Spinal cord injury necessitates effective rehabilitation strategies, with exercise therapies showing promise in promoting recovery. This study investigated the impact of rehabilitation exercise on functional recovery ...Spinal cord injury necessitates effective rehabilitation strategies, with exercise therapies showing promise in promoting recovery. This study investigated the impact of rehabilitation exercise on functional recovery and morphological changes following thoracic contusive spinal cord injury. After a 7-day recovery period after spinal cord injury, mice were assigned to either a trained group(10 weeks of voluntary running wheel or forced treadmill exercise) or an untrained group. Bi-weekly assessments revealed that the exercise-trained group, particularly the voluntary wheel exercise subgroup, displayed significantly improved locomotor recovery, more plasticity of dopaminergic and serotonin modulation compared with the untrained group. Additionally, exercise interventions led to gait pattern restoration and enhanced transcranial magnetic motor-evoked potentials. Despite consistent injury areas across groups, exercise training promoted terminal innervation of descending axons. In summary, voluntary wheel exercise shows promise for enhancing outcomes after thoracic contusive spinal cord injury, emphasizing the role of exercise modality in promoting recovery and morphological changes in spinal cord injuries. Our findings will influence future strategies for rehabilitation exercises, restoring functional movement after spinal cord injury.展开更多
BACKGROUND Among patients with cirrhosis and pre-malignant or early malignant mucosal lesions,surgical intervention carries a much higher bleeding risk.When such lesions are discovered,endoscopic submucosal dissection...BACKGROUND Among patients with cirrhosis and pre-malignant or early malignant mucosal lesions,surgical intervention carries a much higher bleeding risk.When such lesions are discovered,endoscopic submucosal dissection(ESD)may offer curative therapy with lower risks than surgery and improved outcomes compared to traditional endoscopic resection.AIM To evaluate the outcomes of ESD in patients with cirrhosis.METHODS Patients with cirrhosis undergoing ESD between July 2015 and August 2022 were retrospectively matched in 1:2 fashion to controls based on lesion location,size,and anticoagulation use.Procedural outcomes were compared between groups.RESULTS A total of 64 Lesions from 59 patients were included(16 cirrhosis,43 control).There were no differences in patient or lesion characteristics between groups.En bloc and curative resection was achieved in 84.21%,78.94%of the cirrhosis group and 88.89%,68.89%of controls,respectively,with no significant differences.Cirrhotic patients had significantly higher rates of intra-procedural coagulation grasper use for control of bleeding(47.37%vs 20%;P=0.02).There were otherwise no significant differences in adverse event rates.In the 29 patients with follow up,we found higher rates of recurrence in the cirrhosis group compared to controls(40%vs 5.26%;P=0.019),however this effect did not persist on multivariable analysis controlling for known confounders.CONCLUSION ESD may be safe and effective in patients with cirrhosis.Most procedure related outcomes were not significantly different between groups.Intra-procedural bleeding requiring use of the coagulation grasper use was expectedly higher in the cirrhosis group given the known effects of liver disease on hemostasis.展开更多
Background The study objective was to test the hypothesis that low crude protein(CP)diet with crystalline amino acids(CAA)supplementation improves Lys utilization efficiency for milk production and reduces protein tur...Background The study objective was to test the hypothesis that low crude protein(CP)diet with crystalline amino acids(CAA)supplementation improves Lys utilization efficiency for milk production and reduces protein turnover and muscle protein breakdown.Eighteen lactating multiparous Yorkshire sows were allotted to 1 of 2 isocaloric diets(10.80 MJ/kg net energy):control(CON;19.24%CP)and reduced CP with“optimal”AA profile(OPT;14.00%CP).Sow body weight and backfat were recorded on d 1 and 21 of lactation and piglets were weighed on d 1,14,18,and 21 of lactation.Between d 14 and 18,a subset of 9 sows(CON=4,OPT=5)was infused with a mixed solution of 3-[methyl-2H3]histidine(bolus injection)and[13C]bicarbonate(priming dose)first,then a constant 2-h[13C]bicarbonate infusion followed by a 6-h primed constant[1-13C]lysine infusion.Serial blood and milk sampling were performed to determine plasma and milk Lys enrichment,Lys oxidation rate,whole body protein turnover,and muscle protein breakdown.Results Over the 21-d lactation period,compared to CON,sows fed OPT had greater litter growth rate(P<0.05).Compared to CON,sows fed OPT had greater efficiency of Lys(P<0.05),Lys mammary flux(P<0.01)and whole-body protein turnover efficiency(P<0.05).Compared to CON,sows fed OPT tended to have lower whole body protein breakdown rate(P=0.069).Muscle protein breakdown rate did not differ between OPT and CON(P=0.197).Conclusion Feeding an improved AA balance diet increased efficiency of Lys and reduced whole-body protein turnover and protein breakdown.These results imply that the lower maternal N retention observed in lactating sows fed improved AA balance diets in previous studies may be a result of greater partitioning of AA towards milk rather than greater body protein breakdown.展开更多
Traumatic Brain Injury is a major cause of death and long-term disability.The early identification of patients at high risk of mortality is important for both management and prognosis.Although many modified scoring sy...Traumatic Brain Injury is a major cause of death and long-term disability.The early identification of patients at high risk of mortality is important for both management and prognosis.Although many modified scoring systems have been developed for improving the prediction accuracy in patients with trauma,few studies have focused on prediction accuracy and application in patients with traumatic brain injury.The shock index(SI)which was first introduced in the 1960s has shown to strongly correlate degree of circulatory shock with increasing SI.In this editorial we comment on a publication by Carteri et al wherein they perform a retrospective analysis studying the predictive potential of SI and its variants in populations with severe traumatic brain injury.展开更多
