Piroxicam-mediated modulatory action of 5-hydroxytryptamine serves as a “brake” on neuronal excitability in ischemic stroke

Our previous studies indicated an increase in extracellular y-aminobutyric acid （GABA） in rodent＇s ischemic brain after Piroxicam administration, leading to alleviation of glutamate me- diated excitotoxicity through activation of type A GABA receptor （GABAA）. This study was to investigate if GABAA activation by Piroxicam affects extracellular 5-hydroxytryptamine or not. High performance liquid chromatography revealed that there was a significant decrease in extracellular 5-hydroxytryptamine release in ischemic cerebral cortex and striatum in Piroxicam pre-treated rat brains. This suggests a probable role of Piroxicam in reducing extracellular 5-hy- droxytryptamine release in ischemic cerebral cortex and striatum possibly due to the GABAA activation by Piroxicam.

A possible therapeutic potential of quercetin through inhibition of μ-calpain in hypoxia induced neuronal injury:a molecular dynamics simulation study

The neuroprotective property of quercetin is well reported against hypoxia and ischemia in past studies.This property of quercetin lies in its antioxidant property with blood-brain barrier permeability and anti-inflammatory capabilities.μ-Calpain,a calcium ion activated intracellular cysteine protease causes serious cellular insult,leading to cell death in various pathological conditions including hypoxia and ischemic stroke.Hence,it may be considered as a potential drug target for the treatment of hypoxia induced neuronal injury.As the inhibitory property of μ-calpain is yet to be explored in details,hence,in the present study,we investigated the interaction of quercetin with μ-calpain through a molecular dynamics simulation study as a tool through clarifying the molecular mechanism of such inhibition and determining the probable sites and modes of quercetin interaction with the μ-calpain catalytic domain.In addition,we also investigated the structure-activity relationship of quercetin with μ-calpain.Affinity binding of quercetin with μ-calpain had a value of –28.73 k J/mol and a Ki value of 35.87 μM that may be a probable reason to lead to altered functioning of μ-calpain.Hence,quercetin was found to be an inhibitor of μ-calpain which might have a possible therapeutic role in hypoxic injury.

Intracellular compartmentation of cAMP promotes neuroprotection and regeneration of CNS neurons

In the central nervous system（CNS）,cyclic adenosine monophosphate（cAMP）plays a critical role in numerous,often concurrent,neuronal functions including survival,growth,differentiation and synaptogenesis.

Imaging assessment of profound sensorineural deafness with inner ear anatomical abnormalities

Objective: : To explore the value of a combined computed tomography(CT) and magnetic resonance imaging(MRI) in evaluating profound sensorineural deafness patients before cochlear implant(CI) surgery.Methods: A retrospective analysis of 1012 cases of profound sensorineural deafness that received CI was performed.Results: A total of 96 cases were diagnosed with inner ear abnormalities including large vestibular aqueduct syndrome(LVAS, n ? 61), Michel deformity(n ? 3), cochlear incomplete partition I(n ? 2), cochlear incomplete partition II(n ? 6), cochlear hypoplasia with vestibular malformation(n ? 3), cochlear ossification(n ? 3), bilateral internal auditory canal obstruction(n ? 5) and internal auditory canal stenosis(n ? 2).Conclusion: High resolution CT(HRCT) can display bony structures while MRI can image the membranous labyrinth in preoperative evaluation for cochlear implantation. The combination of these two modalities provides reliable anatomical information regarding the bony and membranous labyrinths, as well as the auditory nerve.

