The inability to access brain tissue has greatly hindered our ability to study and care for individuals suffering from psychiatric and neurological conditions.Critics have questioned efforts to develop peripheral bloo...The inability to access brain tissue has greatly hindered our ability to study and care for individuals suffering from psychiatric and neurological conditions.Critics have questioned efforts to develop peripheral blood biomarkers in neurological and psychiatric disorders based on the assertion that disease pathology is limited to the brain.The discovery that all tissues,including the brain,release extracellular vesicles(Raposo and Stoorvogel,2013)and cell free DNAs(Chan et al.,2013)into various body fluids has provided a potential way to measure activity from inaccessible tissues like the central nervous system(CNS)and has given rise to the term“liquid biopsy.”The development of liquid biopsies that can diagnose and predict the course of psychiatric and neurological disorders would be transformative.The ability to predict episodic events such as mania,depression,and risk for suicide would be particularly useful for psychiatric care as it would enable the development of interventions that prevent mortality and improve outcomes.Additionally,biomarkers that are informative about drug response and aid in treatment decisions would be a significant advance in psychiatric care as it would prevent patients from having to endure multiple courses of ineffective treatments and side effects.展开更多
N umerous neurological disorders negatively impact the nervous system,either through loss of neurons or by disrupting the normal functioning of neural networks.These impairments manifest as cognitive defects,memory lo...N umerous neurological disorders negatively impact the nervous system,either through loss of neurons or by disrupting the normal functioning of neural networks.These impairments manifest as cognitive defects,memory loss,behavioral abnormalities,and motor dysfunctions.Decades of research have significantly advanced our understanding of the pathophysiology underlying neurodegene rative diseases,including Alzheimer's disease(AD),Parkinson's disease,amyotrophic lateral sclerosis,and others.展开更多
Obese individuals who subsequently sustain a traumatic brain injury(TBI)exhibit worsened outcomes including longer periods of rehabilitation(Eagle et al.,2023).In obese individuals,prolonged symptomology is associated...Obese individuals who subsequently sustain a traumatic brain injury(TBI)exhibit worsened outcomes including longer periods of rehabilitation(Eagle et al.,2023).In obese individuals,prolonged symptomology is associated with increased levels of circulato ry pro-inflammatory marke rs up to 1 year postTBI(Eagle et al.,2023).展开更多
Pancreatic cysts are mostly incidental findings on computed tomography or magnetic resonance imaging scans,with few patients presenting with abdominal pain or other symptoms.The accurate diagnosis of cysts is importan...Pancreatic cysts are mostly incidental findings on computed tomography or magnetic resonance imaging scans,with few patients presenting with abdominal pain or other symptoms.The accurate diagnosis of cysts is important as management depends on the type(neoplastic or non-neoplastic).Cross-sectional imaging is fast being replaced with endoscopic ultrasound(EUS)and various techniques based on that such as EUS-guided fine needle aspiration,EUS-guided needle confocal laser endomicroscopy,EUS-through-the-needle biopsy,and contrast-enhanced EUS.Clinical studies have reported varying diagnostic and adverse event rates with these modalities.In addition,American,European,and Kyoto guidelines for the diagnosis and management of pancreatic cysts have provided different recommendations.In this editorial,we elaborate on the clinical guidelines,recent studies,and comparison of different endoscopic methods for the diagnosis of pancreatic cysts.展开更多
Background:We aimed to study physician attitudes toward ultrasound-guided procedures and possible improvements.We hypothesized that the usage of ultrasound in procedures may be limited by a high barrier of entry and t...Background:We aimed to study physician attitudes toward ultrasound-guided procedures and possible improvements.We hypothesized that the usage of ultrasound in procedures may be limited by a high barrier of entry and that most physicians would choose to adopt software that provides real-time image guidance if accessible.Methods:A voluntary,cross-sectional survey of physicians at a single site was conducted using a five-point Likert scale.Data analysis included both descriptive and inferential statistical analyses and stratified by categorical descriptors,including variables of formal training,years of experience,and specialty of practice.Results:One hundred sixteen physicians responded to the survey.The majority disagreed that there was a steep learning curve(57.5%)and that they need more time to identify structures under ultrasound(85.0%).Overall attitudes were mixed about the use of additional software to improve ease of use,but most(55.4%)had positive opinions toward the addition of real-time 3D reconstruction.Respondents without formal training were significantly more likely to agree that additional software would improve ease of ultrasound-guided procedures(p=0.0389).Radiologists were significantly more likely to perceive a steeper learning curve and less likely to advocate for supplemental software compared to emergency medicine physicians,surgeons,or anesthesiologists.Conclusions:Surveyed physicians demonstrated comfort with ultrasound-guided procedures and a mixed stance toward the use of additional software to assist with procedures.Those without formal training had significantly more positive attitudes toward the use of additional technology to augment ultrasound-guided procedures,suggesting a knowledge gap that may benefit from such technology.展开更多
BACKGROUND Acute liver failure(ALF)is a life-threatening multisystemic condition with high short-term mortality.With the growing prevalence of obesity and metabolic syndrome,it is important to investigate the clinical...BACKGROUND Acute liver failure(ALF)is a life-threatening multisystemic condition with high short-term mortality.With the growing prevalence of obesity and metabolic syndrome,it is important to investigate the clinical implications of high body mass index(BMI)on survival outcomes in ALF.AIM To explore the impact of overweight and obesity on the clinical outcomes of patients with ALF.METHODS A retrospective observational cohort study was conducted involving patients with ALF admitted to the Johns Hopkins Health System between January 1,2000 and May 1,2020.We performed Cox proportional hazards regression to identify outcomes,including the need for liver transplantation(LT)or all-cause mortality.RESULTS A total of 196 patients were included,the median age was 43.5 years,63.3%were female,and 59.7%were of Caucasian ethnicity.Acetaminophen-induced ALF was the most common etiology(45%).The mean BMI was significantly greater among patients who underwent LT or died(29.64 kg/m^(2)vs 26.59 kg/m^(2),P=0.008)than among survivors.Patients with overweight and obesity had a higher risk of all-cause mortality or need for LT by 2.22-fold(95%CI:1.30-3.78)and 2.04-fold(95%CI:1.29-3.39),respectively.Elevated BMI was associated with renal failure and higher grades of hepatic encephalopathy.Derangements in serologic markers,including alanine transaminase,lactate,and ammonia,were associated with a mortality risk or need for LT.CONCLUSION In this large,retrospective study,with a diverse cohort of United States patients,Overweight and obese were independently associated with an increased risk of all-cause mortality or need for LT.This work highlights the importance of closely monitoring ALF patients who are overweight or obese for adverse complications and measures to improve outcomes in this vulnerable patient population.展开更多