Pneumonia is a disease associated with significant healthcare burden with over 1.5 million hospitalizations annually and is the eighth leading cause of death in the United States.While community-acquired pneumonia(CAP...Pneumonia is a disease associated with significant healthcare burden with over 1.5 million hospitalizations annually and is the eighth leading cause of death in the United States.While community-acquired pneumonia(CAP)is generally considered an acute time-limited illness,it is associated with high long-term mortality,with nearly one-third of patients requiring hospitalization dying within one year.An increasing trend of detecting multidrug-resistant(MDR)organisms causing CAP has been observed,especially in the Western world.In this editorial,we discuss about a publication by Jatteppanavar et al which reported that a case of a MDR organism was the culprit in developing pneumonia,bacteremia,and infective endocarditis that led to the patient’s death.The early detection of these resistant organisms helps improve patient outcomes.Significant advances have been made in the biotechnological and research space,but preventive measures,diagnostic techniques,and treatment strategies need to be developed.展开更多
primarily driven by advancements in technology,changes in healthcare delivery,and a deeper understanding of disease processes.Advancements in technology have revolutionized patient monitoring,diagnosis,and treatment i...primarily driven by advancements in technology,changes in healthcare delivery,and a deeper understanding of disease processes.Advancements in technology have revolutionized patient monitoring,diagnosis,and treatment in the critical care setting.From minimally invasive procedures to advances imaging techniques,clinicians now have access to a wide array of tools to assess and manage critically ill patients more effectively.In this editorial we comment on the review article published by Padte S et al wherein they concisely describe the latest developments in critical care medicine.展开更多
Individuals with NGLY1 Deficiency, an inherited autosomal recessive disorder, exhibit hyperkinetic movements including athetoid, myoclonic, dysmetric, and dystonic movements impacting both upper and lower limb motion....Individuals with NGLY1 Deficiency, an inherited autosomal recessive disorder, exhibit hyperkinetic movements including athetoid, myoclonic, dysmetric, and dystonic movements impacting both upper and lower limb motion. This report provides the first set of laboratory-based measures characterizing the gait patterns of two individuals with NGLY1 Deficiency, using both linear and non-linear measures, during treadmill walking, and compares them to neurotypical controls. Lower limb kinematics were obtained with a camera-based motion analysis system and bilateral time normalized lower limb joint time series waveforms were developed. Linear measures of joint range of motion, stride times and peak angular velocity were obtained, and confidence intervals were used to determine if there were differences between the patients and control. Correlations between participant and control mean joint waveforms were calculated and used to evaluate the similarities between patients and controls. Non-linear measures included: joint angle-angle diagrams, phase-portrait areas, and continuous relative phase (CRP) measures. These measures were used to assess joint coordination and control features of the lower limb motion. Participants displayed high correlations with their control counterparts for the hip and knee joint waveforms, but joint motion was restricted. Peak angular velocities were also significantly less than those of the controls. Both angle-angle and phase-portrait areas were less than the controls although the general shapes of those diagrams were similar to those of the controls. The NGLY1 Deficient participants’ CRP measures displayed disrupted coordination patterns with the knee-ankle patterns displaying more disruption than the hip-knee measures. Overall, the participants displayed a functional walking pattern that differed in many quantitative ways from those of the neurotypical controls. Using both linear and non-linear measures to characterize gait provides a more comprehensive and nuanced characterization of NGLY1 gait and can be used to develop interventions targeted toward specific aspects of disordered gait.展开更多
NGLY1 Deficiency is an ultra-rare autosomal recessively inherited disorder. Characteristic symptoms include among others, developmental delays, movement disorders, liver function abnormalities, seizures, and problems ...NGLY1 Deficiency is an ultra-rare autosomal recessively inherited disorder. Characteristic symptoms include among others, developmental delays, movement disorders, liver function abnormalities, seizures, and problems with tear formation. Movements are hyperkinetic and may include dysmetric, choreo-athetoid, myoclonic and dystonic movement elements. To date, there have been no quantitative reports describing arm movements of individuals with NGLY1 Deficiency. This report provides quantitative information about a series of arm movements performed by an individual with NGLY1 Deficiency and an aged-matched neurotypical participant. Three categories of arm movements were tested: 1) open ended reaches without specific end point targets;2) goal-directed reaches that included grasping an object;3) picking up small objects from a table placed in front of the participants. Arm movement kinematics were obtained with a camera-based motion analysis system and “initiation” and “maintenance” phases were identified for each movement. The combination of the two phases was labeled as a “complete” movement. Three-dimensional analysis techniques were used to quantify the movements and included hand trajectory pathlength, joint motion area, as well as hand trajectory and joint jerk cost. These techniques were required to fully characterize the movements because the NGLY1 individual was unable to perform movements only in the primary plane of progression instead producing motion across all three planes of movement. The individual with NGLY1 Deficiency was unable to pick up objects from a table or effectively complete movements requiring crossing the midline. The successfully completed movements were analyzed using the above techniques and the results of the two participants were compared statistically. Almost all comparisons revealed significant differences between the two participants, with a notable exception of the 3D initiation area as a percentage of the complete movement. The statistical tests of these measures revealed no significant differences between the two participants, possibly suggesting a common underlying motor control strategy. The 3D techniques used in this report effectively characterized arm movements of an individual with NGLY1 deficiency and can be used to provide information to evaluate the effectiveness of genetic, pharmacological, or physical rehabilitation therapies.展开更多
