the Northeast United States between 2009 and 2012. The components of the program included (1) developing an individualized education curriculum and educating LTC interdisciplinary staff; (2) educating patients and caregivers; and (3) developing a clinical care algorithm. Over 500 staff members were educated and achieved competence. There were 1031 residents screened for risk of hypo- or hyperglycemia on admission, and 245 residents (24%) experienced hypoglycemia and 240 residents (23%) experienced hyperglycemia. Hypoglycemia episodes resolved without recurrence in 73%-90% cases because of interventions initiated by LTC staff. The implementation of a practical model of diabetes management in LTC facilities can improve staff education and lead to improved diabetes management. GOLD 2017 report proposed that the combined COPD assessment should be done according only to symptom burden and exacerbation history in the previous year. This study aims to investigate the change in the COPD groups after the GOLD 2017 revision and also to discuss the evaluation of group C and D as a single group after the GOLD 2019 report. The study was designed as a cross-sectional. 251 stable COPD patients admitted to our out-patient clinic; aged ≥40 years, at least one-year diagnosis of COPD and ≥10 pack-year smoking history were consecutively recruited for the study. In GOLD 2017, a significant difference was found between the distribution of all groups compared to GOLD 2011 (P = 0,001). 31 patients included in group C were reclassified into group A and 37 patients in group D were reclassified into group B. The FEV values of group A and B patients were significantly low and group C and D patients had had exacerbations in more frequently the previous year in GOLD 2017 compared to GOLD 2011. After the GOLD 2017 revision, the rate of group C patients decreased even more compared to GOLD 2011 and the group C and D may be considered as a single group in terms of the treatment recommendations with the GOLD 2019 revision. We think that future prospective studies are needed to support this suggestion. After the GOLD 2017 revision, the rate of group C patients decreased even more compared to GOLD 2011 and the group C and D may be considered as a single group in terms of the treatment recommendations with the GOLD 2019 revision. https://www.selleckchem.com/products/diphenhydramine.html We think that future prospective studies are needed to support this suggestion.Inflammation and the proliferation of vascular smooth muscle cells (VSMCs) are seen to play critical roles in the development of vascular complications induced by diabetes and hyperglycemia. Dihydroartemisinin (DHA) has been identified as a semi-synthetic derivative of artemisinin that exhibits broad protective effects. However, the effect of DHA on high glucose (HG)-induced inflammation and proliferation of VSMCs remains unknown. Therefore, this study aims to show that DHA significantly inhibited the proliferation of VSMCs and that expression of the inflammatory cytokines IL-1β and TNF-α was induced by HG in a dose-dependent manner. Additionally, we were able to determine that KLF15 played a critical role in HG-induced VSMC proliferation and inflammation, confirming its protective effects observed after DHA treatment in the HG-induced inflammatory response of VSMCs. DHA was observed to directly depress the HG-induced expression of miR-376b-3p, which targeted the 3'-UTR of KLF15 and inhibited its expression. These results suggested that DHA plays a protective role in HG-induced VSMC proliferation and associated inflammation by inhibiting the miR-376b-3p/KLF15 axis. Our findings provide new evidence of the mechanisms of DHA and its critical role in treating the pathogenesis of diabetic vascular complications.Here, we report genetically encoded AviTag conjugating system for Channelrhodopsin-2(ChR2) in order to attach various nanostructures to the membrane protein in a cell type specific manner. First, AviTag peptide sequence is cloned to N-terminal site of ChR2 construct and expressed at the membrane of primary-cultured hippocampal neurons via lentiviral transduction. Second, with the help of BirA enzyme and ATP, biotin coated quantum dots (Qdots) and streptavidin (SAv) coated Qdots are successfully bound to AviTag sites at the membrane where ChR2 is located and confirmed by fluorescence imaging. Moreover, we synthesize biotinylated Traptavidin-DNA conjugate probes containing a desthio-biotin that has weaker affinity than a regular biotin, and successfully exchange them with pre-conjugated Biotin-AviTag-ChR2 site at the membrane of neuronal cells which can potentially solve the crosslinking issue of Avidin linked probes. Therefore, we expect the AviTag-ChR2 fusion platform to become a great tool for incorporating various nanostructures at the specific sites of a cellular membrane in order to overcome the limits of optogenetic opsins.In lens, ∼90% of ocular proteins are αβγ-crystallins with concentrations ≥400 mg/ml, which need to remain soluble for the whole life-span and their aggregation leads to cataract. The G18V mutation of human γS-crystallin causes hereditary childhood-onset cortical cataract. Mysteriously, despite being a metabolically-quiescent organ, lens maintains ATP concentrations of 3-7 mM. Very recently, we found that ATP has no significant binding to γS-crystallin as well as no alternation of its conformation. Nevertheless, ATP antagonizes the crowding-induced destabilization of γS-crystallin even at 11, most likely by interacting with the hydration shell. Here by DSF and NMR, we characterized the effect of ATP on binding, conformation, stability of G18V γS-crystallin and its interactions with α-crystallin. The results reveal 1) G18V significantly accelerates the crowding-induced destabilization with Tm of 67 °C reduced to 50.5 °C at 1 mM. 2) Most unexpectedly, G18V almost completely eliminates the antagonizing effect of ATP against the crowding-induced destabilization.0 Commenti 0 condivisioni 76 Views 0 AnteprimaEffettua l'accesso per mettere mi piace, condividere e commentare! -
Obesity is a leading comorbidity in psoriatic disease, including both psoriasis (PsO) and psoriatic arthritis (PsA), and is associated with adverse metabolic and cardiovascular (CV) outcomes. Anthropometric parameters, such as weight, body mass index (BMI) and waist-to-hip ratio, have been extensively reported in psoriatic disease. However, the associations of body composition and fat distribution with psoriasis have not yet been fully defined.
To identify whether patients with psoriatic disease, including psoriatic arthritis, have altered body composition compared with the general population, and to review existing modalities for the assessment of body composition.
Electronic searches of the literature were conducted in PubMed, Medline (Ovid®), Embase (Ovid®), Cochrane Central Register of Controlled Trials (CENTRAL) and Google Scholar. Titles and abstracts were reviewed by two authors independently against a set of prespecified inclusion/exclusion criteria. The research question was answered with a sysmodalities for the assessment of body composition. There is no consensus on the optimal assessment method of body composition for this diverse group; hence there is a need for validation of existing modalities and standardization of assessment tools.
Patients with psoriatic disease reveal defined body composition changes that are independent of obesity and the customary metabolic syndrome, including higher overall body fat, visceral fat and sarcopenia. These findings emphasize that patients with psoriatic disease should be screened for abnormal adipose effects beyond their weight and body mass index (BMI). Our findings show that the last decade has seen an exciting expansion of research interest in the development and validation of new modalities for the assessment of body composition. There is no consensus on the optimal assessment method of body composition for this diverse group; hence there is a need for validation of existing modalities and standardization of assessment tools.
Nordihydroguaiaretic acid (NDGA) is a plant extract that has been shown to act as a free radical scavenger and pluripotent inhibitor of pro-inflammatory cytokines, two major cellular processes involved in the pathophysiology of sepsis. We investigated whether NDGA would improve markers of organ injury as well as survival in a rodent model of sepsis.
Abdominal sepsis was induced by cecal ligation and double puncture (CLP) in male Sprague-Dawley rats. NDGA was administered either at the time of injury (pre-) or 6 hours later (post-treatment). A sham surgery group and a vehicle only group were also followed as controls. Blood and lung tissue were collected 24 h after CLP. Lung tissue was used for histopathologic analysis and to measure pulmonary edema. Arterial oxygenation was measured directly to generate PaO2/FiO2, and markers of renal injury (blood urea nitrogen), liver injury (alanine aminotransferase), and tissue hypoxia (lactate) were measured. https://www.selleckchem.com/products/kribb11.html In a separate set of animals consisting of the same treatment groups, animals were followed for up to 36 hours for survival.
NDGA pre-treatment resulted in improved oxygenation, less lung edema, lower lactate, lower BUN, and reduced histologic lung injury. NDGA post-treatment resulted in less lung edema, lower lactate, lower BUN, and less histologic lung injury, but did not significantly change oxygenation. None of the NDGA treatment groups statistically affected ALT or creatinine. NDGA pre-treatment showed improved survival compared with control CLP animals at 36 hours, while post-treatment did not.
NDGA represents a novel pleiotropic anti-inflammatory agent with potential clinical utility for modulation of organ injury secondary to sepsis.
NDGA represents a novel pleiotropic anti-inflammatory agent with potential clinical utility for modulation of organ injury secondary to sepsis.Taste receptor cells use multiple signaling pathways to detect chemicals in potential food items. These cells are functionally grouped into different types Type I cells act as support cells and have glial-like properties; Type II cells detect bitter, sweet, and umami taste stimuli; and Type III cells detect sour and salty stimuli. We have identified a new population of taste cells that are broadly tuned to multiple taste stimuli including bitter, sweet, sour, and umami. The goal of this study was to characterize these broadly responsive (BR) taste cells. We used an IP3R3-KO mouse (does not release calcium (Ca2+) from internal stores in Type II cells when stimulated with bitter, sweet, or umami stimuli) to characterize the BR cells without any potentially confounding input from Type II cells. Using live cell Ca2+ imaging in isolated taste cells from the IP3R3-KO mouse, we found that BR cells are a subset of Type III cells that respond to sour stimuli but also use a PLCβ signaling pathway to respond to bitter, sweet, and umami stimuli. Unlike Type II cells, individual BR cells are broadly tuned and respond to multiple stimuli across different taste modalities. Live cell imaging in a PLCβ3-KO mouse confirmed that BR cells use this signaling pathway to respond to bitter, sweet, and umami stimuli. Short term behavioral assays revealed that BR cells make significant contributions to taste driven behaviors and found that loss of either PLCβ3 in BR cells or IP3R3 in Type II cells caused similar behavioral deficits to bitter, sweet, and umami stimuli. Analysis of c-Fos activity in the nucleus of the solitary tract (NTS) also demonstrated that functional Type II and BR cells are required for normal stimulus induced expression.We have previously described a novel temporal encoding mechanism in the somatosensory system, where mechanical pulses grouped into periodic bursts create a perceived tactile frequency based on the duration of the silent gap between bursts, rather than the mean rate or the periodicity. This coding strategy may offer new opportunities for transmitting information to the brain using various sensory neural prostheses and haptic interfaces. However, it was not known whether the same coding mechanisms apply when using electrical stimulation, which recruits a different spectrum of afferents. Here, we demonstrate that the predictions of the burst gap coding model for frequency perception apply to burst stimuli delivered with electrical pulses, re-emphasising the importance of the temporal structure of spike patterns in neural processing and perception of tactile stimuli. Reciprocally, the electrical stimulation data confirm that the results observed with mechanical stimulation do indeed depend on neural processing mechanisms in the central nervous system, and are not due to skin mechanical factors and resulting patterns of afferent activation.