Traumatic spinal cord injury(SCI)is a devastating exogenous injury with long-lasting consequences and a leading cause of death and disability worldwide.Advances in assistive technology,rehabilitative interventions,and...Traumatic spinal cord injury(SCI)is a devastating exogenous injury with long-lasting consequences and a leading cause of death and disability worldwide.Advances in assistive technology,rehabilitative interventions,and the ability to identify and intervene in secondary conditions have significantly increased the long-term survival rate of SCI patients,with some people even living well into their seventh or eighth decade.These survival changes have led neurotrauma researchers to examine how SCI interacts with brain aging.Public health and epidemiological data showed that patients with long-term SCI can have a lower life expectancy and quality of life,along with a higher risk of comorbidities and complications.展开更多
BACKGROUND To prevent mother to child transmission(MTCT)of human immunodeficiency virus(HIV),sustained maternal viral load suppression(VLS)and early HIV testing among HIV exposed infants(HEI)is critical.AIM To investi...BACKGROUND To prevent mother to child transmission(MTCT)of human immunodeficiency virus(HIV),sustained maternal viral load suppression(VLS)and early HIV testing among HIV exposed infants(HEI)is critical.AIM To investigate maternal viral load results and infant HIV testing uptake at 6-weeks,and 9-months and 18-months in Rwanda.METHODS Between 2015 and 2022,VLS(<200 copies/mL)was measured among pregnant women living with HIV(WLHIV)from 38-healthcare facilities.Viral loads(VL)were measured at 6-months,12-months and 24-months,respectively.For maternal VL,the unit of analysis was visit-pair,and the pairs were created to define those with VL<200 copies/mL at two consecutive visits as having sustained VLS,persistent viremia(VL≥200 copies/mL at two consecutive visits),viral rebound(VL<200 copies/mL at prior visit only)and newly suppressed(VL<200 copies/mL at subsequent visit only).HEI were considered to have persistent HIV testing if they had all three HIV tests.Poisson regression models with generalized estimating equations were used to estimate the adjusted incidence rate ratio(aIRR)and 95%CI for factors associated with sustained VLS and persistent HIV testing.RESULTS A total of 1145 mother-infant pairs were analyzed.Infant HIV testing uptake at 6-weeks,9-months and 18-months was 1145(100.0%),1089(95.1%),1006(87.9%)respectively.Nine hundred ninety-nine HEI(87.3%)tested for HIV persistently.At 18-months,the incidence of HIV among HEI was 8(0.7%).Of 1145 mothers,1076(94.0%)had≥2 VL results making a total of 2010 visit-pairs(142-single;934-double visit-pairs).The incidence rate of sustained VLS,persistent viremia,viral rebound and new suppression were 91.0%,1.3%,3.6%and 4.0%respectively.Maternal disclosure of HIV status(aIRR=1.08,95%CI:1.02-1.14)was associated with increased likelihood of sustained VLS.Having peer support(aIRR=1.0595%CI:1.01-1.10)was associated with persistent HIV testing among HEI.CONCLUSION Sustained VLS is high among pregnant WLHIV in Rwanda.The low incidence of HIV among HEI may be attributed to high VLS levels.Targeted interventions,including enhanced HIV disclosure and peer support,are crucial for improving sustained VLS and increasing infant HIV testing uptake to reduce MTCT.展开更多
Objectives:Teachers are facing unprecedented new challenges leading them to face an increasing number of tasks that are not part of their job,as well as having to cope with the additional skills acquisition that comes...Objectives:Teachers are facing unprecedented new challenges leading them to face an increasing number of tasks that are not part of their job,as well as having to cope with the additional skills acquisition that comes with non-traditional forms of teaching and learning,and increased work pressure leading to an increase in the rate of teachers leaving the profession.Therefore,this study aims to explore the mechanism of the career calling on job burnout through career adaptability and work engagement.Methods:This study conducted a cross-sectional survey of 465 primary and secondary school teachers(PSST)in China's Mainland from the perspective of work adjustment and used structural equation modeling(SEM)to examine the mediating roles of career adaptability and work engagement in the relationship between teachers’career calling and job burnout.Results:The results show that PSSTs are above average in career calling,career adaptability,and work engagement,while job burnout is below average.A significant positive or negative correlation exists between career calling,career adaptability,work engagement,and job burnout.The result of path analysis indicates that career adaptability and work engagement exert an indirect influence on the job burnout of PSST through three paths:namely,the independent intermediary role of career adaptability(EV=−0.144),the independent intermediary role of work engagement(EV=0.172)and the chain intermediary role of the two(EV=0.176).Conclusion:This study emphasizes the importance of career adaptability and work engagement in teacher development in regulating career calling and job burnout.Therefore,on the one hand,we think that if managers want to reduce teachers’job burnout,they need to pay more attention to teachers’career adaptability and work engagement,rather than relying solely on teachers’career calling.On the other hand,it is to remind teachers not to rely on their adjustment to adapt to the work,but also to need outside help as much as possible.展开更多
Dear Editor,Space flight(SF)is substantially increasing at present.The emergence of commercial suborbital SF,such as the Virgin Galactic with VSS Unity and VMS Eve spacecraft,is extending to civilians,being previously...Dear Editor,Space flight(SF)is substantially increasing at present.The emergence of commercial suborbital SF,such as the Virgin Galactic with VSS Unity and VMS Eve spacecraft,is extending to civilians,being previously confined to military and/or professional astronauts only.This new evidence offers additional opportunities for better characterizing the impact that the transition from Earth’s 1G to microgravity in space could have on the astronauts’health while comparing well-trained subjects such as the latt er to space newcomers[1].展开更多