DEAR EDITOR,Breast cancer is the most common malignant tumor in women,posing a serious threat to health. Tree shrews(Tupaia belangeri chinensis) are evolutionarily closer to humans than rodents and are emerging as an ...DEAR EDITOR,Breast cancer is the most common malignant tumor in women,posing a serious threat to health. Tree shrews(Tupaia belangeri chinensis) are evolutionarily closer to humans than rodents and are emerging as an attractive experimental animal model for breast cancer. The PIK3CA gene is frequently mutated in both human and tree shrew breast tumors. Herein, we effectively overexpressed PIK3CA-H1047R in the mammary epithelial cells of tree shrews using a lentivirus to induce breast tumors.展开更多
BACKGROUND Large appendiceal orifice polyps are traditionally treated surgically.Recently,endoscopic mucosal resection(EMR)and endoscopic submucosal dissection(ESD)have been utilized as alternative resection technique...BACKGROUND Large appendiceal orifice polyps are traditionally treated surgically.Recently,endoscopic mucosal resection(EMR)and endoscopic submucosal dissection(ESD)have been utilized as alternative resection techniques.AIM To evaluate the efficacy and safety of endoscopic resection techniques for the management of large appendiceal orifice polyps.METHODS This was a retrospective observational study conducted to assess the feasibility and safety of EMR and ESD for large appendiceal orifice polyps.This project was approved by the Baylor College of Medicine Institutional Review Board.Patients who underwent endoscopic resection of appendiceal orifice polyps≥1 cm from 2015 to 2022 at a tertiary referral endoscopy center in the United States were enrolled.The main outcomes of this study included en bloc resection,R0 resection,post resection adverse events,and polyp recurrence.RESULTS A total of 19 patients were identified.Most patients were female(53%)and Caucasian(95%).The mean age was 63.3±10.8 years,and the average body mass index was 28.8±6.4.The mean polyp size was 25.5±14.2 mm.74%of polyps were localized to the appendix(at or inside the appendiceal orifice)and the remaining extended into the cecum.68%of polyps occupied≥50%of the appendiceal orifice circumference.The mean procedure duration was 61.6±37.9 minutes.Polyps were resected via endoscopic mucosal resection,endoscopic submucosal dissection,and hybrid procedures in 5,6,and 8 patients,respectively.Final pathology was remarkable for tubular adenoma(n=10)[one with high grade dysplasia],sessile serrated adenoma(n=7),and tubulovillous adenoma(n=2)[two with high grade dysplasia].En bloc resection was achieved in 84%with an 88%R0 resection rate.Despite the large polyp sizes and challenging procedures,89%(n=17)of patients were discharged on the same day as their procedure.Two patients were admitted for post-procedure observation for conservative pain management.Eight patients underwent repeat colonoscopy without evidence of residual or recurrent adenomatous polyps.CONCLUSION Our study highlights how endoscopic mucosal resection,endoscopic submucosal dissection,and hybrid procedures are all appropriate techniques with minimal adverse effects,further validating the utility of endoscopic procedures in the management of large appendiceal polyps.展开更多
Objective:The clinical grading system for varicoceles is subjective and dependent on clinician experience.Color Doppler ultrasound(US)has not been standardized in the diagnosis of varicoceles.We aimed to determine if ...Objective:The clinical grading system for varicoceles is subjective and dependent on clinician experience.Color Doppler ultrasound(US)has not been standardized in the diagnosis of varicoceles.We aimed to determine if US measurement of varicocele could be predictive of World Health Organization(WHO)varicocele grade.Methods:Men who presented for either scrotal pain or infertility to a tertiary men’s health clinic underwent physical examination,and varicoceles were graded following WHO criteria(0Zsubclinical,1,2,3).US was used to measure largest venous diameter in the pampiniform plexus bilaterally at rest and during Valsalva maneuver.Receiver operator characteristic curve analysis was used to determine if resting diameter,diameter during Valsalva,or change in diameter between at rest and during Valsalva provided the highest sensitivity and specificity for determining clinical grade.Threshold values for diameter were determined from these receiver operator characteristic curves.Results:A total of 102 men(50 with clinical varicocele and 52 with subclinical varicocele)were included.Diameter at rest was the best ultrasonographic discriminator between subclinical and clinical varicoceles(area under the curve[AUC]Z0.67)with a diameter threshold of 3.0 mm(sensitivity 79%,specificity 42%).Diameter during Valsalva had the greatest AUC for determining clinical Grades 1 versus 2(AUCZ0.57)with diameter threshold of 5.7 mm(sensitivity 71%,specificity 33%).For differentiating between Grades 2 and 3,diameter at rest had the greatest AUC of 0.65 with a threshold of 3.6 mm(sensitivity 71%,specificity 58%).Conclusion:Our results corroborate other studies that have shown a weak correlation between US and clinical grading.The use of diameter during Valsalva was less predictive than diameter at rest and was only clinically significant in differentiating between Grade 1 and 2 varicocele.A standardized method for determining clinically relevant varicoceles on US would allow for improved patient counseling and clinical decision-making.展开更多
Growing evidence demonstrate that cold stimulation as a nonpharmacological strategy can be applied to prevent the development of ageing.However,the optimal ambient temperature to mammals and the mechanism for low temp...Growing evidence demonstrate that cold stimulation as a nonpharmacological strategy can be applied to prevent the development of ageing.However,the optimal ambient temperature to mammals and the mechanism for low temperature to extend lifespan remain poorly understood.In this editorial,we highlight the data presented by Hyun et al.suggesting that a beneficial role of moderate cold temperature in reducing disease-related aggregation thereby age-related deteriorations[1].展开更多
