Glucagon-like peptide-1 receptor agonists as a possible intervention to delay the onset of type 1 diabetes:A new horizon

Type 1 diabetes(T1D)is a chronic autoimmune condition that destroys insulinproducing beta cells in the pancreas,leading to insulin deficiency and hyperglycemia.The management of T1D primarily focuses on exogenous insulin replacement to control blood glucose levels.However,this approach does not address the underlying autoimmune process or prevent the progressive loss of beta cells.Recent research has explored the potential of glucagon-like peptide-1 receptor agonists(GLP-1RAs)as a novel intervention to modify the disease course and delay the onset of T1D.GLP-1RAs are medications initially developed for treating type 2 diabetes.They exert their effects by enhancing glucose-dependent insulin secretion,suppressing glucagon secretion,and slowing gastric emptying.Emerging evidence suggests that GLP-1RAs may also benefit the treatment of newly diagnosed patients with T1D.This article aims to highlight the potential of GLP-1RAs as an intervention to delay the onset of T1D,possibly through their potential immunomodulatory and anti-inflammatory effects and preservation of beta-cells.This article aims to explore the potential of shifting the paradigm of T1D management from reactive insulin replacement to proactive disease modification,which should open new avenues for preventing and treating T1D,improving the quality of life and long-term outcomes for individuals at risk of T1D.

Measurement,associations,patterns,and promotion:Unveiling vital areas in physical activity epidemiology

Physical activity(PA)epidemiology first emerged as a new field of study around the 1950s with publication of seminal investigations on London civil servants1 and has continued to evolve as a scientific discipline to present time.This subdiscipline of epidemiology studies the frequencies,distributions,and dynamics of PA and its impact on human health,morbidity,and mortality.Research over the past 75 years has demonstrated numerous health benefits of PA.Based on these research findings,the World Health Organization recommends adults aged 18-64 years engage in at least 150-300 min of moderate-intensity aerobic PA per week,or at least 75-150 min of vigorous-intensity aerobic PA per week,or a combination of both intensities.

Vibration-assisted vat photopolymerization for pixelated-aliasing-free surface fabrication

Mask image projection-based vat photopolymerization(MIP-VPP)offers advantages like low cost,high resolution,and a wide material range,making it popular in industry and education.Recently,MIP-VPP employing liquid crystal displays(LCDs)has gained traction,increasingly replacing digital micromirror devices,particularly among hobbyists and in educational settings,and is now beginning to be used in industrial environments.However,LCD-based MIP-VPPsuffers from pronounced pixelated aliasing arising from LCD’s discrete image pixels and itsdirect-contact configuration in MIP-VPP machines,leading to rough surfaces on the 3D-printed parts.Here,we propose a vibration-assisted MIP-VPP method that utilizes a microscalevibration to uniformize the light intensity distribution of the LCD-based mask image on VPP’s building platform.By maintaining the same fabrication speed,our technique generates asmoother,non-pixelated mask image,reducing the roughness on flat surfaces and boundary segments of 3D-printed parts.Through light intensity modeling and simulation,we derived an optimal vibration pattern for LCD mask images,subsequently validated by experiments.We assessed the surface texture,boundary integrity,and dimensional accuracy of componentsproduced using the vibration-assisted approach.The notably smoother surfaces and improved boundary roughness enhance the printing quality of MIP-VPP,enabling its promisingapplications in sectors like the production of 3D-printed optical devices and others.

Efficacy of super-pulsed 905 nm Low Level Laser Therapy (LLLT) in the management of Traumatic Brain Injury (TBI): A case study

Traumatic brain injury is a major health concern worldwide with massive financial and social impact. Conventional treatments primarily focus on the prevention of further damage to the brain parenchyma, while failing to address the already existent symptoms. Previous clinical studies have shown that Low Level Laser Therapy (LLLT) can significantly reduce pain and induce temporary vasodilation in capillaries, which the authors hypothesize can be used to improve the quality of life in TBI patients by treating their current symptoms, which are predominately migraine-like headaches. This case report illustrates the use of LLLT in the treatment of a patient with a TBI and the great clinical success achieved in the reduction of pain, as measured by VAS—achievable within five treatments of 10 minutes in duration.

