Deep brain stimulation(DBS)is an established therapeutic intervention for people with Parkinson’s disease(PwPD)and is increasingly being utilized for other neurological disorders.Although effective in alleviating mot...Deep brain stimulation(DBS)is an established therapeutic intervention for people with Parkinson’s disease(PwPD)and is increasingly being utilized for other neurological disorders.Although effective in alleviating motor symptoms and reducing medication requirements,DBS has undergone minimal conceptual evolution and still relies on continuous high-frequency electrical stimulation.In Parkinson’s disease(PD),this persistent stimulation may cause adverse effects,including dysarthria,stimulation-induced dyskinesia,impulsivity,and mood alterations.Additionally,the continuous energy demand of current DBS systems accelerates battery depletion,necessitating more frequent battery charging or battery replacement surgeries,increasing risks,burden,and costs.Basic neuroscience research has long demonstrated that exogenous electrical stimulation can induce persistent changes to synaptic connections,known as long-term plasticity.展开更多
AIM To identify the key epigenetically modulated genes and pathways in HCC by performing an integrative meta-analysis of all major, well-annotated and publicly available methylation datasets using tools of network ana...AIM To identify the key epigenetically modulated genes and pathways in HCC by performing an integrative meta-analysis of all major, well-annotated and publicly available methylation datasets using tools of network analysis.METHODS Pub Med and Gene Expression Omnibus were searched for genome-wide DNA methylation datasets. Patient clinical and demographic characteristics were obtained. DNA methylation data were integrated using the Ingenuity Pathway Analysis, a software package for visualizing and analyzing biological networks. Pathway enrichment analysis was performed using IPA, which also provides literature-driven and computationallypredicted annotations for significant association of genes to curated molecular pathways.RESULTS From an initial 928 potential abstracts, we identified and analyzed 11 eligible high-throughput methylation datasets representing 354 patients. A significant proportion of studies did not provide concomitant clinical data. In the promoter region, HIST1H2AJ and SPDYA were the most commonly methylated, whereas HRNBP3 gene was the most commonly hypomethylated. ESR1 and ERK were central genes in the principal networks. The pathways most associated with the frequently methylated genes were G-protein coupled receptor and c AMP-mediated signalling. CONCLUSION Using an integrative network-based analysis approach of genome-wide DNA methylation data of both the promoter and body of genes, we identified G-protein coupled receptor signalling as the most highly associated with HCC. This encompasses a diverse range of cancer pathways, such as the PI3 K/Akt/m TOR and Ras/Raf/MAPK pathways, and is therefore supportive of previous literature on gene expression in HCC. However, there are novel targetable genes such as HIST1H2 AJ that are epigenetically modified, suggesting their potential as biomarkers and for therapeutic targeting of the HCC epigenome.展开更多
Until recently, older adults with a cognitive impairment (CI) who experienced a hip fracture were filtered from being admitted into active rehabilitation units. The increased complexity of care required for older adul...Until recently, older adults with a cognitive impairment (CI) who experienced a hip fracture were filtered from being admitted into active rehabilitation units. The increased complexity of care required for older adults with a CI may negatively influence the attitudes and job satisfaction of healthcare practitioners working with this population. The current study is a part of a larger intervention study allowing patients with CI following a hip fracture access to rehabilitation care and implementing a patient-centred model to facilitate caring for this new population. This new model required a substantial change in the skillset and knowledge of healthcare practitioners. The focus of this study was to explore the impact on the healthcare practitioners of adopting this new model for providing care to older adults with a CI following a hip fracture. The attitudes, dementia knowledge, job satisfaction, and work stress of healthcare practitioners were the focus of evaluation. Key study findings showed that stress due to relationships with coworkers, workloads and scheduling, and the physical design and conditions at work were moderated post-intervention. Staff responses also improved for job satisfaction, biomedical knowledge of dementia, and degree of hopefulness about dementia. Although we cannot state conclusively that the our model was solely responsible for all the staff improvements observed post-intervention, our findings provide further support to the argument that patients with CI should be allowed access to rehabilitation care. Rehabilitation units need to provide education that utilizes a person-centred approach accepting of patients with CI, and focuses on areas that can bolster staff’s positive, dementia-sensitive attitudes. Ultimately, the aim is to create a culture that provides the highest standard of care for all patients, reduces work-related stress, increases job satisfaction, and leads to the highest quality of life for patients during and after rehabilitation.展开更多
The coronavirus(COVID-19)pandemic has caused severe medical emergencies,economic depression,inflation,social distress,and research burden worldwide.Despite the severity of the spreading COVID-19,individual governments...The coronavirus(COVID-19)pandemic has caused severe medical emergencies,economic depression,inflation,social distress,and research burden worldwide.Despite the severity of the spreading COVID-19,individual governments and the World Health Organization have mandated several safety protocols including quarantine,physical distancing,advanced research in decoding the disease mechanism to build an effective vaccine,and promoting mental health to achieve the aim of coping through this infectious pandemic.Around the globe,mental health research emphasizes how social isolation impacts anxiety and depression,however,the cause of mental health depletion due to the type of individual's living accommodation(apartment and house)during a pandemic remains unexplored.The apartments have high elevation and high population density while the houses have low elevation and low population density as they are more spaced apart.This paper presents a novel hypothesis to maintain/enhance individuals’mental health during the pandemic,known as“Modi’s Pandemic Infrastructure Hypothesis”,which suggests that individuals residing in varying living accommodations(i.e.apartment or house)would exhibit a significant difference in the experienced pandemic(i.e.COVID-19)anxiety due to varying amount of experienced“silent stress”.Hence,any type of infrastructure(medical,residential,educational,or corporate)should be designed following the public survey of that geographic area based on hypotheses laid in this paper,to minimize the magnitude of“silent stress”.