Obesity is a leading comorbidity in psoriatic disease, including both psoriasis (PsO) and psoriatic arthritis (PsA), and is associated with adverse metabolic and cardiovascular (CV) outcomes. Anthropometric parameters, such as weight, body mass index (BMI) and waist-to-hip ratio, have been extensively reported in psoriatic disease. However, the associations of body composition and fat distribution with psoriasis have not yet been fully defined. To identify whether patients with psoriatic disease, including psoriatic arthritis, have altered body composition compared with the general population, and to review existing modalities for the assessment of body composition. Electronic searches of the literature were conducted in PubMed, Medline (Ovid®), Embase (Ovid®), Cochrane Central Register of Controlled Trials (CENTRAL) and Google Scholar. Titles and abstracts were reviewed by two authors independently against a set of prespecified inclusion/exclusion criteria. The research question was answered with a sysmodalities for the assessment of body composition. There is no consensus on the optimal assessment method of body composition for this diverse group; hence there is a need for validation of existing modalities and standardization of assessment tools. Patients with psoriatic disease reveal defined body composition changes that are independent of obesity and the customary metabolic syndrome, including higher overall body fat, visceral fat and sarcopenia. These findings emphasize that patients with psoriatic disease should be screened for abnormal adipose effects beyond their weight and body mass index (BMI). Our findings show that the last decade has seen an exciting expansion of research interest in the development and validation of new modalities for the assessment of body composition. There is no consensus on the optimal assessment method of body composition for this diverse group; hence there is a need for validation of existing modalities and standardization of assessment tools. Nordihydroguaiaretic acid (NDGA) is a plant extract that has been shown to act as a free radical scavenger and pluripotent inhibitor of pro-inflammatory cytokines, two major cellular processes involved in the pathophysiology of sepsis. We investigated whether NDGA would improve markers of organ injury as well as survival in a rodent model of sepsis. Abdominal sepsis was induced by cecal ligation and double puncture (CLP) in male Sprague-Dawley rats. NDGA was administered either at the time of injury (pre-) or 6 hours later (post-treatment). A sham surgery group and a vehicle only group were also followed as controls. Blood and lung tissue were collected 24 h after CLP. Lung tissue was used for histopathologic analysis and to measure pulmonary edema. Arterial oxygenation was measured directly to generate PaO2/FiO2, and markers of renal injury (blood urea nitrogen), liver injury (alanine aminotransferase), and tissue hypoxia (lactate) were measured. https://www.selleckchem.com/products/kribb11.html In a separate set of animals consisting of the same treatment groups, animals were followed for up to 36 hours for survival. NDGA pre-treatment resulted in improved oxygenation, less lung edema, lower lactate, lower BUN, and reduced histologic lung injury. NDGA post-treatment resulted in less lung edema, lower lactate, lower BUN, and less histologic lung injury, but did not significantly change oxygenation. None of the NDGA treatment groups statistically affected ALT or creatinine. NDGA pre-treatment showed improved survival compared with control CLP animals at 36 hours, while post-treatment did not. NDGA represents a novel pleiotropic anti-inflammatory agent with potential clinical utility for modulation of organ injury secondary to sepsis. NDGA represents a novel pleiotropic anti-inflammatory agent with potential clinical utility for modulation of organ injury secondary to sepsis.Taste receptor cells use multiple signaling pathways to detect chemicals in potential food items. These cells are functionally grouped into different types Type I cells act as support cells and have glial-like properties; Type II cells detect bitter, sweet, and umami taste stimuli; and Type III cells detect sour and salty stimuli. We have identified a new population of taste cells that are broadly tuned to multiple taste stimuli including bitter, sweet, sour, and umami. The goal of this study was to characterize these broadly responsive (BR) taste cells. We used an IP3R3-KO mouse (does not release calcium (Ca2+) from internal stores in Type II cells when stimulated with bitter, sweet, or umami stimuli) to characterize the BR cells without any potentially confounding input from Type II cells. Using live cell Ca2+ imaging in isolated taste cells from the IP3R3-KO mouse, we found that BR cells are a subset of Type III cells that respond to sour stimuli but also use a PLCβ signaling pathway to respond to bitter, sweet, and umami stimuli. Unlike Type II cells, individual BR cells are broadly tuned and respond to multiple stimuli across different taste modalities. Live cell imaging in a PLCβ3-KO mouse confirmed that BR cells use this signaling pathway to respond to bitter, sweet, and umami stimuli. Short term behavioral assays revealed that BR cells make significant contributions to taste driven behaviors and found that loss of either PLCβ3 in BR cells or IP3R3 in Type II cells caused similar behavioral deficits to bitter, sweet, and umami stimuli. Analysis of c-Fos activity in the nucleus of the solitary tract (NTS) also demonstrated that functional Type II and BR cells are required for normal stimulus induced expression.We have previously described a novel temporal encoding mechanism in the somatosensory system, where mechanical pulses grouped into periodic bursts create a perceived tactile frequency based on the duration of the silent gap between bursts, rather than the mean rate or the periodicity. This coding strategy may offer new opportunities for transmitting information to the brain using various sensory neural prostheses and haptic interfaces. However, it was not known whether the same coding mechanisms apply when using electrical stimulation, which recruits a different spectrum of afferents. Here, we demonstrate that the predictions of the burst gap coding model for frequency perception apply to burst stimuli delivered with electrical pulses, re-emphasising the importance of the temporal structure of spike patterns in neural processing and perception of tactile stimuli. Reciprocally, the electrical stimulation data confirm that the results observed with mechanical stimulation do indeed depend on neural processing mechanisms in the central nervous system, and are not due to skin mechanical factors and resulting patterns of afferent activation.0 Commenti 0 condivisioni 66 Views 0 Anteprima -
Polycystic ovary syndrome is a common endocrinopathy that has been associated with many medical conditions across nearly every specialty. This chapter reviews the current understanding of polycystic ovary syndrome and associated medical conditions.The pregnant cardiac patient has become a national focus in the United States during the 21st century. Maternal mortality in the United States is on the rise, cardiac disease in pregnancy has been identified as the number one indirect cause and has driven the increase in maternal death rate greatly. This may be explained by the increasing number of women with congenital heart disease reaching reproductive age and a higher prevalence of chronic medical diseases. A triad solution includes cardiovascular screening, patient education and a multidisciplinary team. The Cardio Obstetric team is described here.
To investigate the correlation between the annual axial length (AL) elongation and associated factors in Japanese youth with myopia.
This retrospective study enrolled patients aged 7 to 21 years with myopia. Axial length was measured using ocular biometry. Refractive errors and curvature radius (CR) were measured using an open-field Binocular Auto Ref/Keratometer without cycloplegia. Subjects were divided into five groups using 3-year age intervals, and the relationship between annual AL elongation and age, spherical equivalent (SE), corneal CR, and sex was evaluated.
Four hundred and eighty-two patients (184 male and 298 female subjects) with a mean age of 15.55±4.09 years were included. The annual AL elongation was largest in the youngest group (0.47±0.19) and decreased with age to 0.03±0.04 in the oldest group. The annual change in AL was associated with age and SE (P<0.01) but not with sex or CR (P>0.05). https://www.selleckchem.com/products/agomelatine-hydrochloride.html Axial length elongation stratified by age was significantly correlated with SE in the 15 to 18-year-old (R2=0.20, P<0.01) and 19 to 21-year-old (R2=0.37, P=0.01) groups, whereas there was no significant correlation in the 7 to 9-year-old group (R2=0.04, P=0.14), the 10 to 12-year-old group (R2=0.05, P=0.07), and the 13 to 15-year-old group (R2=0.01, P=0.14).
In Japanese youth with myopia, AL elongation was largest in the youngest group, decreased with age, especially in the group older than 15 years.
In Japanese youth with myopia, AL elongation was largest in the youngest group, decreased with age, especially in the group older than 15 years.
Hormonal therapy is administered for multiple indications including contraception, alleviation of menopausal symptoms, hypogonadism, and more recently, gender-affirming care. Data suggest varying degrees of increased risk for venous thromboembolism (VTE).
While oral progestin only methods do not appear to increase the risk of VTE, an association was seen with injection progestin contraception. Combined oral contraception with low-dose ethinyl estradiol and most types of progestin increased the risk of VTE compared with levonorgestrel-containing oral therapies. While transdermal hormonal contraception has been previously associated with increased VTE, a recently approved levonorgestrel and ethinyl estradiol transdermal patch reported low rates (<0.2%) in a large single-arm open-label study. Women receiving postmenopausal HRT experienced an increased risk of VTE in a dose-dependent manner when using oral hormonal therapy while nonoral methods, such as topical estrogen, did not appear to increase the risk of VTE. Some studies suggest no increased risk of VTE with testosterone therapy, however, a recent case-crossover study suggested higher VTE risk in men on testosterone, particularly men less than age 65 without hypogonadism. Route of administration had no effect on VTE rates. The estimated incidence rate of VTE risk in transgender women receiving estrogen therapy is 2.3 per 1000 person years, but may be imprecise due to heterogeneity in studies included in published meta-analyses. Surgical risk estimates are primarily indirect data drawn from cisgender patients receiving hormone therapy in the perioperative setting.
Hormonal therapy affects VTE risk to varying degrees dependent on specific type of hormone, formulation, and occasionally route of delivery.
Hormonal therapy affects VTE risk to varying degrees dependent on specific type of hormone, formulation, and occasionally route of delivery.
Fundamental knowledge on the role of a disintegrin and metalloprotease with thrombospondin type one repeats, member 13 (ADAMTS13) has been crucial to better understand the pathophysiology of the rare and life-threatening disease thrombotic thrombocytopenic purpura (TTP).
ADAMTS13 works through a molecular zipper mechanism to proteolyze its substrate von Willebrand factor (VWF). Recent insights into the structure and function of ADAMTS13 led to the identification of an allosteric activation mechanism. Therefore, ADAMTS13 is roughly folded in two in which the N-terminal spacer (S) domain and C-terminal T7-CUB2 domains interact to adopt a closed conformation. Upon substrate binding, ADAMTS13 adopts an open conformation in which the S-T7-CUB2 interaction is abrogated to further position VWF towards the catalytic cleft, inducing activation of the latent metalloprotease domain and resulting in cleavage of VWF. Unravelling the structure function relationship of ADAMTS13 helped identifying open ADAMTS13 as a novel and unique biomarker for immune-mediated TTP (iTTP). This novel biomarker has potential in the diagnosis, treatment and follow-up of iTTP.
In this review, the most recent findings on the structure and working mechanism of ADAMTS13 are addressed. In addition, how those findings led to the identification of a novel biomarker, and how this novel biomarker could have an impact on the diagnosis, management and follow-up of iTTP patients are discussed.
In this review, the most recent findings on the structure and working mechanism of ADAMTS13 are addressed. In addition, how those findings led to the identification of a novel biomarker, and how this novel biomarker could have an impact on the diagnosis, management and follow-up of iTTP patients are discussed.