Emerging therapeutic options for non-alcoholic fatty liver disease:A systematic review

BACKGROUND Non-alcoholic fatty liver disease(NAFLD)has become a prevalent cause of chronic liver disease and ranks third among the causes of transplantation.In the United States alone,annual medical costs are approximately 100 billion dollars.Unfortunately,there is no Federal Drug Administration(FDA)-approved medication for its treatment.However,various clinical trials are investigating several therapeutic classes that could potentially treat NAFLD.It is valuable to have a compilation of the data available on their efficacy.AIM To assess the efficacy of cyclophilin inhibitors,fibroblast growth factor 21 analogs(FGF21),and dual and pan peroxisome proliferator-activated receptor(PPAR)agonists for treating NAFLD.METHODS A comprehensive literature search using keywords including cyclophilin inhibitor,FGF agonist,pan-PPAR agonists,dual-PPAR agonist,NAFLD,nonalcoholic steatohepatitis,and fatty liver was conducted on October 29,2022,in PubMed,EMBASE,Cochrane Library,Scopus and Web of Science.Animal and human research,case reports,and published articles in English from all countries with patients aged 18 and above were included.Only articles with a National Institutes of Health(NIH)Quality Assessment score of five or higher out of eight points were included.Articles that were narrative or systematic reviews,abstracts,not in English,focused on patients under 18 years old,did not measure outcomes of interest,were inaccessible,or had a low NIH Quality Assessment score were excluded.Each article was screened by two independent researchers evaluating relevance and quality.Resources were scored based on the NIH Quality Assessment Score;then,pertinent data was extracted in a spreadsheet and descriptively analyzed.RESULTS Of the 681 records screened,29 met the necessary criteria and were included in this review.These records included 12 human studies and 17 animal studies.Specifically,there were four studies on cyclophilin inhibitors,four on FGF agonists/analogs,eleven on pan-PPAR agonists,and ten on dual-PPAR agonists.Different investigational products were assessed:The most common cyclophilin inhibitor was NV556;FGF agonists and analogs was Efruxifermin;pan-PPAR agonists was Lanifibranor;and dual-PPAR agonists was Saroglitazar.All classes were found to be statistically efficacious for the treatment of NAFLD,with animal studies demonstrating improvement in steatosis and/or fibrosis on biopsy and human studies evidencing improvement in different metabolic parameters and/or steatosis and fibrosis on FibroScan(P<0.05).CONCLUSION The data analyzed in this review showed clinically significant improvement in individual histological features of NAFLD in both animal and human trials for all four classes,as well as good safety profiles(P<0.05).We believe this compilation of information will have positive clinical implications in obtaining an FDA-approved therapy for NAFLD.

caspase-3激活在庆大霉素所致耳蜗螺旋神经元延迟性死亡过程中的作用

目的观察毛细胞丢失后耳蜗神经元延迟性死亡模式以及caspase-3的活动。方法采用3mol的庆大霉素作用离体培养的耳蜗24h,损毁全部毛细胞,分别在毛细胞丢失后1、3、5、7和14d收获样本。采用Neurofilament 200KDa标记耳蜗神经元,TRITC-labeled phalloidin标记毛细胞,免疫荧光染色观察神经元和毛细胞的存活数量,采用WesternBlot的方法检测caspase-3特异降解产物α-spectrin,间接确定caspase-3活动。结果3mol庆大霉素作用于培养的耳蜗24h,耳蜗毛细胞几乎全部消失。螺旋神经元和神经纤维的数目随培养时间的延长而减少,神经元存活从第1天的87%降至第14天的5%。神经元变小且形状不规则,在神经纤维上出现实质小体。检测caspse-3激活的特异降解带-120KDa的灰度值,发现在毛细胞丢失后24h,caspase-3活性明显高于毛细胞丢失的初时(P<0.01)。结论毛细胞丢失引起螺旋神经元死亡具有时间依赖效应,神经元出现凋亡的形态学特征,并且有caspase-3的活动。

Epithelial ovarian cancer:An overview

Ovarian cancer is the second most common gyneco-logical cancer and the leading cause of death in the United States. In this article we review the diagnosis and current management of epithelial ovarian cancer which accounts for over 95 percent of the ovarian malignancies. We will present various theories about the potential origin of ovarian malignancies. We will discuss the genetic anomalies and syndromes that may cause ovarian cancers with emphasis on Breast cancer type 1/2 mutations. The pathology and pathogenesis of ovarian carcinoma will also be presented. Lastly, we provide a comprehensive overview of treatment strategies and staging of ovarian cancer, conclusions and future directions.