“Silent stress”can be defined as the stress that is unknowingly experienced in the assimilated living accommodation,which is responsible for depleting individuals’mental health and affecting the ability to cope with the pandemic.In support of this novel hypothesis,previous research has demonstrated that the number of coronavirus per unit area has a positive association with elevation above the ground level while a negative association with the population density.Although the scientific data supports the idea that there would be an equal trade-off in the quantity of coronavirus around an individual in both types of accommodation,however,psychologically the public would perceive it differently.Along with the two key variables(i.e.elevation and population density),other influencing factors would be taken into account while determining the magnitude of silent stress,pandemic anxiety,and the best type of infrastructure.In conclusion,this promising hypothesis will not only help the government to build anxiety-free infrastructure for pandemic times but also increase the effectiveness of medical treatments as mental health and strength is the best medicine to defeat severe diseases.展开更多
Mortality is a well-established patient-important outcome in critical care studies.In contrast,morbidity is less uniformly reported(given the myriad of critical care illnesses and complications of each)but may have a ...Mortality is a well-established patient-important outcome in critical care studies.In contrast,morbidity is less uniformly reported(given the myriad of critical care illnesses and complications of each)but may have a common end-impact on a patient’s functional capacity and health-related quality-of-life(HRQoL).Survival with a poor quality-of-life may not be acceptable depending on individual patient values and preferences.Hence,as mortality decreases within critical care,it becomes increasingly important to measure intensive care unit(ICU)survivor HRQoL.HRQoL measurements with a preference-based scoring algorithm can be converted into health utilities on a scale anchored at 0(representing death)and 1(representing full health).They can be combined with survival to calculate quality-adjusted life-years(QALY),which are one of the most widely used methods of combining morbidity and mortality into a composite outcome.Although QALYs have been use for health-technology assessment decision-making,an emerging and novel role would be to inform clinical decision-making for patients,families and healthcare providers about what expected HRQoL may be during and after ICU care.Critical care randomized control trials(RCTs)have not routinely measured or reported HRQoL(until more recently),likely due to incapacity of some patients to participate in patient-reported outcome measures.Further differences in HRQoL measurement tools can lead to non-comparable values.To this end,we propose the validation of a gold-standard HRQoL tool in critical care,specifically the EQ-5D-5L.Both combined health-utility and mortality(disaggregated)and QALYs(aggregated)can be reported,with disaggregation allowing for determination of which components are the main drivers of the QALY outcome.Increased use of HRQoL,health-utility,and QALYs in critical care RCTs has the potential to:(1)Increase the likelihood of finding important effects if they exist;(2)improve research efficiency;and(3)help inform optimal management of critically ill patients allowing for decision-making about their HRQoL,in additional to traditional health-technology assessments.展开更多
Over the last two decades,the dogma that cell fate is immutable has been increasingly challenged,with important implications for regenerative medicine.The brea kth rough discovery that induced pluripotent stem cells c...Over the last two decades,the dogma that cell fate is immutable has been increasingly challenged,with important implications for regenerative medicine.The brea kth rough discovery that induced pluripotent stem cells could be generated from adult mouse fibroblasts is powerful proof that cell fate can be changed.An exciting extension of the discovery of cell fate impermanence is the direct cellular reprogram ming hypothesis-that terminally differentiated cells can be reprogrammed into other adult cell fates without first passing through a stem cell state.展开更多
Metabolic dysfunction-associated steatotic liver disease is the most prevalent chronic liver condition,affecting over one-third of the global population,with cirrhosis present in up to 3.3%of cases.Early detection of ...Metabolic dysfunction-associated steatotic liver disease is the most prevalent chronic liver condition,affecting over one-third of the global population,with cirrhosis present in up to 3.3%of cases.Early detection of advanced liver disease in at-risk populations can enable timely intervention,prevent progression,and reduce complications.This review focuses on the current recommendations for early detection of advanced liver disease,evaluates the evidence for the performance of non-invasive tests in the target population for screening,and examines the multifaceted burden of screening,including economic implications and psychological impacts.Additionally,we discuss future directions,such as integrating liver health into a multidisciplinary care framework.Current guidelines recommend case-finding,targeting individuals with type 2 diabetes,metabolically complicated obesity,or persistent elevated liver enzymes.The Fibrosis-4 index is widely endorsed as a first-line non-invasive test,yet the diagnostic performance in primary care settings seems suboptimal,particularly for pre-cirrhotic disease.Sequential strategies incorporating novel non-invasive tests may improve accuracy and cost-effectiveness.Confirmation typically involves vibration-controlled transient elastography.Key challenges include a large eligible population,uncertainties in optimal screening intervals,patient adherence to follow-up,and limited real-world cost-effectiveness data.Integrating liver health assessment into cardiometabolic care pathways,reflex testing,telehealth,and patient education may enhance uptake.While challenges remain,early detection of advanced liver disease is already likely cost-effective.Ongoing advances in screening pathways and treatment options are expected to further strengthen the case for widespread implementation.展开更多
