Long-term effects of gestational diabetes mellitus on the pancreas of female mouse offspring

BACKGROUND Prolonged fetal exposure to hyperglycemia may increase the risk of developing abnormal glucose metabolism and type-2 diabetes during childhood,adolescence,and adulthood;however,the mechanisms by which gestational diabetes mellitus(GDM)predisposes offspring to metabolic disorders remain unknown.AIM To quantify the nerve axons,macrophages,and vasculature in the pancreas from adult offspring born from mouse dams with GDM.METHODS GDM was induced by i.p.administration of streptozotocin(STZ)in ICR mouse dams.At 12 wk old,fasting blood glucose levels were determined in offspring.At 15 wk old,female offspring born from dams with and without GDM were sacrificed and pancreata were processed for immunohistochemistry.We quantified the density of sensory[calcitonin gene-related peptide(CGRP)]and tyrosine hydroxylase(TH)axons,blood vessels(endomucin),and macro-phages(CD68)in the splenic pancreas using confocal microscopy.RESULTS Offspring mice born from STZ-treated dams had similar body weight and blood glucose values compared to offspring born from vehicle-treated dams.However,the density of CGRP+and TH+axons,endomucin+blood vessels,and CD68+macrophages in the exocrine pancreas was significantly greater in offspring from mothers with GDM vs control offspring.Likewise,the microvasculature in the islets was significantly greater,but not the number of macrophages within the islets of offspring born from dams with GDM compared to control mice.CONCLUSION GDM induces neuronal,vascular,and inflammatory changes in the pancreas of adult progeny,which may partially explain the higher propensity for offspring of mothers with GDM to develop metabolic diseases.

Associations of accelerometry-measured and self-reported physical activity and sedentary behavior with skeletal muscle energetics:The Study of Muscle,Mobility and Aging(SOMMA)

Background:Skeletal muscle energetics decline with age,and physical activity(PA)has been shown to offset these declines in older adults.Yet,many studies reporting these effects were based on self-reported PA or structured exercise interventions.Therefore,we examined the associations of accelerometry-measured and self-reported PA and sedentary behavior(SB)with skeletal muscle energetics and explored the extent to which PA and sedentary behavior would attenuate the associations of age with muscle energetics.Methods:As part of the Study of Muscle,Mobility and Aging,enrolled older adults(n=879),810(age=76.4±5.0 years old,mean±SD;58%women)had maximal muscle oxidative capacity measured ex vivo via high-resolution re spirometry of permeabilized myofibers(maximal oxidative phosphorylation(maxOXPHOS))and in vivo by ^(31)phosphorus magnetic resonance spectroscopy(maximal adenosine triphosphate(ATP_(max))).Accelerometry-measured sedentary behavior,light activity,and moderate-to-vigorous PA(MVPA)were assessed using a wrist-worn ActiGraph GT9X over 7 days.Self-reported sedentary behavior,MVPA,and all PA were assessed with the Community Healthy Activities Model Program for Seniors(CHAMPS)questionnaire.Linear regression models with progressive covariate adjustments evaluated the associations of sedentary behavior and PA with muscle energetics,as well as the attenuation of the age/muscle energetics association by MVP A and sedentary behavior.As a sensitivity analysis,we also examined activPAL-measured daily step count and time spent in sedentary behavior and their associations with muscle energetics.Results:Every 30 min/day more of ActiGraph-measured MVPA was associated with 0.65 pmol/(s×mg)higher maxOXPHOS and 0.012 mM/s higher ATP_(max)after adjusting for age,site/technician,and sex(p<0.05).Light activity was not associated with maxOXPHOS or ATP_(max).Meanwhile,every 30 min/day spent in ActiGraph-measured sedentary behavior was associated with 0.39 pmol/s×mg lower maxOXPHOS and0.006 mM/s lower ATP_(max)(p<0.05).Only associations with ATP_(max)held after further adjusting for socioeconomic status,body mass index,lifestyle factors,and multimorbidity.CHAMPS MVPA and all PA yielded similar associations with maxOXPHOS and ATP_(max)(p<0.05),but sedentary behavior did not.Higher activPAL step count was associated with higher maxOXHPOS and AT_(Pmax)(p<0.05),but time spent in sedentary behavior was not.Additionally,age was significantly associated with muscle energetics for men only(p<0.05);adjusting for time spent in ActiGraph-measured MVPA attenuated the age association with ATP_(max)by 58%in men.Conclusion:More time spent in accelerometry-measured or self-reported daily PA,especially MVPA,was associated with higher skeletal muscle energetics.Interventions aimed specifically at increasing higher intensity activity might offer potential therapeutic interventions to slow age-related decline in muscle energetics.Our work also emphasizes the importance of taking PA into consideration when evaluating associations related to skeletal muscle energetics.

