Acupuncture in diabetic peripheral neuropathy-neurological outcomes of the randomized acupuncture in diabetic peripheral neuropathy trial

BACKGROUND Diabetic peripheral neuropathy(DPN)is a common complication of diabetes mellitus and can lead to serious complications.Therapeutic strategies for pain control are available but there are few approaches that influence neurological deficits such as numbness.AIM To investigate the effectiveness of acupuncture on improving neurological deficits in patients suffering from type 2 DPN.METHODS The acupuncture in DPN(ACUDPN)study was a two-armed,randomized,controlled,parallel group,open,multicenter clinical trial.Patients were randomized in a 1:1 ratio into two groups:The acupuncture group received 12 acupuncture treatments over 8 wk,and the control group was on a waiting list during the first 16 wk,before it received the same treatment as the other group.Both groups received routine care.Outcome parameters were evaluated after 8,16 and 24 wk and included neurological scores,such as an 11-point numeric rating scale(NRS)11 for hypesthesia,neuropathic pain symptom inventory(NPSI),neuropathy deficit score(NDS),neuropathy symptom score(NSS);nerve conduction studies(NCS)were assessed with a handheld point-of-care device.RESULTSSixty-two participants were included.The NRS for numbness showed a difference of 2.3(P<0.001)in favor of theacupuncture group,the effect persisted until week 16 with a difference of 2.2(P<0.001)between groups and 1.8points at week 24 compared to baseline.The NPSI was improved in the acupuncture group by 12.6 points(P<0.001)at week 8,the NSS score at week 8 with a difference of 1.3(P<0.001);the NDS and the TNSc score improvedfor the acupuncture group in week 8,with a difference of 2.0 points(P<0.001)compared to the control group.Effects were persistent in week 16 with a difference of 1.8 points(P<0.05).The NCS showed no meaningfulchanges.In both groups only minor side effects were reported.CONCLUSION Study results suggest that acupuncture may be beneficial in type 2 diabetic DPN and seems to lead to a reductionin neurological deficits.No serious adverse events were recorded and the adherence to treatment was high.Confirmatory randomized sham-controlled clinical studies with adequate patient numbers are needed to confirmthe results.

Minor Pressure Differences within the Fontan-Anastomosis in Patients with Total Cavopulmonary Connection by 4D-Flow Magnetic Resonance Imaging

Background: Pressure measurement in total cavopulmonary connection (TCPC) patients is a domain of cardiaccatheterization. 4D velocity encoded cardiovascular magnetic resonance (4D–flow MRI) offers an alternative forassessment of even minor pressure differences. The scope of this study was to measure even minor pressure differencesin the anastomosis of TCPC patients, who are clinically uncompromised. Methods: Twenty-four patients(median 15 years [8;34]) with TCPC were studied prospectively by 4D-flow MRI. Pressure differences betweensuperior vena cava (SVC) and extracardiac conduit (C) to both right pulmonary artery (RPA) and left pulmonaryartery (LPA) were assessed. Small fluid obstructions as vortices within the anastomosis were detected by flowpathlines from 4D-flow MRI. In two patients pressure differences were calculated also by computational flowdynamics (CFD) as a plausibility check for the order of magnitude. Results: Median values of pressure differencesin the anastomosis between SVC and RPA were 0.63 (0.21–2.1) mmHg, between C and RPA 0.67 (0.3–2.2)mmHg, between SVC and LPA 0.8 (0.3–2.4) mmHg and between C and LPA 0.7 (0.2–1.9) mmHg. Patients withpotential flow obstruction (stents, occluder, vortices) had significantly higher gradients at the anastomosis (p <0.05) than patients without potential obstructions, although the absolute values were small. CFD- and measurement-based pressure difference showed good agreement. Conclusion: 4D-flow MRI is able to detect minor pressuredifferences within the Fontan circuit even in patients with apparently satisfactory TCPC. Slightly higherpressure differences are due to the presence of small flow obstruction.

chemokine/chemokine receptor pair CC L20/CC R6 in humancolorectal malignancy:An overview

Chemokines belong to a superfamily of small, cytokinelike proteins, which induce multiple physiological functions, particularly cytoskeletal rearrangement and compartment-specific migration through their interaction with G-protein-coupled receptors. Chemokines and their receptors have been widely acknowledged as essential and selective mediators in leukocyte migration in inflammatory response. It is now established that the chemokine/chemokine receptor system is also used by cancer cells to direct lymphatic and haematogenous spreading and additionally has an impact on the site of metastatic growth of different tumours. In recent years an increasing number of studies have drawn attention to CC-chemokine cysteine motif chemokine ligand 20(CCL20) and its physiological sole receptor CCR6 to play a role in the onset, development and metastatic spread of various gastrointestinal cancer entities. Among various cancer types CCR6 was also demonstrated to be significantly overexpressed in colorectal cancer(CRC) and stimulation by its physiological ligand CCL20 has been reported to promote CRC cell proliferation and migration in vitro. Further, the CCL20/CCR6 system apparently plays a role in the organ-selective liver metastasis of CRC. Here we review the literature on expression patterns of CCL20 and CCR6 and their physiological interactions as well as the currently presumed role of CCL20 and CCR6 in the formation of CRC and the development of liver metastasis, providing a potential basis for novel treatment strategies.