Neuromyelitis optica and myelin oligodendrocyte glycoprotein

Neuromyelitis optica(NMO)refers to an antibody mediated,inflammatory disorder of the central nervous system(CNS)characterized by recurrent or monophasic attacks of optic neuritis and myelitis.Most patients with NMO possess a specific serum immunoglobin,NMO-IgG,which can serve as a biomarker for NMO.The autoantibodies target aquaporin-4(AQP4),the main water channel protein found in the CNS including the brain,spinal cord,and optic nerve.The remaining 10-25%of patients are seronegative for NMO-IgG despite meeting the diagnostic criteria for NMO.Recent studies have shown that a subset of these patients is seropositive for antibodies against myelin oligodendrocyte glycoprotein(MOG).This paper will provide an overview of the current English scientific literature published regarding the history,epidemiology,AQP4 biomarker,MOG biomarker,diagnosis,clinical features,related diseases in NMO spectrum disorder(NMOSD),and treatments of NMO.

Progress in neuro-ophthalmology

Change has come slowly to the field of neuro-ophthalmology.The major transformative innovations in diagnostic neuroimaging occurred decades ago but the field remained mostly a diagnostic subspecialty.Over the past few years however a new birth of innovative translational tests and treatments have emerged and have accelerated progress in neuro-ophthalmology.This dramatic wave of new testing and treatment modalities is the impetus for this monograph entitled“Progress in neuro-ophthalmology.”We hope that you enjoy this information and the continued and evolving journey of our specialty from the diagnostic to the therapeutic realm.

Laser speckle contrast imaging compared with indocyanine green in renal perfusion of a porcine model

Background:When viewed under near-infrared light,indocyanine green(ICG)signal for kidney perfusion can be utilized in partial nephrectomy.Laser speckle contrast imaging(LSCI)uses coherent light to detect perfusion during real-time laparoscopic surgery.Materials and methods:Laser speckle contrast imaging or ActivSight,an imaging sensor adapter,was used during laparoscopy of an anesthetized porcine kidney model.ActivSight's"perfusion mode"and"quantification mode"displayed the blood flow as a heatmap and numerical signal intensity,respectively.Results:After the upper segmental renal artery was clamped,ICG was seen in the lower pole,and LSCI showed low unit(dark color)quantification and perfusion in the upper pole.Indocyanine green was retained in the lower pole after the upper segmental artery was unclamped,and LSCI perfusion was demonstrated in the entire kidney.Conclusions:Laser speckle contrast imaging is a dye-free,repeatable,real-time adjunct for renal parenchymal perfusion assessment applicable to minimally invasive renal surgery to complement the technology of ICG near-infrared fluorescence and advance digital surgery.

Effects of dexmedetomidine on the expression of inflammatory factors in children with congenital heart disease undergoing intraoperative cardiopulmonary bypass:A randomized controlled trial

Importance:Dexmedetomidine inhibits the inflammatory response associated with cardiopulmonary bypass(CPB)and protects neural function.However,the mechanism of dexmedetomidine’s anti-inflammatory pathway is unclear.Objective:To investigate the effect of dexmedetomidine on the cognitive level and expression of inflammatory factors in children with congenital heart disease undergoing intraoperative CPB.Methods:Ninety children with congenital heart disease were recruited and randomly divided into 3 groups of 30 children in each.In Group 1,a 1.0μg·kg-1·h-1 intravenous bolus of dexmedetomidine was administered 10 minutes after induction of anesthesia,followed by a 0.2μg·kg-1·h-1 infusion until the surgical incision.In Group 2,a 0.5μg/kg intravenous bolus of dexmedetomidine was administered 10 minutes after induction of anesthesia,followed by a 0.1μg·kg-1·h-1 infusion until the surgical incision.The control group was given physiological saline using the same method as in Groups 1 and 2.The serum levels of nuclear factor-kappa B(NF-κB),S-100βprotein,neuron-specific enolase(NSE),tumor necrosis factor-α(TNF-α),and interleukin-6(IL-6)were measured before the surgery(T1),at the end of CPB(T2),2 hours after CPB(T3),6 hours after CPB(T4),and 24 hours after CPB(T5).The Wechsler Intelligence Scale for children(WISC)was measured before the operation and at 3,6,and 12 months after the operation to evaluate the neurodevelopmental state of the children.Results:The levels of the NF-κB,S-100βprotein,NSE,TNF-α,IL-6 were significantly higher at T2,T3,or T4 than before the surgery(T1)in the control group or the dexmedetomidine groups.However,the increases of NF-κB,TNF-α,IL-6,S-100βand NSE levels were significantly smaller in the dexmedetomidine groups than those in the control group(P<0.017).The WISC scores were similar among the three groups before or after the operation.Interpretation:The increases in NF-κB,TNF-α,and IL-6 levels indicated aggravation of the inflammatory reaction and the increase S-100βprotein and NSE levels indicated that the nervous system was damaged.Administration of dexmedetomidine to children with congenital heart disease undergoing intraoperative CPB can inhibit the inflammatory response and may ameliorate the neurodevelopmental damage caused by CPB.