Polycystic ovary syndrome is a common endocrinopathy that has been associated with many medical conditions across nearly every specialty. This chapter reviews the current understanding of polycystic ovary syndrome and associated medical conditions.The pregnant cardiac patient has become a national focus in the United States during the 21st century. Maternal mortality in the United States is on the rise, cardiac disease in pregnancy has been identified as the number one indirect cause and has driven the increase in maternal death rate greatly. This may be explained by the increasing number of women with congenital heart disease reaching reproductive age and a higher prevalence of chronic medical diseases. A triad solution includes cardiovascular screening, patient education and a multidisciplinary team. The Cardio Obstetric team is described here. To investigate the correlation between the annual axial length (AL) elongation and associated factors in Japanese youth with myopia. This retrospective study enrolled patients aged 7 to 21 years with myopia. Axial length was measured using ocular biometry. Refractive errors and curvature radius (CR) were measured using an open-field Binocular Auto Ref/Keratometer without cycloplegia. Subjects were divided into five groups using 3-year age intervals, and the relationship between annual AL elongation and age, spherical equivalent (SE), corneal CR, and sex was evaluated. Four hundred and eighty-two patients (184 male and 298 female subjects) with a mean age of 15.55±4.09 years were included. The annual AL elongation was largest in the youngest group (0.47±0.19) and decreased with age to 0.03±0.04 in the oldest group. The annual change in AL was associated with age and SE (P<0.01) but not with sex or CR (P>0.05). https://www.selleckchem.com/products/agomelatine-hydrochloride.html Axial length elongation stratified by age was significantly correlated with SE in the 15 to 18-year-old (R2=0.20, P<0.01) and 19 to 21-year-old (R2=0.37, P=0.01) groups, whereas there was no significant correlation in the 7 to 9-year-old group (R2=0.04, P=0.14), the 10 to 12-year-old group (R2=0.05, P=0.07), and the 13 to 15-year-old group (R2=0.01, P=0.14). In Japanese youth with myopia, AL elongation was largest in the youngest group, decreased with age, especially in the group older than 15 years. In Japanese youth with myopia, AL elongation was largest in the youngest group, decreased with age, especially in the group older than 15 years. Hormonal therapy is administered for multiple indications including contraception, alleviation of menopausal symptoms, hypogonadism, and more recently, gender-affirming care. Data suggest varying degrees of increased risk for venous thromboembolism (VTE). While oral progestin only methods do not appear to increase the risk of VTE, an association was seen with injection progestin contraception. Combined oral contraception with low-dose ethinyl estradiol and most types of progestin increased the risk of VTE compared with levonorgestrel-containing oral therapies. While transdermal hormonal contraception has been previously associated with increased VTE, a recently approved levonorgestrel and ethinyl estradiol transdermal patch reported low rates (<0.2%) in a large single-arm open-label study. Women receiving postmenopausal HRT experienced an increased risk of VTE in a dose-dependent manner when using oral hormonal therapy while nonoral methods, such as topical estrogen, did not appear to increase the risk of VTE. Some studies suggest no increased risk of VTE with testosterone therapy, however, a recent case-crossover study suggested higher VTE risk in men on testosterone, particularly men less than age 65 without hypogonadism. Route of administration had no effect on VTE rates. The estimated incidence rate of VTE risk in transgender women receiving estrogen therapy is 2.3 per 1000 person years, but may be imprecise due to heterogeneity in studies included in published meta-analyses. Surgical risk estimates are primarily indirect data drawn from cisgender patients receiving hormone therapy in the perioperative setting. Hormonal therapy affects VTE risk to varying degrees dependent on specific type of hormone, formulation, and occasionally route of delivery. Hormonal therapy affects VTE risk to varying degrees dependent on specific type of hormone, formulation, and occasionally route of delivery. Fundamental knowledge on the role of a disintegrin and metalloprotease with thrombospondin type one repeats, member 13 (ADAMTS13) has been crucial to better understand the pathophysiology of the rare and life-threatening disease thrombotic thrombocytopenic purpura (TTP). ADAMTS13 works through a molecular zipper mechanism to proteolyze its substrate von Willebrand factor (VWF). Recent insights into the structure and function of ADAMTS13 led to the identification of an allosteric activation mechanism. Therefore, ADAMTS13 is roughly folded in two in which the N-terminal spacer (S) domain and C-terminal T7-CUB2 domains interact to adopt a closed conformation. Upon substrate binding, ADAMTS13 adopts an open conformation in which the S-T7-CUB2 interaction is abrogated to further position VWF towards the catalytic cleft, inducing activation of the latent metalloprotease domain and resulting in cleavage of VWF. Unravelling the structure function relationship of ADAMTS13 helped identifying open ADAMTS13 as a novel and unique biomarker for immune-mediated TTP (iTTP). This novel biomarker has potential in the diagnosis, treatment and follow-up of iTTP. In this review, the most recent findings on the structure and working mechanism of ADAMTS13 are addressed. In addition, how those findings led to the identification of a novel biomarker, and how this novel biomarker could have an impact on the diagnosis, management and follow-up of iTTP patients are discussed. In this review, the most recent findings on the structure and working mechanism of ADAMTS13 are addressed. In addition, how those findings led to the identification of a novel biomarker, and how this novel biomarker could have an impact on the diagnosis, management and follow-up of iTTP patients are discussed.0 Commenti 0 condivisioni 53 Views 0 Anteprima -
38 and 4.35. Number of days of progestin per month was a significant modulator of EC risk. A decreased risk of EC was seen in obese women. Two studies documented an increased risk of EC among users of cc/scMHT with micronized progesterone. A significantly increased risk of EC among estrogen-only MHT users was demonstrated in 9/12 studies with ORs/HRs between 1.45 and 4.46. The adverse effect of estrogen-only MHT was greatest among obese women.
ccMHT with SPs reduces the risk of EC, whereas estrogen-only MHT increases the risk. scMHT with SPs and cc/scMHT with micronized progesterone increase the risk of EC depending on type of progestin, progestin dosage, and duration of MHT use.
ccMHT with SPs reduces the risk of EC, whereas estrogen-only MHT increases the risk. scMHT with SPs and cc/scMHT with micronized progesterone increase the risk of EC depending on type of progestin, progestin dosage, and duration of MHT use.We previously reported that serine-47 (S47) phosphorylation of cytochrome c (Cytc) in the brain results in lower cytochrome c oxidase (COX) activity and caspase-3 activity in vitro. We here analyze the effect of S47 modification in fibroblast cell lines stably expressing S47E phosphomimetic Cytc, unphosphorylated WT, or S47A Cytc. Our results show that S47E Cytc results in partial inhibition of mitochondrial respiration corresponding with lower mitochondrial membrane potentials (ΔΨm) and reduced reactive oxygen species (ROS) production. When exposed to an oxygen-glucose deprivation/reoxygenation (OGD/R) model simulating ischemia/reperfusion injury, the Cytc S47E phosphomimetic cell line showed minimal ROS generation compared to the unphosphorylated WT Cytc cell line that generated high levels of ROS upon reoxygenation. Consequently, the S47E Cytc cell line also resulted in significantly lower cell death upon exposure to OGD/R, confirming the cytoprotective role of S47 phosphorylation of Cytc. S47E Cytc also resulted in lower cell death upon H2O2 treatment. Finally, we propose that pro-survival kinase Akt (protein kinase B) is a likely mediator of the S47 phosphorylation of Cytc in the brain. Akt inhibitor wortmannin abolished S47 phosphorylation of Cytc, while the Akt activator SC79 maintained S47 phosphorylation of Cytc. Overall, our results suggest that loss of S47 phosphorylation of Cytc during brain ischemia drives reperfusion injury through maximal electron transport chain flux, ΔΨm hyperpolarization, and ROS-triggered cell death.Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging coronavirus causing respiratory disease commonly known as COVID-19. This novel coronavirus transmits from human to human and has caused profound morbidity and mortality worldwide leading to the ongoing pandemic. Moreover, disease severity differs considerably from individual to individual. Investigating the virology of COVID-19 and immunological pathways underlying its clinical manifestations will enable the identification and design of effective vaccines and potential therapies. In this review, we explore COVID-19 virology, the contribution of the immune system (innate and adaptive) during infection and control of the virus. Finally, we highlight vaccine development and implications of immune system modulation for potential therapeutic interventions to design better therapeutic strategies to guide future cure.The myeloproliferative neoplasms (MPNs) are acquired hematological stem cell neoplasms characterized by driver mutations in JAK2, CALR, or MPL. Additive mutations may appear in predominantly epigenetic regulator, RNA splicing and signaling pathway genes. These molecular mutations are a hallmark of diagnostic, prognostic, and therapeutic assessment in patients with MPNs. Over the past decade, next generation sequencing (NGS) has identified multiple somatic mutations in MPNs and has contributed substantially to our understanding of the disease pathogenesis highlighting the role of clonal evolution in disease progression. In addition, disease prognostication has expanded from encompassing only clinical decision making to include genomics in prognostic scoring systems. Taking into account the decreasing costs and increasing speed and availability of high throughput technologies, the integration of NGS into a diagnostic, prognostic and therapeutic pipeline is within reach. In this review, these aspects will be discussed highlighting their role regarding disease outcome and treatment modalities in patients with MPNs.Pigs are highly susceptible to mycotoxins. This study investigated the effects of a postbiotic yeast cell wall-based blend (PYCW; Nicholasville, KY, USA) on growth and health of newly-weaned pigs under dietary challenge of multiple mycotoxins. https://www.selleckchem.com/products/kribb11.html Forty-eight newly-weaned pigs (21 d old) were individually allotted to four dietary treatments, based on a three phase-feeding, in a randomized complete block design (sex; initial BW) with two factors for 36 d. Two factors were dietary mycotoxins (deoxynivalenol 2000 μg/kg supplemented in three phases; and aflatoxin 200 μg/kg supplemented only in phase 3) and PYCW (0.2%). Growth performance (weekly), blood serum (d 34), and jejunal mucosa immune and oxidative stress markers (d 36) data were analyzed using MIXED procedure of SAS. Mycotoxins reduced (p less then 0.05) average daily feed intake (ADFI) and average daily gain (ADG) during the entire period whereas PYCW did not affect growth performance. Mycotoxins reduced (p less then 0.05) serum protein, albumin, creatinine, and alanine aminotransferase whereas PYCW decreased (p less then 0.05) serum creatine phosphokinase. Neither mycotoxins nor PYCW affected pro-inflammatory cytokines and oxidative damage markers in the jejunal mucosa. No interaction was observed indicating that PYCW improved hepatic enzymes regardless of mycotoxin challenge. In conclusion, deoxynivalenol (2000 μg/kg, for 7 to 25 kg body weight) and aflatoxin B1 (200 μg/kg, for 16 to 25 kg body weight) impaired growth performance and nutrient digestibility of newly-weaned pigs, whereas PYCW could partially improve health of pigs regardless of mycotoxin challenge.
38 and 4.35. Number of days of progestin per month was a significant modulator of EC risk. A decreased risk of EC was seen in obese women. Two studies documented an increased risk of EC among users of cc/scMHT with micronized progesterone. A significantly increased risk of EC among estrogen-only MHT users was demonstrated in 9/12 studies with ORs/HRs between 1.45 and 4.46. The adverse effect of estrogen-only MHT was greatest among obese women. ccMHT with SPs reduces the risk of EC, whereas estrogen-only MHT increases the risk. scMHT with SPs and cc/scMHT with micronized progesterone increase the risk of EC depending on type of progestin, progestin dosage, and duration of MHT use. ccMHT with SPs reduces the risk of EC, whereas estrogen-only MHT increases the risk. scMHT with SPs and cc/scMHT with micronized progesterone increase the risk of EC depending on type of progestin, progestin dosage, and duration of MHT use.We previously reported that serine-47 (S47) phosphorylation of cytochrome c (Cytc) in the brain results in lower cytochrome c oxidase (COX) activity and caspase-3 activity in vitro. We here analyze the effect of S47 modification in fibroblast cell lines stably expressing S47E phosphomimetic Cytc, unphosphorylated WT, or S47A Cytc. Our results show that S47E Cytc results in partial inhibition of mitochondrial respiration corresponding with lower mitochondrial membrane potentials (ΔΨm) and reduced reactive oxygen species (ROS) production. When exposed to an oxygen-glucose deprivation/reoxygenation (OGD/R) model simulating ischemia/reperfusion injury, the Cytc S47E phosphomimetic cell line showed minimal ROS generation compared to the unphosphorylated WT Cytc cell line that generated high levels of ROS upon reoxygenation. Consequently, the S47E Cytc cell line also resulted in significantly lower cell death upon exposure to OGD/R, confirming the cytoprotective role of S47 phosphorylation of Cytc. S47E Cytc also resulted in lower cell death upon H2O2 treatment. Finally, we propose that pro-survival kinase Akt (protein kinase B) is a likely mediator of the S47 phosphorylation of Cytc in the brain. Akt inhibitor wortmannin abolished S47 phosphorylation of Cytc, while the Akt activator SC79 maintained S47 phosphorylation of Cytc. Overall, our results suggest that loss of S47 phosphorylation of Cytc during brain ischemia drives reperfusion injury through maximal electron transport chain flux, ΔΨm hyperpolarization, and ROS-triggered cell death.Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging coronavirus causing respiratory disease commonly known as COVID-19. This novel coronavirus transmits from human to human and has caused profound morbidity and mortality worldwide leading to the ongoing pandemic. Moreover, disease severity differs considerably from individual to individual. Investigating the virology of COVID-19 and immunological pathways underlying its clinical manifestations will enable the identification and design of effective vaccines and potential therapies. In this review, we explore COVID-19 virology, the contribution of the immune system (innate and adaptive) during infection and control of the virus. Finally, we highlight vaccine development and implications of immune system modulation for potential therapeutic interventions to design better therapeutic strategies to guide future cure.The myeloproliferative neoplasms (MPNs) are acquired hematological stem cell neoplasms characterized by driver mutations in JAK2, CALR, or MPL. Additive mutations may appear in predominantly epigenetic regulator, RNA splicing and signaling pathway genes. These molecular mutations are a hallmark of diagnostic, prognostic, and therapeutic assessment in patients with MPNs. Over the past decade, next generation sequencing (NGS) has identified multiple somatic mutations in MPNs and has contributed substantially to our understanding of the disease pathogenesis highlighting the role of clonal evolution in disease progression. In addition, disease prognostication has expanded from encompassing only clinical decision making to include genomics in prognostic scoring systems. Taking into account the decreasing costs and increasing speed and availability of high throughput technologies, the integration of NGS into a diagnostic, prognostic and therapeutic pipeline is within reach. In this review, these aspects will be discussed highlighting their role regarding disease outcome and treatment modalities in patients with MPNs.Pigs are highly susceptible to mycotoxins. This study investigated the effects of a postbiotic yeast cell wall-based blend (PYCW; Nicholasville, KY, USA) on growth and health of newly-weaned pigs under dietary challenge of multiple mycotoxins. https://www.selleckchem.com/products/kribb11.html Forty-eight newly-weaned pigs (21 d old) were individually allotted to four dietary treatments, based on a three phase-feeding, in a randomized complete block design (sex; initial BW) with two factors for 36 d. Two factors were dietary mycotoxins (deoxynivalenol 2000 μg/kg supplemented in three phases; and aflatoxin 200 μg/kg supplemented only in phase 3) and PYCW (0.2%). Growth performance (weekly), blood serum (d 34), and jejunal mucosa immune and oxidative stress markers (d 36) data were analyzed using MIXED procedure of SAS. Mycotoxins reduced (p less then 0.05) average daily feed intake (ADFI) and average daily gain (ADG) during the entire period whereas PYCW did not affect growth performance. Mycotoxins reduced (p less then 0.05) serum protein, albumin, creatinine, and alanine aminotransferase whereas PYCW decreased (p less then 0.05) serum creatine phosphokinase. Neither mycotoxins nor PYCW affected pro-inflammatory cytokines and oxidative damage markers in the jejunal mucosa. No interaction was observed indicating that PYCW improved hepatic enzymes regardless of mycotoxin challenge. In conclusion, deoxynivalenol (2000 μg/kg, for 7 to 25 kg body weight) and aflatoxin B1 (200 μg/kg, for 16 to 25 kg body weight) impaired growth performance and nutrient digestibility of newly-weaned pigs, whereas PYCW could partially improve health of pigs regardless of mycotoxin challenge.0 Commenti 0 condivisioni 82 Views 0 Anteprima -
DN and 40°C heating followed by capsaicin injection improved PPT.
