Expression of Inducible Co-stimulator in Peripheral Blood T Lymphocytes in the Patients with Systemic Lupus Erythematosus

The expression of inducible co-stimulator (ICOS) in peripheral blood T lymphocytes from the patients with systemic lupus erythematosus (SLE) and the role in the pathogenesis of SLE was investigated. By using two-color immunofluorescent staining and flow cytometric assay, the expression levels of ICOS in peripheal blood T lymphocytes from 33 patients with SLE and 16 healthy volunteers were detected. SLE diseases activity index (SLEDAI) of the patients with SLE was used to evaluate the disease activity. The correlation between the ICOS expression and SLEDAI was analyzed among the groups. The results showed that the expression levels of ICOS in T lymphocytes in active SLE group was markedly higher than those in the control and inactive SLE groups (both P<0.01). There was no significant difference in the expression levels of ICOS between the inactive SLE and the control groups (P>0.05). In active SLE and inactive SLE groups, positive linear correlation was found between the levels of the ICOS expression in T lymphocytes and SLEDAI (r=0.711, P=0.001; r=0.561, P=0.03). It was suggested that the expression of ICOS in peripheral blood T lymphocytes from the patients with active SLE was up-regulated and and ICOS might be related to the pathogenesis of SLE.

DI-3-n-butylphthalide exerts neuroprotective effects by modulating hypoxia-inducible factor 1-alpha ubiquitination to attenuate oxidative stress-induced apoptosis

DI-3-n-butylphthalide is used to treat mild and moderate acute ischemic stroke.However,the precise underlying mechanism requires further investigation.In this study,we investigated the molecular mechanism of DI-3-n-butylphthalide action by various means.We used hydrogen peroxide to induce injury to PC12cells and RAW264.7 cells to mimic neuronal oxidative stress injury in stroke in vitro and examined the effects of DI-3-n-butylphthalide.We found that DI-3-nbutylphthalide pretreatment markedly inhibited the reduction in viability and reactive oxygen species production in PC12 cells caused by hydrogen peroxide and inhibited cell apoptosis.Furthermore,DI-3-n-butylphthalide pretreatment inhibited the expression of the pro-apoptotic genes Bax and Bnip3.DI-3-nbutylphthalide also promoted ubiquitination and degradation of hypoxia inducible factor 1α,the key transcription factor that regulates Bax and Bnip3 genes.These findings suggest that DI-3-n-butylphthalide exhibits a neuroprotective effect on stroke by promoting hypoxia inducible factor-1α ubiquitination and degradation and inhibiting cell apoptosis.

Long non-coding RNA H19 regulates neurogenesis of induced neural stem cells in a mouse model of closed head injury

Stem cell-based therapies have been proposed as a potential treatment for neural regeneration following closed head injury.We previously reported that induced neural stem cells exert beneficial effects on neural regeneration via cell replacement.However,the neural regeneration efficiency of induced neural stem cells remains limited.In this study,we explored differentially expressed genes and long non-coding RNAs to clarify the mechanism underlying the neurogenesis of induced neural stem cells.We found that H19 was the most downregulated neurogenesis-associated lnc RNA in induced neural stem cells compared with induced pluripotent stem cells.Additionally,we demonstrated that H19 levels in induced neural stem cells were markedly lower than those in induced pluripotent stem cells and were substantially higher than those in induced neural stem cell-derived neurons.We predicted the target genes of H19 and discovered that H19 directly interacts with mi R-325-3p,which directly interacts with Ctbp2 in induced pluripotent stem cells and induced neural stem cells.Silencing H19 or Ctbp2 impaired induced neural stem cell proliferation,and mi R-325-3p suppression restored the effect of H19 inhibition but not the effect of Ctbp2 inhibition.Furthermore,H19 silencing substantially promoted the neural differentiation of induced neural stem cells and did not induce apoptosis of induced neural stem cells.Notably,silencing H19 in induced neural stem cell grafts markedly accelerated the neurological recovery of closed head injury mice.Our results reveal that H19 regulates the neurogenesis of induced neural stem cells.H19 inhibition may promote the neural differentiation of induced neural stem cells,which is closely associated with neurological recovery following closed head injury.

