Accuracy of endoscopic ultrasound-guided tissue acquisition in the evaluation of lymph nodes enlargement in the absence of on-site pathologist

AIM To evaluate factors that influence the diagnostic accuracy of endoscopic ultrasound(EUS)-guided tissue acquisition for lymph node enlargement in the absence of an on-site pathologist. METHODS A retrospective analysis of patients who underwent EUS-guided tissue acquisition for the pathological diagnosis of lymph node enlargement between April2012 and June 2015 is reported. Tissue acquisition was performed with both cytology and biopsy needles of different calibers. The variables evaluated were lymph node location and size, number of passes and type of needle used. Final diagnosis was based on surgical histopathology or, in non-operated cases, on EUSguided tissue acquisition and imaging assessment with a minimum clinical follow-up of 6 mo. RESULTS During the study period, 168 lymph nodes with a median size of 20.3 mm(range 12.5-27) were sampled from 152 patients. Ninety lymph nodes(53.6%) were located at mediastinum, and 105(62.5%) were acquired with biopsy needles. The final diagnosis was benign/reactive origin in 87 cases(51.8%), malignant in 65 cases(38.7%), and lymphoma in 16 cases(9.5%). The sensitivity, specificity, positive predictive value and negative predictive value for the detection of malignancy were 74.1%, 100%, 100% and 80.6%, respectively. The overall accuracy was 87.5%(95%CI: 81.7-91.7). No variables were independently associated with a correct final diagnosis according to the multivariate analysis. CONCLUSION EUS-guided tissue acquisition is a highly accurate technique for assessing lymph node enlargement. None of the variables evaluated were associated with diagnostic accuracy.

CD34^(+ )progenitor cells as diagnostic and therapeutic targets in Alzheimer's disease

Alzheimer’s disease(AD)is the main neurodegenerative disease leading to dementia and cognitive impairment in the elderly.Considering AD to be an epidemic,an increase from the current 50 million to more than 150 million patients is expected by the year 2050.

Light at night and lung cancer risk:A worldwide interdisciplinary and time-series study

Background:Light at night(LAN)has become a concern in interdisciplinary research in recent years.This global interdisciplinary study aimed to explore the exposure-lag-response association between LAN exposure and lung cancer incidence.Methods:LAN data were obtained from the Defense Meteorological Satellite Program’s Operational Linescan System.Data of lung cancer incidence,socio-demographic index,and smoking prevalence of populations in 201 countries/territories from 1992 to 2018 were collected from the Global Burden of Disease Study.Spearman correlation tests and population-weighted linear regression analysis were used to evaluate the correlation between LAN exposure and lung cancer incidence.A distributed lag nonlinear model(DLNM)was used to assess the exposure-lag effects of LAN exposure on lung cancer incidence.Results:The Spearman correlation coefficients were 0.286-0.355 and the population-weighted linear regression correlation coefficients were 0.361-0.527.After adjustment for socio-demographic index and smoking preva-lence,the Spearman correlation coefficients were 0.264-0.357 and the population-weighted linear regression correlation coefficients were 0.346-0.497.In the DLNM,the maximum relative risk was 1.04(1.02-1.06)at LAN exposure of 8.6 with a 2.6-year lag time.After adjustment for socio-demographic index and smoking prevalence,the maximum relative risk was 1.05(1.02-1.07)at LAN exposure of 8.6 with a 2.4-year lag time.Conclusion:High LAN exposure was associated with increased lung cancer incidence,and this effect had a specific lag period.Compared with traditional individual-level studies,this group-level study provides a novel paradigm of effective,efficient,and scalable screening for risk factors.

Endothelial progenitor cells as a therapeutic option in intracerebral hemorrhage

Intracerebral hemorrhage （ICH） is the most severe cerebrovascular disease, which represents a leading cause of death and disability in developed countries. However, therapeutic options are limited, so is mandatory to investigate repairing processes after stroke in order to develop new therapeutic strategies able to promote brain repair processes. Therapeutic angiogenesis and vasculogenesis hold promise to improve outcome of ICH patients. In this regard, circulating endothelial progenitor cells （EPCs） have recently been suggested to be a marker of vascular risk and endothelial function. Moreover, EPC levels have been associated with good neurological and functional outcome as well as reduced residual hematoma volume in ICH patients. Finally, experimental and clinical studies indicate that EPC might mediate endothelial cell regeneration and neovascularization. Therefore, EPC-based therapy could be an excellent therapeutic option in ICH. In this mini-review, we discuss the present status of knowledge about the possible therapeutic role of EPCs in ICH, molecular mechanisms, and the future perspectives and strategies for their use in clinical practice.