DN and 44°C heating had therapeutic effects on rats with MPS at 24 hours and at 7 days after the intervention. DN and 40°C heating had therapeutic effects 7 days after the intervention. DN and 44°C heating might exert therapeutic effects by regulating the transient receptor potential V1 channel.
DN and 44°C heating had therapeutic effects on rats with MPS at 24 hours and at 7 days after the intervention. DN and 40°C heating had therapeutic effects 7 days after the intervention. DN and 44°C heating might exert therapeutic effects by regulating the transient receptor potential V1 channel.
Our aim was to analyze whether shoulder pain is related to scapular upward rotation (SUR) or to the lengths of the pectoralis minor and levator scapulae muscles.
This cross-sectional, observational study was carried out in 3 primary-care centers; 54 individuals with chronic shoulder pain participated. Scapular upward rotation and the lengths of the pectoralis minor and levator scapulae muscles were assessed.
The level of association was small between shoulder pain and function and (1) the lengths of the pectoralis minor (r = 0.08, P = .93) and levator scapulae (r = -0.01, P = .57) muscles and (2) SUR at 45° (r = 0.17, P = .21), 90° (r = 0.08, P = .57), and 135° (r = 0.10, P = 0.45) of shoulder elevation.
The relationship was small between shoulder pain and function and (1) SUR (45°, 90°, and 135° of shoulder elevation) and (2) the lengths of the pectoralis minor and levator scapulae muscles. Thus, the use of SUR and pectoralis minor and levator scapulae lengths in shoulder assessment should be undertaken with caution. Other factors such as psychological factors, central/peripheral sensitization, and intrinsic properties of the tissue have to be taken into account.
The relationship was small between shoulder pain and function and (1) SUR (45°, 90°, and 135° of shoulder elevation) and (2) the lengths of the pectoralis minor and levator scapulae muscles. Thus, the use of SUR and pectoralis minor and levator scapulae lengths in shoulder assessment should be undertaken with caution. Other factors such as psychological factors, central/peripheral sensitization, and intrinsic properties of the tissue have to be taken into account.
The aim of this study was to do a cost-benefit analysis of myofascial release therapy (MRT) compared to manual therapy (MT) for treating occupational mechanical neck pain.
Variables regarding the outcomes of the intervention were intensity of neck pain, cervical disability, quality of life, craniovertebral angle, and ranges of cervical motion. Costs were assessed based on a social perspective using diary costs. Between-groups differences in average cost, cost-effectiveness, and cost-utility ratios were assessed using bootstrap parametric techniques. The economic cost-benefit evaluation was with regard to an experimental parallel group study design. There were 59 participants.
Myofascial released therapy showed significant improvement over MT for cervical mobility (side bending, rotation, and craniovertebral angle). The total cost of MRT was approximately 20% less (-$519.81; 95% confidence interval, -$1193.67 to $100.31) than that of MT, although this was not statistically significant. https://www.selleckchem.com/products/sb290157-tfa.html Cost-effectiveness and cost-utility ratios showed that MRT could be associated with lower economic costs.
With probabilities of 93.9% and 95.8%, MRT seems to be cost-effective for treating mechanical neck pain without the need to add any additional cost to obtain a better clinical benefit. Consequently, we believe it could be included in the clinical practice guidelines of different Spanish health care institutions.
With probabilities of 93.9% and 95.8%, MRT seems to be cost-effective for treating mechanical neck pain without the need to add any additional cost to obtain a better clinical benefit. Consequently, we believe it could be included in the clinical practice guidelines of different Spanish health care institutions.
Germ cell cancer (GCC) is a group of neoplasms with heterogeneity. Predominant in young adults, GCC potentially mitigates a high number of productive years of life lost. Indeed, long-term side effects have arisen as a problem in GCC survivors, especially in adolescent and young adult (AYA) subgroup. The objective of this study is to delineate survival and second primary malignancies (SPMs) in AYA patients with GCC.
We used US population-based Surveillance, Epidemiology and End Results (SEER) 18 Regs Custom Data (1976-2016 varying) and SEER 9 Regs Research Data, November 2019 Sub (1975-2017) for survival analysis and SPM analysis, respectively.
Overall, 5-, 10- and 20-year overall survival rates for AYA patients with GCC were 93%, 91.3%, and 86.9%, respectively. Compared with the general population, a significantly higher risk of SPMs was observed in multiple sites, especially stomach, (standardized incidence ratio [SIR] = 2.94), pancreas (SIR = 3.72), intrahepatic bile duct (SIR = 3.12), soft tissue including heart (SIR = 4.65), leukemia (SIR = 3.70), and testis (SIR = 562.18). The excess risks to develop leukemia were even higher in those with primary mediastinal GCC (SIR = 69.50, P < 0.05, 95% confidence interval = 30.00-136.94). Multivariate analysis indicated age of diagnosis, primary site, race, receipt of radiotherapy, and histological subtype independently correlated with risk of SPMs.
The present study provides risk factors of SPM in AYA patients with GCC, which could facilitate the individualization of long-term surveillance in this population.
The present study provides risk factors of SPM in AYA patients with GCC, which could facilitate the individualization of long-term surveillance in this population.Plant growth is usually constrained by the availability of nutrients, water, or temperature, rather than photosynthetic carbon (C) fixation. Under these conditions leaf growth is curtailed more than C fixation, and the surplus photosynthates are exported from the leaf. In plants limited by nitrogen (N) or phosphorus (P), photosynthates are converted into sugars and secondary metabolites. Some surplus C is translocated to roots and released as root exudates or transferred to root-associated microorganisms. Surplus C is also produced under low moisture availability, low temperature, and high atmospheric CO2 concentrations, with similar below-ground effects. Many interactions among above- and below-ground ecosystem components can be parsimoniously explained by the production, distribution, and release of surplus C under conditions that limit plant growth.
DN and 40°C heating followed by capsaicin injection improved PPT. DN and 44°C heating had therapeutic effects on rats with MPS at 24 hours and at 7 days after the intervention. DN and 40°C heating had therapeutic effects 7 days after the intervention. DN and 44°C heating might exert therapeutic effects by regulating the transient receptor potential V1 channel. DN and 44°C heating had therapeutic effects on rats with MPS at 24 hours and at 7 days after the intervention. DN and 40°C heating had therapeutic effects 7 days after the intervention. DN and 44°C heating might exert therapeutic effects by regulating the transient receptor potential V1 channel. Our aim was to analyze whether shoulder pain is related to scapular upward rotation (SUR) or to the lengths of the pectoralis minor and levator scapulae muscles. This cross-sectional, observational study was carried out in 3 primary-care centers; 54 individuals with chronic shoulder pain participated. Scapular upward rotation and the lengths of the pectoralis minor and levator scapulae muscles were assessed. The level of association was small between shoulder pain and function and (1) the lengths of the pectoralis minor (r = 0.08, P = .93) and levator scapulae (r = -0.01, P = .57) muscles and (2) SUR at 45° (r = 0.17, P = .21), 90° (r = 0.08, P = .57), and 135° (r = 0.10, P = 0.45) of shoulder elevation. The relationship was small between shoulder pain and function and (1) SUR (45°, 90°, and 135° of shoulder elevation) and (2) the lengths of the pectoralis minor and levator scapulae muscles. Thus, the use of SUR and pectoralis minor and levator scapulae lengths in shoulder assessment should be undertaken with caution. Other factors such as psychological factors, central/peripheral sensitization, and intrinsic properties of the tissue have to be taken into account. The relationship was small between shoulder pain and function and (1) SUR (45°, 90°, and 135° of shoulder elevation) and (2) the lengths of the pectoralis minor and levator scapulae muscles. Thus, the use of SUR and pectoralis minor and levator scapulae lengths in shoulder assessment should be undertaken with caution. Other factors such as psychological factors, central/peripheral sensitization, and intrinsic properties of the tissue have to be taken into account. The aim of this study was to do a cost-benefit analysis of myofascial release therapy (MRT) compared to manual therapy (MT) for treating occupational mechanical neck pain. Variables regarding the outcomes of the intervention were intensity of neck pain, cervical disability, quality of life, craniovertebral angle, and ranges of cervical motion. Costs were assessed based on a social perspective using diary costs. Between-groups differences in average cost, cost-effectiveness, and cost-utility ratios were assessed using bootstrap parametric techniques. The economic cost-benefit evaluation was with regard to an experimental parallel group study design. There were 59 participants. Myofascial released therapy showed significant improvement over MT for cervical mobility (side bending, rotation, and craniovertebral angle). The total cost of MRT was approximately 20% less (-$519.81; 95% confidence interval, -$1193.67 to $100.31) than that of MT, although this was not statistically significant. https://www.selleckchem.com/products/sb290157-tfa.html Cost-effectiveness and cost-utility ratios showed that MRT could be associated with lower economic costs. With probabilities of 93.9% and 95.8%, MRT seems to be cost-effective for treating mechanical neck pain without the need to add any additional cost to obtain a better clinical benefit. Consequently, we believe it could be included in the clinical practice guidelines of different Spanish health care institutions. With probabilities of 93.9% and 95.8%, MRT seems to be cost-effective for treating mechanical neck pain without the need to add any additional cost to obtain a better clinical benefit. Consequently, we believe it could be included in the clinical practice guidelines of different Spanish health care institutions. Germ cell cancer (GCC) is a group of neoplasms with heterogeneity. Predominant in young adults, GCC potentially mitigates a high number of productive years of life lost. Indeed, long-term side effects have arisen as a problem in GCC survivors, especially in adolescent and young adult (AYA) subgroup. The objective of this study is to delineate survival and second primary malignancies (SPMs) in AYA patients with GCC. We used US population-based Surveillance, Epidemiology and End Results (SEER) 18 Regs Custom Data (1976-2016 varying) and SEER 9 Regs Research Data, November 2019 Sub (1975-2017) for survival analysis and SPM analysis, respectively. Overall, 5-, 10- and 20-year overall survival rates for AYA patients with GCC were 93%, 91.3%, and 86.9%, respectively. Compared with the general population, a significantly higher risk of SPMs was observed in multiple sites, especially stomach, (standardized incidence ratio [SIR] = 2.94), pancreas (SIR = 3.72), intrahepatic bile duct (SIR = 3.12), soft tissue including heart (SIR = 4.65), leukemia (SIR = 3.70), and testis (SIR = 562.18). The excess risks to develop leukemia were even higher in those with primary mediastinal GCC (SIR = 69.50, P < 0.05, 95% confidence interval = 30.00-136.94). Multivariate analysis indicated age of diagnosis, primary site, race, receipt of radiotherapy, and histological subtype independently correlated with risk of SPMs. The present study provides risk factors of SPM in AYA patients with GCC, which could facilitate the individualization of long-term surveillance in this population. The present study provides risk factors of SPM in AYA patients with GCC, which could facilitate the individualization of long-term surveillance in this population.Plant growth is usually constrained by the availability of nutrients, water, or temperature, rather than photosynthetic carbon (C) fixation. Under these conditions leaf growth is curtailed more than C fixation, and the surplus photosynthates are exported from the leaf. In plants limited by nitrogen (N) or phosphorus (P), photosynthates are converted into sugars and secondary metabolites. Some surplus C is translocated to roots and released as root exudates or transferred to root-associated microorganisms. Surplus C is also produced under low moisture availability, low temperature, and high atmospheric CO2 concentrations, with similar below-ground effects. Many interactions among above- and below-ground ecosystem components can be parsimoniously explained by the production, distribution, and release of surplus C under conditions that limit plant growth.0 Commenti 0 condivisioni 77 Views 0 Anteprima -
