Neuromodulation for diabetic peripheral neuropathy represents a significant area of interest in the management of chronic pain associated with this condition.Diabetic peripheral neuropathy,a common complication of dia...Neuromodulation for diabetic peripheral neuropathy represents a significant area of interest in the management of chronic pain associated with this condition.Diabetic peripheral neuropathy,a common complication of diabetes,is characterized by nerve damage due to high blood sugar levels that lead to symptoms,such as pain,tingling,and numbness,primarily in the hands and feet.The aim of this systematic review was to evaluate the efficacy of neuromodulatory techniques as potential therapeutic interventions for patients with diabetic peripheral neuropathy,while also examining recent developments in this domain.The investigation encompassed an array of neuromodulation methods,including frequency rhythmic electrical modulated systems,dorsal root ganglion stimulation,and spinal cord stimulation.This systematic review suggests that neuromodulatory techniques may be useful in the treatment of diabetic peripheral neuropathy.Understanding the advantages of these treatments will enable physicians and other healthcare providers to offer additional options for patients with symptoms refractory to standard pharmacologic treatments.Through these efforts,we may improve quality of life and increase functional capacity in patients suffering from complications related to diabetic neuropathy.展开更多
Purpose:It is aimed to assess whether school uniforms are associated with population-level gender inequalities in physical activity,and whether associations differ by school level,country/region income,and assessment ...Purpose:It is aimed to assess whether school uniforms are associated with population-level gender inequalities in physical activity,and whether associations differ by school level,country/region income,and assessment method.Methods:An ecological study design was employed.We collected data about global uniform practices using an online survey.We searched for country/region-level estimates of school-aged youth meeting physical activity guidelines from international surveillance studies.Study selection was conducted in duplicate using a systematic process,and a random sample of all data was checked to ensure extraction and pooling processes were accurate.We calculated absolute and relative gender inequalities in physical activity for each country.Linear regression examined associations between country/region-level uniform practices(binary yes/no exposure variable) and country/region-level gender inequalities in physical activity guideline compliance(absolute and relative inequalities).We investigated moderation by school level,stratified analyses by income group,and repeated primary analyses using device-measured data.Results:Pooling data from 135 countries/regions(n=1,089,852),we found no association between population-level uniform practices and gender inequalities in physical activity across all ages(absolute:β=-0.2;95% confidence interval(95%CI):-1.7 to 1.3,p=0.74;relative:β=0.1;95%CI:-0.1 to 0.2,p=0.51).Subgroup analysis suggested a positive association in primary school settings(absolute:β=4.3;95%CI:-0.0 to 8.6,p=0.05).Among high-income countries,absolute inequalities were significantly greater in countries/regions with uniform practices(N=37) compared to those without(N=48)(9.1(SD=3.6) vs.7.8 percentage points(SD=4.3)).Repeating analyses using device-measured data(n=32,130;N=24) did not alter our primary finding.From initial descriptive statistics,we found that in countries/regions where a maj ority of schools(>50%) reportedly use uniforms,there was lower compliance with physical activity guidelines among all genders(median:16.0%,interquartile range:13.2%-19.9%,N=103) compared to generally non-uniform countries/regions(median:19.5%,interquartile range:16.4%-23.5 %,N=32)(z=3.04,p=0.002).(N=countries,regions and studies repre sented;n=sample size or participants included).Conclusion:School uniforms are associated with greater gender inequalities in physical activity in primary school settings and in high-income countries.Our population-level findings warrant testing using individual-level data across contexts.展开更多
Background Major depressive disorders(MDDs)impose substantial burdens on individuals and society;however,further detailed analysis is still needed for its long-term trends.Aims This study aimed to analyse the gender-s...Background Major depressive disorders(MDDs)impose substantial burdens on individuals and society;however,further detailed analysis is still needed for its long-term trends.Aims This study aimed to analyse the gender-specific temporal trends and cohort variations of MDD incidence among Chinese residents over the past three decades.Methods Employing the age-period-cohort-interaction model and leveraging data from the Global Burden of Disease Study 2019,this research identified and analysed incidence trends of MDD among Chinese males and females aged 5-94 years from 1990 to 2019 across three dimensions,encompassing age,period and birth cohort.Results The analysis reveals age-related effects,indicating heightened MDD risk among adolescents and older adults.Specifically,individuals entering the older adulthood at the age of 65-69 significantly increased the risk of MDD by 64.9%.People aged 90-94 years witnesseda 105.4%increase in MDD risk for the overall population,with females and males in this age group experiencing a 75.1%and 103.4%increase,respectively.In terms of period effects,the risk of MDD displayed a decline from 1990 to 1994,followed by a rebound in 2008.Cohort effects demonstrated diverse generational patterns,with generationⅠand generationⅢmanifesting opposing‘age-as-level'trends.GenerationⅡand generationⅣexhibited'cumulative disadvantage'and'cumulative advantage'patterns,respectively.Age effects indicated an overall higher risk of MDD incidence in females,while cohort effects showed greater variations of MDD incidence among females.Conclusions The study underscores the substantial effects of age,period and cohort on MDD across genders in China.Priority interventions targeting vulnerable populations,including children,adolescents,older adults,females and the post-millennium birth cohort,are crucial to mitigate the impact of MDD.展开更多
Background:Physical inactivity and insomnia symptoms are independently associated with increased risk of depression and anxiety;however,few studies jointly examine these risk factors.This study aimed to prospectively ...Background:Physical inactivity and insomnia symptoms are independently associated with increased risk of depression and anxiety;however,few studies jointly examine these risk factors.This study aimed to prospectively examine the joint association of physical activity(PA)and insomnia symptoms with onset of poor mental health in adults.Methods:Participants from the 2013 to 2018 annnual waves of the Household Income and Labour Dynamics in Australia panel study who had good mental health(Mental Health Inventory-5>54)in 2013,and who completed at least 1 follow-up survey(2014-2018),were included(n=10,977).Poor mental health(Mental Health Inventory-5≤54)was assessed annually.Baseline(2013)PA was classified as high/moderate/low,and insomnia symptoms(i.e.,trouble sleeping)were classified as no insomnia symptoms/insomnia symptoms,with 6 mutually exclusive PAinsomnia symptom groups derived.Associations of PA-insomnia symptom groups with onset of poor mental health were examined using discrete-time proportional-hazards logit-hazard models.Results:There were 2322 new cases of poor mental health(21.2%).Relative to the high PA/no insomnia symptoms group,there were higher odds(odds ratio and 95%confidence interval(95%CI))of poor mental health among the high PA/insomnia symptoms(OR=1.87,95%CI:1.57-2.23),moderate PA/insomnia symptoms(OR=1.93,95%CI:1.61-2.31),low PA/insomnia symptoms(OR=2.33,95%CI:1.96-2.78),and low PA/no insomnia symptoms(OR=1.14,95%CI:1.01-1.29)groups.Any level of PA combined with insomnia symptoms was associated with increased odds of poor mental health,with the odds increasing as PA decreased.Conclusion:The se findings highlight the potential benefit of interventions targeting both PA and insomnia symptoms for promoting mental health.展开更多
After spinal cord injury,there is an extensive infiltration of immune cells,which exacerbates the injury and leads to further neural degeneration.Therefore,a major aim of current research involves targeting the immune...After spinal cord injury,there is an extensive infiltration of immune cells,which exacerbates the injury and leads to further neural degeneration.Therefore,a major aim of current research involves targeting the immune response as a treatment for spinal cord injury.Although much research has been performed analyzing the complex inflammatory process following spinal cord injury,there remain major discrepancies within previous literature regarding the timeline of local cytokine regulation.The objectives of this study were to establish an overview of the timeline of cytokine regulation for 2 weeks after spinal cord injury,identify sexual dimorphisms in terms of cytokine levels,and determine local cytokines that significantly change based on the severity of spinal cord injury.Rats were inflicted with either a mild contusion,moderate contusion,severe contusion,or complete transection,7 mm of spinal cord centered on the injury was harvested at varying times post-injury,and tissue homogenates were analyzed with a Cytokine/Chemokine 27-Plex assay.Results demonstrated pro-inflammatory cytokines including tumor necrosis factorα,interleukin-1β,and interleukin-6 were all upregulated after spinal cord injury,but returned to uninjured levels within approximately 24 hours post-injury,while chemokines including monocyte chemoattractant protein-1 remained upregulated for days post-injury.In contrast,several anti-inflammatory cytokines and growth factors including interleukin-10 and vascular endothelial growth factor were downregulated by 7 days post-injury.After spinal cord injury,tissue inhibitor of metalloproteinase-1,which specifically affects astrocytes involved in glial scar development,increased more than all other cytokines tested,reaching 26.9-fold higher than uninjured rats.After a mild injury,11 cytokines demonstrated sexual dimorphisms;however,after a severe contusion only leptin levels were different between female and male rats.In conclusion,pro-inflammatory cytokines initiate the inflammatory process and return to baseline within hours post-injury,chemokines continue to recruit immune cells for days post-injury,while anti-inflammatory cytokines are downregulated by a week post-injury,and sexual dimorphisms observed after mild injury subsided with more severe injuries.Results from this work define critical chemokines that influence immune cell infiltration and important cytokines involved in glial scar development after spinal cord injury,which are essential for researchers developing treatments targeting secondary damage after spinal cord injury.展开更多