Prevalence of Induced Abortion among Female Students in Selected Tertiary Learning Institutions in Gaborone City, Botswana

Induced abortion signifies that pregnancy has been tempered with. Abortion is the removal of an embryo or fetus weighing less than 500 grams from its mother. It can either be spontaneous (unprompted) or induced. Abortion remains one of the leading causes of maternal deaths in developing countries with induced abortion being the key cause. In 2014 from January to August, 9 abortion related deaths occurred in Botswana. There are several reasons female students in tertiary institutions resort to seeking induced abortion which include the socio-demographics like age and socio-economic factors like financial instability. Parental fears, unintended pregnancy and pressure from the partner also force females to terminate pregnancy. Induced abortion has claimed many women’s lives especially in developing countries with very restrictive abortion laws like Botswana as women do not access safe abortion care services. The study intends to establish the determinants of induced abortion among female students in selected tertiary learning institutions in Gaborone City, Botswana. It concentrated primarily on determining the prevalence of induced abortion. This was a descriptive cross-sectional study using both quantitative and qualitative data collection techniques. Systematic random sampling technique was used to come up with 278 participants. Prior to commencement of data collection, all ethical and logistical prerequisites were satisfied. Informed consent was solicited from all the study participants and the purpose of the study was fully explained. A self-administered questionnaire was used to collect data. Microsoft Excel spread sheet was used to code, clean, and enter the data, which was then exported for analysis to the statistical package for social sciences version 24. Frequency distribution tables, percentages graphs, and pie charts were used to illustrate the descriptive information. The study revealed that prevalence of induced abortion among female students in Gaborone City is 7.9%. They even suggested that induced abortion be liberalized. Age was the only socio-demographic factor associated with induced abortion with p = 0.047 using Chi Square test χ2 = 7.609, df = 3. The study findings concluded that female students resort to induced abortion as a result of pressure from both parents and male partners especially when the pregnancy is unintended. The study recommends that the abortion law in Botswana be made liberal to ease access to safe abortion care services. It also recommends that contraceptive commodities should consistently be available in public health facilities.

Advanced Machine Learning Methods for Prediction of Blast-Induced Flyrock Using Hybrid SVR Methods

Blasting in surface mines aims to fragment rock masses to a proper size.However,flyrock is an undesirable effect of blasting that can result in human injuries.In this study,support vector regression(SVR)is combined with four algorithms:gravitational search algorithm(GSA),biogeography-based optimization(BBO),ant colony optimization(ACO),and whale optimization algorithm(WOA)for predicting flyrock in two surface mines in Iran.Additionally,three other methods,including artificial neural network(ANN),kernel extreme learning machine(KELM),and general regression neural network(GRNN),are employed,and their performances are compared to those of four hybrid SVR models.After modeling,the measured and predicted flyrock values are validated with some performance indices,such as root mean squared error(RMSE).The results revealed that the SVR-WOA model has the most optimal accuracy,with an RMSE of 7.218,while the RMSEs of the KELM,GRNN,SVR-GSA,ANN,SVR-BBO,and SVR-ACO models are 10.668,10.867,15.305,15.661,16.239,and 18.228,respectively.Therefore,combining WOA and SVR can be a valuable tool for accurately predicting flyrock distance in surface mines.

Cellular strategies to induce immune tolerance after liver transplantation:Clinical perspectives

Liver transplantation(LT)has become the most efficient treatment for pediatric and adult end-stage liver disease and the survival time after transplantation is becoming longer due to the development of surgical techniques and perioperative management.However,long-term side-effects of immunosuppressants,like infection,metabolic disorders and malignant tumor are gaining more attention.Immune tolerance is the status in which LT recipients no longer need to take any immunosuppressants,but the liver function and intrahepatic histology maintain normal.The approaches to achieve immune tolerance after transplantation include spontaneous,operational and induced tolerance.The first two means require no specific intervention but withdrawing immunosuppressant gradually during follow-up.No clinical factors or biomarkers so far could accurately predict who are suitable for immunosuppressant withdraw after transplantation.With the understanding to the underlying mechanisms of immune tolerance,many strategies have been developed to induce tolerance in LT recipients.Cellular strategy is one of the most promising methods for immune tolerance induction,including chimerism induced by hematopoietic stem cells and adoptive transfer of regulatory immune cells.The safety and efficacy of various cell products have been evaluated by prospective preclinical and clinical trials,while obstacles still exist before translating into clinical practice.Here,we will summarize the latest perspectives and concerns on the clinical application of cellular strategies in LT recipients.