Social media growth of orthopaedic surgery residency programs in response to the COVID-19 pandemic

BACKGROUND In the Spring of 2020,residency programs across the country experienced rapid and drastic changes to their application process as a result of the coronavirus disease 2019(COVID-19)pandemic.In response,residency programs shifted to virtual events and began harnessing social media to communicate with applicants.AIM To analyze the changes in social media usage by orthopaedic surgery programs in response to the COVID-19 pandemic.METHODS Based on the 2019 residency and fellowship electronic database,accredited US orthopaedic surgery programs were reviewed for social media presence on Instagram and Twitter.Approximately 47000 tweets from 2011-2021 were extracted through the Twitter application programming interface.We extracted:Total number of followers,accounts following,tweets,likes,date of account creation,hashtags,and mentions.Natural language processing was utilized for tweet sentiment analysis and classified as positive,neutral,or negative.Instagram data was collected and deemed current as of August 11,2021.The account foundation date analysis was based on the date recognized as the start of the COVID-19 outbreak in the United States,before or after March 1,2020.RESULTS A total of 85(42.3%)orthopaedic surgery residency program Twitter handles were identified.Thirty-five(41.2%)programs joined Twitter in the nine months after the 2020 covid outbreak.In 2020,there was a 126.6%increase in volume of tweets by orthopaedic surgery residency accounts as compared to 2019.The median number of followers was 474.5(interquartile range 205.0-796.5).The account with the highest number of tweets was Hospital for Special Surgery(@HSpecialSurgery)with 13776 tweets followed by University of Virginia(@UVA_Ortho)with 5063 and Yale(@OrthoAtYale)with 899.Sentiment analysis before 2020 revealed 30.4%positive,60.8%neutral,and 8.8%negative sentiments across tweets.Interestingly,the positive sentiment percentage increased in 2020 from 30.4%to 34.5%.Of the 201 ACGME-accredited orthopaedic residency programs on Fellowship and Residency Electronic Interactive Database,115(57.2%)participate on Instagram,with 101(87.8%)identified as“resident”-managed vs 14(12.2%)identified as“department”-managed.Over three quarters(77.4%)of Instagram accounts were created after March 1,2020.The average number of followers per account was 1089.5 with an average of 58.9 total posts.CONCLUSION Our study demonstrates a substantial growth of Instagram and Twitter presence by orthopaedic surgery residency programs during the COVID-19 pandemic.These data suggest that orthopaedic residency programs have utilized social media as a new way to communicate with applicants and showcase their programs in light of the challenges presented by the pandemic.

The Use of Bovine Collagen and Skin Graft for Reconstruction of the Glans Penis Following Cancer Resection

Penile reconstruction following cancer resection has long been a challenge due to demand for both aesthetic and functional preservation. Although various methods have attempted to achieve both goals, none have succeeded entirely. In this report, we introduce a novel reconstructive technique on a 64-year-old patient with squamous cell carcinoma of the glans penis. The technique consisted of two staged procedures. First, a dermal substitute, consisting of bovine collagen, was sutured onto the defect after partial glansectomy and three weeks later, the integrated dermis was covered with autologous non-meshed partial thickness skin graft. Use of this dermal substitute in a staged fashion allowed for ability to await final pathologic margins prior to definitive reconstruction and increased dermal thickness. After 9-month follow-up, sexual function returned within 3 months and the patient remained healed. We found this technique to be useful in concurrently preserving penile function and cosmesis. Future studies should include more patients and longer follow-up.

Review of intraoperative parathormone monitoring with the miami criterion: A 25-year experience

With the development of imaging and localization studies,focused parathyroidectomy with use of intraope-rative parathormone monitoring(IPM)is the mainstay of treatment for primary hyperparathyroidism at many health care centers both nationally and internationally.Focused parathyroidectomy guided by IPM allows for surgical excision of the offending parathyroid gland through smaller incisions.The Miami criterion is a protocol that uses a">50%parathormone(PTH)drop"from either the greatest pre-incision or pre-excision measurement of PTH in a blood sample taken 10 min following resection of hyperfunctioning glands.Following removal of the hyperfunctioning parathyroid gland,a>50%PTH drop at 10 min indicates completion of parathyroidectomy,and predicts operative success at6 mo.IPM using the Miami criterion has demonstrated equal curative rates of>97%,which is comparable to the traditional bilateral neck exploration.The focused approach,however,is associated with shorter recovery times,improved cosmesis,and lower risk of postoperative hypocalcemia.