BACKGROUND Old donor allografts in liver transplantation(LT)account for 25%of all allografts,and their utilization is projected to increase with the aging general population.Older allografts are associated with higher...BACKGROUND Old donor allografts in liver transplantation(LT)account for 25%of all allografts,and their utilization is projected to increase with the aging general population.Older allografts are associated with higher rates of all-cause mortality and graft failure;however,there is limited literature exploring the specific phenotypic changes(e.g.,functional status,cause-specific mortality)observed in different donor:recipient age pairs.AIM To investigate differences in functional impairment and cause-specific mortality between different donor:recipient age pairs.METHODS This was a retrospective analysis of LT patients from the Scientific Registry of Transplant Recipients from 2002 to 2022.Donors were categorized into younger age donors,≤45-years(YAD),middle-aged donors,46-69-years(MAD),and older age donors,≥70-years(OAD).Recipients were categorized into younger age recipients,≤55-years(YAR)and older age recipients,>55-years(OAR)age recipients.Multivariate Fine-Gray competing risk and logistic regression analyses identified independent risk factors for cause-specific mortality and improvements in functional status,respectively.RESULTS Overall,126185 patients were included in the analysis:YAD:YAR(32.7%), YAD:OAR (25.2%), MAD:YAR (17.5%), MAD:OAR (20.7%), OAD:YAR (1.3%), and OAD:OAR (2.7%). Compared toYAD:YAR, OAD pairs had the lowest likelihoods of improved functional status 5 years post-LT (OAD:YAR oddsratio 0.53, 95% confidence interval 0.42-0.67, P < 0.001;OAD:OAR odds ratio 0.67, 95% confidence interval 0.51-0.89, P = 0.006). Donor:recipient age pairs with older donors had higher rates of graft- and infection-relatedmortality compared to those with younger donors (P < 0.001). Meanwhile, donor:recipient age pairs with olderrecipients had higher cardioneurovascular- or malignancy-related deaths compared to those with youngerrecipients (P < 0.001).CONCLUSIONDonor:recipient age mismatch was associated with differences in cause-specific mortality and functional status.These insights could potentially inform age-matched organ allocation strategies, though future work is warranted.展开更多
Currently,the worldwide prevalence of morbid obesity has increased.1 The National Health and Nutrition Examination Survey from the Centers for Disease Control and Prevention revealed that the prevalence of obesity in ...Currently,the worldwide prevalence of morbid obesity has increased.1 The National Health and Nutrition Examination Survey from the Centers for Disease Control and Prevention revealed that the prevalence of obesity in the adult population between 20 and 74 years old had more than doubled from 13.3%to 31.1%from 1960 to 2002.2 Metabolic and bariatric surgery(MBS)is now suggested for patients with a body mass index(BMI)of more than 35 kg/m^(2),comorbidities or no comorbidities.Furthermore,MBS should be offered to people with metabolic disease and a BMI of 30e34.9 kg/m^(2) who have failed to gain a meaningful amount of weight or have failed to keep it off with non-surgical management.However,the BMI cutoff points should be modified for the Asian population.展开更多
Background The heterogeneity of depression limits the treatment outcomes of intermittent theta burst stimulation(iTBS)and hinders the identification of predictive factors.This study investigated functional network con...Background The heterogeneity of depression limits the treatment outcomes of intermittent theta burst stimulation(iTBS)and hinders the identification of predictive factors.This study investigated functional network connectivity and predictors of iTBS treatment outcomes in adolescents and young adults with depression.Aim This study aimed to identify default mode network(DMN)-based connectivity patterns associated with varying iTBS treatment outcomes in depression.Methods Data from a randomised controlled trial of iTBS in depression(n=82)were analysed using a data-driven approach to classify homogeneous subgroups based on the DMN.Connectivity subgroups were compared on depressive symptoms and cognitive function at pretreatment and post-treatment.Furthermore,the predictive significance of baseline inflammatory cytokines on post-treatment outcomes was evaluated.Results Two distinct subgroups were identified.Subgroup 1 exhibited high heterogeneity and greater centrality in the posterior cingulate cortex and retrosplenial cortex,while subgroup 2 showed more homogeneous connectivity patterns and greater centrality in the temporoparietal junction and posterior inferior parietal lobule.No main effect for subgroup,treatment or subgroup×treatment interaction was revealed in the improvement of depressive symptoms.A significant subgroup×treatment interaction related to symbol coding improvement was detected(F=5.22,p=0.026).Within subgroup 1,the active group showed significantly greater improvement in symbol coding compared with the sham group(t=2.30,p=0.028),while baseline levels of interleukin-6 and C-reactive protein emerged as significant indicators for predicting improvements in symbolic coding(R2=0.35,RMSE(root-mean-square error)=5.72,p=0.013).Subgroup 2 showed no significant findings in terms of cognitive improvement or inflammatory cytokines predictions.展开更多
Liver cirrhosis is a common and growing public health problem globally.The diagnosis of cirrhosis portends an increased risk of morbidity and mortality.Liver biopsy is considered the gold standard for diagnosis of cir...Liver cirrhosis is a common and growing public health problem globally.The diagnosis of cirrhosis portends an increased risk of morbidity and mortality.Liver biopsy is considered the gold standard for diagnosis of cirrhosis and staging of fibrosis.However,despite its universal use,liver biopsy is an invasive and inaccurate gold standard with numerous drawbacks.In order to overcome the limitations of liver biopsy,a number of non-invasive techniques have been investigated for the assessment of cirrhosis.This review will focus on currently available non-invasive markers of cirrhosis.The evidence behind the use of these markers will be highlighted,along with an assessment of diagnostic accuracy and performance characteristics of each test.Non-invasive markers of cirrhosis can be radiologic or serum-based.Radiologic techniques based on ultrasound,magnetic resonance imaging and elastography have been used to assess liver fibrosis.Serum-based biomarkers of cirrhosis have also been developed.These are broadly classified into indirect and direct markers.Indirect biomarkers reflect liver function,which may decline with the onset of cirrhosis.Direct biomarkers,reflect extracellular matrix turnover,and include molecules involved in hepatic fibrogenesis.On the whole,radiologic and serum markers of fibrosis correlate well with biopsy scores,especially when excluding cirrhosis or excluding fibrosis.This feature is certainly clinically useful,and avoids liver biopsy in many cases.展开更多