Transplantation of fibrin-thrombin encapsulated human induced neural stem cells promotes functional recovery of spinal cord injury rats through modulation of the microenvironment

Recent studies have mostly focused on engraftment of cells at the lesioned spinal cord,with the expectation that differentiated neurons facilitate recovery.Only a few studies have attempted to use transplanted cells and/or biomaterials as major modulators of the spinal cord injury microenvironment.Here,we aimed to investigate the role of microenvironment modulation by cell graft on functional recovery after spinal cord injury.Induced neural stem cells reprogrammed from human peripheral blood mononuclear cells,and/or thrombin plus fibrinogen,were transplanted into the lesion site of an immunosuppressed rat spinal cord injury model.Basso,Beattie and Bresnahan score,electrophysiological function,and immunofluorescence/histological analyses showed that transplantation facilitates motor and electrophysiological function,reduces lesion volume,and promotes axonal neurofilament expression at the lesion core.Examination of the graft and niche components revealed that although the graft only survived for a relatively short period(up to 15 days),it still had a crucial impact on the microenvironment.Altogether,induced neural stem cells and human fibrin reduced the number of infiltrated immune cells,biased microglia towards a regenerative M2 phenotype,and changed the cytokine expression profile at the lesion site.Graft-induced changes of the microenvironment during the acute and subacute stages might have disrupted the inflammatory cascade chain reactions,which may have exerted a long-term impact on the functional recovery of spinal cord injury rats.

Recent advances in the diagnosis of drug-induced liver injury

Drug-induced liver injury(DILI)is a major problem in the United States,commonly leading to hospital admission.Diagnosing DILI is difficult as it is a diagnosis of exclusion requiring a temporal relationship between drug exposure and liver injury and a thorough work up for other causes.In addition,DILI has a very variable clinical and histologic presentation that can mimic many different etiologies of liver disease.Objective scoring systems can assess the probability that a drug caused the liver injury but liver biopsy findings are not part of the criteria used in these systems.This review will address some of the recent updates to the scoring systems and the role of liver biopsy in the diagnosis of DILI.

Boulder-induced form roughness and skin shear stresses in a gravel-bed stream

Boulder spacing in mountain rivers and near-wake flow zones within the boulder array is very useful for fish habitat and growth of aquatic organisms.The present study aims to investigate how the boulder array and spacing influence the near-bed flow structures in a gravel-bed stream.Boulders are staggered over a gravel-bed stream with three different inter-boulder spacing namely(a)large(b)medium and(c)small spacing.An acoustic Doppler velocimeter was used for flow measurements in a rectangular channel and the results were compared with those acquired from numerical simulation.The time-averaged velocity profiles at the near-wake flow zones of boulders experience maximum flow retardation which is an outcome of the boulder-induced form roughness.The ratio of velocity differences associated to form and skin roughness and its positive magnitude reveals the dominance of form roughness closest to the boulders.Form roughness computed is 1.75 to 2 times higher than the skin roughness at the near-wake flow region.In particular,the collective immobile boulders placed at different inter-boulder spacings developed high and low bed shear stresses closest to the boulders.The low bed shear stresses characterised by a secondary peak developed at the trough location of the boulders is attributed to the skin shear stress.Further,the spatial averaging of time-averaged flow quantities gives additional impetus to present an improved illustration of fluid shear stresses.The formation of form-induced shear stress is estimated to be 17%to 23%of doubleaveraged Reynolds shear stress and partially compensates for the damping of time-averaged Reynolds shear stress in the interfacial sub-layer.The quadrant analysis of spatial velocity fluctuations depicts that the form-induced shear stresses are dominant in the interfacial sub-layer and have no significance above the gravel-bed surface.