Background/Purpose: Hispanic/Latinos in the US are at increased risk for type 2 diabetes (T2D). Data suggest that avocado intake is associated with better glycemic control, but whether this translates to protection fr...Background/Purpose: Hispanic/Latinos in the US are at increased risk for type 2 diabetes (T2D). Data suggest that avocado intake is associated with better glycemic control, but whether this translates to protection from T2D has not been studied. The goal of the current analyses was to examine whether consuming avocados at baseline is associated with lower incident T2D over a six-year period, compared to not consuming avocados at baseline. Subjects/Methods: Using data from a large population of US adults with Hispanic ancestry, without known or unknown T2D at baseline (N = 6159), participants were classified as avocado consumers (N = 983) or non-consumers (N = 5176) based on the mean of two 24-hour dietary recalls. Cox proportional hazard models estimated the association of avocado consumption with incident T2D (N = 656 cases) over a six-year follow-up period, in the population as a whole, and separately in those with normoglycemia vs. prediabetes at baseline. A set of three sequential models were run: the first controlling only for sociodemographic factors (“minimally adjusted” models), the second for these and health behaviors (“fully adjusted” models), and a third for both sets of covariates and also body mass index (BMI;“fully adjusted + BMI” models). Results: In the population as a whole, avocado intake at baseline was associated with reduced incident T2D in both the minimally adjusted (hazard ratio [HR] (±95% confidence intervals [CIs]): 0.70 (0.52 - 0.94), P = 0.04) and the fully adjusted models (HR: 0.72 (0.54 - 0.97), P = 0.03). This association was observed in both those with prediabetes and with normoglycemia at baseline, but only reached significance in those with prediabetes (minimally adjusted model: HR: 0.68 (0.48 - 0.97), P = 0.03;fully adjusted model: HR: 0.69 (0.48 - 0.98), P = 0.04), not in those with normoglycemia (minimally adjusted model: HR: 0.86 (0.45 - 1.65), P = 0.65;fully adjusted model: HR: 0.80 (0.41 - 1.55), P = 0.50). In models which additionally controlled for BMI (“fully adjusted + BMI model”), the associations were slightly attenuated (overall population: HR: 0.79 (0.59 - 1.06), P = 0.60;normoglycemia: HR: 0.83 (0.42 - 1.64), P = 0.60;prediabetes: HR = 0.75 (0.54 - 1.05), P = 0.09). Conclusions: In our longitudinal analyses, adults with Hispanic/Latino ancestry who consumed avocado were less likely to develop T2D than those who did not consume avocado at baseline, especially if they had prediabetes at baseline.展开更多
Interstitial lung disease(ILD)is typically managed on an outpatient basis.Critical care physicians manage patients with ILD in the setting of an acute exacerbation(ILD flare)causing severe hypoxia.The principles of ma...Interstitial lung disease(ILD)is typically managed on an outpatient basis.Critical care physicians manage patients with ILD in the setting of an acute exacerbation(ILD flare)causing severe hypoxia.The principles of management of acute exacerbation of ILD are different from those used to manage patients with acute respiratory distress syndrome from sepsis,etc.Selected patients may be candidates for aggressive measures like extracorporeal membrane oxygenation and lung transplantation,while almost all patients will benefit from early palliative care.This review focused on the types of ILD,diagnosis,and management pathways for this challenging condition.展开更多
Neuron-astrocyte interactions are vital for the brain’s connectome.Understanding astrocyte activities is crucial for comprehending the complex neural network,particularly the population-level functions of neurons in ...Neuron-astrocyte interactions are vital for the brain’s connectome.Understanding astrocyte activities is crucial for comprehending the complex neural network,particularly the population-level functions of neurons in different cortical states and associated behaviors in mammals.Studies on animal sleep and wakefulness have revealed distinct cortical synchrony patterns between neurons.Astrocytes,outnumbering neurons by nearly fivefold,support and regulate neuronal and synaptic function.Recent research on astrocyte activation during cortical state transitions has emphasized the influence of norepinephrine as a neurotransmitter and calcium waves as key components of ion channel signaling.This summary focuses on a few recent studies investigating astrocyte-neuron interactions in mouse models during sleep,wakefulness,and arousal levels,exploring the involvement of noradrenaline signaling,ion channels,and glutamatergic signaling in different cortical states.These findings highlight the significant impact of astrocytes on large-scale neuronal networks,influencing brain activity and responsiveness.Targeting astrocytic signaling pathways shows promise for treating sleep disorders and arousal dysregulation.More research is needed to understand astrocytic calcium signaling in different brain regions and its implications for dysregulated brain states,requiring future human studies to comprehensively investigate neuron-astrocyte interactions and pave the way for therapeutic interventions in sleep-and arousal-related disorders.展开更多
Glucose is the primary fuel source of the brain,and therefore glucose levels need to be tightly regulated and maintained within a small physiological range.Certainly,the body necessitates a stable supply of energy mai...Glucose is the primary fuel source of the brain,and therefore glucose levels need to be tightly regulated and maintained within a small physiological range.Certainly,the body necessitates a stable supply of energy mainly provided by glucose for various bodily functions.High or low blood glucose levels would impair the physiological functions of various organs of the body.展开更多