Non-alcoholic fatty liver disease(NAFLD) is an important health problem worldwide. NAFLD encompasses a histological spectrum ranging from bland liver steatosis to severe steatohepatitis(nonalcoholic steatohepatitis, N...Non-alcoholic fatty liver disease(NAFLD) is an important health problem worldwide. NAFLD encompasses a histological spectrum ranging from bland liver steatosis to severe steatohepatitis(nonalcoholic steatohepatitis, NASH) with the potential of progressing to cirrhosis and its associated morbidity and mortality. NAFLD is thought to be the hepatic manifestation of insulin resistance(or the metabolic syndrome); its prevalence is increasing worldwide in parallel with the obesity epidemic. In many developed countries, NAFLD is the most common cause of liver disease and NASH related cirrhosis is currently the third most common indication for liver transplantation. NASH related cirrhosis is anticipated to become the leading indication for liver transplantation within the next one or two decades. In this review, we discuss how liver transplantation is affected by NAFLD, specifically the following:(1) the increasing need for liver transplantation due to NASH;(2) the impact of the increasing prevalence of NAFLD in the general population on the quality of deceased and live donor livers available for transplantation;(3) the long term graft and patient outcomes after liver transplantation forNASH,and finally;and(4)the de novo occurrence of NAFLD/NASH after liver transplantation and its impact on graft and patient outcomes.展开更多
High intraglomerular pressure is associated with renal hyperf iltration, leading to the initiation and progression of kidney disease in experimental models of diabetes mellitus (DM). In humans, hyperf iltration is obs...High intraglomerular pressure is associated with renal hyperf iltration, leading to the initiation and progression of kidney disease in experimental models of diabetes mellitus (DM). In humans, hyperf iltration is observed in patients with type 1 and type 2 DM, and is also seen in patients with pre-diabetic conditions, such as the metabolic syndrome. From a mechanistic perspective, both vascular and tubular factors likely contribute to the pathogenesis of hyperf iltration. Until now, human studies have primarily focused on the use of medications that inhibit the renin angiotensin system to reduce efferent vasoconstriction and thereby improve hyperfiltration. More recent advances in the development of investigational adenosine antagonists and inhibitors of sodium glucose cotransport may help to elucidate tubular factors that contribute to afferent vasodilatation. In this review, we summarize available data from experimental and human studies of type 1 and type 2 DM and obesity to provide an overview of factors that contribute to the hyperf iltration state. We have focused on the renin angiotensin system, cyclooxygenase-2 system, nitric oxide, protein kinase C and endothelin as vascular determinants of hyperfiltration. We also dis-cuss relevant tubular factors, since experimental models have suggested that inhibition of sodium-glucose cotransport may be renoprotective.展开更多
Non-alcoholic fatty liver disease(NAFLD)ranges from simple steatosis to nonalcoholic steatohepatitis(NASH),leading to fibrosis and potentially cirrhosis,and it is one of the most common causes of liver disease worldwi...Non-alcoholic fatty liver disease(NAFLD)ranges from simple steatosis to nonalcoholic steatohepatitis(NASH),leading to fibrosis and potentially cirrhosis,and it is one of the most common causes of liver disease worldwide.NAFLD is associated with other medical conditions such as metabolic syndrome,obesity,cardiovascular disease and diabetes.NASH can only be diagnosed through liver biopsy,but noninvasive techniques have been developed to identify patients who are most likely to have NASH or fibrosis,reducing the need for liver biopsy and risk to patients.Disease progression varies between individuals and is linked to a number of risk factors.Mechanisms involved in the pathogenesis are associated with diet and lifestyle,influx of free fatty acids to the liver from adipose tissue due to insulin resistance,hepatic oxidative stress,cytokines production,reduced very low-density lipoprotein secretion and intestinal microbiome.Weight loss through improved diet and increased physical activity has been the cornerstone therapy of NAFLD.Recent therapies such as pioglitazone and vitamin E have been shown to be beneficial.Omega 3 polyunsaturated fatty acids and statins may offer additional benefits.Bariatric surgery should be considered in morbidly obese patients.More research is needed to assess the impact of these treatments on a long-term basis.The objective of this article is to briefly review the diagnosis,management and treatment of this disease in order to aid clinicians in managing these patients.展开更多
The intestinal microbiome(IM) is altered in patients with cirrhosis,and emerging literature suggests that this impacts on the development of complications.The Pub Med database was searched from January 2000 to May 201...The intestinal microbiome(IM) is altered in patients with cirrhosis,and emerging literature suggests that this impacts on the development of complications.The Pub Med database was searched from January 2000 to May 2015 for studies and review articles on the composition,pathophysiologic effects and therapeutic modulation of the IM in cirrhosis.The following combination of relevant text words and MeS H terms were used,namely intestinal microbiome,microbiota,or dysbiosis,and cirrhosis,encephalopathy,spontaneous bacterial peritonitis,hepatorenal syndrome,variceal bleeding,hepatopulmonary syndrome,portopulmonary hypertension and hepatocellular carcinoma.The search results were evaluated for pertinence to the subject of IM and cirrhosis,as well as for quality of study design.The IM in cirrhosis is characterized by a decreased proportion of Bacteroides and Lactobacilli,and an increased proportion of Enterobacteriaceae compared to healthy controls.Except for alcoholic cirrhosis,the composition of the IM in cirrhosis is not affected by the etiology of the liver disease.The percentage of Enterobacteriaceae increases with worsening liver disease severity and decompensation and is associated with bacteremia,spontaneous bacterial peritonitis and hepatic encephalopathy.Lactulose,rifaximin and Lactobacillus-containing probiotics have been shown to partial y reverse the cirrhosis associated enteric dysbiosis,in conjunction with improvement in encephalopathy.The IM is altered in cirrhosis,and this may contribute to the development of complications associated with end-stage liver disease.Therapies such as lactulose,rifaximin and probiotics may,at least partially,reverse the cirrhosisassociated changes in the IM.This,in turn,may prevent or alleviate the severity of complications.展开更多
文摘Deep brain stimulation(DBS)is an established therapeutic intervention for people with Parkinson’s disease(PwPD)and is increasingly being utilized for other neurological disorders.Although effective in alleviating motor symptoms and reducing medication requirements,DBS has undergone minimal conceptual evolution and still relies on continuous high-frequency electrical stimulation.In Parkinson’s disease(PD),this persistent stimulation may cause adverse effects,including dysarthria,stimulation-induced dyskinesia,impulsivity,and mood alterations.Additionally,the continuous energy demand of current DBS systems accelerates battery depletion,necessitating more frequent battery charging or battery replacement surgeries,increasing risks,burden,and costs.Basic neuroscience research has long demonstrated that exogenous electrical stimulation can induce persistent changes to synaptic connections,known as long-term plasticity.