Background: Hypertensive disease in pregnancy is an important cause of morbidity, long-term disability, and maternal and neonatal mortality. The aim is to determine the socio-demographic characteristics and maternal p...Background: Hypertensive disease in pregnancy is an important cause of morbidity, long-term disability, and maternal and neonatal mortality. The aim is to determine the socio-demographic characteristics and maternal prognosis of these women with Hypertension during pregnancy. Material and Method: We conducted a cross-sectional study, we interview patients and after discussion we transcripts in a database in Excel software before analysis with SPSS version 20.0 and Stata 14.0 The qualitative variables have been summarised by the Percentage and the quantitative variables will be summarised by Means and Standard Deviation. The associations of the variables were calculated by Pearson’s chi-square test with a significance level set at a p-value Result: The average age of the patients was 30.33 ± 7.020 years, 92.1% were married, 79.8% lived in urban areas, most of the patients were overweight (43%), 92.1% of them had monofetal pregnancies, 36% were multiparous, 34.2% had a previous history of preeclampsia in pregnancy and 14% were known to have hypertension. Pre-eclampsia was the most frequent form of hypertension in pregnancy with 73.68% of cases and represents 84.8% of severe forms of hypertension in pregnancy, 53.4% of the patients delivered vaginally. Eclampsia was the most frequent complication in our patients with 31.7% frequency and among the socio-demographic parameters, age and body mass index were significantly associated with maternal complications. Conclusion: Maternal age and body mass index are important socio-demographic factors associated with the occurrence of maternal complications in women with hypertensive disorders in pregnancy.展开更多
Background:Current protein biomarkers are only moderately predictive at identifying individuals with mild traumatic brain injury or concussion.Therefore,more accurate diagnostic markers are needed for sport-related co...Background:Current protein biomarkers are only moderately predictive at identifying individuals with mild traumatic brain injury or concussion.Therefore,more accurate diagnostic markers are needed for sport-related concussion.Methods:This was a multicenter,prospective,case-control study of athletes who provided blood samples and were diagnosed with a concussion or were a matched non-concussed control within the National Collegiate Athletic Association-Department of Defense Concussion Assessment,Research,and Education Consortium conducted between 2015 and 2019.The blood was collected within 48 h of injury to identify protein abnormalities at the acute and subacute timepoints.Athletes with concussion were divided into 6 h post-injury(0-6 h post-injury)and after 6 h postinjury(7-48 h post-injury)groups.We applied a highly multiplexed proteomic technique that used a DNA aptamers assay to target 1305proteins in plasma samples from athletes with and without sport-related concussion.Results:A total of 140 athletes with concussion(79.3%males;aged 18.71±1.10 years,mean±SD)and 21 non-concussed athletes(76.2%males;19.14±1.10 years)were included in this study.We identified 338 plasma proteins that significantly differed in abundance(319 upregulated and 19 downregulated)in concussed athletes compared to non-concussed athletes.The top 20 most differentially abundant proteins discriminated concussed athletes from non-concussed athletes with an area under the curve(AUC)of 0.954(95%confidence interval:0.922-0.986).Specifically,after 6 h of injury,the individual AUC of plasma erythrocyte membrane protein band 4.1(EPB41)and alpha-synuclein(SNCA)were 0.956 and 0.875,respectively.The combination of EPB41 and SNCA provided the best AUC(1.000),which suggests this combination of candidate plasma biomarkers is the best for diagnosing concussion in athletes after 6 h of injury.Conclusion:Our data suggest that proteomic profiling may provide novel diagnostic protein markers and that a combination of EPB41 and SNCA is the most predictive biomarker of concussion after 6 h of injury.展开更多
The advent of the metaverse,including virtual reality,augmented reality,andartificial intelligence,is an undeniable issue that health care scientists need toupdate.It influences all fields of knowledge,interpersonal r...The advent of the metaverse,including virtual reality,augmented reality,andartificial intelligence,is an undeniable issue that health care scientists need toupdate.It influences all fields of knowledge,interpersonal relationships,andhealth.Regarding mental health since the post-coronavirus disease 2019 pandemic,it is necessary to consider and understand the potential,possibilities,weaknesses,and consequences arising from and provided by this new scenario.Due tothe increasing need for mental health monitoring and care,mental health treatmentsrequire in-depth training and preparation to achieve the maximum use of themetaverse advantages and possibilities.Currently,very little is known about theeffectiveness of remote mental health treatment,but it is certainly suggested thataccessibility and the characteristics associated with the use of metaverse technologiesmay represent new horizons for accessibility and approach tools,as long asmore studies are carried out and more evidence is collected to develop accurateguidelines,safe training,solve ethical concerns,and overcome limitations.展开更多
BACKGROUND Kidney transplant recipients(KTR)are at risk of severe coronavirus disease 2019(COVID-19)disease and mortality after severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection.We predicted that ho...BACKGROUND Kidney transplant recipients(KTR)are at risk of severe coronavirus disease 2019(COVID-19)disease and mortality after severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection.We predicted that hospitalization for COVID-19 and subsequent admission to the intensive care unit(ICU)would yield worse outcomes in KTRs.cohort was stratified by ICU admission.Outcomes of interest included risk factors for ICU admission and mortality,length of stay(LOS),respiratory symptoms at admission,all-cause graft failure at the last follow-up,and death related to COVID-19.RESULTS 96 KTRs were hospitalized for SARS-COV-2 infection.21(22%)required ICU admission.The ICU group had longer hospital LOS(21.8 vs 8.6 days,P<0.001)and were more likely to experience graft failure(81%vs 31%,P<0.001).Of those admitted to the ICU,76%had death at last-follow up,and 71%had death related to COVID-19.Risk factors for ICU admission included male sex(aHR:3.11,95%CI:1.04-9.34;P=0.04).Risk factors for all-cause mortality and COVID-19-related mortality included ICU admission and advanced age at SARS-CoV-2 diagnosis.Mortality was highest within a month of COVID-19 diagnosis,with the ICU group having increased risk of all-cause(aHR:11.2,95%CI:5.11-24.5;P<0.001)and COVID-19-related mortality(aHR:27.2,95%CI:8.69-84.9;P<0.001).CONCLUSION ICU admission conferred an increased risk of mortality,graft failure,and longer LOS.One-fifth of those hospit-alized died of COVID-19,reflecting the impact of COVID-19-related morbidity and mortality among KTRs.展开更多
Background: Cardiovascular diseases (CVD) are major causes of death in Japan, and controlling the risk factors for CVD is an important public health task. Lifestyle factors, for example, diet and stress, have impacts ...Background: Cardiovascular diseases (CVD) are major causes of death in Japan, and controlling the risk factors for CVD is an important public health task. Lifestyle factors, for example, diet and stress, have impacts on risk factors such as hypertension and hyperlipidemia. Deterioration of mental health is related to CVD pathogenesis. Aim: We investigated the relationships between levels of mental health, 4-year changes in lifestyle, and CVD risk factors among Japanese workers, using the SF-36 (Japanese version), which is a comprehensive scale measuring health-related quality of life. We hypothesized that workers’ mental health levels would influence 4-year changes in their lifestyles and CVD risk factors. Methods: Data from the High-Risk and Population Strategy for Occupational Health Promotion (HIPOP-OHP) study, which were collected by examination and administration of the SF-36, were used. The relationships between mental health levels at baseline, lifestyle chan- ges, and cardiovascular risk factors were longitudinally analyzed. Subjects with total SF-36 scores ≥65 were classified as the “Good Mental Health Group,” and those with total scores <65 were classified as the “Poor Mental Health Group.” Results: Multiple logistic regression analyses showed that, as compared to people who had poor mental health, those who had good mental health at baseline had a significantly higher probability of good maintenance of improvements in body mass index, (OR = 1.20, 95% CI: 1.03 - 1.39), blood pressure (OR = 1.20, 95% CI: 1.01 - 1.43), total cholesterol (OR = 1.07, 95% CI: 0.86 - 1.33) and HDL cholesterol (OR = 1.26, 95% CI: 1.07 - 1.47). Conclusion: Japanese workers with good mental health tend to improve or maintain good lifestyle conditions and minimize CVD risk factors, while those with poor mental health generally have difficulty improving their lifestyles and lowering their CVD risk.展开更多