Stress signaling following axon injury stimulates a transcriptional program for regeneration that might be exploited to promote central nervous system repair.However,this stress response drives neuronal apoptosis in n...Stress signaling following axon injury stimulates a transcriptional program for regeneration that might be exploited to promote central nervous system repair.However,this stress response drives neuronal apoptosis in non-regenerative environments.This duality presents a quandary for the development of therapeutic interventions:manipulating stress signaling to enhance recovery of damaged neurons risks accelerating neurodegeneration or restricting regenerative potential.This dichotomy is well illustrated by the fates of retinal ganglion cells(RGCs)following optic nerve crush.In this central nervous system injury model,disruption of a stress-activated MAP kinase(MAPK)cascade blocks the extensive apoptosis of RGCs that occurs in wild-type mice(Watkins et al.,2013;Welsbie et al.,2017).展开更多
A common feature among neurodegenerative conditions is that ce rtain neuronal populations are selectively vulnerable to loss(Fu et al.,2018).By corollary,other neurons are selectively resilient,suggesting they may pos...A common feature among neurodegenerative conditions is that ce rtain neuronal populations are selectively vulnerable to loss(Fu et al.,2018).By corollary,other neurons are selectively resilient,suggesting they may possess unique features that support their survival.U nderstanding the basis of neuronal resilience or vulnerability would provide a logical strategy to identify factors that could be targeted therapeutically.展开更多
基金supported by the NIH (R01NS103481, R01NS111776, and R01NS131489)Indiana Department of Health (ISDH58180)(all to WW)。
文摘Spinal cord injury necessitates effective rehabilitation strategies, with exercise therapies showing promise in promoting recovery. This study investigated the impact of rehabilitation exercise on functional recovery and morphological changes following thoracic contusive spinal cord injury. After a 7-day recovery period after spinal cord injury, mice were assigned to either a trained group(10 weeks of voluntary running wheel or forced treadmill exercise) or an untrained group. Bi-weekly assessments revealed that the exercise-trained group, particularly the voluntary wheel exercise subgroup, displayed significantly improved locomotor recovery, more plasticity of dopaminergic and serotonin modulation compared with the untrained group. Additionally, exercise interventions led to gait pattern restoration and enhanced transcranial magnetic motor-evoked potentials. Despite consistent injury areas across groups, exercise training promoted terminal innervation of descending axons. In summary, voluntary wheel exercise shows promise for enhancing outcomes after thoracic contusive spinal cord injury, emphasizing the role of exercise modality in promoting recovery and morphological changes in spinal cord injuries. Our findings will influence future strategies for rehabilitation exercises, restoring functional movement after spinal cord injury.
基金reviewed and approved by the Baylor College of Medicine Institutional Review Board.
文摘BACKGROUND Among patients with cirrhosis and pre-malignant or early malignant mucosal lesions,surgical intervention carries a much higher bleeding risk.When such lesions are discovered,endoscopic submucosal dissection(ESD)may offer curative therapy with lower risks than surgery and improved outcomes compared to traditional endoscopic resection.AIM To evaluate the outcomes of ESD in patients with cirrhosis.METHODS Patients with cirrhosis undergoing ESD between July 2015 and August 2022 were retrospectively matched in 1:2 fashion to controls based on lesion location,size,and anticoagulation use.Procedural outcomes were compared between groups.RESULTS A total of 64 Lesions from 59 patients were included(16 cirrhosis,43 control).There were no differences in patient or lesion characteristics between groups.En bloc and curative resection was achieved in 84.21%,78.94%of the cirrhosis group and 88.89%,68.89%of controls,respectively,with no significant differences.Cirrhotic patients had significantly higher rates of intra-procedural coagulation grasper use for control of bleeding(47.37%vs 20%;P=0.02).There were otherwise no significant differences in adverse event rates.In the 29 patients with follow up,we found higher rates of recurrence in the cirrhosis group compared to controls(40%vs 5.26%;P=0.019),however this effect did not persist on multivariable analysis controlling for known confounders.CONCLUSION ESD may be safe and effective in patients with cirrhosis.Most procedure related outcomes were not significantly different between groups.Intra-procedural bleeding requiring use of the coagulation grasper use was expectedly higher in the cirrhosis group given the known effects of liver disease on hemostasis.
基金financially supported by funds from the USDA-NIFA(award number 2014-67015-21832)。
文摘Background The study objective was to test the hypothesis that low crude protein(CP)diet with crystalline amino acids(CAA)supplementation improves Lys utilization efficiency for milk production and reduces protein turnover and muscle protein breakdown.Eighteen lactating multiparous Yorkshire sows were allotted to 1 of 2 isocaloric diets(10.80 MJ/kg net energy):control(CON;19.24%CP)and reduced CP with“optimal”AA profile(OPT;14.00%CP).Sow body weight and backfat were recorded on d 1 and 21 of lactation and piglets were weighed on d 1,14,18,and 21 of lactation.Between d 14 and 18,a subset of 9 sows(CON=4,OPT=5)was infused with a mixed solution of 3-[methyl-2H3]histidine(bolus injection)and[13C]bicarbonate(priming dose)first,then a constant 2-h[13C]bicarbonate infusion followed by a 6-h primed constant[1-13C]lysine infusion.Serial blood and milk sampling were performed to determine plasma and milk Lys enrichment,Lys oxidation rate,whole body protein turnover,and muscle protein breakdown.Results Over the 21-d lactation period,compared to CON,sows fed OPT had greater litter growth rate(P<0.05).Compared to CON,sows fed OPT had greater efficiency of Lys(P<0.05),Lys mammary flux(P<0.01)and whole-body protein turnover efficiency(P<0.05).Compared to CON,sows fed OPT tended to have lower whole body protein breakdown rate(P=0.069).Muscle protein breakdown rate did not differ between OPT and CON(P=0.197).Conclusion Feeding an improved AA balance diet increased efficiency of Lys and reduced whole-body protein turnover and protein breakdown.These results imply that the lower maternal N retention observed in lactating sows fed improved AA balance diets in previous studies may be a result of greater partitioning of AA towards milk rather than greater body protein breakdown.