文摘AIM To identify the key epigenetically modulated genes and pathways in HCC by performing an integrative meta-analysis of all major, well-annotated and publicly available methylation datasets using tools of network analysis.METHODS Pub Med and Gene Expression Omnibus were searched for genome-wide DNA methylation datasets. Patient clinical and demographic characteristics were obtained. DNA methylation data were integrated using the Ingenuity Pathway Analysis, a software package for visualizing and analyzing biological networks. Pathway enrichment analysis was performed using IPA, which also provides literature-driven and computationallypredicted annotations for significant association of genes to curated molecular pathways.RESULTS From an initial 928 potential abstracts, we identified and analyzed 11 eligible high-throughput methylation datasets representing 354 patients. A significant proportion of studies did not provide concomitant clinical data. In the promoter region, HIST1H2AJ and SPDYA were the most commonly methylated, whereas HRNBP3 gene was the most commonly hypomethylated. ESR1 and ERK were central genes in the principal networks. The pathways most associated with the frequently methylated genes were G-protein coupled receptor and c AMP-mediated signalling. CONCLUSION Using an integrative network-based analysis approach of genome-wide DNA methylation data of both the promoter and body of genes, we identified G-protein coupled receptor signalling as the most highly associated with HCC. This encompasses a diverse range of cancer pathways, such as the PI3 K/Akt/m TOR and Ras/Raf/MAPK pathways, and is therefore supportive of previous literature on gene expression in HCC. However, there are novel targetable genes such as HIST1H2 AJ that are epigenetically modified, suggesting their potential as biomarkers and for therapeutic targeting of the HCC epigenome.
文摘Until recently, older adults with a cognitive impairment (CI) who experienced a hip fracture were filtered from being admitted into active rehabilitation units. The increased complexity of care required for older adults with a CI may negatively influence the attitudes and job satisfaction of healthcare practitioners working with this population. The current study is a part of a larger intervention study allowing patients with CI following a hip fracture access to rehabilitation care and implementing a patient-centred model to facilitate caring for this new population. This new model required a substantial change in the skillset and knowledge of healthcare practitioners. The focus of this study was to explore the impact on the healthcare practitioners of adopting this new model for providing care to older adults with a CI following a hip fracture. The attitudes, dementia knowledge, job satisfaction, and work stress of healthcare practitioners were the focus of evaluation. Key study findings showed that stress due to relationships with coworkers, workloads and scheduling, and the physical design and conditions at work were moderated post-intervention. Staff responses also improved for job satisfaction, biomedical knowledge of dementia, and degree of hopefulness about dementia. Although we cannot state conclusively that the our model was solely responsible for all the staff improvements observed post-intervention, our findings provide further support to the argument that patients with CI should be allowed access to rehabilitation care. Rehabilitation units need to provide education that utilizes a person-centred approach accepting of patients with CI, and focuses on areas that can bolster staff’s positive, dementia-sensitive attitudes. Ultimately, the aim is to create a culture that provides the highest standard of care for all patients, reduces work-related stress, increases job satisfaction, and leads to the highest quality of life for patients during and after rehabilitation.