Neurons are highly polarized,morphologically asymmetric,and functionally compartmentalized cells that contain long axons extending from the cell body.For this reason,their maintenance relies on spatiotemporal regulati...Neurons are highly polarized,morphologically asymmetric,and functionally compartmentalized cells that contain long axons extending from the cell body.For this reason,their maintenance relies on spatiotemporal regulation of organelle distribution between the somatodendritic and axonal domains.Although some organelles,such as mitochondria and smooth endoplasmic reticulum,are widely distributed throughout the neuron,others are segregated to either the somatodendritic or axonal compartment.For example,Golgi outposts and acidified lysosomes are predominantly present in the somatodendritic domain and rarely distributed along the axon,whereas newly formed autophagosomes and synaptic vesicles are mainly distributed in the distal axon(Britt et al.,2016).展开更多
Alzheimer's disease (AD) is characterized by an imbalance between excitatory and inhibitory brain networks,leading to aberrant homeostatic synaptic plasticity.AD has progressively been recognized as syna ptopathy ...Alzheimer's disease (AD) is characterized by an imbalance between excitatory and inhibitory brain networks,leading to aberrant homeostatic synaptic plasticity.AD has progressively been recognized as syna ptopathy and syna ptic dysfunction has been identified as a key component of its pathogenesis (Schirinzi et al.,2020).Syna ptic dysfunction is believed to precede synapse loss,a primary biological correlate of cognitive decline in AD,inevita bly associated with neuronal death.展开更多
Peripheral neuropathy is a common complication in diabetes,affecting around 50%of the diabetic population.Co-occurrence of diabetic peripheral neuropathy(DPN)and diabetic bone disease has led to the hypothesis that DP...Peripheral neuropathy is a common complication in diabetes,affecting around 50%of the diabetic population.Co-occurrence of diabetic peripheral neuropathy(DPN)and diabetic bone disease has led to the hypothesis that DPN influences bone metabolism,although little experimental evidence has yet supported this premise.To investigate,mice were fed a high-fat diet(HFD)followed by phenotyping of skeletal-innervating neurons and bone architectural parameters.Results showed that HFD feeding resulted in a marked decrease in skeletal innervation(69%–41%reduction in Beta-III-Tubulin-stained nerves,38%reduction in CGRP-stained nerves in long bone periosteum).展开更多
Calvarial nerves,along with vasculature,influence skull formation during development and following injury,but it remains unclear how calvarial nerves are spatially distributed during postnatal growth and aging.Studyin...Calvarial nerves,along with vasculature,influence skull formation during development and following injury,but it remains unclear how calvarial nerves are spatially distributed during postnatal growth and aging.Studying the spatial distribution of nerves in the skull remains a challenge due to a lack of methods to quantify 3D structures in intact bone.To visualize calvarial 3D neurovascular architecture,we imaged nerves and endothelial cells with lightsheet microscopy.展开更多
Extracorporeal membrane oxygenation(ECMO)has emerged as a vital circulatory life support measure for patients with critical cardiac or pulmonary conditions unresponsive to conventional therapies.ECMO allows blood to b...Extracorporeal membrane oxygenation(ECMO)has emerged as a vital circulatory life support measure for patients with critical cardiac or pulmonary conditions unresponsive to conventional therapies.ECMO allows blood to be extracted from a patient and introduced to a machine that oxygenates blood and removes carbon dioxide.This blood is then reintroduced into the patient’s circulatory system.This process makes ECMO essential for treating various medical conditions,both as a standalone therapy and as adjuvant therapy.Veno-venous(VV)ECMO primarily supports respiratory function and indicates respiratory distress.Simultaneously,veno-arterial(VA)ECMO provides hemodynamic and respiratory support and is suitable for cardiac-related complications.This study reviews recent literature to elucidate the evolving role of ECMO in trauma care,considering its procedural intricacies,indications,contraindications,and associated complications.Notably,the use of ECMO in trauma patients,particularly for acute respiratory distress syndrome and cardiogenic shock,has demonstrated promising outcomes despite challenges such as anticoagulation management and complications such as acute kidney injury,bleeding,thrombosis,and hemolysis.Some studies have shown that VV ECMO was associated with significantly higher survival rates than conventional mechanical ventilation,whereas other studies have reported that VA ECMO was associated with lower survival rates than VV ECMO.ECMO plays a critical role in managing trauma patients,particularly those with acute respiratory failure.Further research is necessary to explore the full potential of ECMO in trauma care.Clinicians should have a clear understanding of the indications and contraindications for the use of ECMO to maximize its benefits in treating trauma patients.展开更多
Chronic pain after spine surgery(CPSS)is a complex disorder characterized by multifactorial pathogenesis that occurs in 8%–40%of patients undergoing lumbar spine surgery.We aimed to develop a rat model that mimics cl...Chronic pain after spine surgery(CPSS)is a complex disorder characterized by multifactorial pathogenesis that occurs in 8%–40%of patients undergoing lumbar spine surgery.We aimed to develop a rat model that mimics clinical CPSS conditions by taking two sequential surgical procedures.Step 1:A plastic rod was inserted into the left L5 intervertebral foramen to produce a steady compression on the dorsal root ganglion(DRG)and the spinal nerve,a common cause of low back pain(LBP).Step 2:The rod was removed after 7 days when rats exhibited mechanical and heat hypersensitivity in the ipsilateral hindpaw,followed by a full L5 laminectomy to mimic spine decompression surgery in LBP patients.The retention of the rod induced a prolonged LBP-like behavior but was quickly resolved after rod removal without laminectomy.However,rats that received laminectomy after rod removal developed heightened mechanical and heat sensitivity in the hindpaw,impaired gait,and reduced spontaneous exploration activity,indicating CPSS.Patch clamp recording revealed a significant augmentation in the intrinsic excitability of smalldiameter DRG neurons in CPSS rats.Administration of Dermorphin[D-Arg2,Lys4](1–4)amide(DALDA,5mg/kg,i.p.),a peripherally acting mu-opioid receptor(MOR)-preferred agonist,attenuated pain hypersensitivity,capsaicin-induced[Ca^(2+)]i rising and the increased intrinsic excitability of DRG neurons from CPSS rats.Our findings suggest that this new model,which mirrors the nature of CPSS developed in patients,may be useful for future studies of the underlying mechanisms.展开更多