Exploring Chemovar-Specific Cannabis Extracts Quantification and Evaluation of Cytotoxic Compounds for Targeting Glioblastoma Multiforme

Glioblastoma Multiforme (GBM) represents one of the most aggressive and metastatic brain tumors, with a dismal success rate of less than three percent after five years, particularly in tumors with active immune checkpoints. This necessitates the development of targeted endogenous agents for precise GBM treatment. Previous experiments utilizing Chemovar Specific Cannabis Extractions (CSCEs), fractionated with polar solvents and quantified using Liquid and Gas Column Chromatography combined with Mass Spectrometry (LC/GCMS), have shown reduced viability and motility in human GBM cell lines. However, the complexity of the botanical substance has hindered the personalization of standard cannabis medicines for GBM due to unknown synergistic effects of multiple compounds. To address this limitation, our study focuses on exposing AM251 cells to chemovar fractions extracted using a non-polar solvent, thereby isolating a broader spectrum of constituents. By employing LC/GCMS in conjunction with Nuclear Magnetic Resonance (NMR), we have identified and quantified nine* compounds present in the non-polar CSCE that exhibit significant efficacy (0.1 μM) in inducing cytotoxicity* in GBM tumor cells. Conversely, the polar fraction in our experiment did not demonstrate efficacy against UM251 cells. The quantification of individual compounds within a cannabis extraction that selectively induces cell death in brain tumors holds promise for guiding future research and facilitating the development of a standardized CSCE for GBM therapy.

Vanishing bile duct syndrome in human immunodeficiency virus infected adults:A report of two cases

Vanishing bile duct syndrome(VBDS) is a group of rare disorders characterized by ductopenia,the progressive destruction and disappearance of intrahepatic bile ducts leading to cholestasis.Described in association with medications,autoimmune disorders,cancer,transplantation,and infections,the specific mechanisms of disease are not known.To date,only 4 cases of VBDS have been reported in human immunodeficiency virus(HIV) infected patients.We report 2 additional cases of HIV-associated VBDS and review the features common to the HIV-associated cases.Presentation includes hyperbilirubinemia,normal liver imaging,and negative viral and autoimmune hepatitis studies.In HIV-infected subjects,VBDS occurred at a range of CD4+ T-cell counts,in some cases following initiation or change in antiretroviral therapy.Lymphoma was associated with two cases;nevirapine,antibiotics,and viral co-infection were suggested as etiologies in the other cases.In HIV-positive patients with progressive cholestasis,early identification of VBDS and referral for transplantation may improve outcomes.

Epigenetic profiles of pre-diabetes transitioning to type 2 diabetes and nephropathy

AIM: To examine DNA methylation profiles in a longitudinal comparison of pre-diabetes mellitus(Pre-DM) subjects who transitioned to type 2 diabetes mellitus(T2DM).METHODS: We performed DNA methylation study in bisulphite converted DNA from Pre-DM(n = 11) at baseline and at their transition to T2 DM using Illumina Infinium Human Methylation27 Bead Chip, that enables the query of 27578 individual cytosines at Cp G loci throughout the genome, which are focused on the promoter regions of 14495 genes.RESULTS: There were 694 Cp G sites hypomethylated and 174 Cp G sites hypermethylated in progression from Pre-DM to T2 DM, representing putative genes involved in glucose and fructose metabolism, inflammation, oxidative and mitochondrial stress, and fatty acid metabolism. These results suggest that this high throughput platform is able to identify hundreds of prospective Cp G sites associated with diverse genes that may reflect differences in Pre-DM compared with T2 DM. In addition, there were Cp G hypomethylation changes associated with a number of genes that may be associated with development of complications of diabetes, such as nephropathy. These hypomethylation changes were observed in all of the subjects.CONCLUSION: These data suggest that some epigenomic changes that may be involved in the progression of diabetes and/or the development of complications may be apparent at the Pre-DM state or during the transition to diabetes. Hypomethylation of a number of genes related to kidney function may be an early marker for developing diabetic nephropathy.