BACKGROUND Focal cortical dysplasia (FCD) is a neuronal migration disorder and is a major cause of drug-resistant epilepsy. https://www.selleckchem.com/products/motolimod-vtx-2337.html However, many focal abnormalities remain undetected during routine visual inspection, and many patients with histologically confirmed FCD have normal fluid-attenuated inversion recovery (FLAIR-negative) images. The aim of this study was to quantitatively evaluate the changes in cortical thickness with magnetic resonance (MR) imaging of patients to identify FCD lesions from FLAIR-negative images. METHODS We first used the three-dimensional (3D) Laplace method to calculate the cortical thickness for individuals and obtained the cortical thickness mean image and cortical thickness standard deviation (SD) image based on all 32 healthy controls. Then, a cortical thickness extension map was computed by subtracting the cortical thickness mean image from the cortical thickness image of each patient and dividing the result by the cortical thickness SD image. Finally, clusters of voxels larger than three were defined as the FCD lesion area from the cortical thickness extension map. RESULTS The results showed that three of the four lesions that occurred in non-temporal areas were detected in three patients, but the detection failed in three patients with lesions that occurred in the temporal area. The quantitative analysis of the detected lesions in voxel-wise on images revealed the following specificity (99.78%), accuracy (99.76%), recall (67.45%), precision (20.42%), Dice coefficient (30.01%), Youden index (67.23%) and area under the curve (AUC) (83.62%). CONCLUSION Our studies demonstrate an effective method to localize lesions in non-temporal lobe regions. This novel method automatically detected FCD lesions using only FLAIR-negative images from patients and was based only on cortical thickness feature. The method is noninvasive and more effective than a visual analysis for helping doctors make a diagnosis.BACKGROUND In recent years, some studies have shown that there is a positive association between the number of oocytes retrieved and the cumulative live birth rate (CLBR) after fresh and frozen cycles of one oocyte retrieval. However, almost no studies have examined the association between the number of oocytes retrieved and the CLBR when using the "freeze-all" strategy. We performed this study to investigate the effects of an extreme oocyte yield during the first "freeze-all" cycle on the cumulative live birth rate among patients younger than 35 years old. METHODS This was a retrospective cohort study performed in a university-affiliated reproductive medicine centre. Data obtained from 3276 women aged younger than 35 years who underwent their first "freeze-all" cycle (IVF/ICSI) were collected between January 2009 and December 2016. In all, 5025 frozen cycles took place during the follow-up period from January 2009 to December 2018. Patients were divided into five groups according to oocytes retrieved (group ield should be no more than 30.BACKGROUND American tegumentary leishmaniasis (ATL) is a widespread anthropozoonosis caused by protozoa of the genus Leishmania and is considered a serious public health problem. The aim of this study was to provide a descriptive analysis of confirmed ATL cases and evaluate the spatial distribution of ATL in high-risk transmission areas from the state of Minas Gerais, Brazil. METHODS An ecological, analytical, and retrospective study of the confirmed cases of ATL in Minas Gerais from 2007 to 2017 was conducted. To characterize these cases, multiple correspondence analysis and georeferencing of the ATL prevalence rates in the municipalities were conducted based on variables obtained at Sistema Nacional de Agravos de Notificação and Instituto Brasileiro de Geografia e Estatística databases. RESULTS There were 13,025 confirmed cases of ATL from 74.4% (635) municipalities of Minas Gerais, corresponding to a prevalence rate of 66.5 cases for every 100,000 inhabitants. Males aged 20 to 59 years and individuals who attended elementary school were most affected with ATL. Multiple correspondence analysis presented an accumulated qui-squared value of 44.74%, proving that there was a relationship between the variables, including ethnicity, age, pregnancy status, zone of infection, and number of cases. CONCLUSION We confirmed that ATL is endemic to Minas Gerais, and there is high risk of infection within the municipalities due to a high rate of parasite transmission. The occurrence of infection in children, pregnant women, and the indigenous population demonstrates the need for the government to expand social policies aimed at vulnerable groups.BACKGROUND In this study, we evaluated the genetic relatedness of extended-spectrum beta-lactamase-producing Klebsiella pneumoniae (ESBL-KPN) isolates from an outbreak in a neonatal intensive care unit (NICU) in August 2017, We implemented an active countermeasure to control this outbreak successfully. METHODS The incidence of healthcare-associated ESBL-KPN bacteremia was evaluated before and after initiating enhanced infection control (IC) practices in January 2018. Surveillance cultures were set up and monitored for neonates, medical personnel, and NICU environments. Molecular analyses, including pulse-field gel electrophoresis (PFGE), sequence typing, and ESBL genotyping, were performed for the isolated KPN strains. RESULTS After implementing the enhanced IC procedures, the healthcare-associated bacteremia rate decreased from 6.0 to 0.0 per 1000 patient-days. Samples from neonates (n = 11/15, 73.3%), medical personnel (n = 1/41, 2.4%), and medical devices and the environments (6/181, 3.3%) tested positive for ESBL-KPN in the surveillance cultures in December 2017. Active surveillance cultures revealed that 23 of 72 neonates who were screened (31.9%) were colonized with ESBL-KPN between January and March 2018. All the isolates demonstrated closely related PFGE patterns and were identified as ST307 strain carrying the CTX-M-15 gene. CONCLUSIONS Contaminated NICU environments and medical devices, as well as transmission by medical personnel, appeared to be the source of the outbreak of ESBL-KPN infection. We employed an enhanced IC strategy during January-March 2018 and successfully controlled the clonal outbreak of CTX-M-15-positive KPN. ST307 has emerged as an important bacteremia-causing pathogen in the NICU and should be carefully monitored.
BACKGROUND Focal cortical dysplasia (FCD) is a neuronal migration disorder and is a major cause of drug-resistant epilepsy. https://www.selleckchem.com/products/motolimod-vtx-2337.html However, many focal abnormalities remain undetected during routine visual inspection, and many patients with histologically confirmed FCD have normal fluid-attenuated inversion recovery (FLAIR-negative) images. The aim of this study was to quantitatively evaluate the changes in cortical thickness with magnetic resonance (MR) imaging of patients to identify FCD lesions from FLAIR-negative images. METHODS We first used the three-dimensional (3D) Laplace method to calculate the cortical thickness for individuals and obtained the cortical thickness mean image and cortical thickness standard deviation (SD) image based on all 32 healthy controls. Then, a cortical thickness extension map was computed by subtracting the cortical thickness mean image from the cortical thickness image of each patient and dividing the result by the cortical thickness SD image. Finally, clusters of voxels larger than three were defined as the FCD lesion area from the cortical thickness extension map. RESULTS The results showed that three of the four lesions that occurred in non-temporal areas were detected in three patients, but the detection failed in three patients with lesions that occurred in the temporal area. The quantitative analysis of the detected lesions in voxel-wise on images revealed the following specificity (99.78%), accuracy (99.76%), recall (67.45%), precision (20.42%), Dice coefficient (30.01%), Youden index (67.23%) and area under the curve (AUC) (83.62%). CONCLUSION Our studies demonstrate an effective method to localize lesions in non-temporal lobe regions. This novel method automatically detected FCD lesions using only FLAIR-negative images from patients and was based only on cortical thickness feature. The method is noninvasive and more effective than a visual analysis for helping doctors make a diagnosis.BACKGROUND In recent years, some studies have shown that there is a positive association between the number of oocytes retrieved and the cumulative live birth rate (CLBR) after fresh and frozen cycles of one oocyte retrieval. However, almost no studies have examined the association between the number of oocytes retrieved and the CLBR when using the "freeze-all" strategy. We performed this study to investigate the effects of an extreme oocyte yield during the first "freeze-all" cycle on the cumulative live birth rate among patients younger than 35 years old. METHODS This was a retrospective cohort study performed in a university-affiliated reproductive medicine centre. Data obtained from 3276 women aged younger than 35 years who underwent their first "freeze-all" cycle (IVF/ICSI) were collected between January 2009 and December 2016. In all, 5025 frozen cycles took place during the follow-up period from January 2009 to December 2018. Patients were divided into five groups according to oocytes retrieved (group ield should be no more than 30.BACKGROUND American tegumentary leishmaniasis (ATL) is a widespread anthropozoonosis caused by protozoa of the genus Leishmania and is considered a serious public health problem. The aim of this study was to provide a descriptive analysis of confirmed ATL cases and evaluate the spatial distribution of ATL in high-risk transmission areas from the state of Minas Gerais, Brazil. METHODS An ecological, analytical, and retrospective study of the confirmed cases of ATL in Minas Gerais from 2007 to 2017 was conducted. To characterize these cases, multiple correspondence analysis and georeferencing of the ATL prevalence rates in the municipalities were conducted based on variables obtained at Sistema Nacional de Agravos de Notificação and Instituto Brasileiro de Geografia e Estatística databases. RESULTS There were 13,025 confirmed cases of ATL from 74.4% (635) municipalities of Minas Gerais, corresponding to a prevalence rate of 66.5 cases for every 100,000 inhabitants. Males aged 20 to 59 years and individuals who attended elementary school were most affected with ATL. Multiple correspondence analysis presented an accumulated qui-squared value of 44.74%, proving that there was a relationship between the variables, including ethnicity, age, pregnancy status, zone of infection, and number of cases. CONCLUSION We confirmed that ATL is endemic to Minas Gerais, and there is high risk of infection within the municipalities due to a high rate of parasite transmission. The occurrence of infection in children, pregnant women, and the indigenous population demonstrates the need for the government to expand social policies aimed at vulnerable groups.BACKGROUND In this study, we evaluated the genetic relatedness of extended-spectrum beta-lactamase-producing Klebsiella pneumoniae (ESBL-KPN) isolates from an outbreak in a neonatal intensive care unit (NICU) in August 2017, We implemented an active countermeasure to control this outbreak successfully. METHODS The incidence of healthcare-associated ESBL-KPN bacteremia was evaluated before and after initiating enhanced infection control (IC) practices in January 2018. Surveillance cultures were set up and monitored for neonates, medical personnel, and NICU environments. Molecular analyses, including pulse-field gel electrophoresis (PFGE), sequence typing, and ESBL genotyping, were performed for the isolated KPN strains. RESULTS After implementing the enhanced IC procedures, the healthcare-associated bacteremia rate decreased from 6.0 to 0.0 per 1000 patient-days. Samples from neonates (n = 11/15, 73.3%), medical personnel (n = 1/41, 2.4%), and medical devices and the environments (6/181, 3.3%) tested positive for ESBL-KPN in the surveillance cultures in December 2017. Active surveillance cultures revealed that 23 of 72 neonates who were screened (31.9%) were colonized with ESBL-KPN between January and March 2018. All the isolates demonstrated closely related PFGE patterns and were identified as ST307 strain carrying the CTX-M-15 gene. CONCLUSIONS Contaminated NICU environments and medical devices, as well as transmission by medical personnel, appeared to be the source of the outbreak of ESBL-KPN infection. We employed an enhanced IC strategy during January-March 2018 and successfully controlled the clonal outbreak of CTX-M-15-positive KPN. ST307 has emerged as an important bacteremia-causing pathogen in the NICU and should be carefully monitored.0 Commenti 0 condivisioni 54 Views 0 Anteprima -