Multiple factors to assist human-derived induced pluripotent stem cells to efficiently differentiate into midbrain dopaminergic neurons

Midbrain dopaminergic neurons play an important role in the etiology of neurodevelopmental and neurodegenerative diseases.They also represent a potential source of transplanted cells for therapeutic applications.In vitro differentiation of functional midbrain dopaminergic neurons provides an accessible platform to study midbrain neuronal dysfunction and can be used to examine obstacles to dopaminergic neuronal development.Emerging evidence and impressive advances in human induced pluripotent stem cells,with tuned neural induction and differentiation protocols,makes the production of induced pluripotent stem cell-derived dopaminergic neurons feasible.Using SB431542 and dorsomorphin dual inhibitor in an induced pluripotent stem cell-derived neural induction protocol,we obtained multiple subtypes of neurons,including 20%tyrosine hydroxylase-positive dopaminergic neurons.To obtain more dopaminergic neurons,we next added sonic hedgehog(SHH)and fibroblast growth factor 8(FGF8)on day 8 of induction.This increased the proportion of dopaminergic neurons,up to 75%tyrosine hydroxylase-positive neurons,with 15%tyrosine hydroxylase and forkhead box protein A2(FOXA2)co-expressing neurons.We further optimized the induction protocol by applying the small molecule inhibitor,CHIR99021(CHIR).This helped facilitate the generation of midbrain dopaminergic neurons,and we obtained 31-74%midbrain dopaminergic neurons based on tyrosine hydroxylase and FOXA2 staining.Thus,we have established three induction protocols for dopaminergic neurons.Based on tyrosine hydroxylase and FOXA2 immunostaining analysis,the CHIR,SHH,and FGF8 combined protocol produces a much higher proportion of midbrain dopaminergic neurons,which could be an ideal resource for tackling midbrain-related diseases.

Patient-derived induced pluripotent stem cells with a MERTK mutation exhibit cell junction abnormalities and aberrant cellular differentiation potential

BACKGROUND Human induced pluripotent stem cell(hiPSC)technology is a valuable tool for generating patient-specific stem cells,facilitating disease modeling,and invest-igating disease mechanisms.However,iPSCs carrying specific mutations may limit their clinical applications due to certain inherent characteristics.AIM To investigate the impact of MERTK mutations on hiPSCs and determine whether hiPSC-derived extracellular vesicles(EVs)influence anomalous cell junction and differentiation potential.METHODS We employed a non-integrating reprogramming technique to generate peripheral blood-derived hiPSCs with and hiPSCs without a MERTK mutation.Chromo-somal karyotype analysis,flow cytometry,and immunofluorescent staining were utilized for hiPSC identification.Transcriptomics and proteomics were employed to elucidate the expression patterns associated with cell junction abnormalities and cellular differentiation potential.Additionally,EVs were isolated from the supernatant,and their RNA and protein cargos were examined to investigate the involvement of hiPSC-derived EVs in stem cell junction and differentiation.RESULTS The generated hiPSCs,both with and without a MERTK mutation,exhibited normal karyotype and expressed pluripotency markers;however,hiPSCs with a MERTK mutation demonstrated anomalous adhesion capability and differentiation potential,as confirmed by transcriptomic and proteomic profiling.Furthermore,hiPSC-derived EVs were involved in various biological processes,including cell junction and differentiation.CONCLUSION HiPSCs with a MERTK mutation displayed altered junction characteristics and aberrant differentiation potential.Furthermore,hiPSC-derived EVs played a regulatory role in various biological processes,including cell junction and differentiation.

Research on the mechanism of rockburst induced by mined coal-rock linkage of sharply inclined coal seams