The influence of prostate volume on cancer detection in the Chinese population

In western populations, prostate volume （PV） has been proven to be one of the strongest predictors of detecting prostate cancer （PCa） in biopsies. We performed this study in a biopsy cohort, to evaluate associations among the prostate volume, prostate-specific antigen （PSA） and PCa detection in the Chinese population. Between the years, 2007-13, 1486 men underwent prostate biopsy at Huashan Hospital, Fudan University, Shanghai, China. The study population was divided into two groups for analysis according to total PSA （tPSA） range （4 ng m1-1 〈tPSA 〈20 ng m1-1 and tPSA 〉20 ng ml-1）. PV, age, tPSA, digital rectal examination （DRE） and transrectal ultrasound （TRUS） results were also included in the analysis. Although the positive biopsy rates decreased in both tPSA range groups, the downtrend was more pronounced in the 4 ng ml-2 〈tPSA 〈20 ng m1-1 group; therefore, we focused on 853 men in this group with increasing PV. In multivariate logistic regression analysis, only DRE was found to be associated with PCa in four PV groups （P 〈 0.05） and tPSA did not show a good predictive ability when PV exceeded 50 ml （P 〉 0.05）. Further, it may suggest that with increasing PV, the cancer detection rate decreased in men with different tPSA, DRE and TRUS nodule statuses （all P values for trends were 〈0.001）. Our study indicates that in tPSA ranging from 4 to 20 ng ml-1, the use of PV ranges of 0-35 ml, 35-50 ml and 〉50 ml might be taken into consideration for the biopsy decision-making in the Chinese population.

Outcomes of percutaneous coronary intervention in patients ≥ 75 years： one-center study in a Chinese patient group

ObjectiveTo 调查临床并且病人 &#x02265 的 perioperative 特征；75 经历经皮的冠的干预(一种总线标准) 并且从 2011 年 12 月经历了一种总线标准到 2013 年 11 月的连续题目被划分在这特定的病人 group.Methods1,035 评估与短期的一种总线标准以后的死亡有关的风险因素成四个范畴：(1 ) 有稳定的咽峡炎(SA ) 的病人 &#x02265；75 年(n = 58 ) ；(2 ) 有 SA &#x0003c 的病人；75 年(n = 218 ) ；(3 ) 有急性冠的症候群(交流) 的病人 &#x02265；75 年(n = 155 ) ；(4 ) 有交流 &#x0003c 的病人；75 年(n = 604 ) 。multivariable 逻辑回归分析被进行在病人 &#x02265 检测六月的死亡的风险因素；75 年经历了一种总线标准。临床的 comorbidities，在里面医院生物化学的指示物， perioperative 数据，在里面医院和六月的结果与更年轻的组，一起在四 groups.ResultsCompared 之中被分析并且比较病人 &#x02265；75 年是更可能的有高血压，中风的历史，长期的妨碍的肺的疾病，外部脉管的疾病，心脏性的吃惊和恶意的心律不齐，并且他们与相对更低的重量，血红素，白朊， triglyceride，更高的 creatinine，尿酸，脲氮和 pro-BNP 进入医院。左主要动脉损害，多容器，钙化的损害，长期完全吸藏也是更可能的在老组被看。Univariate 分析揭示了那年龄 &#x02265；在承认，紧急情况一种总线标准，优先的击和长期的肾疾病的 85 年，心脏性的吃惊或严重心律不齐与在老病人 &#x02265 的六月的死亡有关；75 年经历了一种总线标准。Multivariable 逻辑回归证明在承认，长期的肾疾病和优先的击的心脏性的吃惊或严重心律不齐是在老病人 &#x02265 预言六月的死亡的独立风险因素；75 年经历了 PCI.ConclusionsOur 数据的人，显示出那与在 75 年下面的病人相比，老病人(&#x02265；75 年) 经历了一种总线标准的人，有经常伴有 multi-comorbidities， severer 承认条件和复杂冠的损害的死亡，和更多的相对更高的风险。因素和更多强烈地在乎的风险的更好的评估应该被带去病人 &#x02265；75 年经历了一种总线标准治疗减少复杂并发症。

