Enhancement of motor functional recovery in thoracic spinal cord injury: voluntary wheel running versus forced treadmill exercise

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.

Outcomes of endoscopic submucosal dissection in cirrhotic patients: First American cohort

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.

Community-acquired pneumonia:The importance of the early detection of drug-resistant organisms

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.

3-Dimensional Kinematic Comparison of Arm Movements between an Individual with NGLY1 Deficiency and a Neurotypical Individual

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.

Generation of a tree shrew breast cancer model using lentivirus expressing PIK3CA-H1047R

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.

Color Doppler ultrasound imaging in varicoceles: Is the difference in venous diameter encountered during Valsalva predictive of palpable varicocele grade?

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.

Expanding endoscopic boundaries:Endoscopic resection of large appendiceal orifice polyps with endoscopic mucosal resection and endoscopic submucosal dissection

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.

Moderate cold exposure contributes to the extension of lifespan by alleviating the aggregation of disease-related proteins

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].

Associations between Avocado Intake and Lower Rates of Incident Type 2 Diabetes in US Adults with Hispanic/Latino Ancestry

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.

Acute exacerbation of interstitial lung disease in the intensive care unit:Principles of diagnostic evaluation and management

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.

妇科经自然腔道单孔手术发展现状与未来方向

经自然腔道单孔内镜手术创伤小,美容效果好,术后康复快,并发症发生率低,符合现代无瘢痕、无痛的微创理念,是妇科微创外科的发展方向。妇科经自然腔道单孔内镜手术主要分为经脐入路与经阴道入路。经阴道入路腹部无瘢痕,切口愈合快,术后疼痛程度低,并发症发生率低,是目前妇科微创手术的研究热点。近年来,机器人手术系统快速发展,与经自然腔道单孔内镜手术结合可实现三维成像放大术野,灵活的机械臂实现复杂手术操作,拓宽了手术适应证,提高了手术精准度,被认为是微创手术的革命性突破。该文就妇科经自然腔道单孔手术发展现状与未来方向进行阐述。

Astrocytic calcium waves:unveiling their roles in sleep and arousal modulation

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.

A lead role for a“secondary”axonal injury response

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).

Cell-type resolved transcriptomic approaches for dissecting selective vulnerability in neurodgeneration

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.

糖尿病相关的足病的定义和标准(2023年更新版)

糖尿病相关的足病管理涉及多个学科,通用的专业词汇对于各学科间准确沟通交流至关重要。国际糖尿病足工作组(IWGDF)对相关文献进行了系统综述,构成了制定IWGDF指南的基础,并且明确了糖尿病相关的足病的一系列定义、标准及名词解释。本文介绍2023年IWGDF对这些定义和标准的更新,并建议在临床实践和研究中一致使用,以利于世界各地不同学科人员针对糖尿病相关的足病的专业性交流。

Circulating microRNA expression and nonalcoholic fatty liver disease in adolescents with severe obesity

BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is one of the most common chronic liver diseases in children and adolescents.NAFLD ranges in severity from isolated hepatic steatosis to nonalcoholic steatohepatitis(NASH),wherein hepatocellular inflammation and/or fibrosis coexist with steatosis.Circulating microRNA(miRNA)levels have been suggested to be altered in NAFLD,but the extent to which miRNA are related to NAFLD features remains unknown.This analysis tested the hypothesis that plasma miRNAs are significantly associated with histological features of NAFLD in adolescents.AIM To investigate the relationship between plasma miRNA expression and NAFLD features among adolescents with NAFLD.METHODS This study included 81 adolescents diagnosed with NAFLD and 54 adolescents without NAFLD from the Teen-Longitudinal Assessment of Bariatric Surgery study.Intra-operative core liver biopsies were collected from participants and used to characterize histological features of NAFLD.Plasma samples were collected during surgery for miRNA profiling.A total of 843 plasma miRNAs were profiled using the HTG EdgeSeq platform.We examined associations of plasma miRNAs and NAFLD features using logistic regression after adjusting for age,sex,race,and other key covariates.Ingenuity Pathways Analysis was used to identify biological functions of miRNAs that were associated with multiple histological features of NAFLD.RESULTS We identified 16 upregulated plasma miRNAs,including miR-193a-5p and miR-193b-5p,and 22 downregulated plasma miRNAs,including miR-1282 and miR-6734-5p,in adolescents with NAFLD.Moreover,52,16,15,and 9 plasma miRNAs were associated with NASH,fibrosis,ballooning degeneration,and lobular inflammation,respectively.Collectively,16 miRNAs were associated with two or more histological features of NAFLD.Among those miRNAs,miR-411-5p was downregulated in NASH,ballooning,and fibrosis,while miR-122-5p,miR-1343-5p,miR-193a-5p,miR-193b-5p,and miR-7845-5p were consistently and positively associated with all histological features of NAFLD.Pathway analysis revealed that most common pathways of miRNAs associated with multiple NAFLD features have been associated with tumor progression,while we also identified linkages between miR-122-5p and hepatitis C virus and between miR-199b-5p and chronic hepatitis B.CONCLUSION Plasma miRNAs were associated with NAFLD features in adolescent with severe obesity.Larger studies with more heterogeneous NAFLD phenotypes are needed to evaluate miRNAs as potential biomarkers of NAFLD.