Objective:Depression is a global and growing health issue.Complementary and alternative medicines (CAM) use is common among people with depression.We examined the baseline use of CAM (products,not services) in central...Objective:Depression is a global and growing health issue.Complementary and alternative medicines (CAM) use is common among people with depression.We examined the baseline use of CAM (products,not services) in centrally obese adults with depression,a specific and increasingly important population who were part of a trial of Tai Chi and Qigong for depression.Methods:Self-reported use of CAM products (four major groups:vitamins,herbal medicines,mineral supplements and purified chemicals as nutritional supplements) together with demographic,lifestyle and health status characteristics were collected using validated questions within a written survey.We used descriptive statistics to understand patterns of use.Results:Two hundred and sixty patients participated in the assessment.Half of the patients stated they were using CAM,on average reporting 2.3 CAM per patient.Women were more likely than men,and older people (>60 years) more likely than younger people (<40 years) to use any CAM products.Patients reported using CAM mostly for general health and alleviating aches and pains.CAM use was not associated with health state,use of a prescription antidepressant medicine,nor (self-reported) comorbidities such as arthritis,diabetes,hypertension or alcohol or tobacco use.Conclusions:CAM products are commonly used in Australians with moderate depression,particularly in female or older patients.The range and number of CAM in this group with common comorbidity may present additional unknown risks due to potential interactions with other prescribed medications with a myriad of biological and pharmacological effects.The importance of establishing whether depressed patients are taking CAM,the particular CAM and whether the CAM interacts with each other,other drugs used for depression or the biological process of the depression itself are factors to be considered at each assessment.展开更多
Neutrophils have recently emerged as promising carriers for drug delivery due to their unique properties including rapid response toward inflammation,chemotaxis,and transmigration.When integrated with nanotechnology t...Neutrophils have recently emerged as promising carriers for drug delivery due to their unique properties including rapid response toward inflammation,chemotaxis,and transmigration.When integrated with nanotechnology that has enormous advantages in improving treatment efficacy and reducing side effects,neutrophil-based nano-drug delivery systems have expanded the repertoire of nanoparticles employed in precise therapeutic interventions by either coating nanoparticles with their membranes,loading nanoparticles inside living cells,or engineering chimeric antigen receptor(CAR)-neutrophils.These neutrophil-inspired therapies have shown superior biocompatibility,targeting ability,and therapeutic robustness.In this review,we summarized the benefits of combining neutrophils and nanotechnologies,the design principles and underlying mechanisms,and various applications in disease treatments.The challenges and prospects for neutrophil-based drug delivery systems were also discussed.展开更多
Non-alcoholic fatty liver disease(NAFLD) associated hepatocellular carcinoma(HCC) incidence is increasing worldwide, paralleling the obesity epidemic. Although most cases are associated with cirrhosis, HCC can occur w...Non-alcoholic fatty liver disease(NAFLD) associated hepatocellular carcinoma(HCC) incidence is increasing worldwide, paralleling the obesity epidemic. Although most cases are associated with cirrhosis, HCC can occur without cirrhosis in NAFLD. Diabetes and obesity are associated risk factors for HCC in patients. Given the sheer magnitude of the underlying risk factors(diabetes, obesity, non-cirrhotic NAFLD) screening for HCC in the non-cirrhotic population is not recommended. Optimal screening strategies in NAFLD cirrhosis are not completely elucidated with Ultrasound having significant limitations in detection of liver lesions in the presence of obesity and steatosis. Consequently NAFLD-HCC is more often diagnosed at a later stage with larger tumors and reduced opportunities for curative treatments as opposed to HCC in other causes of cirrhosis. When HCC is found at a curative stage treatments including liver transplantation, resection and loco-regional therapies are associated with good results similar to that seen in HCV-HCC. Future strategies under study include the use of chemopreventive and antioxidant agents to reduce development of cirrhosis and non-alcoholic steatohepatitis(NASH). Strategies to reverse NASH via weight loss, control of associated conditions like diabetes are key strategies in reducing the increasing incidence of NASH-HCC. Novel therapeutic agents for NASH are in trials and if successful in achieving reversal of NASH will be an important strategy in reducing NAFLD-HCC.展开更多
BACKGROUND Variceal hemorrhage is associated with high mortality and is the cause of death for 20–30%of patients with cirrhosis.Nonselectiveβblockers(NSBBs)or endoscopic variceal ligation(EVL)are recommended for pri...BACKGROUND Variceal hemorrhage is associated with high mortality and is the cause of death for 20–30%of patients with cirrhosis.Nonselectiveβblockers(NSBBs)or endoscopic variceal ligation(EVL)are recommended for primary prevention of variceal bleeding in patients with medium to large esophageal varices.Meanwhile,combination of EVL and NSBBs is the recommended approach for the secondary prevention.Carvedilol has greater efficacy than other NSBBs as it decreases intrahepatic resistance.We hypothesized that there was no difference between carvedilol and EVL intervention for primary and secondary prevention of variceal bleeding in cirrhosis patients.AIM To evaluate the efficacy of carvedilol compared to EVL for primary and secondary prevention of variceal bleeding in cirrhotic patients METHODS We searched relevant literatures in major journal databases(CENTRAL,MEDLINE,and EMBASE)from March to August 2018.Patients with cirrhosis and portal hypertension,regardless of aetiology and severity,with or without a history of variceal bleeding,and aged≥18 years old were included in this review.Only randomized controlled trials(RCTs)that compared the efficacy of carvedilol and that of EVL for primary and secondary prevention of variceal bleeding and mortality in patients with cirrhosis and portal hypertension were considered,irrespective of publication status,year of publication,and language.RESULTS Seven RCTs were included.In four trials assessing the primary prevention,no significant difference was found on the events of variceal bleeding(RR:0.74,95%CI:0.37-1.49),all-cause mortality(RR:1.10,95%CI:0.76-1.58),and bleedingrelated mortality(RR:1.02,95%CI:0.34-3.10)in patients who were treated with carvedilol compared to EVL.In three trials assessing secondary prevention,there was no difference between two interventions for the incidence of rebleeding(RR:1.10,95%CI:0.75-1.61).The fixed-effect model showed that,compared to EVL,carvedilol decreased all-cause mortality by 49%(RR:0.51,95%CI:0.33-0.79),with little or no evidence of heterogeneity.CONCLUSION Carvedilol had similar efficacy to EVL in preventing the first variceal bleeding in cirrhosis patients with esophageal varices.It was superior to EVL alone for secondary prevention of variceal bleeding in regard to all-cause mortality reduction.展开更多
The delivery of medical student education has changed rapidly during the coronavirus disease 2019(COVID-19)pandemic.Students in their pre-clinical years have transitioned to online courses and examinations.Students in...The delivery of medical student education has changed rapidly during the coronavirus disease 2019(COVID-19)pandemic.Students in their pre-clinical years have transitioned to online courses and examinations.Students in their clinical years are not permitted on clinical rotations,and face uncertainties in career exploration and the residency application process.Medical students in all stages of training are volunteering and helping their communities.The future presence of COVID-19 throughout the United States is unknown,and medical students are eager to return to their training.This paper outlines current challenges in medical student education and the various responses that have been adopted.We also discuss possible future directions for students through involvement in telemedicine,outpatient clinic visits,and non-respiratory inpatient care tasks as adequate personal protective equipment,COVID-19 testing,and resources become more widely available.展开更多
