Liver transplantation as an alternative for the treatment of perihilar cholangiocarcinoma: A critical review

Background:Perihilar cholangiocarcinoma(phCCC)is a dismal malignancy.There is no consensus regard-ing the best treatment for patients with unresectable phCCC.The present review aimed to gather the current pieces of evidence for liver transplantation and liver resection as a treatment for phCCC and to build better guidance for clinical practice.Data sources:The search was conducted in PubMed,Embase,Cochrane,and LILACS.The related references were searched manually.Inclusion criteria were:reports in English or Portuguese literature that a)patients with confirmed diagnosis of phCCC;b)patients treated with a curative intent;c)patients with the outcomes of liver resection and liver transplantation.Case reports,reviews,letters,editorials,conference abstracts and papers with full-text unavailability were excluded from the analysis.Results:Most of the current literature is based on observational retrospective studies with low grades of evidence.Liver resection has better long-term outcomes than systemic chemotherapy or palliation ther-apy and liver transplantation is a good alternative for selected patients with unresectable phCCC.All candidates for resection or transplantation should be medically fit and free of intrahepatic or extrahep-atic diseases.As a general rule,patients presenting with a tumor having a longitudinal size>3 cm or extending below the cystic duct,lymph node disease,confirmed extrahepatic dissemination;intraoper-atively diagnosed metastatic disease;a history of other malignancies within the last five years,and did not complete chemoradiation regimen and were medically unfit should not be considered for transplan-tation.Some of these criteria should be individually assessed.Liver transplantation or resection should only be considered in highly experienced hepatobiliary centers,and any decision-making must be based on a multidisciplinary evaluation.Conclusions:phCCC is a complex condition with high morbidity.Surgical therapies,including hepatec-tomy and liver transplantation,are the best option for better long-term disease-free survival.

Assessment of programmed death-ligand 1 expression in primary tumors and paired lymph node metastases of gastric adenocarcinoma

BACKGROUND Anti-programmed death-1/programmed death-ligand 1(PD-1/PD-L1)immuno-therapy has demonstrated promising results on gastric cancer(GC).However,PD-L1 can express differently between metastatic sites and primary tumors(PT).AIM To compare PD-L1 status in PT and matched lymph node metastases(LNM)of GC patients and to determine the correlation between the PD-L1 status and clinicopathological characteristics.METHODS We retrospectively reviewed 284 GC patients who underwent D2-gastrectomy.PD-L1 was evaluated by immunohistochemistry(clone SP142)using the com-bined positive score.All PD-L1+PT staged as pN+were also tested for PD-L1 expression in their LNM.PD-L1(-)GC with pN+served as the comparison group.RESULTS Among 284 GC patients included,45 had PD-L1+PT and 24 of them had pN+.For comparison,44 PD-L1(-)cases with pN+were included(sample loss of 4 cases).Of the PD-L1+PT,54.2%(13/24 cases)were also PD-L1+in the LNM.Regarding PD-L1(-)PT,9.1%(4/44)had PD-L1+in the LNM.The agreement between PT and LNM had a kappa value of 0.483.Larger tumor size and moderate/severe peritumoral inflammatory response were associated with PD-L1 positivity in both sites.There was no statistical difference in overall survival for PT and LNM according to the PD-L1 status(P=0.166 and P=0.837,respectively).CONCLUSION Intra-patient heterogeneity in PD-L1 expression was observed between the PT and matched LNM.This disagreement in PD-L1 status may emphasize the importance of considering different tumor sites for analyses to select patients for immunotherapy.