Nasal endoscopy protocols in the era of COVID-19

Introduction COVID-19,the respiratory illness caused by the novel SARSCoV-2 virus has rapidly emerged as a serious global health concern.As of March 12,2020,the World Health Organization(WHO)has declared this virus a pandemic.1 In the United States,there have been 35,841 cases diagnosed and 465 deaths,with both prevalence and mortality continuing to escalate.2 The WHO and has enacted various protocols for healthcare institutions internationally in an attempt to slow the spread of disease,3 including adjustments for procedures performed by otolaryngologists.This paper aims to review the current literature pertaining to adjustments in nasal endoscopy protocols and appropriate precautions in the era of COVID-19.

Carboplatin致灰鼠内毛细胞损害的扫描电镜观察

应用扫描电镜观察了 Carboplatin 耳中毒引起的内毛细胞表面显微结构的改变,发现用药后仅1d,内毛细胞即开始出现球状物,同时伴有个别内毛细胞坏死。注药后30d 坏死的内毛细胞处为支持细胞所替代,残存的内毛细胞表面结构可恢复正常。

Newborn screening for Duchenne muscular dystrophy in China: follow-up diagnosis and subsequent treatment

Background:Newborn screening for Duchenne muscular dystrophy (DMD) is currently being initiated in Zhejiang Province,China and is under consideration in other countries,including the United States.As China begins to implement DMD newborn screening (DMD-NBS),there is ongoing discussion regarding the steps forward for follow up care of positively identified patients as well as false positive and false negative results.Data sources:Relevant papers related to DMD-NBS,and NBS in China were reviewed in PubMed.Results:The current state of DMD-NBS is discussed,along with the steps needed to effectively screen infants for this disease in China,recommendations for establishment of follow up care in patients with positive and negative screens,and measurement of patient outcomes.Conclusions:Zhejiang Province,China is ready to implement DMD-NBS.Future challenges that exist for this program,and other countries,include the ability to track patients,assist with access to care,and ensure adequate follow-up care according to evidence-based guidelines.In addition,China's large rural population,lack of specialty providers,and difficulty in educating patients regarding the benefits of treatment create challenges that will need to be addressed.

Weather-based interruption prediction in the smart grid utilizing chronological data

This unique study will demonstrate a combined effect of weather parameters on the total number of power distribution interruptions in a region.Based on common weather conditions,a theoretical model can predict interruptions and risk assessment with immediate weather conditions.Using daily and hourly weather data,the created models will predict the number of daily or by-shift interruptions.The weather and environmental conditions to be addressed will include rain,wind,temperature,lightning density,humidity,barometric pressure,snow and ice.Models will be developed to allow broad applications.Statistical and deterministic simulations of the models using the data collected will be conducted by employing existing software,and the results will be used to refine the models.Models developed in this study will be used to predict power interruptions in areas that can be readily monitored,thus validating the models.The application has resulted in defining the predicted number of interruptions in a region with a specific confidence level.Reliability is major concern for every utility.Prediction and timely action to minimize the outage duration improves reliability.Use of this predictor model with existing smart grid self-healing technology is proposed.