Background:This essay examines how nineteenth-century Anglo-American physicians and scientists constructed racial hierarchies through theories of pain insensitivity,advancing the notion of“organic insensibility”to p...Background:This essay examines how nineteenth-century Anglo-American physicians and scientists constructed racial hierarchies through theories of pain insensitivity,advancing the notion of“organic insensibility”to pathologize the bodies-particularly the crania,epidermis,and reproductive organs-of American Indians,African Americans,and East Asians.Methods:Drawing on medical texts,ethnographic accounts,and the writings of proslavery and colonial ideologues,the essay explores how perceptions of diminished pain sensitivity were used to justify settler colonialism,slavery,and imperialism from the period of Indian Removal to the expansion of the Cotton Kingdom and the Opium Wars.Results:Practices such as cranial deformation,parturient pain,surgical endurance,skin experiments,and foot binding,were racialized to support claims of biological inferiority and moral deficiency.Conclusion:Integrating insights from the history and philosophy of science and medicine,and phenomenology,the essay demonstrates how pain was not only a medical concern but a political feeling-central to the denial of full humanity to racialized populations.展开更多
Inflammatory bowel disease(IBD),encompassing Crohn's disease and ulcerative colitis,is a chronic condition marked by recurring gastrointestinal inflammation.While immune,genetic,and environmental factors are well-...Inflammatory bowel disease(IBD),encompassing Crohn's disease and ulcerative colitis,is a chronic condition marked by recurring gastrointestinal inflammation.While immune,genetic,and environmental factors are well-studied,the gut virome has received less attention.This editorial highlights the work which investigates the gut virome’s role in IBD and its interactions with the bacterial microbiome and host immune system.The gut virome consists of bacteriophages,eukaryotic viruses,and endogenous retroviruses.Among these,Caudovirales bacteriophages are predominant and influence bacterial communities via lysogenic and lytic cycles.Eukaryotic viruses infect host cells directly,while endogenous retroviruses impact gene regulation and immune responses.In IBD,the virome shows distinct alterations,including an increased abundance of Caudovirales phages and reduced Microviridae diversity,suggesting a pro-inflammatory viral environment.Dysbiosis,chronic inflammation,and aberrant immune responses contribute to these changes by disrupting microbial communities and modifying virome composition.Phages affect bacterial dynamics through lysis,lysogeny,and horizontal gene transfer,shaping microbial adaptability and resilience.Understanding these interactions is crucial for identifying novel therapeutic targets and restoring microbial balance in IBD.展开更多
Background:Traditional imaging approaches to keratoconus(KCN)have thus far failed to produce a standardized approach for diagnosis.While many diagnostic modalities and metrics exist,none have proven robust enough to b...Background:Traditional imaging approaches to keratoconus(KCN)have thus far failed to produce a standardized approach for diagnosis.While many diagnostic modalities and metrics exist,none have proven robust enough to be considered a gold standard.This study aims to introduce novel metrics to differentiate between KCN and healthy corneas using three-dimensional(3D)measurements of surface area and volume.Methods:This retrospective observational study examined KCN patients along with healthy control patients between the ages of 20 and 79 years old at the University of Maryland,Baltimore.The selected patients underwent a nine-line raster scan anterior segment optical coherence tomography(AS-OCT).ImageJ was used to determine the central 6 mm of each image and each corneal image was then divided into six 1 mm segments.Free-D software was then used to render the nine different images into a 3D model to calculate corneal surface area and volume.A two-tailed Mann-Whitney test was used to assess statistical significance when comparing these subsets.Results:Thirty-three eyes with KCN,along with 33 healthy control,were enrolled.There were statistically significant differences between the healthy and KCN groups in the metric of anterior corneal surface area(13.927 vs.13.991 mm^(2),P=0.046),posterior corneal surface area(14.045 vs.14.173 mm^(2),P<0.001),and volume(8.430 vs.7.773 mm3,P<0.001)within the central 6 mm.Conclusions:3D corneal models derived from AS-OCT can be used to measure anterior corneal surface area,posterior corneal surface area,and corneal volume.All three parameters are statistically different between corneas with KCN and healthy corneas.Further study and application of these parameters may yield new methodologies for the detection of KCN.展开更多
The resting zone(RZ)in mammalian growth plates is critical for maintaining and regulating chondrocyte turnover during longitudinal bone growth as a control tower and stem cell reservoir.Although recent lineage tracing...The resting zone(RZ)in mammalian growth plates is critical for maintaining and regulating chondrocyte turnover during longitudinal bone growth as a control tower and stem cell reservoir.Although recent lineage tracing studies have identified several markers for stem cells in the RZ,these markers only partially label chondrocytes in the RZ,suggesting that the resting chondrocytes(RCs)are a heterogeneous population with different types of stem cells.Since a comprehensive marker for RCs is still lacking,the RZ is generally determined based on ambiguous histological criteria,such as small and round chondrocytes without columnar formation,which may lead to inconsistencies among researchers.Therefore,in this study,we used single-cell RNA sequencing(scRNAseq)of growth plate chondrocytes followed by validation by fluorescence in situ hybridization(FISH)to precisely annotate cell clusters in scRNAseq and search for a marker of RCs.The scRNAseq analysis revealed that apolipoprotein E(Apoe)was the tophit gene,which was ubiquitously expressed in the RC cluster.FISH confirmed that Apoe was exclusively localized to the histologically defined RZ.In newly generated Apoe^(mCherry)knock-in mice,we further confirmed that mCherry expression mirrored the distribution of Apoe-expressing chondrocytes in the RZ particularly after the formation of the secondary ossification center.These mCherry+RCs were slow cycling in vivo and exhibited stem cell properties in vitro.Moreover,APOE was detected in human growth plate RCs.These findings suggest that apolipoprotein E is a novel pan-RC marker in both mouse and human growth plates.展开更多
基金supported by Department of Defense grant HT9425-24-1-0030 a grant from the Stanley Medical Research Institute(to SS).