A Rapid Parameter of Enzyme-Treated Cellulosic Material Revealed by Reducing Sugar Release

This study was conducted to evaluate the effectiveness of enzymes in purifying and reducing the degree of polymerization of cellulose for the production of dissolving pulp.Our goal was to determine the contributions of xylanase(X)and endoglucanase(EG)in the treatment of pulp,specifically by quantifying the formation of soluble and insoluble reducing sugars using the dinitrosalycilic acid(DNS)test.Predominantly,the release of soluble reducing sugars(RSSol)was enhanced after xylanase treatment,while endoglucanase(EG)treatment led to changes in insoluble reducing sugars(RSIns).The maximum synergism was observed for RSIns when a high ratio of endoglucanase to xylanase(320EG:5X/g pulp)was used.The relative contribution of endoglucanase to RSins was determined to be 15.6%of the total reducing sugar.The viscosity of pulps treated with xylanase decreased only by 7%,whereas endoglucanase treatment significantly reduced viscosity by 45%.Modifications in the particle size were observed after pulp treatment with the combination of endoglucanase and xylanase.In summary,the DNS test is a rapid and effective method for evaluating the efficiency of enzyme treatments on pulps.The measurement of RSIns correlates with changes in pulp viscosity to different extents,providing valuable insights into the effectiveness of enzyme treatments.

Prognosis value of heat-shock proteins in esophageal and esophagogastric cancer:A systematic review and meta-analysis

BACKGROUND Heat shock proteins(HSPs)are molecular chaperones that play an important role in cellular protection against stress events and have been reported to be overex-pressed in many cancers.The prognostic significance of HSPs and their regulatory factors,such as heat shock factor 1(HSF1)and CHIP,are poorly understood.AIM To investigate the relationship between HSP expression and prognosis in esophageal and esophagogastric cancer.METHODS A systematic review was conducted in accordance with PRISMA recommend-ations(PROSPERO:CRD42022370653),on Embase,PubMed,Cochrane,and LILACS.Cohort,case-control,and cross-sectional studies of patients with eso-phagus or esophagogastric cancer were included.HSP-positive patients were compared with HSP-negative,and the endpoints analyzed were lymph node metastasis,tumor depth,distant metastasis,and overall survival(OS).HSPs were stratified according to the HSP family,and the summary risk difference(RD)was calculated using a random-effect model.RESULTS The final selection comprised 27 studies,including esophageal squamous cell carcinoma(21),esophagogastric adenocarcinoma(5),and mixed neoplasms(1).The pooled sample size was 3465 patients.HSP40 and 60 were associated with a higher 3-year OS[HSP40:RD=0.22;95%confidence interval(CI):0.09-0.35;HSP60:RD=0.33;95%CI:0.17-0.50],while HSF1 was associated with a poor 3-year OS(RD=-0.22;95%CI:-0.32 to-0.12).The other HSP families were not associated with long-term survival.HSF1 was associated with a higher probability of lymph node metastasis(RD=-0.16;95%CI:-0.29 to-0.04).HSP40 was associated with a lower probability of lymph node dissemination(RD=0.18;95%CI:0.03-0.33).The expression of other HSP families was not significantly related to tumor depth and lymph node or distant metastasis.CONCLUSION The expression levels of certain families of HSP,such as HSP40 and 60 and HSF1,are associated with long-term survival and lymph node dissemination in patients with esophageal and esophagogastric cancer.

Solar-driven CO_(2) conversion to methane and methanol using different nanostructured Cu_(2)O-based catalysts modified with Au nanoparticles

This work describes the use of TiO_(2)nanotubes-based electrodes(TNT)modified with Cu_(2)O nanostructures and gold nanoparticles for the photoelectroreduction of CO_(2)to produce value-added compounds.A thin layer of polydopamine was used as both an adherent agent and an electron transfer mediator,due to itsπ-conjugated electron system.The highest production yield was achieved using a TNT@PDA/Nc/Au40%electrode,with Faradaic efficiencies of 47.4%(110.5μM cm^(-2))and 27.8%(50.4μM cm^(-2))for methanol and methane,respectively.The performance of the photoelectrodes was shown to be Cu_(2)O facet-dependent,with cubic structures leading to greater conversion of CO_(2)to methanol(43%)and methane(27%),compared to the octahedral morphology,while a higher percentage of metallic gold on the nanostructured Cu_(2)O surface was mainly important for CH4production.Density functional theory(DFT)calculations supported these findings,attributing the superior photoelectrocatalytic performance of the TNT@PDA/Nc/Au40%electrode for CH4generation to the formation of an OCH3intermediate bonded to Au atoms.Studies using isotope-labeling and analysis by gas chromatograph-mass(GC-MS)demonstrated that13CO_(2)was the source for photoelectrocatalytic generation of13CH3OH and13CH313CH2OH.