Functional Surfactants for Molecular Fishing,Capsule Creation,and Single-Cell Gene Expression

Creating a single surfactant that is open to manipulation,while maintaining its surface activity,robustness,and compatibility,to expand the landscape of surfactant-dependent assays is extremely challenging.We report an oxidation-responsive precursor with thioethers and multiple 1,2-diols for creating a variety of functional surfactants from one parent surfactant.Using these multifunctional surfactants,we stabilize microfluidics-generated aqueous droplets.The droplets encapsulate different components and immerse in a bioinert oil with distinct interfaces where an azide-bearing surfactant allow fishing of biomolecules from the droplets,aldehyde-bearing surfactant allow fabrication of microcapsules,and hydroxyl-bearing surfactants,with/without oxidized thioethers,allow monitoring of single-cell gene expression.Creating multifunctional surfactants poses opportunities for broad applications,including adsorption,bioanalytics,catalysis,formulations,coatings,and programmable subset of emulsions.

Apolipoprotein E polymorphism influences orthotopic liver transplantation outcomes in patients with hepatitis C virus-induced liver cirrhosis

BACKGROUND Hepatitis C virus(HCV)infection is responsible for a chronic liver inflammation,which may cause end-stage liver disease and hepatocellular carcinoma.Apolipoprotein E(protein:ApoE,gene:APOE),a key player in cholesterol metabolism,is mainly synthesized in the liver and APOE polymorphisms may influence HCV-induced liver damage.AIM To determine whether APOE alleles affect outcomes in HCV-infected patients with liver cirrhosis following orthotopic liver transplantation(OLT).METHODS This was a cohort study in which 179 patients,both genders and aged 34-70 years,were included before or after(up to 10 years follow-up)OLT.Liver injury severity was assessed using different criteria,including METAVIR and models for endstage liver disease.APOE polymorphisms were analyzed by quantitative real-time polymerase chain reaction.RESULTS The APOE3 allele was the most common(67.3%).In inflammation severity of biopsies from 89 OLT explants and 2 patients in pre-transplant,the degree of severe inflammation(A3F4,0.0%)was significantly less frequent than in patients with minimal and moderate degree of inflammation(≤A2F4,16.2%)P=0.048,in patients carrying the APOE4 allele when compared to non-APOE4.In addition,a significant difference was also found(≤A2F4,64.4%vs A3F4,0.0%;P=0.043)and(A1F4,57.4%vs A3F4,0.0%;P=0.024)in APOE4 patients when compared to APOE3 carriers.The fibrosis degree of the liver graft in 8 of 91 patients and the lack of the E4 allele was associated with more moderate fibrosis(F2)(P=0.006).CONCLUSION Our results suggest that the E4 allele protects against progression of liver fibrosis and degree of inflammation in HCV-infected patients.

Human primary muscle stem cells regenerate injured urethral sphincter in athymic rats

Background:The aim of the study was to demonstrate the efficacy of human muscle stem cells(MuSCs)isolated using innovative technology in restoring internal urinary sphincter function in a preclinical animal model.Methods:Colonies of pure human MuSCs were obtained from muscle biopsy speci-mens.Athymic rats were subjected to internal urethral sphincter damage by electro-cauterization.Five days after injury,2×105 muscle stem cells or medium as control were injected into the area of sphincter damage(n=5 in each group).Peak bladder pressure and rise in pressure were chosen as outcome measures.To repeatedly obtain the necessary pressure values,telemetry sensors had been implanted into the rat bladders 10 days prior to injury.Results:There was a highly significant improvement in the ability to build up peak pressure as well as a pressure rise in animals that had received muscle stem cells as compared to control(p=0.007)3 weeks after the cells had been injected.Only mini-mal histologic evidence of scarring was observed in treated rats.Conclusion:Primary human muscle stem cells obtained using innovative technology functionally restore internal urethral sphincter function after injury.Translation into use in clinical settings is foreseeable.