Summary： This study investigated the expression of interleukin-17 （IL-17） and T cell immunoglobulin mucin and domain-containing molecule-3 （Tim-3） in bronchoalveolar lavage fluid （BALF） of asthmatic mice and th...Summary： This study investigated the expression of interleukin-17 （IL-17） and T cell immunoglobulin mucin and domain-containing molecule-3 （Tim-3） in bronchoalveolar lavage fluid （BALF） of asthmatic mice and the effect of dexamethasone （DEX） on these factors. Thirty-six mice were randomly divided into three groups： normal group, asthmatic group and DEX group. The mouse model of asthma was es- tablished by sensitization with ovalbumin in both the asthmatic and DEX groups. The levels of IL-6, IL-10, IL-17 and TGF-β were measured in BALF by enzyme-linked immunesorbent assay （ELISA）. The mRNA expression level of Tim-3 was detected by reverse transcription polymerase chain reaction （RT-PCR）. The ratio of Tim-3＋CD4＋ cells to total CD4＋ cells in BALF was determined by flow cy- tometry. Differential inflammatory cells in BALF were detected. The correlations among IL-17, IL-6, IL-10, Tim-3 and inflammatory cells were analyzed. The results showed that the levels of IL-17, IL-6 and Tim-3 were substantially increased and the IL-10 level decreased in BALF in the asthmatic mice, which was significantly reversed by DEX treatment. IL-17 expression was positively correlated with IL-6 and Tim-3 expression and the number of inflammatory cells but negatively with IL-10 expression. These results indicate that the increased expression of IL-17 and Tim-3 in BALF may be implicated in the occurrence and development of asthmatic inflammation; the mechanism by which DEX suppresses asthmatic airway inflammation involves down-regulation of IL-17 and Tim-3 levels.展开更多
<strong>Purpose:</strong> The energy spectrum of a linear accelerator used for dose calculations is determined during beam commissioning by iteratively adjusting the spectrum and comparing calculated and m...<strong>Purpose:</strong> The energy spectrum of a linear accelerator used for dose calculations is determined during beam commissioning by iteratively adjusting the spectrum and comparing calculated and measured percent depth-dose curves. Direct measurement of the energy spectrum using pulse mode detectors is particularly challenging because of the high-energy, high fluence nature of these beams and limitations of the detector systems. This work implements a Compton scattering (CS) spectroscopy setup and presents detector corrections and spectral unfolding techniques to measure the spectrum of a 6 MV linear accelerator using a pulse mode detector. <strong>Methods:</strong> Spectral measurements were performed using a Varian Clinac 21EX linear accelerator and a high-purity germanium (HPGe) detector. To reduce fluence to the detector, a custom-built lead shield and a CS spectrometry setup were used. The detector was placed at CS angles of 46<span style="font-family:Verdana, Helvetica, Arial;white-space:normal;background-color:#FFFFFF;">°</span>, 89<span style="font-family:Verdana, Helvetica, Arial;white-space:normal;background-color:#FFFFFF;">°</span>, and 125<span style="font-family:Verdana, Helvetica, Arial;white-space:normal;background-color:#FFFFFF;">°</span>. At each of these locations, a detector response function was generated to account for photon interactions within the experimental geometry. Gold’s deconvolution algorithm was used to unfold the energy spectrum. The measured spectra were compared to simulated spectra, which were obtained using an experimentally benchmarked model of the Clinac 21EX in MCNP6. <strong>Results:</strong> Measurements were acquired and detector response corrections were calculated for all three CS angles. A comparison of spectra for all CS angles showed good agreement with one another. The spectra for all three angles were averaged and showed good agreement with the MCNP6 simulated spectrum, with all points above 400 keV falling within 4%, which was within the uncertainty of the measurement and statistical uncertainty. <strong>Conclusions:</strong> The measurement of the energy spectrum of a 6 MV linear accelerator using a pulse-mode detector is presented in this work. For accurate spectrum determination, great care must be taken to optimize the detector setup, determine proper corrections, and to unfold the spectrum.展开更多
Human T-cell lymphotropic virus type 1(HTLV-1)is associated with the development of HTLV-1-associated myelopathy/tropical spastic paraparesis(HAM/TSP).It has been reported that the HTLV-1 proteins(specifically TAX and...Human T-cell lymphotropic virus type 1(HTLV-1)is associated with the development of HTLV-1-associated myelopathy/tropical spastic paraparesis(HAM/TSP).It has been reported that the HTLV-1 proteins(specifically TAX and HBZ)can modulate FOXp3,resulting in an immune imbalance that can favor the progression of HAM/TSP.This review aims to summarize the literature in order to clarify the relationship between the expression of HTLV-1 m RNAs and/or viral proteins(TAX and HBZ)with the expression of mRNA and/or protein FOXp3 and their correlation with HAM/TSP development.This systematic review was conducted according to the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis.The search strategy was performed on the Medical Literature Analysis and Retrieval System Online and Latin American and Caribbean Literature in Health Sciences Platform using subject descriptors.After screening,six articles were included in this review.The studies suggested that TAX and HBZ have a directly proportional correlation with FOXp3 in individuals with HAM/TSP,which also presented an increased expression of FOXp3 compared to asymptomatic controls and/or healthy donors.This systematic review indicates that TAX and HBZ can interact with FOXp3 and that interaction may influence HAM/TSP development.展开更多
Tacrolimus(Tac)is currently the most common calcineurin-inhibitor employed in solid organ transplantation.High intra-patient variability(IPV)of Tac(Tac IPV)has been associated with an increased risk of immune-mediated...Tacrolimus(Tac)is currently the most common calcineurin-inhibitor employed in solid organ transplantation.High intra-patient variability(IPV)of Tac(Tac IPV)has been associated with an increased risk of immune-mediated rejection and poor outcomes after kidney transplantation.Few data are available concerning the impact of high Tac IPV in non-kidney transplants.However,even in kidney transplantation,there is still a controversy whether high Tac IPV is indeed detrimental in respect to graft and/or patient survival.This may be due to different methods employed to evaluate IPV and distinct time frames adopted to assess graft and patient survival in those reports published up to now in the literature.Little is also known about the influence of high Tac IPV in the development of other untoward adverse events,update of the current knowledge regarding the impact of Tac IPV in different outcomes following kidney,liver,heart,lung,and pancreas tran-splantation to better evaluate its use in clinical practice.展开更多
Introduction: High postprandial triglyceride levels and obesity are associated with coronaropathy, and influence the pathogenesis and progression of atherosclerosis. Objective: To evaluate the effect of immediate acut...Introduction: High postprandial triglyceride levels and obesity are associated with coronaropathy, and influence the pathogenesis and progression of atherosclerosis. Objective: To evaluate the effect of immediate acute physical exercise on postprandial hyperlipaemia in individuals with central obesity. Methods: Study included sedentary, normolipidemic individuals aged 18 - 30 years, with waist circumference >80 in for women and >94 for men. The physical exercise was performed for 45 minutes with 55% - 60% of the heart rate reserve. Triglyceride level tests were performed after fasting, and at time intervals of 1h and 3 h after lipid overload, a week before and immediately after a session of physical exercise. Results: Thirty-six individuals were evaluated (mean age 23.74 ± 4.05 years, 88.2% women, BMI = 28.4 ± 3.4). Fasting and post-prandial triglyceride levels were similar before and after the exercise (p = 0.87). A smaller rise in triglyceride levels was observed in the 1st hour in obese individuals (5%) compared with over-weight individuals (21%) p = 0.001. Conclusion: In individuals with central obesity, moderate intensity physical exercise performed immediately before lipid overload does not reduce the hyperlipidemic peak.展开更多
文摘Neuromodulation for diabetic peripheral neuropathy represents a significant area of interest in the management of chronic pain associated with this condition.Diabetic peripheral neuropathy,a common complication of diabetes,is characterized by nerve damage due to high blood sugar levels that lead to symptoms,such as pain,tingling,and numbness,primarily in the hands and feet.The aim of this systematic review was to evaluate the efficacy of neuromodulatory techniques as potential therapeutic interventions for patients with diabetic peripheral neuropathy,while also examining recent developments in this domain.The investigation encompassed an array of neuromodulation methods,including frequency rhythmic electrical modulated systems,dorsal root ganglion stimulation,and spinal cord stimulation.This systematic review suggests that neuromodulatory techniques may be useful in the treatment of diabetic peripheral neuropathy.Understanding the advantages of these treatments will enable physicians and other healthcare providers to offer additional options for patients with symptoms refractory to standard pharmacologic treatments.Through these efforts,we may improve quality of life and increase functional capacity in patients suffering from complications related to diabetic neuropathy.