文摘Traumatic Brain Injury is a major cause of death and long-term disability.The early identification of patients at high risk of mortality is important for both management and prognosis.Although many modified scoring systems have been developed for improving the prediction accuracy in patients with trauma,few studies have focused on prediction accuracy and application in patients with traumatic brain injury.The shock index(SI)which was first introduced in the 1960s has shown to strongly correlate degree of circulatory shock with increasing SI.In this editorial we comment on a publication by Carteri et al wherein they perform a retrospective analysis studying the predictive potential of SI and its variants in populations with severe traumatic brain injury.
文摘Pneumonia is a disease associated with significant healthcare burden with over 1.5 million hospitalizations annually and is the eighth leading cause of death in the United States.While community-acquired pneumonia(CAP)is generally considered an acute time-limited illness,it is associated with high long-term mortality,with nearly one-third of patients requiring hospitalization dying within one year.An increasing trend of detecting multidrug-resistant(MDR)organisms causing CAP has been observed,especially in the Western world.In this editorial,we discuss about a publication by Jatteppanavar et al which reported that a case of a MDR organism was the culprit in developing pneumonia,bacteremia,and infective endocarditis that led to the patient’s death.The early detection of these resistant organisms helps improve patient outcomes.Significant advances have been made in the biotechnological and research space,but preventive measures,diagnostic techniques,and treatment strategies need to be developed.
文摘primarily driven by advancements in technology,changes in healthcare delivery,and a deeper understanding of disease processes.Advancements in technology have revolutionized patient monitoring,diagnosis,and treatment in the critical care setting.From minimally invasive procedures to advances imaging techniques,clinicians now have access to a wide array of tools to assess and manage critically ill patients more effectively.In this editorial we comment on the review article published by Padte S et al wherein they concisely describe the latest developments in critical care medicine.
文摘Individuals with NGLY1 Deficiency, an inherited autosomal recessive disorder, exhibit hyperkinetic movements including athetoid, myoclonic, dysmetric, and dystonic movements impacting both upper and lower limb motion. This report provides the first set of laboratory-based measures characterizing the gait patterns of two individuals with NGLY1 Deficiency, using both linear and non-linear measures, during treadmill walking, and compares them to neurotypical controls. Lower limb kinematics were obtained with a camera-based motion analysis system and bilateral time normalized lower limb joint time series waveforms were developed. Linear measures of joint range of motion, stride times and peak angular velocity were obtained, and confidence intervals were used to determine if there were differences between the patients and control. Correlations between participant and control mean joint waveforms were calculated and used to evaluate the similarities between patients and controls. Non-linear measures included: joint angle-angle diagrams, phase-portrait areas, and continuous relative phase (CRP) measures. These measures were used to assess joint coordination and control features of the lower limb motion. Participants displayed high correlations with their control counterparts for the hip and knee joint waveforms, but joint motion was restricted. Peak angular velocities were also significantly less than those of the controls. Both angle-angle and phase-portrait areas were less than the controls although the general shapes of those diagrams were similar to those of the controls. The NGLY1 Deficient participants’ CRP measures displayed disrupted coordination patterns with the knee-ankle patterns displaying more disruption than the hip-knee measures. Overall, the participants displayed a functional walking pattern that differed in many quantitative ways from those of the neurotypical controls. Using both linear and non-linear measures to characterize gait provides a more comprehensive and nuanced characterization of NGLY1 gait and can be used to develop interventions targeted toward specific aspects of disordered gait.
文摘NGLY1 Deficiency is an ultra-rare autosomal recessively inherited disorder. Characteristic symptoms include among others, developmental delays, movement disorders, liver function abnormalities, seizures, and problems with tear formation. Movements are hyperkinetic and may include dysmetric, choreo-athetoid, myoclonic and dystonic movement elements. To date, there have been no quantitative reports describing arm movements of individuals with NGLY1 Deficiency. This report provides quantitative information about a series of arm movements performed by an individual with NGLY1 Deficiency and an aged-matched neurotypical participant. Three categories of arm movements were tested: 1) open ended reaches without specific end point targets;2) goal-directed reaches that included grasping an object;3) picking up small objects from a table placed in front of the participants. Arm movement kinematics were obtained with a camera-based motion analysis system and “initiation” and “maintenance” phases were identified for each movement. The combination of the two phases was labeled as a “complete” movement. Three-dimensional analysis techniques were used to quantify the movements and included hand trajectory pathlength, joint motion area, as well as hand trajectory and joint jerk cost. These techniques were required to fully characterize the movements because the NGLY1 individual was unable to perform movements only in the primary plane of progression instead producing motion across all three planes of movement. The individual with NGLY1 Deficiency was unable to pick up objects from a table or effectively complete movements requiring crossing the midline. The successfully completed movements were analyzed using the above techniques and the results of the two participants were compared statistically. Almost all comparisons revealed significant differences between the two participants, with a notable exception of the 3D initiation area as a percentage of the complete movement. The statistical tests of these measures revealed no significant differences between the two participants, possibly suggesting a common underlying motor control strategy. The 3D techniques used in this report effectively characterized arm movements of an individual with NGLY1 deficiency and can be used to provide information to evaluate the effectiveness of genetic, pharmacological, or physical rehabilitation therapies.
