Integrin β4 in Breast Cancer: A Focused Review

Integrin β4 (ITGB4) is emerging as a pivotal player in breast cancer progression, particularly in aggressive and invasive subtypes such as triple-negative breast cancer (TNBC). This review broadly summarizes current research on ITGB4’s involvement in breast cancer, focusing on its role in metastasis, metabolic reprogramming, drug resistance, and immunoregulation that collectively influence tumor behavior with implications for the development of innovative and more efficacious therapeutic modalities.

Systematic overview of hepatitis C infection in the Middle East and North Africa

AIM To assess the quality of and to critically synthesize the available data on hepatitis C infections in the Middle East and North Africa(MENA) region to map evidence gaps.METHODS We conducted an overview of systematic reviews(SRs) following an a priori developed protocol(CRD42017076736). Our overview followed the preferred reporting items for systematic reviews and metaanalyses guidelines for reporting SRs and abstracts and did not receive any funding. Two independent reviewers systematically searched MEDLINE and conducted a multistage screening of the identified articles. Out of 5758 identified articles, 37 SRs of hepatitis C virus(HCV) infection in populations living in 20 countries in the MENA region published between 2008 and 2016 were included in our overview. The nine primary outcomes of interest were HCV antibody(anti-) prevalences and incidences in different at-risk populations; the HCV viremic(RNA positive) rate in HCV-positive individuals; HCV viremic prevalence in the general population(GP); the prevalence of HCV co-infection with the hepatitis B virus, human immunodeficiency virus, or schistosomiasis; the HCV genotype/subtype distribution; and the risk factors for HCV transmission. The conflicts of interest declared by the authors of the SRs were also extracted. Good quality outcomes reported by the SRs were defined as having the population, outcome, study time and setting defined as recommended by the PICOTS framework and a sample size > 100.RESULTS We included SRs reporting HCV outcomes with different levels of quality and precision. A substantial proportion of them synthesized data from mixed populations at differing levels of risk for acquiring HCV or at different HCV infection stages(recent and prior HCV transmissions). They also synthesized the data over long periods of time(e.g., two decades). Anti-HCV prevalence in the GP varied widely in the MENA region from 0.1%(study dates not reported) in the United Arab Emirates to 2.1%-13.5%(2003-2006) in Pakistan and 14.7%(2008) in Egypt. Data were not identified for Bahrain, Jordan, or Palestine. Good quality estimates of anti-HCV prevalence in the GP were reported for Algeria, Djibouti, Egypt, Iraq, Morocco, Pakistan, Syria, Sudan, Tunisia, and Yemen. Anti-HCV incidence estimates in the GP were reported only for Egypt(0.8-6.8 per 1000 person-year, 1997-2003). In Egypt, Morocco, and the United Arab Emirates, viremic rates in anti-HCV-positive individuals from the GP were approximately 70%. In the GP, the viremic prevalence varied from 0.7%(2011) in Saudi Arabia to 5.8%(2007-2008) in Pakistan and 10.0%(2008) in Egypt. Anti-HCV prevalence was lower in blood donors than in the GP, ranging from 0.2%(1992-1993) in Algeria to 1.7%(2005) in Yemen. The reporting quality of the outcomes in blood donors was good in the MENA countries, except in Qatar where no time framework was reported for the outcome. Some countries had anti-HCV prevalence estimates for children, transfused patients, contacts of HCV-infected patients, prisoners, sex workers, and men who have sex with men.CONCLUSION A substantial proportion of the reported outcomes may not help policymakers to develop micro-elimination strategies with precise HCV infection prevention and treatment programs in the region, as nowcasting HCV epidemiology using these data is potentially difficult. In addition to providing accurate information on HCV epidemiology, outcomes should also demonstrate practical and clinical significance and relevance. Based on the available data, most countries in the region have low to moderate anti-HCV prevalence. To achieve HCV elimination by 2030, up-to-date, good quality data on HCV epidemiology are required for the GP and key populations such as people who inject drugs and men who have sex with men.