基金supported by the Economic and Social Research Council(ES/P000738/1)the Medical Research Council(MC_UU_00006/5)the University of Cambridge,and the National Health and Medical Research Council(GS2000053).
文摘Purpose:It is aimed to assess whether school uniforms are associated with population-level gender inequalities in physical activity,and whether associations differ by school level,country/region income,and assessment method.Methods:An ecological study design was employed.We collected data about global uniform practices using an online survey.We searched for country/region-level estimates of school-aged youth meeting physical activity guidelines from international surveillance studies.Study selection was conducted in duplicate using a systematic process,and a random sample of all data was checked to ensure extraction and pooling processes were accurate.We calculated absolute and relative gender inequalities in physical activity for each country.Linear regression examined associations between country/region-level uniform practices(binary yes/no exposure variable) and country/region-level gender inequalities in physical activity guideline compliance(absolute and relative inequalities).We investigated moderation by school level,stratified analyses by income group,and repeated primary analyses using device-measured data.Results:Pooling data from 135 countries/regions(n=1,089,852),we found no association between population-level uniform practices and gender inequalities in physical activity across all ages(absolute:β=-0.2;95% confidence interval(95%CI):-1.7 to 1.3,p=0.74;relative:β=0.1;95%CI:-0.1 to 0.2,p=0.51).Subgroup analysis suggested a positive association in primary school settings(absolute:β=4.3;95%CI:-0.0 to 8.6,p=0.05).Among high-income countries,absolute inequalities were significantly greater in countries/regions with uniform practices(N=37) compared to those without(N=48)(9.1(SD=3.6) vs.7.8 percentage points(SD=4.3)).Repeating analyses using device-measured data(n=32,130;N=24) did not alter our primary finding.From initial descriptive statistics,we found that in countries/regions where a maj ority of schools(>50%) reportedly use uniforms,there was lower compliance with physical activity guidelines among all genders(median:16.0%,interquartile range:13.2%-19.9%,N=103) compared to generally non-uniform countries/regions(median:19.5%,interquartile range:16.4%-23.5 %,N=32)(z=3.04,p=0.002).(N=countries,regions and studies repre sented;n=sample size or participants included).Conclusion:School uniforms are associated with greater gender inequalities in physical activity in primary school settings and in high-income countries.Our population-level findings warrant testing using individual-level data across contexts.
基金supported by the National Natural Science Foundation of China(grant number 82103955)the Cyrus Tang Foundation(grant number 050459)the Clinical Medicine Plus X-Young Scholars Project,Peking University,the Fundamental Research Funds for the Central Universities(grant number 7100604313).
文摘Background Major depressive disorders(MDDs)impose substantial burdens on individuals and society;however,further detailed analysis is still needed for its long-term trends.Aims This study aimed to analyse the gender-specific temporal trends and cohort variations of MDD incidence among Chinese residents over the past three decades.Methods Employing the age-period-cohort-interaction model and leveraging data from the Global Burden of Disease Study 2019,this research identified and analysed incidence trends of MDD among Chinese males and females aged 5-94 years from 1990 to 2019 across three dimensions,encompassing age,period and birth cohort.Results The analysis reveals age-related effects,indicating heightened MDD risk among adolescents and older adults.Specifically,individuals entering the older adulthood at the age of 65-69 significantly increased the risk of MDD by 64.9%.People aged 90-94 years witnesseda 105.4%increase in MDD risk for the overall population,with females and males in this age group experiencing a 75.1%and 103.4%increase,respectively.In terms of period effects,the risk of MDD displayed a decline from 1990 to 1994,followed by a rebound in 2008.Cohort effects demonstrated diverse generational patterns,with generationⅠand generationⅢmanifesting opposing‘age-as-level'trends.GenerationⅡand generationⅣexhibited'cumulative disadvantage'and'cumulative advantage'patterns,respectively.Age effects indicated an overall higher risk of MDD incidence in females,while cohort effects showed greater variations of MDD incidence among females.Conclusions The study underscores the substantial effects of age,period and cohort on MDD across genders in China.Priority interventions targeting vulnerable populations,including children,adolescents,older adults,females and the post-millennium birth cohort,are crucial to mitigate the impact of MDD.
基金supported by a Career Development Fellowship(APP1141606)from the National Health and Medical Research Council,Australia。
文摘Background:Physical inactivity and insomnia symptoms are independently associated with increased risk of depression and anxiety;however,few studies jointly examine these risk factors.This study aimed to prospectively examine the joint association of physical activity(PA)and insomnia symptoms with onset of poor mental health in adults.Methods:Participants from the 2013 to 2018 annnual waves of the Household Income and Labour Dynamics in Australia panel study who had good mental health(Mental Health Inventory-5>54)in 2013,and who completed at least 1 follow-up survey(2014-2018),were included(n=10,977).Poor mental health(Mental Health Inventory-5≤54)was assessed annually.Baseline(2013)PA was classified as high/moderate/low,and insomnia symptoms(i.e.,trouble sleeping)were classified as no insomnia symptoms/insomnia symptoms,with 6 mutually exclusive PAinsomnia symptom groups derived.Associations of PA-insomnia symptom groups with onset of poor mental health were examined using discrete-time proportional-hazards logit-hazard models.Results:There were 2322 new cases of poor mental health(21.2%).Relative to the high PA/no insomnia symptoms group,there were higher odds(odds ratio and 95%confidence interval(95%CI))of poor mental health among the high PA/insomnia symptoms(OR=1.87,95%CI:1.57-2.23),moderate PA/insomnia symptoms(OR=1.93,95%CI:1.61-2.31),low PA/insomnia symptoms(OR=2.33,95%CI:1.96-2.78),and low PA/no insomnia symptoms(OR=1.14,95%CI:1.01-1.29)groups.Any level of PA combined with insomnia symptoms was associated with increased odds of poor mental health,with the odds increasing as PA decreased.Conclusion:The se findings highlight the potential benefit of interventions targeting both PA and insomnia symptoms for promoting mental health.