Impact of immunosuppression minimization and withdrawal in long-term hepatitis C virus liver transplant recipients

AIM:To investigate the effects of different immunosuppressive regimens and avoidance on fibrosis progression in hepatitis C virus(HCV)liver transplant(LT)recipients.METHODS:We retrospectively compared the liver biopsies of well-matched HCV LT recipients under calcineurin inhibitors(CNI group,n=21)and mycophenolate(MMF group,n=15)monotherapy,with those patients who successfully withdrawn immunosuppression(IS)therapy from at least 3 years(TOL group,n=10).To perform the well-matched analysis,all HCV transplanted patients from December 1993 were screened.Only those HCV patients who reached the following criteria were considered for the analysis:(1)at least3 years of post-operative follow-up;(2)patients with normal liver graft function under low dose CNI monotherapy(CNI group);(3)patients with normal liver graft function under antimetabolite(Micophenolate Mofetil or coated mycophenolate sodium)monotherapy(MMF group);and(4)recipients with normal liver function without any IS.We excluded from the analysis recipients who were IS free or under monotherapy for<36 mo,recipients with cirrhosis or with unstable liver function tests.RESULTS:Thirty six recipients were enrolled in the study.Demographics,clinical data,time after LT and baseline liver biopsies were comparable in the three groups.After six years of follow-up,there was no worsening of hepatic fibrosis in the MMF group(2.5±1.5Ishak Units vs 2.9±1.7 Ishak Units,P=0.5)and TOL group(2.7±10.7 vs 2.5±1.2,P=0.2).In contrast,a significant increase in the fibrosis score was observed in the CNI group(2.2±1.7 vs 3.9±1.6,P=0.008).The yearly fibrosis progression rate was significantly worse in the CNI group(0.32±0.35)vs MMF group(0.03±0.31,P=0.03),and TOL group(-0.02±0.27,P=0.02).No differences have been reported in grading scores for CNI group(2.79±1.9,P=0.7),MMF group(3.2±1.5,P=0.9)and TOL group(3.1±1.4,P=0.2).Twenty four patients were treated with low dose ribavirin(8TOL,7 MMF,9 CNI).The hepatitis C titers were comparable in the three groups.No episodes of rejection have been reported despite differences of liver function test in the three groups during the observational period.CONCLUSION:IS withdrawal and MMF monotherapy is safe and seems to be associated with the slowest fibrosis progression in HCV LT recipients.

Current state of endohepatology: Diagnosis and treatment of portal hypertension and its complications with endoscopic ultrasound

The diagnosis and management of cirrhosis and portal hypertension(PH)with its complications including variceal hemorrhage,ascites,and hepatic encephalopathy continues to evolve.Although there are established“standards of care”in liver biopsy and measurement of PH,gastric varices remain an area without a universally accepted therapeutic approach.The concept of“Endo Hepatology”has been used to describe of the applications of endoscopic ultrasound(EUS)to these challenges.EUS-liver biopsy(EUS-LB)offers an alternative to percutaneous and transjuglar liver biopsy without compromising safety or efficacy,and with added advantages including the potential to reduce sampling error by allowing biopsies in both hepatic lobes.Furthermore,EUS-LB can be performed during the same procedure as EUS-guided portal pressure gradient(PPG)measurements,allowing for the collection of valuable diagnostic and prognostic data.EUS-guided PPG measurements provide an appealing alternative to the transjugular approach,with proposed advantages including the ability to directly measure portal vein pressure.In addition,EUS-guided treatment of gastric varices(GV)offers several possible advantages to current therapies.EUS-guided treatment of GV allows detailed assessment of the vascular anatomy,similar efficacy and safety to current therapies,and allows the evaluation of treatment effect through doppler ultrasound visualization.The appropriate selection of patients for these procedures is paramount to ensuring generation of useful clinical data and patient safety.