文摘The inability to access brain tissue has greatly hindered our ability to study and care for individuals suffering from psychiatric and neurological conditions.Critics have questioned efforts to develop peripheral blood biomarkers in neurological and psychiatric disorders based on the assertion that disease pathology is limited to the brain.The discovery that all tissues,including the brain,release extracellular vesicles(Raposo and Stoorvogel,2013)and cell free DNAs(Chan et al.,2013)into various body fluids has provided a potential way to measure activity from inaccessible tissues like the central nervous system(CNS)and has given rise to the term“liquid biopsy.”The development of liquid biopsies that can diagnose and predict the course of psychiatric and neurological disorders would be transformative.The ability to predict episodic events such as mania,depression,and risk for suicide would be particularly useful for psychiatric care as it would enable the development of interventions that prevent mortality and improve outcomes.Additionally,biomarkers that are informative about drug response and aid in treatment decisions would be a significant advance in psychiatric care as it would prevent patients from having to endure multiple courses of ineffective treatments and side effects.
基金supported by the National Institute on Aging(Nos.AG000723 and AG000578)(to VAB)the Fondation Sante(No.19656),Greece 2.0+1 种基金the National Recovery and Resilience Plan’s flagship program TAEDR-0535850the European Research Council(No.101077374-Synapto Mitophagy)(to KP)。
文摘N umerous neurological disorders negatively impact the nervous system,either through loss of neurons or by disrupting the normal functioning of neural networks.These impairments manifest as cognitive defects,memory loss,behavioral abnormalities,and motor dysfunctions.Decades of research have significantly advanced our understanding of the pathophysiology underlying neurodegene rative diseases,including Alzheimer's disease(AD),Parkinson's disease,amyotrophic lateral sclerosis,and others.
文摘Obese individuals who subsequently sustain a traumatic brain injury(TBI)exhibit worsened outcomes including longer periods of rehabilitation(Eagle et al.,2023).In obese individuals,prolonged symptomology is associated with increased levels of circulato ry pro-inflammatory marke rs up to 1 year postTBI(Eagle et al.,2023).
文摘Pancreatic cysts are mostly incidental findings on computed tomography or magnetic resonance imaging scans,with few patients presenting with abdominal pain or other symptoms.The accurate diagnosis of cysts is important as management depends on the type(neoplastic or non-neoplastic).Cross-sectional imaging is fast being replaced with endoscopic ultrasound(EUS)and various techniques based on that such as EUS-guided fine needle aspiration,EUS-guided needle confocal laser endomicroscopy,EUS-through-the-needle biopsy,and contrast-enhanced EUS.Clinical studies have reported varying diagnostic and adverse event rates with these modalities.In addition,American,European,and Kyoto guidelines for the diagnosis and management of pancreatic cysts have provided different recommendations.In this editorial,we elaborate on the clinical guidelines,recent studies,and comparison of different endoscopic methods for the diagnosis of pancreatic cysts.
文摘Background:We aimed to study physician attitudes toward ultrasound-guided procedures and possible improvements.We hypothesized that the usage of ultrasound in procedures may be limited by a high barrier of entry and that most physicians would choose to adopt software that provides real-time image guidance if accessible.Methods:A voluntary,cross-sectional survey of physicians at a single site was conducted using a five-point Likert scale.Data analysis included both descriptive and inferential statistical analyses and stratified by categorical descriptors,including variables of formal training,years of experience,and specialty of practice.Results:One hundred sixteen physicians responded to the survey.The majority disagreed that there was a steep learning curve(57.5%)and that they need more time to identify structures under ultrasound(85.0%).Overall attitudes were mixed about the use of additional software to improve ease of use,but most(55.4%)had positive opinions toward the addition of real-time 3D reconstruction.Respondents without formal training were significantly more likely to agree that additional software would improve ease of ultrasound-guided procedures(p=0.0389).Radiologists were significantly more likely to perceive a steeper learning curve and less likely to advocate for supplemental software compared to emergency medicine physicians,surgeons,or anesthesiologists.Conclusions:Surveyed physicians demonstrated comfort with ultrasound-guided procedures and a mixed stance toward the use of additional software to assist with procedures.Those without formal training had significantly more positive attitudes toward the use of additional technology to augment ultrasound-guided procedures,suggesting a knowledge gap that may benefit from such technology.