基金supported by the National Key Research and Development Program of China(2020YFA0112300,2018YFC2000400)National Natural Science Foundation of China(81830087 and U2102203 to C.S.C.,82000817 to F.B.L.)+1 种基金CAS“Light of West China”Program(xbzg-zdsys-201909)Yunnan Fundamental Research Projects(202101AS070050)。
文摘DEAR EDITOR,Breast cancer is the most common malignant tumor in women,posing a serious threat to health. Tree shrews(Tupaia belangeri chinensis) are evolutionarily closer to humans than rodents and are emerging as an attractive experimental animal model for breast cancer. The PIK3CA gene is frequently mutated in both human and tree shrew breast tumors. Herein, we effectively overexpressed PIK3CA-H1047R in the mammary epithelial cells of tree shrews using a lentivirus to induce breast tumors.
文摘BACKGROUND Large appendiceal orifice polyps are traditionally treated surgically.Recently,endoscopic mucosal resection(EMR)and endoscopic submucosal dissection(ESD)have been utilized as alternative resection techniques.AIM To evaluate the efficacy and safety of endoscopic resection techniques for the management of large appendiceal orifice polyps.METHODS This was a retrospective observational study conducted to assess the feasibility and safety of EMR and ESD for large appendiceal orifice polyps.This project was approved by the Baylor College of Medicine Institutional Review Board.Patients who underwent endoscopic resection of appendiceal orifice polyps≥1 cm from 2015 to 2022 at a tertiary referral endoscopy center in the United States were enrolled.The main outcomes of this study included en bloc resection,R0 resection,post resection adverse events,and polyp recurrence.RESULTS A total of 19 patients were identified.Most patients were female(53%)and Caucasian(95%).The mean age was 63.3±10.8 years,and the average body mass index was 28.8±6.4.The mean polyp size was 25.5±14.2 mm.74%of polyps were localized to the appendix(at or inside the appendiceal orifice)and the remaining extended into the cecum.68%of polyps occupied≥50%of the appendiceal orifice circumference.The mean procedure duration was 61.6±37.9 minutes.Polyps were resected via endoscopic mucosal resection,endoscopic submucosal dissection,and hybrid procedures in 5,6,and 8 patients,respectively.Final pathology was remarkable for tubular adenoma(n=10)[one with high grade dysplasia],sessile serrated adenoma(n=7),and tubulovillous adenoma(n=2)[two with high grade dysplasia].En bloc resection was achieved in 84%with an 88%R0 resection rate.Despite the large polyp sizes and challenging procedures,89%(n=17)of patients were discharged on the same day as their procedure.Two patients were admitted for post-procedure observation for conservative pain management.Eight patients underwent repeat colonoscopy without evidence of residual or recurrent adenomatous polyps.CONCLUSION Our study highlights how endoscopic mucosal resection,endoscopic submucosal dissection,and hybrid procedures are all appropriate techniques with minimal adverse effects,further validating the utility of endoscopic procedures in the management of large appendiceal polyps.
文摘Objective:The clinical grading system for varicoceles is subjective and dependent on clinician experience.Color Doppler ultrasound(US)has not been standardized in the diagnosis of varicoceles.We aimed to determine if US measurement of varicocele could be predictive of World Health Organization(WHO)varicocele grade.Methods:Men who presented for either scrotal pain or infertility to a tertiary men’s health clinic underwent physical examination,and varicoceles were graded following WHO criteria(0Zsubclinical,1,2,3).US was used to measure largest venous diameter in the pampiniform plexus bilaterally at rest and during Valsalva maneuver.Receiver operator characteristic curve analysis was used to determine if resting diameter,diameter during Valsalva,or change in diameter between at rest and during Valsalva provided the highest sensitivity and specificity for determining clinical grade.Threshold values for diameter were determined from these receiver operator characteristic curves.Results:A total of 102 men(50 with clinical varicocele and 52 with subclinical varicocele)were included.Diameter at rest was the best ultrasonographic discriminator between subclinical and clinical varicoceles(area under the curve[AUC]Z0.67)with a diameter threshold of 3.0 mm(sensitivity 79%,specificity 42%).Diameter during Valsalva had the greatest AUC for determining clinical Grades 1 versus 2(AUCZ0.57)with diameter threshold of 5.7 mm(sensitivity 71%,specificity 33%).For differentiating between Grades 2 and 3,diameter at rest had the greatest AUC of 0.65 with a threshold of 3.6 mm(sensitivity 71%,specificity 58%).Conclusion:Our results corroborate other studies that have shown a weak correlation between US and clinical grading.The use of diameter during Valsalva was less predictive than diameter at rest and was only clinically significant in differentiating between Grade 1 and 2 varicocele.A standardized method for determining clinically relevant varicoceles on US would allow for improved patient counseling and clinical decision-making.
文摘Growing evidence demonstrate that cold stimulation as a nonpharmacological strategy can be applied to prevent the development of ageing.However,the optimal ambient temperature to mammals and the mechanism for low temperature to extend lifespan remain poorly understood.In this editorial,we highlight the data presented by Hyun et al.suggesting that a beneficial role of moderate cold temperature in reducing disease-related aggregation thereby age-related deteriorations[1].