Dehydration and volume depletion:How to handle the misconceptions

Dehydration and volume depletion describe two distinct body fluid deficit disorders with differing pathophysiology,clinical manifestations and treatment approaches.However,the two are often confused or equated with each other.Here,we address a number of commonly encountered misconceptions about body-fluid deficit disorders,analyse their origins and propose approaches to overcome them.

Cardiogenic shock in the setting of acute myocardial infarction:Another area of sex disparity?

Cardiogenic shock in the setting of acute myocardial infarction(AMI)carries significant morbidity and mortality,despite advances in pharmacological,mechanical and reperfusion therapies.Studies suggest that there is evidence of sex disparities in the risk profile,management,and outcomes of cardiogenic shock complicating AMI.Compared with men,women tend to have more comorbidities,greater variability in symptom presentation and are less likely to receive timely revascularization and mechanical circulatory support.These factors might explain why women tend to have worse outcomes.In this review,we highlight sex-based differences in the prevalence,management,and outcomes of cardiogenic shock due to AMI,and discuss potential ways to mitigate them.

Dimensional(premenstrual symptoms screening tool)vs categorical(mini diagnostic interview,module U)for assessment of premenstrual disorders

BACKGROUND Premenstrual syndrome(PMS)is the constellation of physical and psychological symptoms before menstruation.Premenstrual dysphoric disorder(PMDD)is a severe form of PMS with more depressive and anxiety symptoms.The Mini international neuropsychiatric interview,module U(MINI-U),assesses the diagnostic criteria for probable PMDD.The Premenstrual Symptoms screening tool(PSST)measures the severity of these symptoms.AIM To compare the PSST ordinal scores with the corresponding dichotomous MINI-U answers.METHODS Arab women(n=194)residing in Doha,Qatar,received the MINI-U and PSST.Receiver Operating Characteristics(ROC)analyses provided the cut-off scores on the PSST using MINI-U as a gold standard.RESULTS All PSST ratings were higher in participants with positive responses on MINI-U.In addition,ROC analyses showed that all areas under the curves were significant with the cutoff scores on PSST.CONCLUSION This study confirms that the severity measures from PSST can recognize patients with moderate/severe PMS and PMDD who would benefit from immediate treatment.

Hepatitis C virus among blood donors and general population in Middle East and North Africa:Meta-analyses and meta-regressions

BACKGROUND Despite the Middle East and North Africa(MENA)Region reported to have the highest prevalence of hepatitis C virus(HCV)globally,HCV infection levels in the majority of MENA countries remain inadequately characterized.Blood donor data have been previously used as a proxy to assess levels and trends of HCV in the general population,however,it is unclear how comparable these populations are in MENA and whether blood donors provide an appropriate proxy.AIM To delineate HCV epidemiology among blood donors and the general population in the MENA.METHODS The data source was the systematically gathered MENA HCV Epidemiology Synthesis Project Database.Random-effects meta-analyses and meta-regressions were conducted.For comparison,analyses were conducted for Europe,utilizing the Hepatitis C Prevalence Database of the European Centre for Disease Prevention and Control.RESULTS One thousand two hundred and thirteen HCV antibody prevalence measures and 84 viremic rate measures were analyzed for MENA.Three hundred and seventyseven antibody prevalence measures were analyzed for Europe.In MENA,pooled mean prevalence was 1.58%[95%confidence interval(CI):1.48%–1.69%]among blood donors and 4.49%(95%CI:4.10%–4.90%)in the general population.In Europe,pooled prevalence was 0.11%(95%CI:0.10%–0.13%)among blood donors and 1.59%(95%CI:1.25%–1.97%)in the general population.Prevalence in the general population was 1.72-fold(95%CI:1.50–1.97)higher than that in blood donors in MENA,but it was 15.10-fold(95%CI:11.48–19.86)higher in Europe.Prevalence was declining at a rate of 4%per year in both MENA and Europe[adjusted risk ratio:0.96(95%CI:0.95–0.97)in MENA and 0.96(95%CI:0.92–0.99)in Europe].Pooled mean viremic rate in MENA was 76.29%(95%CI:67.64%–84.02%)among blood donors and 65.73%(95%CI:61.03%–70.29%)in the general population.CONCLUSION Blood donor data provide a useful proxy for HCV infection in the wider population in MENA,but not Europe,and could improve HCV burden estimations and assess progress toward HCV elimination by 2030.