文摘The coronavirus(COVID-19)pandemic has caused severe medical emergencies,economic depression,inflation,social distress,and research burden worldwide.Despite the severity of the spreading COVID-19,individual governments and the World Health Organization have mandated several safety protocols including quarantine,physical distancing,advanced research in decoding the disease mechanism to build an effective vaccine,and promoting mental health to achieve the aim of coping through this infectious pandemic.Around the globe,mental health research emphasizes how social isolation impacts anxiety and depression,however,the cause of mental health depletion due to the type of individual's living accommodation(apartment and house)during a pandemic remains unexplored.The apartments have high elevation and high population density while the houses have low elevation and low population density as they are more spaced apart.This paper presents a novel hypothesis to maintain/enhance individuals’mental health during the pandemic,known as“Modi’s Pandemic Infrastructure Hypothesis”,which suggests that individuals residing in varying living accommodations(i.e.apartment or house)would exhibit a significant difference in the experienced pandemic(i.e.COVID-19)anxiety due to varying amount of experienced“silent stress”.Hence,any type of infrastructure(medical,residential,educational,or corporate)should be designed following the public survey of that geographic area based on hypotheses laid in this paper,to minimize the magnitude of“silent stress”.“Silent stress”can be defined as the stress that is unknowingly experienced in the assimilated living accommodation,which is responsible for depleting individuals’mental health and affecting the ability to cope with the pandemic.In support of this novel hypothesis,previous research has demonstrated that the number of coronavirus per unit area has a positive association with elevation above the ground level while a negative association with the population density.Although the scientific data supports the idea that there would be an equal trade-off in the quantity of coronavirus around an individual in both types of accommodation,however,psychologically the public would perceive it differently.Along with the two key variables(i.e.elevation and population density),other influencing factors would be taken into account while determining the magnitude of silent stress,pandemic anxiety,and the best type of infrastructure.In conclusion,this promising hypothesis will not only help the government to build anxiety-free infrastructure for pandemic times but also increase the effectiveness of medical treatments as mental health and strength is the best medicine to defeat severe diseases.
基金Supported by the EuroQol Research Foundation,No. 299-RA
文摘Mortality is a well-established patient-important outcome in critical care studies.In contrast,morbidity is less uniformly reported(given the myriad of critical care illnesses and complications of each)but may have a common end-impact on a patient’s functional capacity and health-related quality-of-life(HRQoL).Survival with a poor quality-of-life may not be acceptable depending on individual patient values and preferences.Hence,as mortality decreases within critical care,it becomes increasingly important to measure intensive care unit(ICU)survivor HRQoL.HRQoL measurements with a preference-based scoring algorithm can be converted into health utilities on a scale anchored at 0(representing death)and 1(representing full health).They can be combined with survival to calculate quality-adjusted life-years(QALY),which are one of the most widely used methods of combining morbidity and mortality into a composite outcome.Although QALYs have been use for health-technology assessment decision-making,an emerging and novel role would be to inform clinical decision-making for patients,families and healthcare providers about what expected HRQoL may be during and after ICU care.Critical care randomized control trials(RCTs)have not routinely measured or reported HRQoL(until more recently),likely due to incapacity of some patients to participate in patient-reported outcome measures.Further differences in HRQoL measurement tools can lead to non-comparable values.To this end,we propose the validation of a gold-standard HRQoL tool in critical care,specifically the EQ-5D-5L.Both combined health-utility and mortality(disaggregated)and QALYs(aggregated)can be reported,with disaggregation allowing for determination of which components are the main drivers of the QALY outcome.Increased use of HRQoL,health-utility,and QALYs in critical care RCTs has the potential to:(1)Increase the likelihood of finding important effects if they exist;(2)improve research efficiency;and(3)help inform optimal management of critically ill patients allowing for decision-making about their HRQoL,in additional to traditional health-technology assessments.
基金supported by Canada First Research Excellence Fund,Medicine by Design(to CMM)。
文摘Over the last two decades,the dogma that cell fate is immutable has been increasingly challenged,with important implications for regenerative medicine.The brea kth rough discovery that induced pluripotent stem cells could be generated from adult mouse fibroblasts is powerful proof that cell fate can be changed.An exciting extension of the discovery of cell fate impermanence is the direct cellular reprogram ming hypothesis-that terminally differentiated cells can be reprogrammed into other adult cell fates without first passing through a stem cell state.
文摘Metabolic dysfunction-associated steatotic liver disease is the most prevalent chronic liver condition,affecting over one-third of the global population,with cirrhosis present in up to 3.3%of cases.Early detection of advanced liver disease in at-risk populations can enable timely intervention,prevent progression,and reduce complications.This review focuses on the current recommendations for early detection of advanced liver disease,evaluates the evidence for the performance of non-invasive tests in the target population for screening,and examines the multifaceted burden of screening,including economic implications and psychological impacts.Additionally,we discuss future directions,such as integrating liver health into a multidisciplinary care framework.Current guidelines recommend case-finding,targeting individuals with type 2 diabetes,metabolically complicated obesity,or persistent elevated liver enzymes.The Fibrosis-4 index is widely endorsed as a first-line non-invasive test,yet the diagnostic performance in primary care settings seems suboptimal,particularly for pre-cirrhotic disease.Sequential strategies incorporating novel non-invasive tests may improve accuracy and cost-effectiveness.Confirmation typically involves vibration-controlled transient elastography.Key challenges include a large eligible population,uncertainties in optimal screening intervals,patient adherence to follow-up,and limited real-world cost-effectiveness data.Integrating liver health assessment into cardiometabolic care pathways,reflex testing,telehealth,and patient education may enhance uptake.While challenges remain,early detection of advanced liver disease is already likely cost-effective.Ongoing advances in screening pathways and treatment options are expected to further strengthen the case for widespread implementation.