文摘Background/Purpose: Hispanic/Latinos in the US are at increased risk for type 2 diabetes (T2D). Data suggest that avocado intake is associated with better glycemic control, but whether this translates to protection from T2D has not been studied. The goal of the current analyses was to examine whether consuming avocados at baseline is associated with lower incident T2D over a six-year period, compared to not consuming avocados at baseline. Subjects/Methods: Using data from a large population of US adults with Hispanic ancestry, without known or unknown T2D at baseline (N = 6159), participants were classified as avocado consumers (N = 983) or non-consumers (N = 5176) based on the mean of two 24-hour dietary recalls. Cox proportional hazard models estimated the association of avocado consumption with incident T2D (N = 656 cases) over a six-year follow-up period, in the population as a whole, and separately in those with normoglycemia vs. prediabetes at baseline. A set of three sequential models were run: the first controlling only for sociodemographic factors (“minimally adjusted” models), the second for these and health behaviors (“fully adjusted” models), and a third for both sets of covariates and also body mass index (BMI;“fully adjusted + BMI” models). Results: In the population as a whole, avocado intake at baseline was associated with reduced incident T2D in both the minimally adjusted (hazard ratio [HR] (±95% confidence intervals [CIs]): 0.70 (0.52 - 0.94), P = 0.04) and the fully adjusted models (HR: 0.72 (0.54 - 0.97), P = 0.03). This association was observed in both those with prediabetes and with normoglycemia at baseline, but only reached significance in those with prediabetes (minimally adjusted model: HR: 0.68 (0.48 - 0.97), P = 0.03;fully adjusted model: HR: 0.69 (0.48 - 0.98), P = 0.04), not in those with normoglycemia (minimally adjusted model: HR: 0.86 (0.45 - 1.65), P = 0.65;fully adjusted model: HR: 0.80 (0.41 - 1.55), P = 0.50). In models which additionally controlled for BMI (“fully adjusted + BMI model”), the associations were slightly attenuated (overall population: HR: 0.79 (0.59 - 1.06), P = 0.60;normoglycemia: HR: 0.83 (0.42 - 1.64), P = 0.60;prediabetes: HR = 0.75 (0.54 - 1.05), P = 0.09). Conclusions: In our longitudinal analyses, adults with Hispanic/Latino ancestry who consumed avocado were less likely to develop T2D than those who did not consume avocado at baseline, especially if they had prediabetes at baseline.
文摘Interstitial lung disease(ILD)is typically managed on an outpatient basis.Critical care physicians manage patients with ILD in the setting of an acute exacerbation(ILD flare)causing severe hypoxia.The principles of management of acute exacerbation of ILD are different from those used to manage patients with acute respiratory distress syndrome from sepsis,etc.Selected patients may be candidates for aggressive measures like extracorporeal membrane oxygenation and lung transplantation,while almost all patients will benefit from early palliative care.This review focused on the types of ILD,diagnosis,and management pathways for this challenging condition.
基金supported by the Corbett Estate Fund(62285-531021-41800,to EW)the Helen Vosburg McCrillus Plummer and Robert Edward Lee Plummer,Jr.Chair Fund(to JHH).
文摘Neuron-astrocyte interactions are vital for the brain’s connectome.Understanding astrocyte activities is crucial for comprehending the complex neural network,particularly the population-level functions of neurons in different cortical states and associated behaviors in mammals.Studies on animal sleep and wakefulness have revealed distinct cortical synchrony patterns between neurons.Astrocytes,outnumbering neurons by nearly fivefold,support and regulate neuronal and synaptic function.Recent research on astrocyte activation during cortical state transitions has emphasized the influence of norepinephrine as a neurotransmitter and calcium waves as key components of ion channel signaling.This summary focuses on a few recent studies investigating astrocyte-neuron interactions in mouse models during sleep,wakefulness,and arousal levels,exploring the involvement of noradrenaline signaling,ion channels,and glutamatergic signaling in different cortical states.These findings highlight the significant impact of astrocytes on large-scale neuronal networks,influencing brain activity and responsiveness.Targeting astrocytic signaling pathways shows promise for treating sleep disorders and arousal dysregulation.More research is needed to understand astrocytic calcium signaling in different brain regions and its implications for dysregulated brain states,requiring future human studies to comprehensively investigate neuron-astrocyte interactions and pave the way for therapeutic interventions in sleep-and arousal-related disorders.
基金supported by grants from the NIH(P01DK113954,R01DK115761,R01DK117281,R01DK125480 and R01DK120858 to YXR01DK129548 to YH)+1 种基金USDA/CRIS(51000-064-01S to YX)Postdoctoral Fellowship(2020AHA000POST000204188)to LT。
文摘Glucose is the primary fuel source of the brain,and therefore glucose levels need to be tightly regulated and maintained within a small physiological range.Certainly,the body necessitates a stable supply of energy mainly provided by glucose for various bodily functions.High or low blood glucose levels would impair the physiological functions of various organs of the body.
基金supported by grants from Mission Connect, a project of the TIRR Foundation, the Glaucoma Research FoundationNIH grants R01NS112691 and R01NS076708 (to TAW)
文摘Stress signaling following axon injury stimulates a transcriptional program for regeneration that might be exploited to promote central nervous system repair.However,this stress response drives neuronal apoptosis in non-regenerative environments.This duality presents a quandary for the development of therapeutic interventions:manipulating stress signaling to enhance recovery of damaged neurons risks accelerating neurodegeneration or restricting regenerative potential.This dichotomy is well illustrated by the fates of retinal ganglion cells(RGCs)following optic nerve crush.In this central nervous system injury model,disruption of a stress-activated MAP kinase(MAPK)cascade blocks the extensive apoptosis of RGCs that occurs in wild-type mice(Watkins et al.,2013;Welsbie et al.,2017).
基金funded by the National Eye Institute(NIH) EY029360the Whitehall Foundation+1 种基金the TIRR Foundationthe Levy-Longenbaugh Research Award to NMT National Institute on Aging (NIH) F31AG067676 to CAW。
文摘A common feature among neurodegenerative conditions is that ce rtain neuronal populations are selectively vulnerable to loss(Fu et al.,2018).By corollary,other neurons are selectively resilient,suggesting they may possess unique features that support their survival.U nderstanding the basis of neuronal resilience or vulnerability would provide a logical strategy to identify factors that could be targeted therapeutically.