New frontiers for the materials genome initiative

The Materials Genome Initiative(MGI)advanced a new paradigm for materials discovery and design,namely that the pace of new materials deployment could be accelerated through complementary efforts in theory,computation,and experiment.Along with numerous successes,new challenges are inviting researchers to refocus the efforts and approaches that were originally inspired by the MGI.In May 2017,the National Science Foundation sponsored the workshop“Advancing and Accelerating Materials Innovation Through the Synergistic Interaction among Computation,Experiment,and Theory:Opening New Frontiers”to review accomplishments that emerged from investments in science and infrastructure under the MGI,identify scientific opportunities in this new environment,examine how to effectively utilize new materials innovation infrastructure,and discuss challenges in achieving accelerated materials research through the seamless integration of experiment,computation,and theory.This article summarizes key findings from the workshop and provides perspectives that aim to guide the direction of future materials research and its translation into societal impacts.

Polychlorinated biphenyls and omega-3 fatty acid exposure from fish consumption,and thyroid cancer among New York anglers

Fish from the Great Lakes contain polychlorinated biphenyls（PCBs）which have been shown to disrupt endocrine function and mimic thyroid hormones,but they also contain beneficial omega-3 fatty acids that may offer protection against endocrine cancers.The purpose of this study was to examine the effects of Lake Ontario fish consumption and the estimated consumption of PCBs and omega-3 fatty acids on the risk of thyroid cancer in a group of sport fishermen.Anglers from the New York State Angler Cohort Study were followed for cancer incidence from 1991–2008.Twenty-seven cases of incident thyroid cancer and 108 controls were included in the analyses.Total estimated fish consumption,estimated omega-3 fatty acid consumption,and estimated PCB consumption from Lake Ontario fish were examined for an association with the incidence of thyroid cancer,while matching on sex,and controlling for age and smoking status.Results from logistic regression indicate no significant associations between fish consumption,short-term estimated omega-3 fatty acids,or estimated PCB consumption from Great Lakes fish and the development of thyroid cancer,but it was suggested that long-term omega-3 fatty acid from Great Lakes fish may be protective of the development of thyroid cancer.In conclusion,fish consumption,with the possible concomitant PCBs,from the Great Lakes does not appear to increase the risk of thyroid cancer in New York anglers.Further research is needed in order to separate the individual health effects of PCBs from omega-3 fatty acids contained within the fish.

耳蜗Corti氏隧道中传出神经纤维的定量观察方法

应用乙酰胆碱酯酶组织化学染色技术特异显示耳蜗传出神经纤维和末梢,结合耳蜗铺片技术在光学显微镜下定量观察穿越 Corti 氏隧道的传出神经纤维数量,发现在正常灰鼠耳蜗底回和第二回的密度为每0.24mm 距离中约有22根传出神经纤维,顶回的密度为每0.24mm 距离中约有15根传出神经纤维。经手术切除传出神经的耳蜗铺片则显示穿越 Corti 氏隧道的传出神经纤维消失或减少。此方法为验证手术的成功提供了有价值的形态学观察手段。

豚鼠内耳结构的死后变化

应用透射电镜观察了15只窒息致死豚鼠的内耳各终器及血管纹。发现窒息5min 时,仅壶腹嵴毛细胞和血管纹上皮细胞开始发生形态改变,窒息10min 豚鼠心跳停止时,外毛细胞和椭圆囊斑Ⅰ型毛细胞亦开始发生改变,30min 时内毛细胞和球囊斑毛细胞才开始发生形态变化,提示内耳各终器死后变化开始发生的时间与程度均有所不同。

Structure and transport studies on nanometer YBCO/PBCGO multilayers

We have fabricated M doped (M = Al, Co, Fe, Ga, Ni and Zn) PrBa2Cu3O7 (PBCO), i.e. PrBa2(Cu1-xMx)3O7. The doping levels x are 0.05, 0.10, 0.15, and 0.20. X-ray data indicated no significant second phase for substituting Cu by Al, Co, Fe and Ga up to 20%. However impurity phases were detected for Ni and Zn substituted samples with doping levels equal to and higher than 15%. At 77 K the electrical resistivity of these compounds is orders in magnitude higher than that of PBCO. We also found that although the lattice parameters in the doped samples differ from PBCO, all samples remain orthorhombic. The lattice parameters of the doped sample are very close to those of YBa2Cu3O7-δ (YBCO) and PBCO. For this reason these compounds are better materials to be used as the I-layer for YBCO SIS junctions. Results of structural and transport studies on 2000 thick PrBa2[Cu0.80G0.2]3O7 (PBCGO) and YBCO/PBCGO multilayers are presented in this paper.