文摘BACKGROUND Acute liver failure(ALF)is a life-threatening multisystemic condition with high short-term mortality.With the growing prevalence of obesity and metabolic syndrome,it is important to investigate the clinical implications of high body mass index(BMI)on survival outcomes in ALF.AIM To explore the impact of overweight and obesity on the clinical outcomes of patients with ALF.METHODS A retrospective observational cohort study was conducted involving patients with ALF admitted to the Johns Hopkins Health System between January 1,2000 and May 1,2020.We performed Cox proportional hazards regression to identify outcomes,including the need for liver transplantation(LT)or all-cause mortality.RESULTS A total of 196 patients were included,the median age was 43.5 years,63.3%were female,and 59.7%were of Caucasian ethnicity.Acetaminophen-induced ALF was the most common etiology(45%).The mean BMI was significantly greater among patients who underwent LT or died(29.64 kg/m^(2)vs 26.59 kg/m^(2),P=0.008)than among survivors.Patients with overweight and obesity had a higher risk of all-cause mortality or need for LT by 2.22-fold(95%CI:1.30-3.78)and 2.04-fold(95%CI:1.29-3.39),respectively.Elevated BMI was associated with renal failure and higher grades of hepatic encephalopathy.Derangements in serologic markers,including alanine transaminase,lactate,and ammonia,were associated with a mortality risk or need for LT.CONCLUSION In this large,retrospective study,with a diverse cohort of United States patients,Overweight and obese were independently associated with an increased risk of all-cause mortality or need for LT.This work highlights the importance of closely monitoring ALF patients who are overweight or obese for adverse complications and measures to improve outcomes in this vulnerable patient population.
基金supported by NIH funding(RF1NS110637,2RF1NS094527,R01NS110635)to JW.
文摘Traumatic spinal cord injury(SCI)is a devastating exogenous injury with long-lasting consequences and a leading cause of death and disability worldwide.Advances in assistive technology,rehabilitative interventions,and the ability to identify and intervene in secondary conditions have significantly increased the long-term survival rate of SCI patients,with some people even living well into their seventh or eighth decade.These survival changes have led neurotrauma researchers to examine how SCI interacts with brain aging.Public health and epidemiological data showed that patients with long-term SCI can have a lower life expectancy and quality of life,along with a higher risk of comorbidities and complications.
文摘BACKGROUND To prevent mother to child transmission(MTCT)of human immunodeficiency virus(HIV),sustained maternal viral load suppression(VLS)and early HIV testing among HIV exposed infants(HEI)is critical.AIM To investigate maternal viral load results and infant HIV testing uptake at 6-weeks,and 9-months and 18-months in Rwanda.METHODS Between 2015 and 2022,VLS(<200 copies/mL)was measured among pregnant women living with HIV(WLHIV)from 38-healthcare facilities.Viral loads(VL)were measured at 6-months,12-months and 24-months,respectively.For maternal VL,the unit of analysis was visit-pair,and the pairs were created to define those with VL<200 copies/mL at two consecutive visits as having sustained VLS,persistent viremia(VL≥200 copies/mL at two consecutive visits),viral rebound(VL<200 copies/mL at prior visit only)and newly suppressed(VL<200 copies/mL at subsequent visit only).HEI were considered to have persistent HIV testing if they had all three HIV tests.Poisson regression models with generalized estimating equations were used to estimate the adjusted incidence rate ratio(aIRR)and 95%CI for factors associated with sustained VLS and persistent HIV testing.RESULTS A total of 1145 mother-infant pairs were analyzed.Infant HIV testing uptake at 6-weeks,9-months and 18-months was 1145(100.0%),1089(95.1%),1006(87.9%)respectively.Nine hundred ninety-nine HEI(87.3%)tested for HIV persistently.At 18-months,the incidence of HIV among HEI was 8(0.7%).Of 1145 mothers,1076(94.0%)had≥2 VL results making a total of 2010 visit-pairs(142-single;934-double visit-pairs).The incidence rate of sustained VLS,persistent viremia,viral rebound and new suppression were 91.0%,1.3%,3.6%and 4.0%respectively.Maternal disclosure of HIV status(aIRR=1.08,95%CI:1.02-1.14)was associated with increased likelihood of sustained VLS.Having peer support(aIRR=1.0595%CI:1.01-1.10)was associated with persistent HIV testing among HEI.CONCLUSION Sustained VLS is high among pregnant WLHIV in Rwanda.The low incidence of HIV among HEI may be attributed to high VLS levels.Targeted interventions,including enhanced HIV disclosure and peer support,are crucial for improving sustained VLS and increasing infant HIV testing uptake to reduce MTCT.
基金funded by Humanities and Social Sciences Foundation and Natural Science Foundation of Nanjing University of Posts and Telecommunications(NYY222055,NY224176)General Subject of Educational Science Planning in Jiangsu Province(C/2024/01/76)National Natural Science Foundation of China(62307025).
文摘Objectives:Teachers are facing unprecedented new challenges leading them to face an increasing number of tasks that are not part of their job,as well as having to cope with the additional skills acquisition that comes with non-traditional forms of teaching and learning,and increased work pressure leading to an increase in the rate of teachers leaving the profession.Therefore,this study aims to explore the mechanism of the career calling on job burnout through career adaptability and work engagement.Methods:This study conducted a cross-sectional survey of 465 primary and secondary school teachers(PSST)in China's Mainland from the perspective of work adjustment and used structural equation modeling(SEM)to examine the mediating roles of career adaptability and work engagement in the relationship between teachers’career calling and job burnout.Results:The results show that PSSTs are above average in career calling,career adaptability,and work engagement,while job burnout is below average.A significant positive or negative correlation exists between career calling,career adaptability,work engagement,and job burnout.The result of path analysis indicates that career adaptability and work engagement exert an indirect influence on the job burnout of PSST through three paths:namely,the independent intermediary role of career adaptability(EV=−0.144),the independent intermediary role of work engagement(EV=0.172)and the chain intermediary role of the two(EV=0.176).Conclusion:This study emphasizes the importance of career adaptability and work engagement in teacher development in regulating career calling and job burnout.Therefore,on the one hand,we think that if managers want to reduce teachers’job burnout,they need to pay more attention to teachers’career adaptability and work engagement,rather than relying solely on teachers’career calling.On the other hand,it is to remind teachers not to rely on their adjustment to adapt to the work,but also to need outside help as much as possible.
基金supported by the Hyperbaric Med School of the Department of Biomedical Sciences at the University of Padova,the Italian Air Force,and the Institute of Clinical Physiology(Milan)-National Research Council(IFC-CNR).