Driving pressure decoded:Precision strategies in adult respiratory distress syndrome management

Mechanical ventilation(MV)is an important strategy for improving the survival of patients with respiratory failure.However,MV is associated with aggravation of lung injury,with ventilator-induced lung injury(VILI)becoming a major concern.Thus,ventilation protection strategies have been developed to minimize complications from MV,with the goal of relieving excessive breathing workload,improving gas exchange,and minimizing VILI.By opting for lower tidal volumes,clinicians seek to strike a balance between providing adequate ventilation to support gas exchange and preventing overdistension of the alveoli,which can contribute to lung injury.Additionally,other factors play a role in optimizing lung protection during MV,including adequate positive end-expiratory pressure levels,to maintain alveolar recruitment and prevent atelectasis as well as careful consideration of plateau pressures to avoid excessive stress on the lung parenchyma.

Quantifying Kinematic Tremor in an NGLY1-Deficient Individual: A Case Study

NGLY1 Deficiency is an autosomal recessive congenital disorder that has been identified in less than 100 individuals. Most individuals with NGLY1 Deficiency display hyperkinetic movement disorders, including choreiform, athetoid, dystonic myoclonic, dyskinetic, and dysmetric movements. Developing a consistent and concise consensus on the classification and evaluation of tremors is essential to forward the research and treatment of tremors. It has also been reported that some individuals with NGLY1 Deficiency demonstrate tremor, but such tremor has never been formally investigated. The primary objective of this study is to determine if an individual with NGLY1 Deficiency demonstrates an identifiable tremor during a series of arm movements and, if so, describe the frequency and power characteristics of that tremor. Arm movement kinematics were obtained using a 16-camera Vicon system, and time series trajectory waveforms for three planes of a marker placed on the hand were developed. Custom MATLAB scripts were utilized to compute Fast Fourier Transformations of the data within the identified waveform segments. A mean frequency of 2.30 Hz (SD = 1.05) with a mean power of 5.02 |P1(f)| (SD = 4.63) suggests that our participant’s kinematic data did display a persistent tremor in both hands across all tasks and movement planes. Analyses of the reaching hand and the non-reaching hand suggest the participant displayed an action tremor in both postural and intention (kinetic) tremors. Future directions should include assessing additional individuals with NGLY1 Deficiency to determine if the tremor is a distinguishable disorder behavior. Additionally, evaluating other anatomical sites, such as the elbow, head, and lower limbs, would provide further insights into the characteristics of this tremor.

History of Helicobacter pylori,duodenal ulcer,gastric ulcer and gastric cancer

Helicobacter pylori(H.pylori)infection underlies gastric ulcer disease,gastric cancer and duodenal ulcer disease.The disease expression reflects the pattern and extent of gastritis/gastric atrophy(i.e.,duodenal ulcer with non-atrophic and gastric ulcer and gastric cancer with atrophic gastritis).Gastric and duodenal ulcers and gastric cancer have been known for thousands of years.Ulcers are generally non-fatal and until the 20th century were difficult to diagnose.However,the presence and pattern of gastritis in past civilizations can be deduced based on the diseases present.It has been suggested that gastric ulcer and duodenal ulcer both arose or became more frequent in Europe in the 19th century.Here,we show that gastric cancer and gastric ulcer were present throughout the 17th to 19th centuries consistent with atrophic gastritis being the predominant pattern,as it proved to be when it could be examined directly in the late 19th century.The environment before the 20th century favored acquisition of H.pylori infection and atrophic gastritis(e.g.,poor sanitation and standards of living,seasonal diets poor in fresh fruits and vegetables,especially in winter,vitamin deficiencies,and frequent febrile infections in childhood).The latter part of the 19th century saw improvements in standards of living,sanitation,and diets with a corresponding decrease in rate of development of atrophic gastritis allowing duodenal ulcers to become more prominent.In the early 20th century physician’s believed they could diagnose ulcers clinically and that the diagnosis required hospitalization for"surgical disease"or for"Sippy"diets.We show that while H.pylori remained common and virulent in Europe and the United States,environmental changes resulted in changes of the pattern of gastritis producing a change in the manifestations of H.pylori infections and subsequently to a rapid decline in transmission and a rapid decline in all H.pylori-related diseases.

Hepatocellular carcinoma review:Current treatment,and evidence-based medicine

Hepatocellular carcinoma(HCC)is the fifth most common tumor worldwide.Multiple treatment options are available for HCC including curative resection,liver transplantation,radiofrequency ablation,trans-arterial chemoembolization,radioembolization and systemic targeted agent like sorafenib.The treatment of HCC depends on the tumor stage,patient performance status and liver function reserve and requires a multidisciplinary approach.In the past few years with significant advances in surgical treatments and locoregional therapies,the short-term survival of HCC has improved but the recurrent disease remains a big problem.The pathogenesis of HCC is a multistep and complex process,wherein angiogenesis plays an important role.For patients with advanced disease,sorafenib is the only approved therapy,but novel systemic molecular targeted agents and their combinations are emerging.This article provides an overview of treatment of early and advanced stage HCC based on our extensive review of relevant literature.