Season of the year influences infection rates following total hip arthroplasty

AIM To research the influence of season of the year on periprosthetic joint infections.METHODS We conducted a retrospective review of the entire Medicare files from 2005 to 2014. Seasons were classified as spring, summer, fall or winter. Regional variations were accounted for by dividing patients into four geographic regions as per the United States Census Bureau(Northeast, Midwest, West and South). Acute postoperative infection and deep periprosthetic infections within 90 d after surgery were tracked. RESULTS In all regions, winter had the highest incidence of periprosthetic infections(mean 0.98%, SD 0.1%) and was significantly higher than other seasons in the Midwest, South and West(P < 0.05 for all) but not the Northeast(P = 0.358). Acute postoperative infection rates were more frequent in the summer and were significantly affected by season of the year in the West.CONCLUSION Season of the year is a risk factor for periprosthetic joint infection following total hip arthroplasty(THA). Understanding the influence of season on outcomes following THA is essential when risk-stratifying patients to optimize outcomes and reduce episode of care costs.

Tissue engineering for neuromuscular disorders of the gastrointestinal tract

The digestive tract is designed for the optimal processing of food that nourishes all organ systems.The esophagus,stomach,small bowel,and colon are sophisticated neuromuscular tubes with specialized sphincters that transport ingested food-stuffs from one region to another.Peristaltic contractions move ingested solids and liquids from the esophagus into the stomach;the stomach mixes the ingested nutrients into chyme and empties chyme from the stomach into the duodenum.The to-and-fro movement of the small bowel maximizes absorption of fat,protein,and carbohydrates.Peristaltic contractions are necessary for colon function and defecation.

Single vs dual(en bloc) kidney transplants from donors ≤ 5 years of age: A single center experience

AIM: To compare outcomes between single and dual en bloc(EB) kidney transplants(KT) from small pediatric donors. METHODS: Monocentric nonprospective review of KTs from pediatric donors ≤ 5 years of age. Dual EB KT was defined as keeping both donor kidneys attached tothe inferior vena cava and aorta, which were then used as venous and arterial conduits for the subsequent transplant into a single recipient. Donor age was less useful than either donor weight or kidney size in decision-making for kidney utilization as kidneys from donors < 8 kg or kidneys < 6 cm in length were not transplanted. Post-transplant management strategies were standardized in all patients.RESULTS: From 2002-2015, 59 KTs were performed including 34 dual EB and 25 single KTs. Mean age of donors(17 mo vs 38 mo, P < 0.001), mean weight(11.0 kg vs 17.4 kg, P = 0.046) and male donors(50% vs 84%, P = 0.01) were lower in the dual EB compared to the single KT group, respectively. Mean cold ischemia time(21 h), kidney donor profile index(KDPI; 73% vs 62%) and levels of serum creatinine(SCr, 0.37 mg/d L vs 0.49 mg/d L, all P = NS) were comparable in the dual EB and single KT groups, respectively. Actuarial graft and patient survival rates at 5-years follow-up were comparable. There was one case of thrombosis resulting in graft loss in each group. Delayed graft function incidence(12% dual EB vs 20% single KT, P = NS) was slightly lower in dual EB KT recipients. Initial duration of hospital stay(mean 5.4 d vs 5.6 d) and the one-year incidences of acute rejection(6% vs 16%), operative complications(3% vs 4%), and major infection were comparable in the dual EB and single KT groups, respectively(all P = NS). Mean 12 mo SCr and abbreviated MDRD levels were 1.17 mg/d L vs 1.35 mg/d L and 72.5 m L/min per 1.73 m^2 vs 60.5 m L/min per 1.73 m^2(both P = NS) in the dual EB and single KT groups, respectively. CONCLUSION: By transplanting kidneys from young pediatric donors into adult recipients, one can effectively expand the limited donor pool and achieve excellent medium-term outcomes.

Role of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in cryoballoon ablation outcomes for paroxysmal atrial fibrillation