Treatment with analgesics after mouse sciatic nerve injury does not alter expression of wound healingassociated genes

Animal models of sciatic nerve injury are commonly used to study neuropathic pain as well as axon regeneration. Administration of post-surgical analgesics is an important consideration for animal welfare, but the actions of the analgesic must not interfere with the scientific goals of the experiment. In this study, we show that treatment with either buprenorphine or acetaminophen following a bilateral sciatic nerve crush surgery does not alter the expression in dorsal root ganglion（DRG） sensory neurons of a panel of genes associated with wound healing. These findings indicate that the post-operative use of buprenorphine or acetaminophen at doses commonly suggested by Institutional Animal Care and Use Committees does not change the intrinsic gene expression response of DRG neurons to a sciatic nerve crush injury, for many wound healing-associated genes. Therefore, administration of post-operative analgesics may not confound the results of transcriptomic studies employing this injury model.

AME证据系列001--转化医学协会:脓毒症诊断和早期识别的临床实践指南

脓毒症是一种由感染引起的异质性疾病,感染触发了一系列复杂的局部或者全身的免疫炎症反应,引起多器官功能衰竭,发病率和病死率显著升高。由于至今仍然没有诊断脓毒症的金标准,所以脓毒症的临床诊断仍是一个难题。因此,脓毒症的临床诊断需要不断改变来满足临床和研究的要求。然而,尽管有许多新型的生物标记和筛选工具去预测脓毒症发生的风险,但是这些措施的诊断价值和有效性不足以让人满意,并且没有充分的证据去建议临床使用这些新技术。因此,脓毒症的临床诊断标准需要定期更新去适应不断产生的新证据。这篇综述旨在呈现当前脓毒症的诊断和早期识别方面的最新研究证据。临床运用不同的诊断方法的推荐意见依赖于推荐、评价、发展和评估分级体系(Grades of Recommendation Assessment,Development and Evaluation,GRADE),因为大部分的研究是观察性研究,并没有对这些方法进行可靠评估,采用的是两步推理方法。未来需要更多研究来确认或者反驳某一特殊的指标检测,同时应该直接采用相关病人的结果数据。

Resveratrol inhibits matrix metalloproteinases to attenuate neuronal damage in cerebral ischemia:a molecular docking study exploring possible neuroprotection

The main pathophysiology of cerebral ischemia is the structural alteration in the neurovascular unit, coinciding with neurovascular matrix degradation. Resveratrol has been reported to be one of the most potent chemopreventive agents that can inhibit cellular processes associated with ischemic stroke. Matrix metalloproteinases （MMPs） has been considered as a potential drug target for the treatment of cerebral ischemia. To explore this, we tried to investigate the inter-action of resveratrol with MMPs through molecular docking studies. At 30 minutes before and 2 hours after cerebral ischemia/reperfusion induced by occlusion of the middle cerebral artery, 40 mg/kg resveratrol was intraperitoneally administered. After resveratrol administration, neu-rological function and brain edema were significantly alleviated, cerebral infarct volume was signiifcantly reduced, and nitrite and malondialdehyde levels in the cortical and striatal regions were signiifcantly decreased. The molecular docking study of resveratrol and MMPs revealed that resveratrol occupied the active site of MMP-2 and MMP-9. The binding energy of the complexes was –37.848672 kJ/mol and –36.6345 kJ/mol for MMP-2 and MMP-9, respectively. In case of MMP-2, Leu 164, Ala 165 and Thr 227 were engaged in H-Bonding with resveratrol and in case of MMP-9, H-bonding was found with Glu 402, Ala 417 and Arg 424 residues. These ifndings collectively reveal that resveratrol exhibits neuroprotective effects on cerebral ischemia through inhibiting MMP-2 and MMP-9 activity.

Present and future cell therapies for pancreatic beta cell replenishment

If only at a small scale,islet transplantation has successfully addressed what ought to be the primary endpoint of any cell therapy:the functional replenishment of damaged tissue in patients.After years of less-thanoptimal approaches to immunosuppression,recent advances consistently yield long-term graft survival rates comparable to those of whole pancreas transplantation.Limited organ availability is the main hurdle that stands in the way of the widespread clinical utilization of this pioneering intervention.Progress in stem cell research over the past decade,coupled with our decades-long experience with islet transplantation,is shaping the future of cell therapies for the treatment of diabetes.Here we review the most promising avenues of research aimed at generating an inexhaustible supply of insulin-producing cells for islet regeneration,including the differentiation of pluripotent and multipotent stem cells of embryonic and adult origin along the beta cell lineage and the direct reprogramming of non-endocrine tissues into insulin-producing cells.