基金supported by the National Institutes of HealthNo.R56 NS117935(to ASH and WLM)+1 种基金funded by Institutional Clinical and Translational Science AwardNo.UL1 TR002373。
文摘After spinal cord injury,there is an extensive infiltration of immune cells,which exacerbates the injury and leads to further neural degeneration.Therefore,a major aim of current research involves targeting the immune response as a treatment for spinal cord injury.Although much research has been performed analyzing the complex inflammatory process following spinal cord injury,there remain major discrepancies within previous literature regarding the timeline of local cytokine regulation.The objectives of this study were to establish an overview of the timeline of cytokine regulation for 2 weeks after spinal cord injury,identify sexual dimorphisms in terms of cytokine levels,and determine local cytokines that significantly change based on the severity of spinal cord injury.Rats were inflicted with either a mild contusion,moderate contusion,severe contusion,or complete transection,7 mm of spinal cord centered on the injury was harvested at varying times post-injury,and tissue homogenates were analyzed with a Cytokine/Chemokine 27-Plex assay.Results demonstrated pro-inflammatory cytokines including tumor necrosis factorα,interleukin-1β,and interleukin-6 were all upregulated after spinal cord injury,but returned to uninjured levels within approximately 24 hours post-injury,while chemokines including monocyte chemoattractant protein-1 remained upregulated for days post-injury.In contrast,several anti-inflammatory cytokines and growth factors including interleukin-10 and vascular endothelial growth factor were downregulated by 7 days post-injury.After spinal cord injury,tissue inhibitor of metalloproteinase-1,which specifically affects astrocytes involved in glial scar development,increased more than all other cytokines tested,reaching 26.9-fold higher than uninjured rats.After a mild injury,11 cytokines demonstrated sexual dimorphisms;however,after a severe contusion only leptin levels were different between female and male rats.In conclusion,pro-inflammatory cytokines initiate the inflammatory process and return to baseline within hours post-injury,chemokines continue to recruit immune cells for days post-injury,while anti-inflammatory cytokines are downregulated by a week post-injury,and sexual dimorphisms observed after mild injury subsided with more severe injuries.Results from this work define critical chemokines that influence immune cell infiltration and important cytokines involved in glial scar development after spinal cord injury,which are essential for researchers developing treatments targeting secondary damage after spinal cord injury.
文摘Background: Hypertensive disease in pregnancy is an important cause of morbidity, long-term disability, and maternal and neonatal mortality. The aim is to determine the socio-demographic characteristics and maternal prognosis of these women with Hypertension during pregnancy. Material and Method: We conducted a cross-sectional study, we interview patients and after discussion we transcripts in a database in Excel software before analysis with SPSS version 20.0 and Stata 14.0 The qualitative variables have been summarised by the Percentage and the quantitative variables will be summarised by Means and Standard Deviation. The associations of the variables were calculated by Pearson’s chi-square test with a significance level set at a p-value Result: The average age of the patients was 30.33 ± 7.020 years, 92.1% were married, 79.8% lived in urban areas, most of the patients were overweight (43%), 92.1% of them had monofetal pregnancies, 36% were multiparous, 34.2% had a previous history of preeclampsia in pregnancy and 14% were known to have hypertension. Pre-eclampsia was the most frequent form of hypertension in pregnancy with 73.68% of cases and represents 84.8% of severe forms of hypertension in pregnancy, 53.4% of the patients delivered vaginally. Eclampsia was the most frequent complication in our patients with 31.7% frequency and among the socio-demographic parameters, age and body mass index were significantly associated with maternal complications. Conclusion: Maternal age and body mass index are important socio-demographic factors associated with the occurrence of maternal complications in women with hypertensive disorders in pregnancy.
基金supported by the Grand Alliance CARE Consortiumfunded in part by the National Collegiate Athletic Association(NCAA)+1 种基金the Department of Defense(DoD).supported by the Office of the Assistant Secretary of Defense for Health Affairs,through the Combat Casualty Care Research Program,endorsed by the Department of Defense,under Award No.W81XWH1420151。
文摘Background:Current protein biomarkers are only moderately predictive at identifying individuals with mild traumatic brain injury or concussion.Therefore,more accurate diagnostic markers are needed for sport-related concussion.Methods:This was a multicenter,prospective,case-control study of athletes who provided blood samples and were diagnosed with a concussion or were a matched non-concussed control within the National Collegiate Athletic Association-Department of Defense Concussion Assessment,Research,and Education Consortium conducted between 2015 and 2019.The blood was collected within 48 h of injury to identify protein abnormalities at the acute and subacute timepoints.Athletes with concussion were divided into 6 h post-injury(0-6 h post-injury)and after 6 h postinjury(7-48 h post-injury)groups.We applied a highly multiplexed proteomic technique that used a DNA aptamers assay to target 1305proteins in plasma samples from athletes with and without sport-related concussion.Results:A total of 140 athletes with concussion(79.3%males;aged 18.71±1.10 years,mean±SD)and 21 non-concussed athletes(76.2%males;19.14±1.10 years)were included in this study.We identified 338 plasma proteins that significantly differed in abundance(319 upregulated and 19 downregulated)in concussed athletes compared to non-concussed athletes.The top 20 most differentially abundant proteins discriminated concussed athletes from non-concussed athletes with an area under the curve(AUC)of 0.954(95%confidence interval:0.922-0.986).Specifically,after 6 h of injury,the individual AUC of plasma erythrocyte membrane protein band 4.1(EPB41)and alpha-synuclein(SNCA)were 0.956 and 0.875,respectively.The combination of EPB41 and SNCA provided the best AUC(1.000),which suggests this combination of candidate plasma biomarkers is the best for diagnosing concussion in athletes after 6 h of injury.Conclusion:Our data suggest that proteomic profiling may provide novel diagnostic protein markers and that a combination of EPB41 and SNCA is the most predictive biomarker of concussion after 6 h of injury.
文摘The advent of the metaverse,including virtual reality,augmented reality,andartificial intelligence,is an undeniable issue that health care scientists need toupdate.It influences all fields of knowledge,interpersonal relationships,andhealth.Regarding mental health since the post-coronavirus disease 2019 pandemic,it is necessary to consider and understand the potential,possibilities,weaknesses,and consequences arising from and provided by this new scenario.Due tothe increasing need for mental health monitoring and care,mental health treatmentsrequire in-depth training and preparation to achieve the maximum use of themetaverse advantages and possibilities.Currently,very little is known about theeffectiveness of remote mental health treatment,but it is certainly suggested thataccessibility and the characteristics associated with the use of metaverse technologiesmay represent new horizons for accessibility and approach tools,as long asmore studies are carried out and more evidence is collected to develop accurateguidelines,safe training,solve ethical concerns,and overcome limitations.
文摘BACKGROUND Kidney transplant recipients(KTR)are at risk of severe coronavirus disease 2019(COVID-19)disease and mortality after severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection.We predicted that hospitalization for COVID-19 and subsequent admission to the intensive care unit(ICU)would yield worse outcomes in KTRs.cohort was stratified by ICU admission.Outcomes of interest included risk factors for ICU admission and mortality,length of stay(LOS),respiratory symptoms at admission,all-cause graft failure at the last follow-up,and death related to COVID-19.RESULTS 96 KTRs were hospitalized for SARS-COV-2 infection.21(22%)required ICU admission.The ICU group had longer hospital LOS(21.8 vs 8.6 days,P<0.001)and were more likely to experience graft failure(81%vs 31%,P<0.001).Of those admitted to the ICU,76%had death at last-follow up,and 71%had death related to COVID-19.Risk factors for ICU admission included male sex(aHR:3.11,95%CI:1.04-9.34;P=0.04).Risk factors for all-cause mortality and COVID-19-related mortality included ICU admission and advanced age at SARS-CoV-2 diagnosis.Mortality was highest within a month of COVID-19 diagnosis,with the ICU group having increased risk of all-cause(aHR:11.2,95%CI:5.11-24.5;P<0.001)and COVID-19-related mortality(aHR:27.2,95%CI:8.69-84.9;P<0.001).CONCLUSION ICU admission conferred an increased risk of mortality,graft failure,and longer LOS.One-fifth of those hospit-alized died of COVID-19,reflecting the impact of COVID-19-related morbidity and mortality among KTRs.