In recent years,the mining depth of steeply inclined coal seams in the Urumqi mining area has gradually increased.Local deformation of mining coal-rock results in frequent rockbursts.This has become a critical issue that affects the safe mining of deep,steeply inclined coal seams.In this work,we adopt a perspective centered on localized deformation in coal-rock mining and systematically combine theoretical analyses and extensive data mining of voluminous microseismic data.We describe a mechanical model for the urgently inclined mining of both the sandwiched rock pillar and the roof,explaining the mechanical response behavior of key disaster-prone zones within the deep working face,affected by the dynamics of deep mining.By exploring the spatial correlation inherent in extensive microseismic data,we delineate the“time-space”response relationship that governs the dynamic failure of coal-rock during the progression of the sharply inclined working face.The results disclose that(1)the distinctive coal-rock occurrence structure characterized by a“sandwiched rock pillar-B6 roof”constitutes the origin of rockburst in the southern mining area of the Wudong Coal Mine,with both elements presenting different degrees of deformation localization with increasing mining depth.(2)As mining depth increases,the bending deformation and energy accumulation within the rock pillar and roof show nonlinear acceleration.The localized deformation of deep,steeply inclined coal-rock engenders the spatial superposition of squeezing and prying effects in both the strike and dip directions,increasing the energy distribution disparity and stress asymmetry of the“sandwiched rock pillar-B3+6 coal seam-B6 roof”configuration.This makes worse the propensity for frequent dynamic disasters in the working face.(3)The developed high-energy distortion zone“inner-outer”control technology effectively reduces high stress concentration and energy distortion in the surrounding rock.After implementation,the average apparent resistivity in the rock pillar and B6 roof substantially increased by 430%and 300%,respectively,thus guaranteeing the safe and efficient development of steeply inclined coal seams.

Coupled multiphysical model for investigation of influence factors in the application of microbially induced calcite precipitation

The study presents a comprehensive coupled thermo-bio-chemo-hydraulic(T-BCH)modeling framework for stabilizing soils using microbially induced calcite precipitation(MICP).The numerical model considers relevant multiphysics involved in MICP,such as bacterial ureolytic activities,biochemical reactions,multiphase and multicomponent transport,and alteration of the porosity and permeability.The model incorporates multiphysical coupling effects through well-established constitutive relations that connect parameters and variables from different physical fields.It was implemented in the open-source finite element code OpenGeoSys(OGS),and a semi-staggered solution strategy was designed to solve the couplings,allowing for flexible model settings.Therefore,the developed model can be easily adapted to simulate MICP applications in different scenarios.The numerical model was employed to analyze the effect of various factors,including temperature,injection strategies,and application scales.Besides,a TBCH modeling study was conducted on the laboratory-scale domain to analyze the effects of temperature on urease activity and precipitated calcium carbonate.To understand the scale dependency of MICP treatment,a large-scale heterogeneous domain was subjected to variable biochemical injection strategies.The simulations conducted at the field-scale guided the selection of an injection strategy to achieve the desired type and amount of precipitation.Additionally,the study emphasized the potential of numerical models as reliable tools for optimizing future developments in field-scale MICP treatment.The present study demonstrates the potential of this numerical framework for designing and optimizing the MICP applications in laboratory-,prototype-,and field-scale scenarios.

Mechanism of Thermally Radiative Prandtl Nanofluids and Double-Diffusive Convection in Tapered Channel on Peristaltic Flow with Viscous Dissipation and Induced Magnetic Field

The application of mathematical modeling to biological fluids is of utmost importance, as it has diverse applicationsin medicine. The peristaltic mechanism plays a crucial role in understanding numerous biological flows. In thispaper, we present a theoretical investigation of the double diffusion convection in the peristaltic transport of aPrandtl nanofluid through an asymmetric tapered channel under the combined action of thermal radiation andan induced magnetic field. The equations for the current flow scenario are developed, incorporating relevantassumptions, and considering the effect of viscous dissipation. The impact of thermal radiation and doublediffusion on public health is of particular interest. For instance, infrared radiation techniques have been used totreat various skin-related diseases and can also be employed as a measure of thermotherapy for some bones toenhance blood circulation, with radiation increasing blood flow by approximately 80%. To solve the governingequations, we employ a numerical method with the aid of symbolic software such as Mathematica and MATLAB.The velocity, magnetic force function, pressure rise, temperature, solute (species) concentration, and nanoparticlevolume fraction profiles are analytically derived and graphically displayed. The results outcomes are compared withthe findings of limiting situations for verification.

Insights into skullcap herb-induced liver injury

This editorial addresses the growing concern of herb-induced liver injury(HILI),focusing on a unique case of Skullcap-induced HILI report.This editorial underscore the significant mortality rate linked to Skullcap-induced HILI,emphasizing the importance of vigilant monitoring and intervention.As herbal supplement usage rises,collaboration among clinicians and researchers is crucial to comprehend and address the complexities of HILI,particularly those involving Skullcap.