New strategies for ischemic stroke: internal photobiomodulation therapy

Epidemiology and physiopathology of ischemic stroke:Every year, around 15 million of people suffer a stroke event all around the world. Among those, around 6.7 million will die, and most of the survivors will suffer some grade of disability.

Targeting the overexpressed mitochondrial protein VDAC1 in a mouse model of Alzheimer’s disease protects against mitochondrial dysfunction and mitigates brain pathology

Background Alzheimer’s disease(AD)exhibits mitochondrial dysfunctions associated with dysregulated metabolism,brain inflammation,synaptic loss,and neuronal cell death.As a key protein serving as the mitochondrial gatekeeper,the voltage-dependent anion channel-1(VDAC1)that controls metabolism and Ca2+homeostasis is positioned at a convergence point for various cell survival and death signals.Here,we targeted VDAC1 with VBIT-4,a newly developed inhibitor of VDAC1 that prevents its pro-apoptotic activity,and mitochondria dysfunction.Methods To address the multiple pathways involved in AD,neuronal cultures and a 5×FAD mouse model of AD were treated with VBIT-4.We addressed multiple topics related to the disease and its molecular mechanisms using immunoblotting,immunofluorescence,q-RT-PCR,3-D structural analysis and several behavioral tests.Results In neuronal cultures,amyloid-beta(Aβ)-induced VDAC1 and p53 overexpression and apoptotic cell death were prevented by VBIT-4.Using an AD-like 5×FAD mouse model,we showed that VDAC1 was overexpressed in neurons surrounding Aβplaques,but not in astrocytes and microglia,and this was associated with neuronal cell death.VBIT-4 prevented the associated pathophysiological changes including neuronal cell death,neuroinflammation,and neuro-metabolic dysfunctions.VBIT-4 also switched astrocytes and microglia from being pro-inflammatory/neurotoxic to neuroprotective phenotype.Moreover,VBIT-4 prevented cognitive decline in the 5×FAD mice as evaluated using several behavioral assessments of cognitive function.Interestingly,VBIT-4 protected against AD pathology,with no significant change in phosphorylated Tau and only a slight decrease in Aβ-plaque load.Conclusions The study suggests that mitochondrial dysfunction with its gatekeeper VDAC1 is a promising target for AD therapeutic intervention,and VBIT-4 is a promising drug candidate for AD treatment.

Effect of Temperature on Emergency Ambulance Call-Outs for Cardiovascular Causes:A Scoping Review

Climate change has increased interest in the effects of the thermal environment on cardiovascular health.Most studies have focused on mortality data.However,pre-hospital care data are better able to evaluate these effects,as they can register the full spectrum of the disease in real time.This scoping review aims to synthesize the epidemiological evidence regarding the effects of the thermal environment on cardiovascular morbidity in the pre-hospital setting,evaluated through ambulance calls.A staged literature search was performed using the PubMed database for the period between 1st January 2000 and 30th March 2023,using the MeSH terms“Weather”AND“Emergency Medical Services”.A total of 987 publications were identified that examined the correlation between the thermal environment and ambulance call-outs for cardiovascular causes.The studies were mostly ecological time series,with significant variability in the methodological aspects employed.An increase in the number of ambulance call-outs has been observed in association with low temperatures,both for overall cardiovascular pathologies and for certain pathological subtypes.For high temperatures,no effect has been observed in overall call-outs,although an increase has been observed during heat waves.The demand for ambulances for cardiac arrests is increased by both low and high temperatures and during heat waves.Ambulance call-outs for cardiovascular causes increase with low temperatures and heat waves,with no significant increase in the overall demand associated with high temperatures.Ambulance call-outs for cardiac arrests are the only subtype that is increased by high temperatures.

sTWEAK is a marker of early haematoma growth and leukoaraiosis in intracerebral haemorrhage