文摘Background: Cardiovascular diseases (CVD) are major causes of death in Japan, and controlling the risk factors for CVD is an important public health task. Lifestyle factors, for example, diet and stress, have impacts on risk factors such as hypertension and hyperlipidemia. Deterioration of mental health is related to CVD pathogenesis. Aim: We investigated the relationships between levels of mental health, 4-year changes in lifestyle, and CVD risk factors among Japanese workers, using the SF-36 (Japanese version), which is a comprehensive scale measuring health-related quality of life. We hypothesized that workers’ mental health levels would influence 4-year changes in their lifestyles and CVD risk factors. Methods: Data from the High-Risk and Population Strategy for Occupational Health Promotion (HIPOP-OHP) study, which were collected by examination and administration of the SF-36, were used. The relationships between mental health levels at baseline, lifestyle chan- ges, and cardiovascular risk factors were longitudinally analyzed. Subjects with total SF-36 scores ≥65 were classified as the “Good Mental Health Group,” and those with total scores <65 were classified as the “Poor Mental Health Group.” Results: Multiple logistic regression analyses showed that, as compared to people who had poor mental health, those who had good mental health at baseline had a significantly higher probability of good maintenance of improvements in body mass index, (OR = 1.20, 95% CI: 1.03 - 1.39), blood pressure (OR = 1.20, 95% CI: 1.01 - 1.43), total cholesterol (OR = 1.07, 95% CI: 0.86 - 1.33) and HDL cholesterol (OR = 1.26, 95% CI: 1.07 - 1.47). Conclusion: Japanese workers with good mental health tend to improve or maintain good lifestyle conditions and minimize CVD risk factors, while those with poor mental health generally have difficulty improving their lifestyles and lowering their CVD risk.
文摘Objective:Depression is a global and growing health issue.Complementary and alternative medicines (CAM) use is common among people with depression.We examined the baseline use of CAM (products,not services) in centrally obese adults with depression,a specific and increasingly important population who were part of a trial of Tai Chi and Qigong for depression.Methods:Self-reported use of CAM products (four major groups:vitamins,herbal medicines,mineral supplements and purified chemicals as nutritional supplements) together with demographic,lifestyle and health status characteristics were collected using validated questions within a written survey.We used descriptive statistics to understand patterns of use.Results:Two hundred and sixty patients participated in the assessment.Half of the patients stated they were using CAM,on average reporting 2.3 CAM per patient.Women were more likely than men,and older people (>60 years) more likely than younger people (<40 years) to use any CAM products.Patients reported using CAM mostly for general health and alleviating aches and pains.CAM use was not associated with health state,use of a prescription antidepressant medicine,nor (self-reported) comorbidities such as arthritis,diabetes,hypertension or alcohol or tobacco use.Conclusions:CAM products are commonly used in Australians with moderate depression,particularly in female or older patients.The range and number of CAM in this group with common comorbidity may present additional unknown risks due to potential interactions with other prescribed medications with a myriad of biological and pharmacological effects.The importance of establishing whether depressed patients are taking CAM,the particular CAM and whether the CAM interacts with each other,other drugs used for depression or the biological process of the depression itself are factors to be considered at each assessment.
基金supported,in part,by METAVIVOR Foundation Early Career Research Grant Award,American Cancer Society Research Scholar Grant(Grant number:RSG-23-1140821-01-ET)the University of Wisconsin Carbone Cancer Center Research Collaborative and the Pancreas Cancer Task Force,and the start-up package from the University of Wisconsin-Madison.
文摘Neutrophils have recently emerged as promising carriers for drug delivery due to their unique properties including rapid response toward inflammation,chemotaxis,and transmigration.When integrated with nanotechnology that has enormous advantages in improving treatment efficacy and reducing side effects,neutrophil-based nano-drug delivery systems have expanded the repertoire of nanoparticles employed in precise therapeutic interventions by either coating nanoparticles with their membranes,loading nanoparticles inside living cells,or engineering chimeric antigen receptor(CAR)-neutrophils.These neutrophil-inspired therapies have shown superior biocompatibility,targeting ability,and therapeutic robustness.In this review,we summarized the benefits of combining neutrophils and nanotechnologies,the design principles and underlying mechanisms,and various applications in disease treatments.The challenges and prospects for neutrophil-based drug delivery systems were also discussed.
文摘Non-alcoholic fatty liver disease(NAFLD) associated hepatocellular carcinoma(HCC) incidence is increasing worldwide, paralleling the obesity epidemic. Although most cases are associated with cirrhosis, HCC can occur without cirrhosis in NAFLD. Diabetes and obesity are associated risk factors for HCC in patients. Given the sheer magnitude of the underlying risk factors(diabetes, obesity, non-cirrhotic NAFLD) screening for HCC in the non-cirrhotic population is not recommended. Optimal screening strategies in NAFLD cirrhosis are not completely elucidated with Ultrasound having significant limitations in detection of liver lesions in the presence of obesity and steatosis. Consequently NAFLD-HCC is more often diagnosed at a later stage with larger tumors and reduced opportunities for curative treatments as opposed to HCC in other causes of cirrhosis. When HCC is found at a curative stage treatments including liver transplantation, resection and loco-regional therapies are associated with good results similar to that seen in HCV-HCC. Future strategies under study include the use of chemopreventive and antioxidant agents to reduce development of cirrhosis and non-alcoholic steatohepatitis(NASH). Strategies to reverse NASH via weight loss, control of associated conditions like diabetes are key strategies in reducing the increasing incidence of NASH-HCC. Novel therapeutic agents for NASH are in trials and if successful in achieving reversal of NASH will be an important strategy in reducing NAFLD-HCC.
文摘BACKGROUND Variceal hemorrhage is associated with high mortality and is the cause of death for 20–30%of patients with cirrhosis.Nonselectiveβblockers(NSBBs)or endoscopic variceal ligation(EVL)are recommended for primary prevention of variceal bleeding in patients with medium to large esophageal varices.Meanwhile,combination of EVL and NSBBs is the recommended approach for the secondary prevention.Carvedilol has greater efficacy than other NSBBs as it decreases intrahepatic resistance.We hypothesized that there was no difference between carvedilol and EVL intervention for primary and secondary prevention of variceal bleeding in cirrhosis patients.AIM To evaluate the efficacy of carvedilol compared to EVL for primary and secondary prevention of variceal bleeding in cirrhotic patients METHODS We searched relevant literatures in major journal databases(CENTRAL,MEDLINE,and EMBASE)from March to August 2018.Patients with cirrhosis and portal hypertension,regardless of aetiology and severity,with or without a history of variceal bleeding,and aged≥18 years old were included in this review.Only randomized controlled trials(RCTs)that compared the efficacy of carvedilol and that of EVL for primary and secondary prevention of variceal bleeding and mortality in patients with cirrhosis and portal hypertension were considered,irrespective of publication status,year of publication,and language.RESULTS Seven RCTs were included.In four trials assessing the primary prevention,no significant difference was found on the events of variceal bleeding(RR:0.74,95%CI:0.37-1.49),all-cause mortality(RR:1.10,95%CI:0.76-1.58),and bleedingrelated mortality(RR:1.02,95%CI:0.34-3.10)in patients who were treated with carvedilol compared to EVL.In three trials assessing secondary prevention,there was no difference between two interventions for the incidence of rebleeding(RR:1.10,95%CI:0.75-1.61).The fixed-effect model showed that,compared to EVL,carvedilol decreased all-cause mortality by 49%(RR:0.51,95%CI:0.33-0.79),with little or no evidence of heterogeneity.CONCLUSION Carvedilol had similar efficacy to EVL in preventing the first variceal bleeding in cirrhosis patients with esophageal varices.It was superior to EVL alone for secondary prevention of variceal bleeding in regard to all-cause mortality reduction.
