Diabetes as a consequence of acute pancreatitis

Diabetes is a highly prevalent disease that was initially simplified into three major types:Type 1,type 2 and gestational diabetes.With the global rise in incidence of acute pancreatitis(AP),a lesser-known type of diabetes referred to as diabetes of the exocrine pancreas(DEP)is becoming more recognized.However,there is a poor understanding of the inherent relationship between diabetes and AP.There is established data about certain diseases affecting the exocrine function of the pancreas which can lead to diabetes.More specifically,there are well established guidelines for diagnosis and management of DEP caused be chronic pancreatitis.Conversely,the sequelae of AP leading to diabetes has limited recognition and data.The purpose of this review is to provide a comprehensive summary of the prevalence,epidemiology,pathophysiology and future research aims of APrelated diabetes.In addition,we propose a screening and diagnostic algorithm to aid clinicians in providing better care for their patients.

Covalently closed-circular hepatitis B virus DNA reduction with entecavir or lamivudine

AIM: To investigate the reduction in hepatitis B virus(HBV) covalently closed-circular DNA(ccc DNA) with entecavir(ETV) or lamivudine(LAM). METHODS: This analysis included patients who had participated in the randomized Phase Ⅲ study ETV-022 comparing ETV vs LAM in nucleos(t)ide-naive, HBe Agpositive patients. Patients received ETV(0.5 mg daily) or LAM(100 mg daily) for a minimum of 52 wk. Patients were eligible to participate in this sub-study if they had paired biopsies at baseline and week 48 with evaluable measurements for hepatic HBV ccc DNA and total hepatic HBV DNA. The main objective was to compare changes in hepatic HBV ccc DNA and total hepatic HBV DNA at week 48 of ETV or LAM treatment, which was a secondary endpoint of study ETV-022. Additional post hoc analyses included linear regression analyses to assess associations of baseline levels and on-treatment changes of ccc DNA with other baseline factors [sex,age, serum HBV DNA, alanine aminotransferase(ALT), Knodell necroinflammatory score, Ishak fibrosis score, total hepatic HBV DNA, and HBV genotype], or ontreatment factors(changes from baseline at week 48 in serum HBV DNA, ALT, Knodell necroinflammatory score, Ishak fibrosis score, total hepatic HBV DNA, and HBe Ag loss at week 48).RESULTS: Overall, 305 patients(ETV = 159; LAM = 146) of ETV-022 had paired baseline and week 48 liver biopsies with evaluable measurements for hepatic HBV ccc DNA and total hepatic HBV DNA, and were included in this analysis. Baseline demographics and disease characteristics were comparable between the two arms. After 48 wk, ETV resulted in significantly greater reductions in hepatic HBV ccc DNA [-0.9 log10 copies/human genome equivalent(HGEq) vs-0.7 log10 copies/HGEq; P = 0.0033] and total hepatic DNA levels(-2.1 log10 copies/HGEq vs-1.6 log10 copies/HGEq; P < 0.0001) than LAM. Virologic, biochemical, and histologic response rates at week 48 were also greater with ETV than with LAM. Baseline HBV ccc DNA levels were positively associated with baseline levels of serum HBV DNA and total hepatic HBV DNA, and negatively associated with HBV genotype F. On-treatment changes in HBV ccc DNA levels were negatively associated with baseline levels of serum HBV DNA and baseline ALT, and were positively associated with on-treatment changes in the levels of serum HBV DNA, total hepatic HBV DNA levels, and ALT, change in Knodell necroinflammatory score, and HBe Ag loss.CONCLUSION: Forty-eight weeks of ETV resulted in greater reductions in ccc DNA and total hepatic HBV DNA than LAM, but long-term therapy may be needed for ccc DNA elimination.