Local Climate Change Induced by Urbanization on a South China Sea Island

The South China Sea is a hotspot for regional climate research.Over the past 40 years,considerable improvement has been made in the development and utilization of the islands in the South China Sea,leading to a substantial change in the land-use of the islands.However,research on the impact of human development on the local climate of these islands is lacking.This study analyzed the characteristics of local climate changes on the islands in the South China Sea based on data from the Yongxing Island Observation Station and ERA5 re-analysis.Furthermore,the influence of urbanization on the local climate of the South China Sea islands was explored in this study.The findings revealed that the 10-year average temperature in Yongxing Island increased by approximately 1.11℃from 1961 to 2020,and the contribution of island development and urbanization to the local warming rate over 60 years was approximately 36.2%.The linear increasing trend of the annual hot days from 1961–2020 was approximately 14.84 days per decade.The diurnal temperature range exhibited an increasing trend of 0.05℃per decade,whereas the number of cold days decreased by 1.06days per decade.The rapid increase in construction on Yongxing Island from 2005 to 2021 led to a decrease in observed surface wind speed by 0.32 m s^(-1)per decade.Consequently,the number of days with strong winds decreased,whereas the number of days with weak winds increased.Additionally,relative humidity exhibited a rapid decline from 2001 to 2016 and then rebounded.The study also found substantial differences between the ERA5 re-analysis and observation data,particularly in wind speed and relative humidity,indicating that the use of re-analysis data for climate resource assessment and climate change evaluation on island areas may not be feasible.

Heat and Mass Transfer for a Nanofluid Flow in Fluidized Bed Dryer in Presence of Induced Magnetic Field

This research entails the study of heat and mass transfer of nanofluid flow in a fluidized bed dryer used in tea drying processes in presence of induced magnetic field. A mathematical model describing the fluid flow in a Fluidized bed dryer was developed using the nonlinear partial differential equations. Due to their non-linearity, the equations were solved numerically by use of the finite difference method. The effects of physical flow parameters on velocity, temperature, concentration and magnetic induction profiles were studied and results were presented graphically. From the mathematical analysis, it was deduced that addition of silver nanoparticles into the fluid flow enhanced velocity and temperature profiles. This led to improved heat transfer in the fluidized bed dryer, hence amplifying the tea drying process. Furthermore, it was noted that induced magnetic field tends to decrease the fluid velocity, which results in uniform distribution of heat leading to efficient heat transfer between the tea particles and the fluid, thus improving the drying process. The research findings provide information to industries on ways to optimize thermal performance of fluidized bed dryers.

Dengue induced acute liver failure:A meta summary of case reports

BACKGROUND Dengue fever is the most common cause of viral hemorrhagic fever,with more than 400 million cases being reported annually,worldwide.Even though hepatic involvement is common,acute liver failure(ALF)is a rare complication of dengue fever.AIM To analyze the demographic profile,symptomology,hospital course and outcomes of patients presenting with ALF secondary to dengue infection by reviewing the published case reports.METHODS A systematic search was performed from multiple databases including PubMed,Reference Citation Analysis,Science Direct,and Google Scholar.The search terms used were"dengue"OR"severe dengue"OR"dengue shock syndrome"OR"dengue haemorrhagic syndrome"OR"dengue fever"AND"acute liver failure"OR"hepatic failure"OR"liver injury".The inclusion criteria were:(1)Case reports or case series with individual patient details;(2)Reported acute liver failure secondary to dengue infection;and(3)Published in English language and on adult humans.The data were extracted for patient demographics,clinical sympto-matology,clinical interventions,hospital and intensive care unit course,need for organ support and clinical outcomes.RESULTS Data from 19 case reports fulfilling the predefined inclusion criteria were included.The median age of patients was 38 years(inter quartile range:Q3-Q126.5 years)with a female preponderance(52.6%).The median days from diagnosis of dengue to development of ALF was 4.5 d.The increase in aspartate aminotransferase was higher than that in alanine aminotransferase(median 4625 U/L vs 3100 U/L).All the patients had one or more organ failure,with neurological failure present in 73.7%cases.42.1%patients required vasopressor support and hepatic enceph-alopathy was the most reported complication in 13(68.4%)cases.Most of the patients were managed conser-vatively and 2 patients were taken up for liver transplantation.Only 1 death was reported(5.3%).CONCLUSION Dengue infection may rarely lead to ALF.These patients may frequently require intensive care and organ support.Even though most of these patients may improve with supportive care,liver transplantation may be a therapeutic option in refractory cases.