BACKGROUND Cryoballoon ablation(CBA)is recommended for patients with paroxysmal atrial fibrillation(AF)refractory to antiarrhythmic drugs.However,only 80%of patients benefit from initial CBA.There is growing evidence that pretreatment with angiotensin-converting enzyme inhibitors(ACEIs)and angiotensin receptor blockers(ARBs)decreases the recurrence of AF postablation,particularly in nonparoxysmal AF undergoing radiofrequency ablation.The role of ACEIs and ARBs in patients with paroxysmal AF in CBA remains unknown.We decided to investigate the role of ACEIs and ARBs in preventing the recurrence of atrial arrhythmia(AA)following CBA for paroxysmal AF.AIM To investigate the role of ACEIs and ARBs in preventing recurrence of AA following CBA for paroxysmal AF.METHODS We followed 103 patients(age 60.6±9.1 years,29%women)with paroxysmal AF undergoing CBA 1-year post procedure.Recurrence was assessed by documented AA on electrocardiogram or any form of long-term cardiac rhythm monitoring.A multivariable Cox proportional hazard model was used to assess if ACEI or ARB treatment predicted the risk of AA recurrence.RESULTS After a 1-year follow-up,19(18.4%)participants developed recurrence of AA.Use of ACEI or ARB therapy was noted in the study population.Patients on ACEI/ARB had a greater prevalence of hypertension and coronary artery disease.On a multivariate model adjusted for baseline demographics and risk factors for AF,ACEI or ARB therapy did not prevent recurrence of AA following CBA(P=0.72).Similarly,on Kaplan–Meier analysis pretreatment with ACEI/ARB did not predict the time to first recurrence of AA(P=0.2173).CONCLUSION In our study population,preablation treatment with an ACEI or ARB had no influence on the recurrence of AA following CBA for paroxysmal AF.

Review of current and evolving clinical indications forendoscopic ultrasound

For the first several years after its development,endoscopic ultrasound(EUS) was primarily limited to identification of pancreatic malignancies. Since this time, the field of EUS has advanced at a tremendous speed in terms of additional clinical diagnostic and therapeutic uses. The combination of ultrasound with endoscopy provides a unique interventional modality that is a minimally invasive alternative to various surgical interventions. Given the expanding recommended indications for EUS, this article will serve to review the most common uses with supporting evidence, while also exploring innovative endeavors that may soon become common clinical practice.

Prognostic implications of type 2 myocardial infarctions

Purpose: A type 2 myocardial infarction (MI) is due to ischemia from increased oxygen demand or decreased supply. It is not an infrequent complication following non-cardiac surgery or in the setting of acute medical illness. The purpose of this study was to determine whether type 2 MIs had a worse prognosis than a type 1 MI. Methods: The hospital database of a large terti-ary-level academic medical center was queried for all patients with a troponin I ≥ 1.6 ng/mL during a one-year period. The outcomes of patients with a type 2 MI were compared to those with a type 1 MI. Results: This retrospective study found that a type 2 MI is more lethal than the usual type 1 MI, particularly among women and the elderly. There was no statistical difference in outcomes between those that occurred in the post-operative setting compared to those that occurred in the setting of acute medical illness. Conclusions: Type 2 MIs are common and are associated with increased mortality, as compared with type 1 MIs. To date, no guidelines exist for the management of this type of MI. Further research into underlying mechanisms resulting in type 2 MI as well as potential treatment strategies is needed.

Analytical Calculation of the Compton Single Scatter Component of Pencil Beam Scatter Kernel for Scatter Correction in kV Cone Beam CT (kV-CBCT)

The accuracy of conventional superposition or convolution methods for scatter correction in kV-CBCT is usually compromised by the spatial variation of pencil-beam scatter kernel (PBSK) due to finite size, irregular external contour and heterogeneity of the imaged object. This study aims to propose an analytical method to quantify the Compton single scatter (CSS) component of the PBSK, which dominates the spatial distribution of total scatter assuming that multiple scatter can be estimated as a constant background and Rayleigh scatter is the secondary source of scatter. The CSS component of PBSK is the line integration of scatter production by incident primary photons along the beam line followed by the post-scattering attenuation as the scattered photons traverse the object. We propose to separate the object-specific attenuation term from the line integration and equivalently replace it with an average value such that the line integration of scatter production is object independent but only beam specific. We derived a quartic function formula as an approximate solution to the spatial distribution of the unattenuated CSS component of PBSK. The “effective scattering center” is introduced to calculate the average attenuation. The proposed analytical framework to calculate the CSS was evaluated using parameter settings of the On-Board Imager kV-CBCT system and was found to be in high agreement with the reference results. The proposed method shows highly increased computational efficiency compared to conventional analytical calculation methods based on point scattering model. It is also potentially useful for correcting the spatial variant PBSK in adaptive superposition method.