Extending the previous work done by the authors, this paper develops a time domain synthesis method for the classical guitar based on substructuring concepts and using the Udwadia-Kalaba modeling strategy. Adopting a modal description of the dynamics of the separate flexible subsystems in terms of their unconstrained modes and enforcing coupling constraint conditions for the assembly, the result is an explicit dynamical modal formulation for the coupled system that directly lends itself to time-stepping methods for simulation. The guitar model couples six strings through an experimentally based body model of an actual instrument, includes two string polarizations, and the string geometrical nonlinear effects, as well as the string/fret interaction as the instrument is played. Details are given for putting all the vibrating components together in a satisfying manner, and a specific strategy is explored to allow for a nonrigid fret using flexible-dissipative-inertial constraints. The reliability of the approach is demonstrated with simulation examples that confirm the features one would expect regarding the dynamical behavior of classical guitars. Finally, a pragmatic approach is made to calculate the radiated sound by convolution, combining the computed bridge force with a measured vibro-acoustic impulse response of the instrument, which proved to give satisfactory sounding results.When a transducer is placed on aural cartilage, relatively loud sound becomes audible in a conduction form termed cartilage conduction (CC). Previous studies have revealed the acoustical differences between CC and conventional air or bone conduction. This study elucidates the working principle of CC through measurements of threshold shifts by water injection into the ear canal under various fixation place conditions. Seven volunteers with normal hearing participated. A lightweight transducer was fixed for three CC conductions (on the tragus, antitragus, and intertragal incisure), and two non-CC conditions (on the pre-tragus and mastoid). Thresholds were measured at 500, 1000, and 2000 Hz in the 0%-, 40%-, and 80%-water injection conditions. Results for the three CC conditions revealed unique features different from those for the non-CC conditions. For the CC conditions, the thresholds increased by the 40%-water injection at all frequencies. However, with additional water injection (80%-water injection), the thresholds decreased at 500 and 1000 Hz; in particular, dramatically at 500 Hz. The results suggest that a direct vibration of the aural cartilage is important to obtaining the significant contribution of airborne sound to hearing above 1000 Hz. Fixation place results in no significant difference in acoustic features among CC conditions.A multi-task learning (MTL) method with adaptively weighted losses applied to a convolutional neural network (CNN) is proposed to estimate the range and depth of an acoustic source in deep ocean. The network input is the normalized sample covariance matrices of the broadband data received by a vertical line array. https://www.selleckchem.com/products/r-hts-3.html To handle the environmental uncertainty, both the training and validation data are generated by an acoustic propagation model based on multiple possible sets of environmental parameters. The sensitivity analysis is investigated to examine the effect of mismatched environmental parameters on the localization performance in the South China Sea environment. Among the environmental parameters, the array tilt is found to be the most important factor on the localization. Simulation results demonstrate that, compared with the conventional matched field processing (MFP), the CNN with MTL performs better and is more robust to array tilt in the deep-ocean environment. Tests on real data from the South China Sea also validate the method. In the specific ranges where the MFP fails, the method reliably estimates the ranges and depths of the underwater acoustic source.Ultrasound atomic force microscopy (AFM) has received considerable interest due to its subsurface imaging capabilities, particularly for nanostructure imaging. The local contact stiffness variation due to the presence of a subsurface feature is the origin of the imaging contrast. Several research studies have demonstrated subsurface imaging capabilities with promising resolution. However, there is limited literature available about the definition of spatial resolution in subsurface AFM. The changes in contact stiffness and their link to the subsurface resolution are not well understood. We propose a quantitative approach to assess the resolution in subsurface AFM imaging. We have investigated the influences of several parameters of interest on the lateral resolution. The quantification of the subsurface feature size can be based on threshold criteria (full width at half maximum and Rayleigh criteria). Simulations and experimental measurements were compared, revealing that the optimal choice of parameter settings for surface topography AFM is suboptimal for subsurface AFM imaging.We propose a test method to study the effects of strain on the thermal conductivity of thin films. First, a strain setup was designed to apply stress to a thin film, and a test system was built to measure its thermal conductivity by combining the strain setup with the 3-ω method. The strain setup can apply stress to the specimen by adjusting load weights, while the strain of a thin film was obtained by measuring the applied stress with a force sensor. Second, the effects of strain on the resistance and temperature coefficients of a metal thin film were studied using the strain setup and the four-wire resistance measurement method; the results show that the resistance and temperature coefficients of metal thin films decrease with strain. Finally, the effects of strain on the thermal conductivity of a silicon dioxide thin film and silicon substrate were studied using the proposed method and test system. As the strain increased from 0% to 0.072%, the thermal conductivity of the 300-nm thick silicon dioxide thin film decreased from 0.907 W/(m K) to 0.817 W/(m K). The thermal conductivity of the 0.5-mm thick silicon substrate fluctuated in the range of 130.6 W/(m K) to 118.8 W/(m K) and then tended to stabilize around 126.4 W/(m K).
Extending the previous work done by the authors, this paper develops a time domain synthesis method for the classical guitar based on substructuring concepts and using the Udwadia-Kalaba modeling strategy. Adopting a modal description of the dynamics of the separate flexible subsystems in terms of their unconstrained modes and enforcing coupling constraint conditions for the assembly, the result is an explicit dynamical modal formulation for the coupled system that directly lends itself to time-stepping methods for simulation. The guitar model couples six strings through an experimentally based body model of an actual instrument, includes two string polarizations, and the string geometrical nonlinear effects, as well as the string/fret interaction as the instrument is played. Details are given for putting all the vibrating components together in a satisfying manner, and a specific strategy is explored to allow for a nonrigid fret using flexible-dissipative-inertial constraints. The reliability of the approach is demonstrated with simulation examples that confirm the features one would expect regarding the dynamical behavior of classical guitars. Finally, a pragmatic approach is made to calculate the radiated sound by convolution, combining the computed bridge force with a measured vibro-acoustic impulse response of the instrument, which proved to give satisfactory sounding results.When a transducer is placed on aural cartilage, relatively loud sound becomes audible in a conduction form termed cartilage conduction (CC). Previous studies have revealed the acoustical differences between CC and conventional air or bone conduction. This study elucidates the working principle of CC through measurements of threshold shifts by water injection into the ear canal under various fixation place conditions. Seven volunteers with normal hearing participated. A lightweight transducer was fixed for three CC conductions (on the tragus, antitragus, and intertragal incisure), and two non-CC conditions (on the pre-tragus and mastoid). Thresholds were measured at 500, 1000, and 2000 Hz in the 0%-, 40%-, and 80%-water injection conditions. Results for the three CC conditions revealed unique features different from those for the non-CC conditions. For the CC conditions, the thresholds increased by the 40%-water injection at all frequencies. However, with additional water injection (80%-water injection), the thresholds decreased at 500 and 1000 Hz; in particular, dramatically at 500 Hz. The results suggest that a direct vibration of the aural cartilage is important to obtaining the significant contribution of airborne sound to hearing above 1000 Hz. Fixation place results in no significant difference in acoustic features among CC conditions.A multi-task learning (MTL) method with adaptively weighted losses applied to a convolutional neural network (CNN) is proposed to estimate the range and depth of an acoustic source in deep ocean. The network input is the normalized sample covariance matrices of the broadband data received by a vertical line array. https://www.selleckchem.com/products/r-hts-3.html To handle the environmental uncertainty, both the training and validation data are generated by an acoustic propagation model based on multiple possible sets of environmental parameters. The sensitivity analysis is investigated to examine the effect of mismatched environmental parameters on the localization performance in the South China Sea environment. Among the environmental parameters, the array tilt is found to be the most important factor on the localization. Simulation results demonstrate that, compared with the conventional matched field processing (MFP), the CNN with MTL performs better and is more robust to array tilt in the deep-ocean environment. Tests on real data from the South China Sea also validate the method. In the specific ranges where the MFP fails, the method reliably estimates the ranges and depths of the underwater acoustic source.Ultrasound atomic force microscopy (AFM) has received considerable interest due to its subsurface imaging capabilities, particularly for nanostructure imaging. The local contact stiffness variation due to the presence of a subsurface feature is the origin of the imaging contrast. Several research studies have demonstrated subsurface imaging capabilities with promising resolution. However, there is limited literature available about the definition of spatial resolution in subsurface AFM. The changes in contact stiffness and their link to the subsurface resolution are not well understood. We propose a quantitative approach to assess the resolution in subsurface AFM imaging. We have investigated the influences of several parameters of interest on the lateral resolution. The quantification of the subsurface feature size can be based on threshold criteria (full width at half maximum and Rayleigh criteria). Simulations and experimental measurements were compared, revealing that the optimal choice of parameter settings for surface topography AFM is suboptimal for subsurface AFM imaging.We propose a test method to study the effects of strain on the thermal conductivity of thin films. First, a strain setup was designed to apply stress to a thin film, and a test system was built to measure its thermal conductivity by combining the strain setup with the 3-ω method. The strain setup can apply stress to the specimen by adjusting load weights, while the strain of a thin film was obtained by measuring the applied stress with a force sensor. Second, the effects of strain on the resistance and temperature coefficients of a metal thin film were studied using the strain setup and the four-wire resistance measurement method; the results show that the resistance and temperature coefficients of metal thin films decrease with strain. Finally, the effects of strain on the thermal conductivity of a silicon dioxide thin film and silicon substrate were studied using the proposed method and test system. As the strain increased from 0% to 0.072%, the thermal conductivity of the 300-nm thick silicon dioxide thin film decreased from 0.907 W/(m K) to 0.817 W/(m K). The thermal conductivity of the 0.5-mm thick silicon substrate fluctuated in the range of 130.6 W/(m K) to 118.8 W/(m K) and then tended to stabilize around 126.4 W/(m K).0 Commenti 0 condivisioni 63 Views 0 Anteprima -