S2A-3 The Alpha6*-nAChR is A Highly Sensitive Target for Low Dose Alcohol

Alcohol use disorder(AUD)is a serious public health problem that affects approximately 17 million Americans and results in tremendous social,legal and medical costs to the society.Unlike other addictive drugs(e.g.,morphine,cocaine or nicotine)that have specific molecular targets,ethanol(EtOH)has no specific target.In most previous studies,EtOH concentrations used for investigation were too high(e.g.,>50 mmol·L-1)compared to the EtOH concentrations in human brain after alcohol drinking,and the high dose EtOH may produce nonspecific modulations of a variety of receptors,ion channels,intracellular signaling cascades,and gene expression in the brain.Therefore,it is important to understand low dose(e.g.,<10 mmol·L-1)EtOH effects in the brain.Unfortunately,the molecular and cellular targets that mediate the sensitivity to low dose EtOH remain to be defined.nAChRs containingα6 subunits(α6*-nAChRs)shows a highly restricted distribution in midbrain dopaminergic neurons that are associated with drug dependence and addiction.Here,we report that low dose EtOH(0.1~5 mmol·L-1)significantly potentiatesα6*-nAChR function using patch-clamp whole-cell recordings.Since EtOH modulatesα6*-nAChR-mediated function depending on both EtOH and nicotine concentrations,representing a positive allosteric modulation.In conclusion,our results demonstrate a functionalα6*-nAChR transfected in human SH-EP1 cells that can be used as an excellent cell model to investigateα6*-nAChR function and pharmacology.Under patch-clamp recording condition,low dose EtOH modulatesα6*-nAChR function as a positive allosteric modulator.Through this mechanism,brainα6*-nAChRs may play a critical role in mediating low dose alcohol’effects on alcohol reward and dependence.

Stroke-induced immunosuppression and poststroke infection

Infections occur commonly after stroke and are strongly associated with an unfavourable functional outcome of these patients.Approaches for effective management of poststroke infection remain scarce,presenting an urgent need for preventive anti-infection strategies for patients who have suffered a stroke.Emerging evidence indicates that stroke impairs systemic immune responses and increases the susceptibility to infections,suggesting that the modification of impaired immune defence could be beneficial.In this review,we summarised previous attempts to prevent poststroke infections using prophylactic antibiotics and the current understanding of stroke-induced immunosuppression.Further elucidation of the immune mechanisms of stroke will pave the way to tailored design of new treatment to combat poststroke infection via modifying the immune system.

应用于GABA_(A)型受体激动剂体外活性筛选的新型荧光染料合成及其方法构建

氨基丁酸A型受体(GABA_(A)R)是γ-氨基丁酸门控的氯离子通道,针对该受体激动剂的体外活性筛选依赖于设备昂贵、操作要求高且效率低的电压钳技术,为此本课题合成得到一个新荧光染料C4,用γ-氨基丁酸作为激动剂,构建荧光法α1β2γ2γ-氨基丁酸受体激动剂的体外活性筛选方法,经研究表明当荧光染料C4浓度选用100μM时,能准确筛选激动剂γ-氨基丁酸的体外活性并计算得到其EC_(50)值(29.44±7.45μM),与通过电压钳技术筛选得到的EC_(50)值非常接近,达到高通量、快速、操作简便、设备要求低、精确筛选的要求,同时为其他神经受体激动剂体外活性筛选提供理论依据和技术支持。

Sleep and Cognitive Abnormalities in Acute Minor Thalamic Infarction

In order to characterize sleep and the cognitive patterns in patients with acute minor thalamic infarction （AMTI）, we enrolled 27 patients with AMTI and 12 mat- ched healthy individuals. Questionnaires about sleep and cognition as well as polysomnography （PSG） were performed on days 14 and 90 post-stroke. Compared to heal- thy controls, in patients with AMTI, hyposomnia was more prevalent; sleep architecture was disrupted as indicated by decreased sleep efficiency, increased sleep latency, and decreased non-rapid eye movement sleep stages 2 and 3; more sleep-related breathing disorders occurred; and cog- nitive functions were worse, especially memory. While sleep apnea and long-delay memory recovered to a large extent in the patients, other sleep and cognitive function deficit often persisted. Patients with AMTI are at an increased risk for hyposomnia, sleep structure disturbance, sleep apnea, and memory deficits. Although these abnormalities improved over time, the slow and incomplete improvement suggest that early management should be considered in these patients.

Dissemination of brain inflammation in traumatic brain injury

Traumatic brain injury(TBI)is recognized as a global health problem due to its increasing occurrence,challenging treatment,and persistent impacts on brain pathophysiology.Neural cell death in patients with TBI swiftly causes inflammation in the injured brain areas,which is recognized as focal brain inflammation.Focal brain inflammation causes secondary brain injury by exacerbating brain edema and neuronal death,while also exerting divergent beneficial effects,such as sealing the damaged limitans and removing cellular debris.Recent evidence from patients with TBI and studies on animal models suggest that brain inflammation after TBI is not only restricted to the focal lesion but also disseminates to remote areas of the brain.The dissemination of inflammation has been detected within days after the primary injury and persists chronically.This state of inflammation may be related to remote complications of TBI in patients,such as hyperthermia and hypopituitarism,and may lead to progressive neurodegeneration,such as chronic traumatic encephalopathy.Future studies should focus on understanding the mechanisms that govern the initiation and propagation of brain inflammation after TBI and its impacts on post-trauma brain pathology.