An international guideline with six personalised titration schedules for preventing myocarditis and pneumonia associated with clozapine

White blood cell(WBC)monitoring has reduced clozapinetreated patient deaths associated with agranulocytosis to a rarity.However,clozapine protocols and package inserts worldwide provide no instructions for preventing myocarditis or pneumonia during clozapine titrations.Prescribers worldwide are largely unaware of that.Meanwhile,as they worry about agranulocytosis,their clozapine-treated patients are at risk of dying from pneumonia or myocarditis.Consequently,an international guideline with 104 authors from 50 countries/regions was recently published to provide personalised clozapine titration schedules for adult inpatients.This forum article reviews pneumonia and myocarditis occurring during clozapine titration,as well as the three most innovative aspects of this new guideline:(1)personalised titration,(2)C reactive protein(CRP)measures,and(3)dose predictions based on blood levels.Clozapine metabolism is influenced by 3 levels of complexity:(1)ancestry groups,(2)sex-smoking subgroups,and(3)presence/absence of poor metabolizer status.These 3 groups of variables should determine the maintenance dose and speed of clozapine titration;they are summarised in a table in the full-text.The international clozapine titration guideline recommends measuring CRP levels simultaneously with WBC,at baseline and weekly at least for the first 4 weeks of titration,the highest risk period for clozapine-induced myocarditis.

Mucosa-associated microbiota alterations in primary sclerosing cholangitis(PSC)before and after liver transplantation-who is calling the shots?

Primary sclerosing cholangitis(PSC)is an immune-related chronic cholangiopathy associated with high rates of progression to liver cirrhosis and the need for liver transplantation.Since PSC is frequently associated with inflammatory bowel disease(IBD),several studies have investigated the role of the gut-liver axis in PSC and emerging evidence indicates that gut and bile microbiota are associated with the onset and progression of PSC[reviewed in(1)].

Clinical practice guidelines for acute-on-chronic liver failure: are we ready for reaching global consensus?

The concept of acute-on-chronic liver failure(ACLF)has gained increasing awareness during the last decade.It considers liver cirrhosis as a systemic disease where precipitating events lead to a sudden deterioration,decompensation and extrahepatic organ failures.Disease severity is determined by the number and types of organ failures and patients with ACLF have a distinct and worse prognosis than patients with acute decompensation but not fulfilling ACLF criteria(1-3).

Human embryo models: unveiling sophisticated self-organization of stem cells during post-implantation stages

In three recent articles published in Nature and Cell,Weatherbee et al.1,Pedroza et al.2 and Liu et al.3 have demonstrated how human pluripotent stem cells can be coaxed to self-organize into compartmentalized structures that mirror post-implantation embryos.Building on the successful establishment of stem cell-derived mouse embryo models ex utero,these models now shed light on human embryo development during the period between implantation and gastrulation,which has so far been challenging to investigate.

How cognitive neuroscience can enhance education and population mental health

Adolescence is one of the most critical periods for human brain development,as evidenced by neuronal maturation processes of synaptic pruning and synapse stabilization[1-3],which together improve the efficiency of information transfer in the brain.This development is coincidental with maturing in multiple cognitive and behavioral capabilities,such as better motor skills,abstract thinking,and complex semantic cognition.On the other hand,many psychiatric disorders,such as attention-deficit/hyperactivity disorder(ADHD),conduct disorder,anxiety,and depression,also have their peak onset in adolescence[4].Therefore,it is vital to understand how the maturing process of the brain during adolescence could affect cognitive growth and psychopathology.

Activating Silent Glycolysis Bypasses in Escherichia coli

All living organisms share similar reactions within their central metabolism to provide precursors for all essential building blocksand reducing power. To identify whether alternative metabolic routes of glycolysis can operate in E. coli, we complementarilyemployed in silico design, rational engineering, and adaptive laboratory evolution. First, we used a genome-scale model andidentified two potential pathways within the metabolic network of this organism replacing canonical Embden-Meyerhof-Parnas(EMP) glycolysis to convert phosphosugars into organic acids. One of these glycolytic routes proceeds via methylglyoxal andthe other via serine biosynthesis and degradation. Then, we implemented both pathways in E. coli strains harboring defectiveEMP glycolysis. Surprisingly, the pathway via methylglyoxal seemed to immediately operate in a triosephosphate isomerasedeletion strain cultivated on glycerol. By contrast, in a phosphoglycerate kinase deletion strain, the overexpression ofmethylglyoxal synthase was necessary to restore growth of the strain. Furthermore, we engineered the “serine shunt” whichconverts 3-phosphoglycerate via serine biosynthesis and degradation to pyruvate, bypassing an enolase deletion. Finally, toexplore which of these alternatives would emerge by natural selection, we performed an adaptive laboratory evolution studyusing an enolase deletion strain. Our experiments suggest that the evolved mutants use the serine shunt. Our study reveals theflexible repurposing of metabolic pathways to create new metabolite links and rewire central metabolism.