In the total cohort of 884 patients, RHtyper identified 38 RHD and 28 RHCE distinct alleles, including a novel RHD DAU allele, RHD* 602G, 733C, 744T 1136T. RHtyper provides comprehensive and high-throughput RH genotyping from WGS data, facilitating deconvolution of the extensive RH genetic variation among patients with SCD. We have implemented RHtyper as a cloud-based public access application in DNAnexus (https//platform.dnanexus.com/app/RHtyper), enabling clinicians and researchers to perform RH genotyping with next-generation sequencing data.Diffuse large B-cell lymphoma (DLBCL) and osteoporotic fracture are both more common in older patients. Exposure to R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) is likely to increase the risk of fracture, but evidence is lacking to define fracture incidence in this group. Data on consecutive patients with DLBCL aged ≥70 years treated with 1 to 8 cycles of full or attenuated R-CHOP were retrospectively collected across 10 UK centers (2009-2019). Patients were followed up from starting R-CHOP for a minimum of 6 months and censored at 18 months; at last follow-up if less then 18 months; or at progression or death. Of 877 patients identified, 148 were excluded 121 had progression or died before 6 months; 23 had follow-up less then 6 months. Across 729 remaining patients, the median age was 77 years, and 68% had an Eastern Cooperative Oncology Group performance status of 0 to 1. https://www.selleckchem.com/products/mz-101.html Eighty-one fractures occurred within 18 months of follow-up; 42 were symptomatic, including 30 requiring hospital attendance or admission. The cumulative fracture incidence was 6.2% (95% confidence interval [CI], 4.7-8.2) at 6 months; 9.7% (95% CI, 7.8-12.1) at 12 months; and 11.4% (95% CI, 9.3-14.0) at 18 months. Multivariate analysis identified a predisposing history (osteoporosis, osteopenia, prior fracture, and rheumatoid arthritis [RhA]), DLBCL bone involvement at baseline, and receipt of prephase steroids as independent risk factors for fracture. There is a clinically relevant fracture risk and significant associated morbidity in older patients receiving R-CHOP. Careful attention to bone health is warranted in older patients receiving R-CHOP. Randomized studies are required to better define the most effective strategies to reduce fracture risk.We have shown that patients with suspected heparin-induced thrombocytopenia (HIT) have a high incidence of major bleeding. Recent studies have implicated elevated soluble glycoprotein VI (sGPVI) levels as a potential risk factor for bleeding. We sought to determine if elevated sGPVI plasma levels are associated with major bleeding events in patients with suspected HIT. We used a cohort of 310 hospitalized adult patients with suspected HIT who had a blood sample collected at the time HIT was suspected. Plasma sGPVI levels were measured by using enzyme-linked immunosorbent assay. Patients were excluded who had received a platelet transfusion within 1 day of sample collection because of the high levels of sGPVI in platelet concentrates. We assessed the association of sGPVI (high vs low) with International Society on Thrombosis and Haemostasis major bleeding events by multivariable logistic regression, adjusting for other known risk factors for bleeding. Fifty-four patients were excluded due to recent platelet transfusion, leaving 256 patients for analysis. Eighty-nine (34.8%) patients had a major bleeding event. Median sGPVI levels were significantly elevated in patients with major bleeding events compared with those without major bleeding events (49.09 vs 31.93 ng/mL; P 43 ng/mL was independently associated with major bleeding after adjustment for critical illness, sepsis, cardiopulmonary bypass surgery, and degree of thrombocytopenia (adjusted odds ratio, 2.81; 95% confidence interval, 1.51-5.23). Our findings suggest that sGPVI is associated with major bleeding in hospitalized patients with suspected HIT. sGPVI may be a novel biomarker to predict bleeding risk in patients with suspected HIT.The treatment of older, unfit patients with acute myeloid leukemia (AML) is challenging. Based on preclinical data of Bruton tyrosine kinase expression/phosphorylation and ibrutinib cytotoxicity in AML blasts, we conducted a randomized phase 2 multicenter study to assess the tolerability and efficacy of the addition of ibrutinib to 10-day decitabine in unfit (ie, Hematopoietic Cell Transplantation Comorbidity Index ≥3) AML patients and higher risk myelodysplasia patients (HOVON135/SAKK30/15 trial). In total, 144 eligible patients were randomly (11) assigned to either 10-day decitabine combined with ibrutinib (560 mg; sequentially given, starting the day after the last dose of decitabine) (n = 72) or to 10-day decitabine (n = 72). The addition of ibrutinib was well tolerated, and the number of adverse events was comparable for both arms. In the decitabine plus ibrutinib arm, 41% reached complete remission/complete remission with incomplete hematologic recovery (CR/CRi), the median overall survival (OS) was 11 months, and 2-year OS was 27%; these findings compared with 50% CR/CRi, median OS of 11.5 months, and 2-year OS of 21% for the decitabine group (not significant). Extensive molecular profiling at diagnosis revealed that patients with STAG2, IDH2, and ASXL1 mutations had significantly lower CR/CRi rates, whereas patients with mutations in TP53 had significantly higher CR/CRi rates. Furthermore, multicolor flow cytometry revealed that after 3 cycles of treatment, 28 (49%) of 57 patients with available bone marrow samples had no measurable residual disease. In this limited number of cases, measurable residual disease revealed no apparent impact on event-free survival and OS. In conclusion, the addition of ibrutinib does not improve the therapeutic efficacy of decitabine. This trial was registered at the Netherlands Trial Register (NL5751 [NTR6017]) and has EudraCT number 2015-002855-85.
The association between tumor necrosis factor inhibitors (TNFi) and malignancy in patients with inflammatory bowel disease (IBD) is not well understood. Our aim was to systematically evaluate the impact of TNFi use on risk of malignancy in IBD-patients in daily clinical practice.
We searched Pubmed, Embase, and Scopus until March 1 st 2020 for observational cohort studies on adult IBD-patients reporting malignancy occurrence and TNFi use.
Twenty-eight studies (20 retrospective and 8 prospective) were included, involving 298,717 IBD-patients. Mean age at inclusion ranged from 28 to > 65 years. Mean follow-up varied from 7 to 80 months. Infliximab was the most frequently used TNFi (13/28 studies, 46.4%), followed by adalimumab (3/28, 10.7%), while both infliximab and adalimumab were evaluated in 5 studies (17.8%). In total, 692 malignancies were diagnosed in IBD-patients treated with TNFi accounting for an overall occurrence of 1.0%. The most frequent malignancies were non-melanoma skin cancers (123/692, 17.
In the total cohort of 884 patients, RHtyper identified 38 RHD and 28 RHCE distinct alleles, including a novel RHD DAU allele, RHD* 602G, 733C, 744T 1136T. RHtyper provides comprehensive and high-throughput RH genotyping from WGS data, facilitating deconvolution of the extensive RH genetic variation among patients with SCD. We have implemented RHtyper as a cloud-based public access application in DNAnexus (https//platform.dnanexus.com/app/RHtyper), enabling clinicians and researchers to perform RH genotyping with next-generation sequencing data.Diffuse large B-cell lymphoma (DLBCL) and osteoporotic fracture are both more common in older patients. Exposure to R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) is likely to increase the risk of fracture, but evidence is lacking to define fracture incidence in this group. Data on consecutive patients with DLBCL aged ≥70 years treated with 1 to 8 cycles of full or attenuated R-CHOP were retrospectively collected across 10 UK centers (2009-2019). Patients were followed up from starting R-CHOP for a minimum of 6 months and censored at 18 months; at last follow-up if less then 18 months; or at progression or death. Of 877 patients identified, 148 were excluded 121 had progression or died before 6 months; 23 had follow-up less then 6 months. Across 729 remaining patients, the median age was 77 years, and 68% had an Eastern Cooperative Oncology Group performance status of 0 to 1. https://www.selleckchem.com/products/mz-101.html Eighty-one fractures occurred within 18 months of follow-up; 42 were symptomatic, including 30 requiring hospital attendance or admission. The cumulative fracture incidence was 6.2% (95% confidence interval [CI], 4.7-8.2) at 6 months; 9.7% (95% CI, 7.8-12.1) at 12 months; and 11.4% (95% CI, 9.3-14.0) at 18 months. Multivariate analysis identified a predisposing history (osteoporosis, osteopenia, prior fracture, and rheumatoid arthritis [RhA]), DLBCL bone involvement at baseline, and receipt of prephase steroids as independent risk factors for fracture. There is a clinically relevant fracture risk and significant associated morbidity in older patients receiving R-CHOP. Careful attention to bone health is warranted in older patients receiving R-CHOP. Randomized studies are required to better define the most effective strategies to reduce fracture risk.We have shown that patients with suspected heparin-induced thrombocytopenia (HIT) have a high incidence of major bleeding. Recent studies have implicated elevated soluble glycoprotein VI (sGPVI) levels as a potential risk factor for bleeding. We sought to determine if elevated sGPVI plasma levels are associated with major bleeding events in patients with suspected HIT. We used a cohort of 310 hospitalized adult patients with suspected HIT who had a blood sample collected at the time HIT was suspected. Plasma sGPVI levels were measured by using enzyme-linked immunosorbent assay. Patients were excluded who had received a platelet transfusion within 1 day of sample collection because of the high levels of sGPVI in platelet concentrates. We assessed the association of sGPVI (high vs low) with International Society on Thrombosis and Haemostasis major bleeding events by multivariable logistic regression, adjusting for other known risk factors for bleeding. Fifty-four patients were excluded due to recent platelet transfusion, leaving 256 patients for analysis. Eighty-nine (34.8%) patients had a major bleeding event. Median sGPVI levels were significantly elevated in patients with major bleeding events compared with those without major bleeding events (49.09 vs 31.93 ng/mL; P 43 ng/mL was independently associated with major bleeding after adjustment for critical illness, sepsis, cardiopulmonary bypass surgery, and degree of thrombocytopenia (adjusted odds ratio, 2.81; 95% confidence interval, 1.51-5.23). Our findings suggest that sGPVI is associated with major bleeding in hospitalized patients with suspected HIT. sGPVI may be a novel biomarker to predict bleeding risk in patients with suspected HIT.The treatment of older, unfit patients with acute myeloid leukemia (AML) is challenging. Based on preclinical data of Bruton tyrosine kinase expression/phosphorylation and ibrutinib cytotoxicity in AML blasts, we conducted a randomized phase 2 multicenter study to assess the tolerability and efficacy of the addition of ibrutinib to 10-day decitabine in unfit (ie, Hematopoietic Cell Transplantation Comorbidity Index ≥3) AML patients and higher risk myelodysplasia patients (HOVON135/SAKK30/15 trial). In total, 144 eligible patients were randomly (11) assigned to either 10-day decitabine combined with ibrutinib (560 mg; sequentially given, starting the day after the last dose of decitabine) (n = 72) or to 10-day decitabine (n = 72). The addition of ibrutinib was well tolerated, and the number of adverse events was comparable for both arms. In the decitabine plus ibrutinib arm, 41% reached complete remission/complete remission with incomplete hematologic recovery (CR/CRi), the median overall survival (OS) was 11 months, and 2-year OS was 27%; these findings compared with 50% CR/CRi, median OS of 11.5 months, and 2-year OS of 21% for the decitabine group (not significant). Extensive molecular profiling at diagnosis revealed that patients with STAG2, IDH2, and ASXL1 mutations had significantly lower CR/CRi rates, whereas patients with mutations in TP53 had significantly higher CR/CRi rates. Furthermore, multicolor flow cytometry revealed that after 3 cycles of treatment, 28 (49%) of 57 patients with available bone marrow samples had no measurable residual disease. In this limited number of cases, measurable residual disease revealed no apparent impact on event-free survival and OS. In conclusion, the addition of ibrutinib does not improve the therapeutic efficacy of decitabine. This trial was registered at the Netherlands Trial Register (NL5751 [NTR6017]) and has EudraCT number 2015-002855-85. The association between tumor necrosis factor inhibitors (TNFi) and malignancy in patients with inflammatory bowel disease (IBD) is not well understood. Our aim was to systematically evaluate the impact of TNFi use on risk of malignancy in IBD-patients in daily clinical practice. We searched Pubmed, Embase, and Scopus until March 1 st 2020 for observational cohort studies on adult IBD-patients reporting malignancy occurrence and TNFi use. Twenty-eight studies (20 retrospective and 8 prospective) were included, involving 298,717 IBD-patients. Mean age at inclusion ranged from 28 to > 65 years. Mean follow-up varied from 7 to 80 months. Infliximab was the most frequently used TNFi (13/28 studies, 46.4%), followed by adalimumab (3/28, 10.7%), while both infliximab and adalimumab were evaluated in 5 studies (17.8%). In total, 692 malignancies were diagnosed in IBD-patients treated with TNFi accounting for an overall occurrence of 1.0%. The most frequent malignancies were non-melanoma skin cancers (123/692, 17.0 Commenti 0 condivisioni 68 Views 0 Anteprima -