Rifaximin on epigenetics and autophagy in animal model of hepatocellular carcinoma secondary to metabolic-dysfunction associated steatotic liver disease

BACKGROUND Prevalence of hepatocellular carcinoma(HCC)is increasing,especially in patients with metabolic dysfunctionassociated steatotic liver disease(MASLD).AIM To investigate rifaximin(RIF)effects on epigenetic/autophagy markers in animals.METHODS Adult Sprague-Dawley rats were randomly assigned(n=8,each)and treated from 5-16 wk:Control[standard diet,water plus gavage with vehicle(Veh)],HCC[high-fat choline deficient diet(HFCD),diethylnitrosamine(DEN)in drinking water and Veh gavage],and RIF[HFCD,DEN and RIF(50 mg/kg/d)gavage].Gene expression of epigenetic/autophagy markers and circulating miRNAs were obtained.RESULTS All HCC and RIF animals developed metabolic-dysfunction associated steatohepatitis fibrosis,and cirrhosis,but three RIF-group did not develop HCC.Comparing animals who developed HCC with those who did not,miR-122,miR-34a,tubulin alpha-1c(Tuba-1c),metalloproteinases-2(Mmp2),and metalloproteinases-9(Mmp9)were significantly higher in the HCC-group.The opposite occurred with Becn1,coactivator associated arginine methyltransferase-1(Carm1),enhancer of zeste homolog-2(Ezh2),autophagy-related factor LC3A/B(Map1 Lc3b),and p62/sequestosome-1(p62/SQSTM1)-protein.Comparing with controls,Map1 Lc3b,Becn1 and Ezh2 were lower in HCC and RIF-groups(P<0.05).Carm1 was lower in HCC compared to RIF(P<0.05).Hepatic expression of Mmp9 was higher in HCC in relation to the control;the opposite was observed for p62/Sqstm1(P<0.05).Expression of p62/SQSTM1 protein was lower in the RIF-group compared to the control(P=0.024).There was no difference among groups for Tuba-1c,Aldolase-B,alpha-fetoprotein,and Mmp2(P>0.05).miR-122 was higher in HCC,and miR-34a in RIF compared to controls(P<0.05).miR-26b was lower in HCC compared to RIF,and the inverse was observed for miR-224(P<0.05).There was no difference among groups regarding miR-33a,miR-143,miR-155,miR-375 and miR-21(P>0.05).CONCLUSION RIF might have a possible beneficial effect on preventing/delaying liver carcinogenesis through epigenetic modulation in a rat model of MASLD-HCC.

Choosing the best endoscopic approach for post-bariatric surgical leaks and fistulas:Basic principles and recommendations

Post-surgical leaks and fistulas are the most feared complication of bariatric surgery.They have become more common in clinical practice given the increasing number of these procedures and can be very difficult to treat.These two related conditions must be distinguished and characterized to guide the appropriate treatment.Leak is defined as a transmural defect with communication between the intra and extraluminal compartments,while fistula is defined as an abnormal communication between two epithelialized surfaces.Traditionally,surgical treatment was the preferred approach for leaks and fistulas and was associated with high morbidity with significant mortality rates.However,with the development of novel devices and techniques,endoscopic therapy plays an increasingly essential role in managing these conditions.Early diagnosis and endoscopic therapy initiation after clinical stabilization are crucial to success since clinical success rates are higher for acute leaks and fistulas when compared to late and chronic leaks and fistulas.Several endoscopic techniques are available with different mechanisms of action,including direct closure,covering/diverting or draining.The treatment should be individualized by considering the characteristics of both the patient and the defect.Although there is a lack of high-quality studies to provide standardized treatment algorithms,this narrative review aims to provide a summary of the current scientific evidence and,based on this data and our extensive experience,make recommendations to help choose the best endoscopic approach for the management of post-bariatric surgical leaks and fistulas.