文摘Dear Editor,Space flight(SF)is substantially increasing at present.The emergence of commercial suborbital SF,such as the Virgin Galactic with VSS Unity and VMS Eve spacecraft,is extending to civilians,being previously confined to military and/or professional astronauts only.This new evidence offers additional opportunities for better characterizing the impact that the transition from Earth’s 1G to microgravity in space could have on the astronauts’health while comparing well-trained subjects such as the latt er to space newcomers[1].
基金supported by the Merkin PNNR Center(23-DF/C2/261)(to HS).
文摘Neurons are highly polarized,morphologically asymmetric,and functionally compartmentalized cells that contain long axons extending from the cell body.For this reason,their maintenance relies on spatiotemporal regulation of organelle distribution between the somatodendritic and axonal domains.Although some organelles,such as mitochondria and smooth endoplasmic reticulum,are widely distributed throughout the neuron,others are segregated to either the somatodendritic or axonal compartment.For example,Golgi outposts and acidified lysosomes are predominantly present in the somatodendritic domain and rarely distributed along the axon,whereas newly formed autophagosomes and synaptic vesicles are mainly distributed in the distal axon(Britt et al.,2016).
文摘Alzheimer's disease (AD) is characterized by an imbalance between excitatory and inhibitory brain networks,leading to aberrant homeostatic synaptic plasticity.AD has progressively been recognized as syna ptopathy and syna ptic dysfunction has been identified as a key component of its pathogenesis (Schirinzi et al.,2020).Syna ptic dysfunction is believed to precede synapse loss,a primary biological correlate of cognitive decline in AD,inevita bly associated with neuronal death.
基金supported by NIH/NIAMS(P01 AG066603,R01 AR079171,R21 AR078919)NIH/NIDCR(R01 DE031488,R01 DE031028)+4 种基金Alex’s Lemonade Stand Foundation(22-26743)American Cancer Society(DBG-23-1155131-01-IBCD)the Maryland Stem Cell Research Foundation(2021-MSCRFD-5641),and Department of Defense(USAMRAA HT9425-24-1-0051)MC is supported by Merkin Peripheral Neuropathy and Nerve Regeneration Center(23-DF/C2/260)M.K.is supported by NIH(T32HD044355).
文摘Peripheral neuropathy is a common complication in diabetes,affecting around 50%of the diabetic population.Co-occurrence of diabetic peripheral neuropathy(DPN)and diabetic bone disease has led to the hypothesis that DPN influences bone metabolism,although little experimental evidence has yet supported this premise.To investigate,mice were fed a high-fat diet(HFD)followed by phenotyping of skeletal-innervating neurons and bone architectural parameters.Results showed that HFD feeding resulted in a marked decrease in skeletal innervation(69%–41%reduction in Beta-III-Tubulin-stained nerves,38%reduction in CGRP-stained nerves in long bone periosteum).
基金supported by funding from NIDCR(1R01DE027957)Maryland Stem Cell Research Fund(2022-MSCRFV-5782)the NSF GRFP and NCI(5R01CA237597-05,2R01CA196701-06A1).
文摘Calvarial nerves,along with vasculature,influence skull formation during development and following injury,but it remains unclear how calvarial nerves are spatially distributed during postnatal growth and aging.Studying the spatial distribution of nerves in the skull remains a challenge due to a lack of methods to quantify 3D structures in intact bone.To visualize calvarial 3D neurovascular architecture,we imaged nerves and endothelial cells with lightsheet microscopy.
文摘Extracorporeal membrane oxygenation(ECMO)has emerged as a vital circulatory life support measure for patients with critical cardiac or pulmonary conditions unresponsive to conventional therapies.ECMO allows blood to be extracted from a patient and introduced to a machine that oxygenates blood and removes carbon dioxide.This blood is then reintroduced into the patient’s circulatory system.This process makes ECMO essential for treating various medical conditions,both as a standalone therapy and as adjuvant therapy.Veno-venous(VV)ECMO primarily supports respiratory function and indicates respiratory distress.Simultaneously,veno-arterial(VA)ECMO provides hemodynamic and respiratory support and is suitable for cardiac-related complications.This study reviews recent literature to elucidate the evolving role of ECMO in trauma care,considering its procedural intricacies,indications,contraindications,and associated complications.Notably,the use of ECMO in trauma patients,particularly for acute respiratory distress syndrome and cardiogenic shock,has demonstrated promising outcomes despite challenges such as anticoagulation management and complications such as acute kidney injury,bleeding,thrombosis,and hemolysis.Some studies have shown that VV ECMO was associated with significantly higher survival rates than conventional mechanical ventilation,whereas other studies have reported that VA ECMO was associated with lower survival rates than VV ECMO.ECMO plays a critical role in managing trauma patients,particularly those with acute respiratory failure.Further research is necessary to explore the full potential of ECMO in trauma care.Clinicians should have a clear understanding of the indications and contraindications for the use of ECMO to maximize its benefits in treating trauma patients.
基金supported by the Neurosurgery Pain Research Institute at Johns Hopkins University and by the Lehner Family Foundation.
文摘Chronic pain after spine surgery(CPSS)is a complex disorder characterized by multifactorial pathogenesis that occurs in 8%–40%of patients undergoing lumbar spine surgery.We aimed to develop a rat model that mimics clinical CPSS conditions by taking two sequential surgical procedures.Step 1:A plastic rod was inserted into the left L5 intervertebral foramen to produce a steady compression on the dorsal root ganglion(DRG)and the spinal nerve,a common cause of low back pain(LBP).Step 2:The rod was removed after 7 days when rats exhibited mechanical and heat hypersensitivity in the ipsilateral hindpaw,followed by a full L5 laminectomy to mimic spine decompression surgery in LBP patients.The retention of the rod induced a prolonged LBP-like behavior but was quickly resolved after rod removal without laminectomy.However,rats that received laminectomy after rod removal developed heightened mechanical and heat sensitivity in the hindpaw,impaired gait,and reduced spontaneous exploration activity,indicating CPSS.Patch clamp recording revealed a significant augmentation in the intrinsic excitability of smalldiameter DRG neurons in CPSS rats.Administration of Dermorphin[D-Arg2,Lys4](1–4)amide(DALDA,5mg/kg,i.p.),a peripherally acting mu-opioid receptor(MOR)-preferred agonist,attenuated pain hypersensitivity,capsaicin-induced[Ca^(2+)]i rising and the increased intrinsic excitability of DRG neurons from CPSS rats.Our findings suggest that this new model,which mirrors the nature of CPSS developed in patients,may be useful for future studies of the underlying mechanisms.