Ring sideroblasts show abnormal mitochondrial iron accumulation, and their emergence in the bone marrow is a characteristic of sideroblastic anemias (SAs). SAs are a group of heterogeneous congenital and acquired disorders. Congenital SA is a rare disease caused by gene mutations involved in heme biosynthesis, iron-sulfur cluster biosynthesis, and mitochondrial protein synthesis. SAs can also occur after exposure to certain drugs or alcohol and due to copper deficiency (secondary SA). Furthermore, SAs are associated with myelodysplastic syndrome (idiopathic SA), strongly correlating with specific somatic mutations in splicing factor 3b subunit 1 (SF3B1), which is involved in the RNA splicing machinery. Recent reports have indicated that common defects in iron/heme metabolism underlie in the mechanisms of ring sideroblast formation in congenital and acquired SAs. Current understanding of SA pathophysiology, including the mechanisms of ring sideroblast formation, is discussed in this review.Anemia remains an important complication of patients with chronic kidney disease (CKD). Relative erythropoietin deficiency was assumed to be the main cause of anemia in CKD. In contrast, it is possible that iron dysregulation for erythropoiesis in CKD patients also affects not only anemia but also cardiovascular event or survival of these patients. A prospective observational study was conducted for 3 years on 1,000 maintenance hemodialysis patients. In time-dependent cox hazard analysis, we found the higher risks of cardiovascular disease (HR 4.45, p less then 0.001) and all-cause mortality (HR 5.8, p less then 0.001) in patients with low transferrin saturation (TSAT) ( less then 20%) and high ferritin levels (≥100 ng/ml) who are suspected to have iron dysregulation for erythropoiesis compared with patients with high TSAT and low ferritin level. From these results, we hypothesized that iron dysregulation in CKD patients is closely associated with various complications and survival. Moreover, iron administration should be approached with caution in patients who present with iron dysregulation for erythropoiesis.Iron is essential to maintain cellular homeostasis, such as hemoglobin synthesis, mitochondrial respiratory chain formation, DNA replication, DNA demethylation, and histone demethylation. In addition, iron acts as a catalyst to produce reactive oxygen species, including hydroxyl radicals, which induce 8-OHdG production and DNA double strand breaks. Hence, the total body iron level should be strictly regulated. https://www.selleckchem.com/products/ly3522348.html Recently, hepatic hepcidin was found to inhibit iron absorption from the gastrointestinal tract, and hepcidin production is reduced by erythroid factors, such as growth differentiation factor 15 (GDF15) and erythroferrone. Systemic iron kinetics seem to be regulated by cooperation among the liver, gastrointestinal tract, and hematopoietic tissues. However, this cooperation could be disturbed in bone marrow failure syndrome (BMFS). In some anemic disorders, such as β-thalassemia, and some categories of MDS, GDF15 or erythroferrone were overproduced and promoted iron absorption. Frequent blood transfusions rapidly increase iron accumulation in the body and eventually result in irreversible organ damage, such as heart failure. Therefore, the introduction of an early intervention to improve iron overload in BMFS is necessary. In recent years, oral chelators have been introduced for clinical use. Erythropoiesis-stimulating agents and thrombopoietin receptor agonists could also improve refractory anemia or BMFS and improve iron overload.A 72-year-old man with ileocecal lymphadenopathy was found to have Epstein-Barr virus-positive diffuse large B-cell lymphoma using open biopsy, and an ileostoma was created. R-CHOP-like chemotherapy was initiated, but his malnutrition did not improve. After 3 cycles of chemotherapy, a 2-m-long Cestoda was removed from the stoma and was identified as Diphyllobothrium nihonkaiense using mitochondria cytochrome c oxidase subunit 1 targeted polymerase chain reaction analysis. Although D. nihonkaiense infections are asymptomatic, the ileostomy was thought to have exacerbated the malabsorption in this patient. Parasitic infections are rare; however, they should be added to the differential diagnosis of malnutrition of unknown cause during chemotherapy for hematological malignancies.A 56-year-old woman was referred to our hospital with symptoms of swelling, purpura, and pain in her limbs. Prior to referral, bleeding in her limbs had spontaneously appeared and disappeared several times. Prothrombin time (PT) and activated partial thromboplastin time (aPTT) were prolonged, and the factor II level was 17%. The plasma-mixing test indicated lupus anticoagulant (LA), which was confirmed using aPTT-LA and dilute Russell's viper venom time (dRVVT). Therefore, she was diagnosed with lupus anticoagulant-hypoprothrombinemia syndrome (LAHPS). During screening for underlying disorders, chest computed tomography (CT) revealed a retrosternal mass. Biopsy was not performed because the administration of freshly frozen plasma failed to correct her coagulopathy. Prednisolone (PSL) treatment (1 mg/kg) was initiated, which normalized the coagulation tests. The retrosternal mass also disappeared. PSL was tapered without LAHPS recurrence; however, the follow-up CT revealed systemic lymphadenopathy. Follicular lymphoma was diagnosed using lymph-node biopsy. Considering the subsequent LAHPS recurrence, six cycles of bendamustine + rituximab were administered. Complete response with no LAHPS recurrence was observed at the time of drafting this report. LAHPS is rare and distinct from antiphospholipid syndrome because it can cause severe bleeding. Underlying disorders should be evaluated in cases of LAHPS.A 58-year-old man was admitted with shortness of breath in September 2019. He had a severe hemolytic anemia with a high cold agglutinin (CA) titer. He also had arthralgia and finger deformation. He was diagnosed with cold agglutinin syndrome (CAS) secondary to rheumatoid arthritis (RA) based on the clinical course. Occasionally, CAS has been reported to occur in parallel with collagen disease, infectious disease, or malignant tumor. CAS developing secondary to collagen disease occurs less frequently than that to infectious disease or malignant tumors. Furthermore, CAS caused by RA is very rare, even among patients with collagen diseases. Our patient was effectively treated with immunosuppressive therapy including abatacept, which attenuated the symptoms of CAS and RA.
Ring sideroblasts show abnormal mitochondrial iron accumulation, and their emergence in the bone marrow is a characteristic of sideroblastic anemias (SAs). SAs are a group of heterogeneous congenital and acquired disorders. Congenital SA is a rare disease caused by gene mutations involved in heme biosynthesis, iron-sulfur cluster biosynthesis, and mitochondrial protein synthesis. SAs can also occur after exposure to certain drugs or alcohol and due to copper deficiency (secondary SA). Furthermore, SAs are associated with myelodysplastic syndrome (idiopathic SA), strongly correlating with specific somatic mutations in splicing factor 3b subunit 1 (SF3B1), which is involved in the RNA splicing machinery. Recent reports have indicated that common defects in iron/heme metabolism underlie in the mechanisms of ring sideroblast formation in congenital and acquired SAs. Current understanding of SA pathophysiology, including the mechanisms of ring sideroblast formation, is discussed in this review.Anemia remains an important complication of patients with chronic kidney disease (CKD). Relative erythropoietin deficiency was assumed to be the main cause of anemia in CKD. In contrast, it is possible that iron dysregulation for erythropoiesis in CKD patients also affects not only anemia but also cardiovascular event or survival of these patients. A prospective observational study was conducted for 3 years on 1,000 maintenance hemodialysis patients. In time-dependent cox hazard analysis, we found the higher risks of cardiovascular disease (HR 4.45, p less then 0.001) and all-cause mortality (HR 5.8, p less then 0.001) in patients with low transferrin saturation (TSAT) ( less then 20%) and high ferritin levels (≥100 ng/ml) who are suspected to have iron dysregulation for erythropoiesis compared with patients with high TSAT and low ferritin level. From these results, we hypothesized that iron dysregulation in CKD patients is closely associated with various complications and survival. Moreover, iron administration should be approached with caution in patients who present with iron dysregulation for erythropoiesis.Iron is essential to maintain cellular homeostasis, such as hemoglobin synthesis, mitochondrial respiratory chain formation, DNA replication, DNA demethylation, and histone demethylation. In addition, iron acts as a catalyst to produce reactive oxygen species, including hydroxyl radicals, which induce 8-OHdG production and DNA double strand breaks. Hence, the total body iron level should be strictly regulated. https://www.selleckchem.com/products/ly3522348.html Recently, hepatic hepcidin was found to inhibit iron absorption from the gastrointestinal tract, and hepcidin production is reduced by erythroid factors, such as growth differentiation factor 15 (GDF15) and erythroferrone. Systemic iron kinetics seem to be regulated by cooperation among the liver, gastrointestinal tract, and hematopoietic tissues. However, this cooperation could be disturbed in bone marrow failure syndrome (BMFS). In some anemic disorders, such as β-thalassemia, and some categories of MDS, GDF15 or erythroferrone were overproduced and promoted iron absorption. Frequent blood transfusions rapidly increase iron accumulation in the body and eventually result in irreversible organ damage, such as heart failure. Therefore, the introduction of an early intervention to improve iron overload in BMFS is necessary. In recent years, oral chelators have been introduced for clinical use. Erythropoiesis-stimulating agents and thrombopoietin receptor agonists could also improve refractory anemia or BMFS and improve iron overload.A 72-year-old man with ileocecal lymphadenopathy was found to have Epstein-Barr virus-positive diffuse large B-cell lymphoma using open biopsy, and an ileostoma was created. R-CHOP-like chemotherapy was initiated, but his malnutrition did not improve. After 3 cycles of chemotherapy, a 2-m-long Cestoda was removed from the stoma and was identified as Diphyllobothrium nihonkaiense using mitochondria cytochrome c oxidase subunit 1 targeted polymerase chain reaction analysis. Although D. nihonkaiense infections are asymptomatic, the ileostomy was thought to have exacerbated the malabsorption in this patient. Parasitic infections are rare; however, they should be added to the differential diagnosis of malnutrition of unknown cause during chemotherapy for hematological malignancies.A 56-year-old woman was referred to our hospital with symptoms of swelling, purpura, and pain in her limbs. Prior to referral, bleeding in her limbs had spontaneously appeared and disappeared several times. Prothrombin time (PT) and activated partial thromboplastin time (aPTT) were prolonged, and the factor II level was 17%. The plasma-mixing test indicated lupus anticoagulant (LA), which was confirmed using aPTT-LA and dilute Russell's viper venom time (dRVVT). Therefore, she was diagnosed with lupus anticoagulant-hypoprothrombinemia syndrome (LAHPS). During screening for underlying disorders, chest computed tomography (CT) revealed a retrosternal mass. Biopsy was not performed because the administration of freshly frozen plasma failed to correct her coagulopathy. Prednisolone (PSL) treatment (1 mg/kg) was initiated, which normalized the coagulation tests. The retrosternal mass also disappeared. PSL was tapered without LAHPS recurrence; however, the follow-up CT revealed systemic lymphadenopathy. Follicular lymphoma was diagnosed using lymph-node biopsy. Considering the subsequent LAHPS recurrence, six cycles of bendamustine + rituximab were administered. Complete response with no LAHPS recurrence was observed at the time of drafting this report. LAHPS is rare and distinct from antiphospholipid syndrome because it can cause severe bleeding. Underlying disorders should be evaluated in cases of LAHPS.A 58-year-old man was admitted with shortness of breath in September 2019. He had a severe hemolytic anemia with a high cold agglutinin (CA) titer. He also had arthralgia and finger deformation. He was diagnosed with cold agglutinin syndrome (CAS) secondary to rheumatoid arthritis (RA) based on the clinical course. Occasionally, CAS has been reported to occur in parallel with collagen disease, infectious disease, or malignant tumor. CAS developing secondary to collagen disease occurs less frequently than that to infectious disease or malignant tumors. Furthermore, CAS caused by RA is very rare, even among patients with collagen diseases. Our patient was effectively treated with immunosuppressive therapy including abatacept, which attenuated the symptoms of CAS and RA.0 Commenti 0 condivisioni 41 Views 0 Anteprima
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