Current overview of induced pluripotent stem cell-based blood-brain barrier-on-a-chip

BACKGROUND Induced pluripotent stem cells(iPSCs)show great ability to differentiate into any tissue,making them attractive candidates for pathophysiological investigations.The rise of organ-on-a-chip technology in the past century has introduced a novel way to make in vitro cell cultures that more closely resemble their in vivo environments,both structural and functionally.The literature still lacks consensus on the best conditions to mimic the blood-brain barrier(BBB)for drug screening and other personalized therapies.The development of models based on BBB-on-achip using iPSCs is promising and is a potential alternative to the use of animals in research.AIM To analyze the literature for BBB models on-a-chip involving iPSCs,describe the microdevices,the BBB in vitro construction,and applications.METHODS We searched for original articles indexed in PubMed and Scopus that used iPSCs to mimic the BBB and its microenvironment in microfluidic devices.Thirty articles were identified,wherein only 14 articles were finally selected according to the inclusion and exclusion criteria.Data compiled from the selected articles were organized into four topics:(1)Microfluidic devices design and fabrication;(2)characteristics of the iPSCs used in the BBB model and their differentiation conditions;(3)BBB-on-a-chip reconstruction process;and(4)applications of BBB microfluidic three-dimensional models using iPSCs.RESULTS This study showed that BBB models with iPSCs in microdevices are quite novel in scientific research.Important technological advances in this area regarding the use of commercial BBB-on-a-chip were identified in the most recent articles by different research groups.Conventional polydimethylsiloxane was the most used material to fabricate in-house chips(57%),whereas few studies(14.3%)adopted polymethylmethacrylate.Half the models were constructed using a porous membrane made of diverse materials to separate the channels.iPSC sources were divergent among the studies,but the main line used was IMR90-C4 from human fetal lung fibroblast(41.2%).The cells were differentiated through diverse and complex processes either to endothelial or neural cells,wherein only one study promoted differentiation inside the chip.The construction process of the BBB-on-a-chip involved previous coating mostly with fibronectin/collagen Ⅳ(39.3%),followed by cell seeding in single cultures(36%)or co-cultures(64%)under controlled conditions,aimed at developing an in vitro BBB that mimics the human BBB for future applications.CONCLUSION This review evidenced technological advances in the construction of BBB models using iPSCs.Nonetheless,a definitive BBB-on-a-chip has not yet been achieved,hindering the applicability of the models.

Metastasis-associated lung adenocarcinoma transcript 1 molecular mechanisms in gastric cancer progression

Gastric cancer(GC)remains among the most common cancers worldwide with a high mortality-to-incidence ratio.Accumulated evidence suggests that long noncoding RNAs(lncRNAs)are involved in gastric carcinogenesis.These transcripts are longer than 200 nucleotides and modulate gene expression at multiple molecular levels,inducing or inhibiting biological processes and diseases.Metastasis-associated lung adenocarcinoma transcript 1(MALAT1)is one of the best-studied lncRNAs with comprehensive actions contributing to cancer progression.This lncRNA regulates gene expression at the transcriptional and posttranscriptional levels through interactions with microRNAs and proteins.In the present review,we discussed the molecular mechanism of MALAT1 and summarized the current knowledge of its expression in GC.Moreover,we highlighted the potential use of MALAT1 as a biomarker,including liquid biopsy.

Ca^(2+)/cAMP ratio:An inflammatory index for diabetes,hypertension,and COVID-19

Ca^(2+)/cAMP ratio could serve as an inflammatory index for diseases like hypertension,diabetes,and coronavirus disease 2019.