Clinical outcomes for Conduits and Scaffolds in peripheral nerve repair

The gold standard of peripheral nerve repair is nerve autograft when tensionless repair is not possible. Use of nerve autograft has several shortcomings, however.These include limited availability of donor tissue,sacrifice of a functional nerve, and possible neuroma formation. In order to address these deficiencies,researchers have developed a variety of biomaterials available for repair of peripheral nerve gaps. We review the clinical studies published in the English literature detailing outcomes and reconstructive options.Regardless of the material used or the type of nerve repaired, outcomes are generally similar to nerve autograft in gaps less than 3 cm. New biomaterials currently under preclinical evaluation may provide improvements in outcomes.

Obesity and cardiometabolic disease risk factors among US adolescents with disabilities

AIM: To generate prevalence estimates of weight status and cardiometabolic disease risk factors among adolescents with and without disabilities.METHODS: Analysis of the 1999-2010 National Health and Nutrition Examination Survey data was conducted among 12-18 years old with(n = 256) and without disabilities(n = 5020). Mean values of waist circumference, fasting glucose, high-density-lipoprotein cholesterol, triglycerides, systolic and diastolic blood pressure and metabolic syndrome(Met S, ≥ 3 risk factors present) were examined by the following standardized body mass index(BMI) categories for those with and without disabilities; overweight(BMI ≥ 85th- < 95 th percentile for age and sex), obesity(BMI ≥ 95 th percentile) and severe obesity(BMI ≥35 kg/m2). Linear regression models were fit with each cardiometabolic disease risk factor independently as continuous outcomes to show relationships with disability status. RESULTS: Adolescents with disabilities were significantlymore likely to be overweight(49.3%), obese(27.6%) and severely obese(12%) vs their peers without disabilities(33.1%, 17.5% and 3.6%, respectively, P ≤ 0.01 for all). A higher proportion of overweight, obese and severely obese children with disabilities had abnormal SBP, fasting lipids and glucose as well as Met S(18.9% of overweight, 32.3% of obese, 55% of severely obese) vs their peers without disabilities(9.7%, 16.8%, 36.3%, respectively). US adolescents with disabilities are over three times as likely to have Met S(OR = 3.45, 95%CI: 1.08-10.99, P = 0.03) vs their peers with no disabilities.CONCLUSION: Results show that adolescents with disabilities are disproportionately affected by obesity and poor cardiometabolic health vs their peers with no disabilities. Health care professionals should monitor the cardiometabolic health of adolescents with disabilities.

Intractable hematuria due to giant prostatic hyperplasia effectively treated with prostatic artery embolization

Giant prostatic hyperplasia(GPH)is a rare pathology traditionally treated with an open suprapubic prostatectomy.This procedure is risky,and fatal hemorrhagic complications can occur.Often,patients with GPH present with diminished renal function due to obstructive nephropathy,making them unfit for less invasive endovascular therapies using traditional contrast agents.Here we present a case of a patient with intractable hematuria due to GPH,as well as diminished renal function,who was successfully treated using prostatic artery embolization with CO2 digital subtraction arteriography as a contrast agent.

Clinical significance and potential translation of neural regeneration and functional recovery in monkeys after spinal cord injury

The recent manuscript by Dr. Rao and colleagues （Rao et al., 2018） reports on a new combinational strategy that significantly promotes neural regeneration and improves motor and sensory function in nonhuman primates after severe spinal cord injury （SCI）. This acute reparative strategy that included the insertion of neurotrophin 3-loaded chitosan biodegradable material into a l-cm gap of the hemisectioned spinal cord had previously been tested in rodent models of SCI. In addition to showing that this reparative approach led to corticospinal tract axonal growth across the lesion area with extension into the distal spinal cord.