文摘Background:This essay examines how nineteenth-century Anglo-American physicians and scientists constructed racial hierarchies through theories of pain insensitivity,advancing the notion of“organic insensibility”to pathologize the bodies-particularly the crania,epidermis,and reproductive organs-of American Indians,African Americans,and East Asians.Methods:Drawing on medical texts,ethnographic accounts,and the writings of proslavery and colonial ideologues,the essay explores how perceptions of diminished pain sensitivity were used to justify settler colonialism,slavery,and imperialism from the period of Indian Removal to the expansion of the Cotton Kingdom and the Opium Wars.Results:Practices such as cranial deformation,parturient pain,surgical endurance,skin experiments,and foot binding,were racialized to support claims of biological inferiority and moral deficiency.Conclusion:Integrating insights from the history and philosophy of science and medicine,and phenomenology,the essay demonstrates how pain was not only a medical concern but a political feeling-central to the denial of full humanity to racialized populations.
文摘Inflammatory bowel disease(IBD),encompassing Crohn's disease and ulcerative colitis,is a chronic condition marked by recurring gastrointestinal inflammation.While immune,genetic,and environmental factors are well-studied,the gut virome has received less attention.This editorial highlights the work which investigates the gut virome’s role in IBD and its interactions with the bacterial microbiome and host immune system.The gut virome consists of bacteriophages,eukaryotic viruses,and endogenous retroviruses.Among these,Caudovirales bacteriophages are predominant and influence bacterial communities via lysogenic and lytic cycles.Eukaryotic viruses infect host cells directly,while endogenous retroviruses impact gene regulation and immune responses.In IBD,the virome shows distinct alterations,including an increased abundance of Caudovirales phages and reduced Microviridae diversity,suggesting a pro-inflammatory viral environment.Dysbiosis,chronic inflammation,and aberrant immune responses contribute to these changes by disrupting microbial communities and modifying virome composition.Phages affect bacterial dynamics through lysis,lysogeny,and horizontal gene transfer,shaping microbial adaptability and resilience.Understanding these interactions is crucial for identifying novel therapeutic targets and restoring microbial balance in IBD.
文摘Background:Traditional imaging approaches to keratoconus(KCN)have thus far failed to produce a standardized approach for diagnosis.While many diagnostic modalities and metrics exist,none have proven robust enough to be considered a gold standard.This study aims to introduce novel metrics to differentiate between KCN and healthy corneas using three-dimensional(3D)measurements of surface area and volume.Methods:This retrospective observational study examined KCN patients along with healthy control patients between the ages of 20 and 79 years old at the University of Maryland,Baltimore.The selected patients underwent a nine-line raster scan anterior segment optical coherence tomography(AS-OCT).ImageJ was used to determine the central 6 mm of each image and each corneal image was then divided into six 1 mm segments.Free-D software was then used to render the nine different images into a 3D model to calculate corneal surface area and volume.A two-tailed Mann-Whitney test was used to assess statistical significance when comparing these subsets.Results:Thirty-three eyes with KCN,along with 33 healthy control,were enrolled.There were statistically significant differences between the healthy and KCN groups in the metric of anterior corneal surface area(13.927 vs.13.991 mm^(2),P=0.046),posterior corneal surface area(14.045 vs.14.173 mm^(2),P<0.001),and volume(8.430 vs.7.773 mm3,P<0.001)within the central 6 mm.Conclusions:3D corneal models derived from AS-OCT can be used to measure anterior corneal surface area,posterior corneal surface area,and corneal volume.All three parameters are statistically different between corneas with KCN and healthy corneas.Further study and application of these parameters may yield new methodologies for the detection of KCN.
基金supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health (R01AR075733, R01AR083363, R21AR077654 to S.O.)by the Maryland Stem Cell Research Fund (MSCRF) Discovery Grant (2023-MSCRFD-6160 to S.O.)supported by the Post-Doctoral Fellowship from MSCRF (2023-MSCRFF-6176)
文摘The resting zone(RZ)in mammalian growth plates is critical for maintaining and regulating chondrocyte turnover during longitudinal bone growth as a control tower and stem cell reservoir.Although recent lineage tracing studies have identified several markers for stem cells in the RZ,these markers only partially label chondrocytes in the RZ,suggesting that the resting chondrocytes(RCs)are a heterogeneous population with different types of stem cells.Since a comprehensive marker for RCs is still lacking,the RZ is generally determined based on ambiguous histological criteria,such as small and round chondrocytes without columnar formation,which may lead to inconsistencies among researchers.Therefore,in this study,we used single-cell RNA sequencing(scRNAseq)of growth plate chondrocytes followed by validation by fluorescence in situ hybridization(FISH)to precisely annotate cell clusters in scRNAseq and search for a marker of RCs.The scRNAseq analysis revealed that apolipoprotein E(Apoe)was the tophit gene,which was ubiquitously expressed in the RC cluster.FISH confirmed that Apoe was exclusively localized to the histologically defined RZ.In newly generated Apoe^(mCherry)knock-in mice,we further confirmed that mCherry expression mirrored the distribution of Apoe-expressing chondrocytes in the RZ particularly after the formation of the secondary ossification center.These mCherry+RCs were slow cycling in vivo and exhibited stem cell properties in vitro.Moreover,APOE was detected in human growth plate RCs.These findings suggest that apolipoprotein E is a novel pan-RC marker in both mouse and human growth plates.