The peptide fraction of Bothrops jararaca snake venom induces toxicological effects on the male reproductive system after local envenomation in mice

Bothrops envenomation is complex and provokes prominent local tissue damage and systemic disturbances,but little is known about their effects on the male reproductive system.After intratesticular injection,the bioactive peptide fraction(Bj-PF)obtained from Bothrops jararaca snake venom changes the structure of different stages of the seminiferous epithelium cycle in adult mice.For the first time,we investigated whether local envenomation of Bj-PF induces toxicological effects on the male reproductive system,particularly on the seminiferous epithelium and Sertoli cells.Male adult mice were treated with 0.24 mg.kg^(-1) by intramuscular(i.m.)injection for 24 h.The testes samples were collected for morphological and morphometric evaluation.The toxicological effects of Bj-PF were also analyzed on mitochondrial metabolism and nitrite(NO2)production in 15P-1 Sertoli cell culture.Bj-PF changed the structure and function of the seminiferous epithelium,particularly the disruption of the epithelium and the presence of degenerated germ cells in the adluminal compartment,but there were no alterations in the basal compartment.Bj-PF increased the thickness of the seminiferous epithelium and decreased the lumen diameter of the tubule.Semiquantitative histological assessment of the degree of tubule degeneration revealed that Bj-PF also increased the number of hypospermatogenic tubules compared to control.Bj-PF reduced NO2 levels in 15P-1 Sertoli cells without changing the mitochondrial metabolism.Overall,the fact that Bj-PF alters the structure and function of the seminiferous epithelium suggests that bioactive peptides found in B.jararaca snake venom can have toxicological effects on the reproductive systems of affected male mice,providing new insight into the biological characteristics of snake venom and therapeutic strategies for envenomation inflammation.

Endoscopic ultrasound artificial intelligence-assisted for prediction of gastrointestinal stromal tumors diagnosis:A systematic review and meta-analysis

BACKGROUND Subepithelial lesions(SELs)are gastrointestinal tumors with heterogeneous malignant potential.Endoscopic ultrasonography(EUS)is the leading method for evaluation,but without histopathological analysis,precise differentiation of SEL risk is limited.Artificial intelligence(AI)is a promising aid for the diagnosis of gastrointestinal lesions in the absence of histopathology.AIM To determine the diagnostic accuracy of AI-assisted EUS in diagnosing SELs,especially lesions originating from the muscularis propria layer.METHODS Electronic databases including PubMed,EMBASE,and Cochrane Library were searched.Patients of any sex and>18 years,with SELs assessed by EUS AIassisted,with previous histopathological diagnosis,and presented sufficient data values which were extracted to construct a 2×2 table.The reference standard was histopathology.The primary outcome was the accuracy of AI for gastrointestinal stromal tumor(GIST).Secondary outcomes were AI-assisted EUS diagnosis for GIST vs gastrointestinal leiomyoma(GIL),the diagnostic performance of experienced endoscopists for GIST,and GIST vs GIL.Pooled sensitivity,specificity,positive,and negative predictive values were calculated.The corresponding summary receiver operating characteristic curve and post-test probability were also analyzed.RESULTS Eight retrospective studies with a total of 2355 patients and 44154 images were included in this meta-analysis.The AI-assisted EUS for GIST diagnosis showed a sensitivity of 92%[95%confidence interval(CI):0.89-0.95;P<0.01),specificity of 80%(95%CI:0.75-0.85;P<0.01),and area under the curve(AUC)of 0.949.For diagnosis of GIST vs GIL by AI-assisted EUS,specificity was 90%(95%CI:0.88-0.95;P=0.02)and AUC of 0.966.The experienced endoscopists’values were sensitivity of 72%(95%CI:0.67-0.76;P<0.01),specificity of 70%(95%CI:0.64-0.76;P<0.01),and AUC of 0.777 for GIST.Evaluating GIST vs GIL,the experts achieved a sensitivity of 73%(95%CI:0.65-0.80;P<0.01)and an AUC of 0.819.CONCLUSION AI-assisted EUS has high diagnostic accuracy for fourth-layer SELs,especially for GIST,demonstrating superiority compared to experienced endoscopists’and improving their diagnostic performance in the absence of invasive procedures.