文摘BACKGROUND Old donor allografts in liver transplantation(LT)account for 25%of all allografts,and their utilization is projected to increase with the aging general population.Older allografts are associated with higher rates of all-cause mortality and graft failure;however,there is limited literature exploring the specific phenotypic changes(e.g.,functional status,cause-specific mortality)observed in different donor:recipient age pairs.AIM To investigate differences in functional impairment and cause-specific mortality between different donor:recipient age pairs.METHODS This was a retrospective analysis of LT patients from the Scientific Registry of Transplant Recipients from 2002 to 2022.Donors were categorized into younger age donors,≤45-years(YAD),middle-aged donors,46-69-years(MAD),and older age donors,≥70-years(OAD).Recipients were categorized into younger age recipients,≤55-years(YAR)and older age recipients,>55-years(OAR)age recipients.Multivariate Fine-Gray competing risk and logistic regression analyses identified independent risk factors for cause-specific mortality and improvements in functional status,respectively.RESULTS Overall,126185 patients were included in the analysis:YAD:YAR(32.7%), YAD:OAR (25.2%), MAD:YAR (17.5%), MAD:OAR (20.7%), OAD:YAR (1.3%), and OAD:OAR (2.7%). Compared toYAD:YAR, OAD pairs had the lowest likelihoods of improved functional status 5 years post-LT (OAD:YAR oddsratio 0.53, 95% confidence interval 0.42-0.67, P < 0.001;OAD:OAR odds ratio 0.67, 95% confidence interval 0.51-0.89, P = 0.006). Donor:recipient age pairs with older donors had higher rates of graft- and infection-relatedmortality compared to those with younger donors (P < 0.001). Meanwhile, donor:recipient age pairs with olderrecipients had higher cardioneurovascular- or malignancy-related deaths compared to those with youngerrecipients (P < 0.001).CONCLUSIONDonor:recipient age mismatch was associated with differences in cause-specific mortality and functional status.These insights could potentially inform age-matched organ allocation strategies, though future work is warranted.
文摘Currently,the worldwide prevalence of morbid obesity has increased.1 The National Health and Nutrition Examination Survey from the Centers for Disease Control and Prevention revealed that the prevalence of obesity in the adult population between 20 and 74 years old had more than doubled from 13.3%to 31.1%from 1960 to 2002.2 Metabolic and bariatric surgery(MBS)is now suggested for patients with a body mass index(BMI)of more than 35 kg/m^(2),comorbidities or no comorbidities.Furthermore,MBS should be offered to people with metabolic disease and a BMI of 30e34.9 kg/m^(2) who have failed to gain a meaningful amount of weight or have failed to keep it off with non-surgical management.However,the BMI cutoff points should be modified for the Asian population.
基金supported by the Guangzhou Municipal Key Discipline in Medicine(2021-2023)the Guangzhou High-level Clinical Key Specialty,the Guangzhou Research-oriented Hospital,the Innovative Clinical Technique of Guangzhou(2024-2026)+6 种基金the Guangdong Basic and Applied Basic Research Foundation(grant number 2022A1515011567,2020A1515110565)the Guangzhou Science,Technology Planning Project(grant number 202201010714,202103000032)the National Natural Science Foundation of China(grant number 82471546)the Guangdong College Students Innovation and Entrepreneurship Training Project(grant number S202310570038)the Guangzhou Health Science and Technology Project(grant number 20231A010038)the Guangzhou Traditional Chinese Medicine and Integrated Traditional Chinese and Western Medicine Technology Project(grant number:20232A010013)the Science and Technology Plan Project of Guangzhou(2023A03J0842).
文摘Background The heterogeneity of depression limits the treatment outcomes of intermittent theta burst stimulation(iTBS)and hinders the identification of predictive factors.This study investigated functional network connectivity and predictors of iTBS treatment outcomes in adolescents and young adults with depression.Aim This study aimed to identify default mode network(DMN)-based connectivity patterns associated with varying iTBS treatment outcomes in depression.Methods Data from a randomised controlled trial of iTBS in depression(n=82)were analysed using a data-driven approach to classify homogeneous subgroups based on the DMN.Connectivity subgroups were compared on depressive symptoms and cognitive function at pretreatment and post-treatment.Furthermore,the predictive significance of baseline inflammatory cytokines on post-treatment outcomes was evaluated.Results Two distinct subgroups were identified.Subgroup 1 exhibited high heterogeneity and greater centrality in the posterior cingulate cortex and retrosplenial cortex,while subgroup 2 showed more homogeneous connectivity patterns and greater centrality in the temporoparietal junction and posterior inferior parietal lobule.No main effect for subgroup,treatment or subgroup×treatment interaction was revealed in the improvement of depressive symptoms.A significant subgroup×treatment interaction related to symbol coding improvement was detected(F=5.22,p=0.026).Within subgroup 1,the active group showed significantly greater improvement in symbol coding compared with the sham group(t=2.30,p=0.028),while baseline levels of interleukin-6 and C-reactive protein emerged as significant indicators for predicting improvements in symbolic coding(R2=0.35,RMSE(root-mean-square error)=5.72,p=0.013).Subgroup 2 showed no significant findings in terms of cognitive improvement or inflammatory cytokines predictions.
文摘Liver cirrhosis is a common and growing public health problem globally.The diagnosis of cirrhosis portends an increased risk of morbidity and mortality.Liver biopsy is considered the gold standard for diagnosis of cirrhosis and staging of fibrosis.However,despite its universal use,liver biopsy is an invasive and inaccurate gold standard with numerous drawbacks.In order to overcome the limitations of liver biopsy,a number of non-invasive techniques have been investigated for the assessment of cirrhosis.This review will focus on currently available non-invasive markers of cirrhosis.The evidence behind the use of these markers will be highlighted,along with an assessment of diagnostic accuracy and performance characteristics of each test.Non-invasive markers of cirrhosis can be radiologic or serum-based.Radiologic techniques based on ultrasound,magnetic resonance imaging and elastography have been used to assess liver fibrosis.Serum-based biomarkers of cirrhosis have also been developed.These are broadly classified into indirect and direct markers.Indirect biomarkers reflect liver function,which may decline with the onset of cirrhosis.Direct biomarkers,reflect extracellular matrix turnover,and include molecules involved in hepatic fibrogenesis.On the whole,radiologic and serum markers of fibrosis correlate well with biopsy scores,especially when excluding cirrhosis or excluding fibrosis.This feature is certainly clinically useful,and avoids liver biopsy in many cases.