Counterion Binding in Aqueous Solutions of Poly(vinylpyridines) as Assessed by Potentiometric Titration

The extent to which counterions bind to polyelectrolytes influences a variety of polymer-based applications, including polyelectrolyte enhanced ultrafiltration and forward osmosis using polyelectrolytes as draw agents. Potentiometric titrations of poly (2-vinylpyridine) (P2VP), poly (3-vinylpyridine) (P3VP), and poly (4-vinylpydine) (P4VP) were performed using HBr, HCl, HNO3, and HClO4 in both the presence and absence of added NaCl. Because of the systematic differences among the three polyelectrolytes, titration results provide insight into the role of polymer structure in the relative extents to which various counterions bind. Titration data reveal that ionization properties vary as functions of polymer investigated, titrant used, degree of protonation, and added salt concentration. Acid dissociation constants of the pyridinium moieties were found to generally increase with increasing degree of protonation, though appreciable differences were exhibited among the three polymers investigated. For all three polymers, Cl- demonstrated the lowest affinity for the charged pyridinium residues, while the affinities associated with Br- and NO-3 were nearly identical to each other. The relative extent of binding for CIO-4 varied across the polymers investigated, and was greatest for P4VP.

Neurolithography:Lithography as an enabling technology in neurology and neuroscience

Modern lithography,which enables the fabrication of complex structures in biomedical devices with exceptional precision,is a potentially transformative force in the neural sciences.Techniques such as photolithography,electron beam lithography,and soft lithography have been utilized to produce devices that guide neuronal growth and differentiation and measure electrophysiological signals at the single-cell level.In the clinical sphere,lithography plays a role in the manufacturing of devices for deep brain stimulation,brain-computer interface,and neuroprosthetics.Here,we briefly review the applications of lithography in basic and translational neuroscience and clinical neurology,with an eye toward future advancement.

Premature ejaculation:an update on definition and pathophysiology

Premature ejaculation(PE)is the most comm on male sexual dysfunction,which represents a diag no stic as well as a therapeutic challenge for physicians.However,no universally accepted definition is currently available for PE.As a result,physicians continue to diagnose patients with PE according to major guidelines set by the professional societies.These guidelines either recommend the use of validated questionnaires or patient-reported outcomes.Recent efforts directed toward classifying PE may help provide a better understanding of the prevalence and risk factors of this disorder.While the exact etiology of PE has not been clearly elucidated,several risk factors have been strongly reported in the literature.Clearly,to understand the revised definition of PE,its etiology and pathophysiology is necessary to improve the clinical management of this medical condition and form the basis of future research in this regard.In this review,we highlight the past and current definitions of PE and present an appraisal on the classifications and theories suggested for the etiopathogenesis of PE.

Correlation of oxidation reduction potential and total motile sperm count:its utility in the evaluation of male fertility potential

Oxidative stress(OS)is detri me ntal to sperm fun ctio ns,and the oxidation reductio n pote ntial(ORP)is a good measure of OS as it considers the balance betwee n oxidants and reducta nts.Total motile sperm count(TMSC)is viewed as the single most im porta nt semen analysis parameter that can predict male infertility severity,and its correlation with ORP has never been undertaken.The objectives of this study were to assess the correlation between ORP and TMSC,to identify the ORP cutoff value based on the TMSC result,and to compare this cutoff value with previously reported ORP cutoff values in literature.One thousand one hundred and sixty-eight infertile patients and 100 fertile controls were enrolled.Demographic and semen data of the participants were retrieved and analyzed.Wilcox on's rank-sum test compared variables betwee n infertile men and fertile controls;Spearman's correlation assessed the static ORP(sORP)-TMSC relationship for the whole sample and among each group individually.Using a 20×10^6TMSC threshold,receiver operator characteristic(ROC)analysis determined the sORP cutoff associated with the highest predictive values.TMSC was significantly negatively correlated with sORP across all participants(r=0.86,P<0.001),among infertile patients(r=0.729,P<0.001),and among fertile controls(r=0.53,P<0.001).A 20-million TMSC threshold determined an sORP cutoff value of 2.34 mV/106sperm/ml to be associated with 82.9%sensitivity,82.8%specificity,91.5%positive predictive value(PPV),68.5%negative predictive value(NPV),and 82.9%overall accuracy.Compared with previously reported cutoff values in searched literature,the 2.34 mV/10^6sperm/ml cutoff value identified in our study yielded the highest overall diagnostic accuracy in the evaluation of in fertile men.