Endoscopic vs radiologic gastrostomy for enteral feeding:A systematic review and meta-analysis

BACKGROUND Percutaneous endoscopic gastrostomy(PEG)and percutaneous radiological gastrostomy(PRG)are minimally invasive techniques commonly used for prolonged enteral nutrition.Despite safe,both techniques may lead to complications,such as bleeding,infection,pain,peritonitis,and tube-related complications.The literature is unclear on which technique is the safest.AIM To establish which approach has the lowest complication rate.METHODS A database search was performed from inception through November 2022,and comparative studies of PEG and PRG were selected following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines.All included studies compared the two techniques directly and provided absolute values of the number of complications.Studies with pediatric populations were excluded.The primary outcome of this study was infection and bleeding.Pneumonia,peritonitis,pain,and mechanical complications were secondary outcomes.The risk of bias was assessed using the Cochrane risk-of-bias tool for randomized trials(RoB2)and we used The Risk of Bias in Nonrandomized Studies(ROBINS-I)to analyze the retrospective studies.We also performed GRADE analysis to assess the quality of evidence.Data on risk differences and 95%confidence intervals were obtained using the Mantel-Haenszel test.RESULTS Seventeen studies were included,including two randomized controlled trials and fifteen retrospective cohort studies.The total population was 465218 individuals,with 273493 having undergone PEG and 191725 PRG.The only outcome that showed a significant difference was tube related complications in retrospective studies favoring PEG(95%CI:0.03 to 0.08;P<0.00001),although this outcome did not show significant difference in randomized studies(95%CI:-0.07 to 0.04;P=0.13).There was no difference in the analyses of the following outcomes:infection in retrospective(95%CI:-0.01 to 0.00;P<0.00001)or randomized(95%CI:-0.06 to 0.04;P=0.44)studies;bleeding in retrospective(95%CI:-0.00 to 0.00;P<0.00001)or randomized(95%CI:-0.06 to 0.02;P=0.43)studies;pneumonia in retrospective(95%CI:-0.04 to 0.00;P=0.28)or randomized(95%CI:-0.09 to 0.11;P=0.39)studies;pain in retrospective(95%CI:-0.05 to 0.02;P<0.00001)studies;peritonitis in retrospective(95%CI:-0.02 to 0.01;P<0.0001)studies.CONCLUSION PEG has lower levels of tube-related complications(such as dislocation,leak,obstruction,or breakdown)when compared to PRG.

Pulmonary Thromboembolism in a Soccer Player after COVID-19 Infection: Case Report

Background:Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),which causes COVID-19,is characterized by an increased risk of thromboembolic events.However,more than 80%of patients are asymptomatic or have only minor/mild symptoms.In addition,diagnosing thromboembolism in athletes is challenging,as symptoms can be confused with musculoskeletal complaints or physical deconditioning.Case presentation:Here we report the case of a previously healthy 34-year-old professional soccer player with COVID-19 infection and genetic predisposition to thrombosis.At baseline,he was fit,had no symptoms,did not require hospital admission due to a COVID-19 infection,and was started on a five-day course of azithromycin and dexamethasone therapy.After 10 days of returning to professional activity,he developed pulmonary embolism following a COVID-19 infection during a physical exercise session.Angiotomography showed positive acute and subacute pulmonary thromboembolism,being treated with rivaroxaban 20 mg/day continuously.The shared decision-making between the medical team and the athlete was not to return to professional soccer,given the quantifiable risk.Considerations:This case illustrates the potential risk of COVID-19-induced pulmonary thromboembolism,which can be affected by genetic predisposition and dexamethasone therapy or the consequences of COVID-19.In this clinical period,the athlete’s condition may be overlooked due to the masking effects of other clinical conditions and physical abnormalities.The residual effects of COVID-19 disease can appear late,requiring caution and follow-up by the medical team before releasing the athlete into a training program.