Objective To study the association between early growth of haematoma with biomarkers of endothelial dysfunction such as leukoaraiosis(LA)and the soluble tumour necrosis factor-like weak inducer of apoptosis(sTWEAK)in patients with intracerebral haemorrhage(ICH).Methods This is a retrospective observational study of patients with nontraumatic ICH.Clinical and biochemical parameters were analysed.sTWEAK levels were measured by ELISA.LA was analysed in the hemisphere without haemorrhage to avoid interference with the acute injury.The main endpoint was the haematoma growth evaluated by the difference in volume between the second and the initial neuroimage.Poor functional outcome,defined as a modified Rankin Scale>2 at 3 months,was considered as secondary endpoint.Receiver operating characteristic curve analysis was performed to stablish the best cut-off for sTWEAK levels associated with haematoma growth.Results We included 653 patients with ICH in our analysis(71.1±11.9 years,44%women).Haematoma growth was observed in 188 patients(28.8%).sTWEAK levels≥5600 pg/mL predicted ICH growth with a sensitivity of 84%and a specificity of 87%.sTWEAK levels≥5600 pg/mL and the presence of LA were associated with haematoma growth(OR:42.46;(CI 95%22.67 to 79.52)and OR:2.73(CI 95%1.39 to 5.34),respectively).Also,the presence of LA(OR:4.31(CI 95%2.89 to 6.42))and the interaction between ICH growth and sTWEAK(OR:2.23(CI 95%1.40 to 3.55))were associated with poor functional outcome at 3 months.Conclusion sTWEAKs,together with the presence and grade of LA,are biomarkers able to predict ICH growth and poor functional outcome in patients with ICH.

Fighting type 2 diabetes: Formulation strategies for peptide-based therapeutics

Diabetes mellitus is a major health problem with increasing prevalence at a global level.The discovery of insulin in the early 1900 s represented a major breakthrough in diabetes management,with further milestones being subsequently achieved with the identification of glucagon-like peptide-1(GLP-1)and the introduction of GLP-1 receptor agonists(GLP-1 RAs)in clinical practice.Moreover,the subcutaneous delivery of biotherapeutics is a well-established route of administration generally preferred over the intravenous route due to better patient compliance and prolonged drug absorption.However,current subcutaneous formulations of GLP-1 RAs present pharmacokinetic problems that lead to adverse reactions and treatment discontinuation.In this review,we discuss the current challenges of subcutaneous administration of peptide-based therapeutics and provide an overview of the formulations available for the different routes of administration with improved bioavailability and reduced frequency of administration.

Correction:Targeting the overexpressed mitochondrial protein VDAC1 in a mouse model of Alzheimer’s disease protects against mitochondrial dysfunction and mitigates brain pathology

Correction:Translational Neurodegeneration(2022)11:58 https://doi.org/10.1186/s40035-022-00329-7 Following publication of this article[1],the authors iden-tified an error in the family name of Alon Monsonego.The incorrect author name is:Alon Monsengo.The correct author name is:Alon Monsonego.The author group has been updated above and the orig-inal article[1]has been corrected.

Engineering hyaluronic acid-based nanoassemblies for monoclonal antibody delivery-design,characterization,and biological insights

The current spotlight of cancer therapeutics is shifting towards personalized medicine with the widespread use of monoclonal antibodies(mAbs).Despite their increasing potential,mAbs have an intrinsic limitation related to their inability to cross cell membranes and reach intracellular targets.Nanotechnology offers promising solutions to overcome this limitation,however,formulation challenges remain.These challenges are the limited loading capacity(often insufficient to achieve clinical dosing),the complex formulation methods,and the insufficient characterization of mAb-loaded nanocarriers.Here,we present a new nanocarrier consisting of hyaluronic acid-based nanoassemblies(HANAs)specifically designed to entrap mAbs with a high efficiency and an outstanding loading capacity(50%,w/w).HANAs composed by an mAb,modified HA and phosphatidylcholine(PC)resulted in sizes of~100 nm and neutral surface charge.Computational modeling identified the principal factors governing the high affinity of mAbs with the amphiphilic HA and PC.HANAs composition and structural configuration were analyzed using the orthogonal techniques cryogenic transmission electron microscopy(cryo-TEM),asymmetrical flow field-flow fractionation(AF4),and small-angle X-ray scattering(SAXS).These techniques provided evidence of the formation of core-shell nanostructures comprising an aqueous core surrounded by a bilayer consisting of phospholipids and amphiphilic HA.In vitro experiments in cancer cell lines and macrophages confirmed HANAs’low toxicity and ability to transport mAbs to the intracellular space.The reproducibility of this assembling process at industrial-scale batch sizes and the long-term stability was assessed.In conclusion,these results underscore the suitability of HANAs technology to load and deliver biologicals,which holds promise for future clinical translation.