Corneal confocal microscopymeets continuousglucose monitoring:ataleof two technologies

Zhao et al1I from Shanghai,China,have undertaken a detailed clinical study in a cohort of 206 asymptomatic patients with type 2'diabetes utilizing advanced in vivo nerve imaging with corneal confocal microscopy(CCMHeidelberg HRT III RCM)and continuous glucose monitoring(CGM-iPro2 system)over 7days.The study provides important insights into the relationship between relatively short-term glucose perturbation over 7 days and corneal nerve loss in diabetic neuropathy.

Use of routine HIV testing data for early detection of emerging HIV epidemics in high-risk subpopulations:A concept demonstration study

Introduction:HIV epidemics in hard-to-reach high-risk subpopulations are often discovered years after epidemic emergence in settings with poor surveillance infrastructure.Using hypothesis-generation modeling,we aimed to investigate and demonstrate the concept of using routine HIV testing data to identify and characterize hidden epidemics in high-risk subpopulations.We also compared this approach to surveillance based on AIDS case notifications.Methods:A deterministic mathematical model was developed to simulate an emerging HIV epidemic in a high-risk subpopulation.A stochastic Monte Carlo simulation was implemented on the total population to simulate the sampling process of generating routine HIV testing data.Epidemiological measures were estimated on the simulated epidemic and on the generated testing sample.Sensitivity analyses were conducted on the results.Results:In the simulated epidemic,HIV prevalence saturated at 32%in the high-risk subpopulation and at 0.33%in the total population.The epidemic started its emergingepidemic phase 28 years after infection introduction,and saturated 67 years after infection introduction.In the simulated HIV testing sample,a significant time trend in prevalence was identified,and the generated metrics of epidemic emergence and saturation were similar to those of the simulated epidemic.The epidemic was identified 4.0(95%CI 3.4e4.6)years after epidemic emergence using routine HIV testing,but 29.7(95%CI 15.8 e52.1)years after emergence using AIDS case notifications.In the sensitivity analyses,none of the sampling biases affected the conclusion of an emerging epidemic,but some affected the estimated epidemic growth rate.Conclusions:Routine HIV testing data provides a tool to identify and characterize hidden and emerging epidemics in high-risk subpopulations.This approach can be specially useful in resource-limited settings,and can be applied alone,or along with other complementary data,to provide a meaningful characterization of emerging but hidden epidemics.

Modelling ocular ageing in adults with well-controlled type I diabetes

Purpose:To develop a paraxial eye model based on a previously collected cohort of adults with well-controlled type 1 diabetes mellitus(DM1)and a limited range of refractive errors.Methods:The study used the previously published biometric data of 72 participants(Age:41.5
12.4 years)with DM1.Measurements included objective refraction,anterior and posterior corneal radii of curvatures,and internal distances.Moreover,phakometry was used to determine the lens radii of curvature and lens equivalent indices,from which the lens powers were calculated.A multivariate linear regression was performed for each biometric parameter with respect to current age(Age),the time since the onset of diabetes(Tdb),and current levels of glycated hemoglobin(HbA1c).The vitreous chamber depth was determined from other distances,and lens equivalent index was chosen to balance the models.These were compared with an existing model for nondiabetic eyes.Results:Some dependent parameters were not affected by the independent variables(spherical equivalent,anterior corneal radius of curvature,central corneal thickness),some were affected by time since onset(the lens radii of curvatures,anterior chamber depth)and others were affected by both age and time since onset(posterior corneal radius of curvature,lens thickness,axial length).None of the dependent parameters were affected by current levels of HbA1c.Conclusions:The proposed model accurately describes the age-related changes in the eyes of people with DM1.In this description the age of diabetes onset plays an important role,especially if the diabetes onset occurred during childhood.