Treatment-induced neuroendocrine prostate cancer and de novo neuroendocrine prostate cancer:Identification,prognosis and survival,genetic and epigenetic factors

Neuroendocrine prostate cancer(NEPC)shows an aggressive behavior compared to prostate cancer(PCa),also known as prostate adenocarcinoma.Scanty foci in PCa can harbor genetic alternation that can arise in a heterogeneity of prostate cancer.NEPC may arise de novo or develop following androgen deprivation therapy(ADT).NEPC that arise following ADT has the nomenclature“treatmentemerging/induced NEPC(t-NEPC)”.t-NEPC would be anticipated in castration resistant prostate cancer(CRPC)and metastatic PCa.t-NEPC is characterized by low or absent androgen receptor(AR)expression,independence of AR signaling,and gain of neuroendocrine phenotype.t-NEPC is an aggressive metastatic tumor,develops from PCa in response to drug induced ADT,and shows very short response to conventional therapy.t-NEPC occurs in 10%-17%of patients with CRPC.De novo NEPC is rare and is accounting for less than 2%of all PCa.The molecular mechanisms underlying the trans-differentiation from CRPC to t-NEPC are not fully elucidated.Sphingosine kinase 1 plays a significant role in t-NEPC development.Although neuroendocrine markers:Synaptophysin,chromogranin A,and insulinoma associated protein 1(INSM1)are expressed in t-NEPC,they are non-specific for diagnosis,prognosis,and follow-up of therapy.t-NEPC shows enriched genomic alteration in tumor protein P53(TP53)and retinoblastoma 1(RB1).There are evidences suggest that t-NEPC might develop through epigenetic evolution.There are genomic,epigenetic,and transcriptional alterations that are reported to be involved in development of t-NEPC.Knock-outs of TP53 and RB1 were found to contribute in development of t-NEPC.PCa is resistant to immunotherapy,and at present there are running trials to approach immunotherapy for PCa,CRPC,and t-NEPC.

Prevalence of Noise-Induced Hearing Loss Related to the Mills in the Markets of the Municipality of Parakou in 2021

Introduction: Noise is the second leading cause of hearing loss in adults after presbycusis. The objective of this work was to study hearing loss induced by the noise of mills in the markets of Parakou. Methods: This was a descriptive and analytical cross-sectional study, conducted from February 3 to June 3, 2021 in the markets of Parakou. It concerned millers and sellers located within a 5 meter radius around the mills and among whom pure-tone audiometry was performed to detect a hearing loss. Subjects with no particular medical health history, under 55 years of age and having been working in these markets since more than 12 months, were included. Results: In this study, 103 subjects were selected, including 43 millers and 61 sellers. Their average age was 29 ± 13 years. The sex ratio was 0.49. The average length of service in the profession was 8 years with the extremes of 3 months and 47 years. They were exposed to noise on average 10 hours per day and 6 days a week. The average duration of weekly noise exposure was 23 h 28 min ± 13 h 32 min with the extremes of 5 h 00 min and 52 h 30 min. The average level of noise exposure was 90 dB with the extremes of 72 and 110 dB. 24 subjects reported symptoms related to noise such as headache, tinnitus, and hearing loss, with respective proportions of 22.33%, 20.39% and 06.80%. The prevalence of noise-related hearing loss was 26.21% (n = 27/103). Subjects with a notch at 4000 Hz and normal Average Hearing Loss (AHL) (20.39%) had a seven-time greater risk of developing noise-induced hearing loss (OR = 6.58;95% CI [2.54 - 18.8], p Conclusion: Hearing loss related to the noise of mills affected both millers and sellers near the mills in markets, hence the importance of regulating mills.