Pedicle screw accuracy assessment in ExcelsiusGPS?robotic spine surgery:evaluation of deviation from pre-planned trajectory

Background: The ExcelsiusGPS?(Globus Medical, Inc., Audubon, PA) is a next-generation spine surgery robotic system recently approved for use in the United States. The objective of the current study is to assess pedicle screw accuracy and clinical outcomes among two of the first operative cases utilizing the ExcelsiusGPS?robotic system and describe a novel metric to quantify screw deviation. Methods: Two patients who underwent lumbar fusion at a single institution with the ExcelsiusGPS?surgical robot were included. Pre-operative trajectory planning was performed from an intra-operative CT scan using the O-arm (Medtronic, Inc., Minneapolis, MN). After robotic-assisted screw implantation, a post-operative CT scan was obtained to confirm ideal screw placement and accuracy with the planned trajectory. A novel pedicle screw accuracy algorithm was devised to measure screw tip/tail deviation distance and angular offset on axial and sagittal planes. Screw accuracy was concurrently determined by a blinded neuroradiologist using the traditional Gertzbein-Robbins method. Clinical variables such as symptomatology, operative data, and post-operative follow-up were also collected. Results: Eight pedicle screws were placed in two L4-L5 fusion cases. Mean screw tip deviation was 2.1 mm (range 0.8-5.2 mm), mean tail deviation was 3.2 mm (range 0.9-5.4 mm), and mean angular offset was 2.4 degrees (range 0.7-3.8 degrees). All eight screws were accurately placed based on the Gertzbein-Robbins scale (88% Grade A and 12% Grade B). There were no cases of screw revision or new post-operative deficit. Both patients experienced improvement in Frankel grade and Karnofsky Performance Status (KPS) score by 6 weeks post-op. Conclusion: The ExcelsiusGPS? robot allows for precise execution of an intended pre-planned trajectory and accurate screw placement in the first patients to undergo robotic-assisted fusion with this technology.

Advances in the imaging of cerebral aneurysm inflammation

Cerebral aneurysm formation,growth and rupture are thought to be the result of a complex interaction between cerebrovascular hemodynamics and pathobiology.Recently,new evidence has emerged regarding the role of inflammation in the walls of cerebral aneurysms.Noninvasive methods to characterize the degree of inflammation in aneurysms could enable clinicians to estimate the risk of future aneurysm growth and rupture,influencing treatment.This review examines emerging techniques of imaging inflammatory biomarkers in cerebral aneurysms.

Airway pressure release ventilation forin-vivodonor lung management and lung transplant outcomes

Background:Airway pressure release ventilation(APRV)can be used for cadaveric donor lung recruitment.APRV elevates PaO_(2)in donor lungs;however,reported outcomes in recipients with APRVmanaged donor lungs are limited.Methods:We retrospectively reviewed patients who underwent lung transplantation(LTx)from 2012 to 2013 and divided them into two groups based on mode of ventilation used during donor management and organ extraction(A:non-APRV;B:APRV).Kaplan-Meier method and multivariate Cox regression were used for analysis.Results:We found 126 LTx recipients(LTxRs);9 were excluded for use of portable ventilation perfusion systems.Of the remaining 117 patients,81(69%)were in Group A;36(31%)were in Group B.Preoperative LTxR characteristics(age,sex,lung allocation score,endstage lung disease type)were comparable between groups.Donors for Group B were older(P=0.03)and had higher body mass index(BMI)(P<0.001),higher incidence of death from chest trauma(P=0.008),longer ventilation duration after brain death(P<0.001),and higher pre-explant PaO_(2)/FiO_(2)ratios(P<0.001).Post-LTx duration of mechanical ventilation,hospital stay,and median survival were similar in both groups.Risk of death was comparable between the two groups at the end of follow-up(HR=1.42;95%CI:0.57-3.56;P=0.45).Conclusions:APRV is a safe and effective pre-LTx donor lung management strategy.Short-and long-term survival outcomes were comparable in LTx recipients,irrespective of donor ventilation mode.APRV may help recruit lungs from older donors with higher BMI who die from chest trauma and have anticipated longer ventilation duration.