文摘Non-alcoholic fatty liver disease(NAFLD) is an important health problem worldwide. NAFLD encompasses a histological spectrum ranging from bland liver steatosis to severe steatohepatitis(nonalcoholic steatohepatitis, NASH) with the potential of progressing to cirrhosis and its associated morbidity and mortality. NAFLD is thought to be the hepatic manifestation of insulin resistance(or the metabolic syndrome); its prevalence is increasing worldwide in parallel with the obesity epidemic. In many developed countries, NAFLD is the most common cause of liver disease and NASH related cirrhosis is currently the third most common indication for liver transplantation. NASH related cirrhosis is anticipated to become the leading indication for liver transplantation within the next one or two decades. In this review, we discuss how liver transplantation is affected by NAFLD, specifically the following:(1) the increasing need for liver transplantation due to NASH;(2) the impact of the increasing prevalence of NAFLD in the general population on the quality of deceased and live donor livers available for transplantation;(3) the long term graft and patient outcomes after liver transplantation forNASH,and finally;and(4)the de novo occurrence of NAFLD/NASH after liver transplantation and its impact on graft and patient outcomes.
基金Supported by A Canadian Diabetes Association-KRESCENT Program Joint New Investigator Awardthe CIHR and the Heart and Stroke Foundation of Canada to Cherney ZID
文摘High intraglomerular pressure is associated with renal hyperf iltration, leading to the initiation and progression of kidney disease in experimental models of diabetes mellitus (DM). In humans, hyperf iltration is observed in patients with type 1 and type 2 DM, and is also seen in patients with pre-diabetic conditions, such as the metabolic syndrome. From a mechanistic perspective, both vascular and tubular factors likely contribute to the pathogenesis of hyperf iltration. Until now, human studies have primarily focused on the use of medications that inhibit the renin angiotensin system to reduce efferent vasoconstriction and thereby improve hyperfiltration. More recent advances in the development of investigational adenosine antagonists and inhibitors of sodium glucose cotransport may help to elucidate tubular factors that contribute to afferent vasodilatation. In this review, we summarize available data from experimental and human studies of type 1 and type 2 DM and obesity to provide an overview of factors that contribute to the hyperf iltration state. We have focused on the renin angiotensin system, cyclooxygenase-2 system, nitric oxide, protein kinase C and endothelin as vascular determinants of hyperfiltration. We also dis-cuss relevant tubular factors, since experimental models have suggested that inhibition of sodium-glucose cotransport may be renoprotective.
文摘Non-alcoholic fatty liver disease(NAFLD)ranges from simple steatosis to nonalcoholic steatohepatitis(NASH),leading to fibrosis and potentially cirrhosis,and it is one of the most common causes of liver disease worldwide.NAFLD is associated with other medical conditions such as metabolic syndrome,obesity,cardiovascular disease and diabetes.NASH can only be diagnosed through liver biopsy,but noninvasive techniques have been developed to identify patients who are most likely to have NASH or fibrosis,reducing the need for liver biopsy and risk to patients.Disease progression varies between individuals and is linked to a number of risk factors.Mechanisms involved in the pathogenesis are associated with diet and lifestyle,influx of free fatty acids to the liver from adipose tissue due to insulin resistance,hepatic oxidative stress,cytokines production,reduced very low-density lipoprotein secretion and intestinal microbiome.Weight loss through improved diet and increased physical activity has been the cornerstone therapy of NAFLD.Recent therapies such as pioglitazone and vitamin E have been shown to be beneficial.Omega 3 polyunsaturated fatty acids and statins may offer additional benefits.Bariatric surgery should be considered in morbidly obese patients.More research is needed to assess the impact of these treatments on a long-term basis.The objective of this article is to briefly review the diagnosis,management and treatment of this disease in order to aid clinicians in managing these patients.
文摘The intestinal microbiome(IM) is altered in patients with cirrhosis,and emerging literature suggests that this impacts on the development of complications.The Pub Med database was searched from January 2000 to May 2015 for studies and review articles on the composition,pathophysiologic effects and therapeutic modulation of the IM in cirrhosis.The following combination of relevant text words and MeS H terms were used,namely intestinal microbiome,microbiota,or dysbiosis,and cirrhosis,encephalopathy,spontaneous bacterial peritonitis,hepatorenal syndrome,variceal bleeding,hepatopulmonary syndrome,portopulmonary hypertension and hepatocellular carcinoma.The search results were evaluated for pertinence to the subject of IM and cirrhosis,as well as for quality of study design.The IM in cirrhosis is characterized by a decreased proportion of Bacteroides and Lactobacilli,and an increased proportion of Enterobacteriaceae compared to healthy controls.Except for alcoholic cirrhosis,the composition of the IM in cirrhosis is not affected by the etiology of the liver disease.The percentage of Enterobacteriaceae increases with worsening liver disease severity and decompensation and is associated with bacteremia,spontaneous bacterial peritonitis and hepatic encephalopathy.Lactulose,rifaximin and Lactobacillus-containing probiotics have been shown to partial y reverse the cirrhosis associated enteric dysbiosis,in conjunction with improvement in encephalopathy.The IM is altered in cirrhosis,and this may contribute to the development of complications associated with end-stage liver disease.Therapies such as lactulose,rifaximin and probiotics may,at least partially,reverse the cirrhosisassociated changes in the IM.This,in turn,may prevent or alleviate the severity of complications.