Analysis of ileal sodium/bile acid cotransporter and related nuclear receptor genes in a family with multiple cases of idiopathic bile acid malabsorption

The etiology of most cases of idiopathic bile acid malabsorption (IBAM) is unknown. In this study, a Swedish family with bile acid malabsorption in three consecutive generations was screened for mutations in the ileal apical sodium-bile acid cotransporter gene (ASBT; gene symbol, SLC10A2) and in the genes for several of the nuclear receptors known to be important for ASBT expression: the farnesoid X receptor (FXR) and peroxisome proliferator activated receptor alpha (PPARa). The patients presented with a clinical history of idiopathic chronic watery diarrhea, which was responsive to cholestyramine treatment and consistent with IBAM. Bile acid absorption was determined using 75Se-homocholic acid taurine (SeHCAT); bile acid synthesis was estimated by measuring the plasma levels of 7a-hydroxy-4-cholesten-3-one (C4). The ASBT, FXR, and PPARa genes in the affected and unaffected family members were analyzed using single stranded conformation polymorphism (SSCP), denaturing HPLC, and direct sequencing. No ASBT mutations were identified and the ASBT gene did not segregate withthe bile acid malabsorption phenotype. Similarly, no mutations or polymorphisms were identified in the FXR or PPARa genes associated with the bile acid malabsorption phenotype. These studies indicate that the intestinal bile acid malabsorption in these patients cannot be attributed to defects in ASBT. In the absence of apparent ileal disease, alternative explanations such as accelerated transit through the small intestine may be responsible for the IBAM.

The Xu＇s chart for prostate biopsy： a visual presentation of the added value of biomarkers to prostate-specific antigen for estimating detection rates of prostate cancer

Elevated serum prostate-specific antigen （PSA） level is the primaryindication for prostate biopsy for detection of prostate cancer （PCa） in the modern era. The detection rate of PCa from biopsy is typically below 30%, especially among patients with PSA levels at 4-10 ng ml-1. In the past several years, additional biomarkers, such as Prostate Health Index, PCA3 and genetic risk score （GRS） derived from multiple PCa risk-associated single nucleotide polymorphisms （SNPs） have been shown to provide added value to PSA in discriminating prostate biopsy outcomes. However,

Pulmonary artery catheterization in acute myocardial infarction complicated by cardiogenic shock:A review of contemporary literature

Acute myocardial infarction(AMI)with left ventricular(LV)dysfunction patients,the most common cause of cardiogenic shock(CS),have acutely deteriorating hemodynamic status.The frequent use of vasopressor and inotropic pharmacologic interventions along with mechanical circulatory support(MCS)in these patients necessitates invasive hemodynamic monitoring.After the pivotal Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness trial failed to show a significant improvement in clinical outcomes in shock patients managed with a pulmonary artery catheter(PAC),the use of PAC has become less popular in clinical practice.In this review,we summarize currently available literature to summarize the indications,clinical relevance,and recommendations for use of PAC in the setting of AMI-CS.

Activation of Astrocytes in Vitro by Macrophages Polarized with Keratin Biomaterial Treatment

Reactive astrocytes contribute to glial scarring by rapid proliferation and up-regulation of glial fibrillary acidic protein (GFAP) expression and production of chondroitin sulfate proteoglycans (CSPGs). CSPGs play a crucial role in formation of the glial scar, which takes over the lesion site following spinal cord injury (SCI). This process corresponds to the inflammatory response of macrophages, which polarize toward a dominant pro-inflammatory M1 phenotype following SCI. The M1 phenotype is known to release various cytotoxic compounds that exacerbate the glial scar, which in turn impedes tissue regeneration. Recent studies have shown that anti-inflammatory M2 macrophages play a role in allowing neurite extensions to occur, even across inhibitory substrates, and can lessen the degree of secondary damage. Based on earlier results demonstrating that keratin biomaterials may polarize macrophages toward an anti-inflammatory M2 phenotype, we test the hypothesis that these polarized macrophages will have the potential to indirectly effect astrogliosis. Using an in vitro model of reactive astrogliosis, macrophage-conditioned media from cells that have been cultured with soluble keratin for 24 hours or 7 days appears to decrease reactivity and associates CSPG production. These results are statistically similar to the control M2 macrophage conditioned media. A comparable collagen-conditioned macrophage media does not resolve astrocyte reactivity, while control M1 macrophage conditioned media results in an increase in GFAP expression. These data suggest keratin-derived macrophages are more functionally similar to M2 macrophages and that keratin treatment may aid in limiting secondary inflammatory-mediated damage.