文摘The delivery of medical student education has changed rapidly during the coronavirus disease 2019(COVID-19)pandemic.Students in their pre-clinical years have transitioned to online courses and examinations.Students in their clinical years are not permitted on clinical rotations,and face uncertainties in career exploration and the residency application process.Medical students in all stages of training are volunteering and helping their communities.The future presence of COVID-19 throughout the United States is unknown,and medical students are eager to return to their training.This paper outlines current challenges in medical student education and the various responses that have been adopted.We also discuss possible future directions for students through involvement in telemedicine,outpatient clinic visits,and non-respiratory inpatient care tasks as adequate personal protective equipment,COVID-19 testing,and resources become more widely available.
基金supported by grants from the National Natural Science Foundation of China(No.81200006)the Natural Science Foundation of Hubei Province(No.2010CDB08804)+1 种基金Wuhan Health Bureau Foundation(No.WX11B10)supported by Wu Jieping Medical Fund(No.32067501285)
文摘Summary： This study investigated the expression of interleukin-17 （IL-17） and T cell immunoglobulin mucin and domain-containing molecule-3 （Tim-3） in bronchoalveolar lavage fluid （BALF） of asthmatic mice and the effect of dexamethasone （DEX） on these factors. Thirty-six mice were randomly divided into three groups： normal group, asthmatic group and DEX group. The mouse model of asthma was es- tablished by sensitization with ovalbumin in both the asthmatic and DEX groups. The levels of IL-6, IL-10, IL-17 and TGF-β were measured in BALF by enzyme-linked immunesorbent assay （ELISA）. The mRNA expression level of Tim-3 was detected by reverse transcription polymerase chain reaction （RT-PCR）. The ratio of Tim-3＋CD4＋ cells to total CD4＋ cells in BALF was determined by flow cy- tometry. Differential inflammatory cells in BALF were detected. The correlations among IL-17, IL-6, IL-10, Tim-3 and inflammatory cells were analyzed. The results showed that the levels of IL-17, IL-6 and Tim-3 were substantially increased and the IL-10 level decreased in BALF in the asthmatic mice, which was significantly reversed by DEX treatment. IL-17 expression was positively correlated with IL-6 and Tim-3 expression and the number of inflammatory cells but negatively with IL-10 expression. These results indicate that the increased expression of IL-17 and Tim-3 in BALF may be implicated in the occurrence and development of asthmatic inflammation; the mechanism by which DEX suppresses asthmatic airway inflammation involves down-regulation of IL-17 and Tim-3 levels.
文摘<strong>Purpose:</strong> The energy spectrum of a linear accelerator used for dose calculations is determined during beam commissioning by iteratively adjusting the spectrum and comparing calculated and measured percent depth-dose curves. Direct measurement of the energy spectrum using pulse mode detectors is particularly challenging because of the high-energy, high fluence nature of these beams and limitations of the detector systems. This work implements a Compton scattering (CS) spectroscopy setup and presents detector corrections and spectral unfolding techniques to measure the spectrum of a 6 MV linear accelerator using a pulse mode detector. <strong>Methods:</strong> Spectral measurements were performed using a Varian Clinac 21EX linear accelerator and a high-purity germanium (HPGe) detector. To reduce fluence to the detector, a custom-built lead shield and a CS spectrometry setup were used. The detector was placed at CS angles of 46<span style="font-family:Verdana, Helvetica, Arial;white-space:normal;background-color:#FFFFFF;">°</span>, 89<span style="font-family:Verdana, Helvetica, Arial;white-space:normal;background-color:#FFFFFF;">°</span>, and 125<span style="font-family:Verdana, Helvetica, Arial;white-space:normal;background-color:#FFFFFF;">°</span>. At each of these locations, a detector response function was generated to account for photon interactions within the experimental geometry. Gold’s deconvolution algorithm was used to unfold the energy spectrum. The measured spectra were compared to simulated spectra, which were obtained using an experimentally benchmarked model of the Clinac 21EX in MCNP6. <strong>Results:</strong> Measurements were acquired and detector response corrections were calculated for all three CS angles. A comparison of spectra for all CS angles showed good agreement with one another. The spectra for all three angles were averaged and showed good agreement with the MCNP6 simulated spectrum, with all points above 400 keV falling within 4%, which was within the uncertainty of the measurement and statistical uncertainty. <strong>Conclusions:</strong> The measurement of the energy spectrum of a 6 MV linear accelerator using a pulse-mode detector is presented in this work. For accurate spectrum determination, great care must be taken to optimize the detector setup, determine proper corrections, and to unfold the spectrum.
基金funded by Conselho Nacional de Desenvolvimento Científico e Tecnológico(426196/2018-0)supported by a scholarship from the Conselho Nacional de Desenvolvimento Científico e Tecnológico(127049/2019-3 and 115208/2020-8)
文摘Human T-cell lymphotropic virus type 1(HTLV-1)is associated with the development of HTLV-1-associated myelopathy/tropical spastic paraparesis(HAM/TSP).It has been reported that the HTLV-1 proteins(specifically TAX and HBZ)can modulate FOXp3,resulting in an immune imbalance that can favor the progression of HAM/TSP.This review aims to summarize the literature in order to clarify the relationship between the expression of HTLV-1 m RNAs and/or viral proteins(TAX and HBZ)with the expression of mRNA and/or protein FOXp3 and their correlation with HAM/TSP development.This systematic review was conducted according to the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis.The search strategy was performed on the Medical Literature Analysis and Retrieval System Online and Latin American and Caribbean Literature in Health Sciences Platform using subject descriptors.After screening,six articles were included in this review.The studies suggested that TAX and HBZ have a directly proportional correlation with FOXp3 in individuals with HAM/TSP,which also presented an increased expression of FOXp3 compared to asymptomatic controls and/or healthy donors.This systematic review indicates that TAX and HBZ can interact with FOXp3 and that interaction may influence HAM/TSP development.
文摘Tacrolimus(Tac)is currently the most common calcineurin-inhibitor employed in solid organ transplantation.High intra-patient variability(IPV)of Tac(Tac IPV)has been associated with an increased risk of immune-mediated rejection and poor outcomes after kidney transplantation.Few data are available concerning the impact of high Tac IPV in non-kidney transplants.However,even in kidney transplantation,there is still a controversy whether high Tac IPV is indeed detrimental in respect to graft and/or patient survival.This may be due to different methods employed to evaluate IPV and distinct time frames adopted to assess graft and patient survival in those reports published up to now in the literature.Little is also known about the influence of high Tac IPV in the development of other untoward adverse events,update of the current knowledge regarding the impact of Tac IPV in different outcomes following kidney,liver,heart,lung,and pancreas tran-splantation to better evaluate its use in clinical practice.
文摘Introduction: High postprandial triglyceride levels and obesity are associated with coronaropathy, and influence the pathogenesis and progression of atherosclerosis. Objective: To evaluate the effect of immediate acute physical exercise on postprandial hyperlipaemia in individuals with central obesity. Methods: Study included sedentary, normolipidemic individuals aged 18 - 30 years, with waist circumference >80 in for women and >94 for men. The physical exercise was performed for 45 minutes with 55% - 60% of the heart rate reserve. Triglyceride level tests were performed after fasting, and at time intervals of 1h and 3 h after lipid overload, a week before and immediately after a session of physical exercise. Results: Thirty-six individuals were evaluated (mean age 23.74 ± 4.05 years, 88.2% women, BMI = 28.4 ± 3.4). Fasting and post-prandial triglyceride levels were similar before and after the exercise (p = 0.87). A smaller rise in triglyceride levels was observed in the 1st hour in obese individuals (5%) compared with over-weight individuals (21%) p = 0.001. Conclusion: In individuals with central obesity, moderate intensity physical exercise performed immediately before lipid overload does not reduce the hyperlipidemic peak.