Treatment of patients with multiple brain metastases by isolated radiosurgery:Toxicity and survival

BACKGROUND Radiosurgery for multiple brain metastases has been more reported recently without using whole-brain radiotherapy.Nevertheless,the sparsity of the data still claims more information about toxicity and survival and their association with both dosimetric and geometric aspects of this treatment.AIM To assess the toxicity and survival outcome of radiosurgery in patients with multiple(four or more lesions)brain metastases.METHODS In a single institution,data were collected retrospectively from patients who underwent radiosurgery to treat brain metastases from diverse primary sites.Patients with 4-21 brain metastases were treated with a single fraction with a dose of 18 Gy or 20 Gy.The clinical variables collected were relevant to toxicity,survival,treatment response,planning,and dosimetric variables.The Spearman’s rank correlation coefficients,Mann-Whitney test,Kruskal-Wallis test,and Log-RESULTS From August 2017 to February 2020,55 patients were evaluated.Headache was the most common complaint(38.2%).The median overall survival(OS)for patients with karnofsky performance status(KPS)>70 was 8.9 mo,and this was 3.6 mo for those with KPS≤70(P=0.047).Patients with treated lesions had a median progression-free survival of 7.6 mo.There were no differences in OS(19.7 vs 9.5 mo)or progression-free survival(10.6 vs 6.3 mo)based on prior irradiation.There was no correlation found between reported toxicities and planning,dosimetric,and geometric variables,implying that no additional significant toxicity risks appear to be added to the treatment of multiple(four or more)lesions.CONCLUSION No associations were found between the evaluated toxicities and the planning dosimetric parameters,and no differences in survival rates were detected based on previous treatment status.

Controller Design for Induction and Brushless Motors Using Matlab with Digital Signal Processor (DSP)

The automation process is a very important pillar for Industry 4.0.One of the first steps is the control of motors to improve production efficiency and generate energy savings.In mass production industries,techniques such as digital signal processing(DSP)systems are implemented to control motors.These systems are efficient but very expensive for certain applications.From this arises the need for a controller capable of handling AC and DC motors that improves efficiency and maintains low energy consumption.This project presents the design of an adaptive control system for brushless AC induction and DC motors,which is functional to any type of plant in the industry.The design was possible by implementing Matlab software and tools such as digital signal processor(DSP)and Simulink.Through an extensive investigation of the state of the art,three models needed to represent the control system have been specified.The first model for the AC motor,the second for the DC motor and the third for the DSP control;this is done in this way so that the probability of failure is lower.Subsequently,these models have been programmed in Simulink,integrating the three main models into one.In this way,the design of a controller for use in AC induction motors,specifically squirrel cage and brushless DC motors,has been achieved.The final model represents a response time of 0.25 seconds,which is optimal for this type of application,where response times of 2e-3 to 3 seconds are expected.

Mechanisms of neuroplasticity and brain degeneration: strategies for protection during the aging process

Aging is a dynamic and progressive process that begins at conception and continues until death.This process leads to a decrease in homeostasis and morphological,biochemical and psychological changes,increasing the individual’s vulnerability to various diseases.The growth in the number of aging populations has increased the prevalence of chronic degenerative diseases,impairment of the central nervous system and dementias,such as Alzheimer’s disease,whose main risk factor is age,leading to an increase of the number of individuals who need daily support for life activities.Some theories about aging suggest it is caused by an increase of cellular senescence and reactive oxygen species,which leads to inflammation,oxidation,cell membrane damage and consequently neuronal death.Also,mitochondrial mutations,which are generated throughout the aging process,can lead to changes in energy production,deficiencies in electron transport and apoptosis induction that can result in decreased function.Additionally,increasing cellular senescence and the release of proinflammatory cytokines can cause irreversible damage to neuronal cells.Recent reports point to the importance of changing lifestyle by increasing physical exercise,improving nutrition and environmental enrichment to activate neuroprotective defense mechanisms.Therefore,this review aims to address the latest information about the different mechanisms related to neuroplasticity and neuronal death and to provide strategies that can improve neuroprotection and decrease the neurodegeneration caused by aging and environmental stressors.

Corneal stem cells and tissue engineering: Current advances and future perspectives

Major advances are currently being made in regenerative medicine for cornea. Stem cell-based therapies represent a novel strategy that may substitute conventional corneal transplantation, albeit there aremany challenges ahead given the singularities of each cellular layer of the cornea. This review recapitulates the current data on corneal epithelial stem cells, corneal stromal stem cells and corneal endothelial cell progenitors. Corneal limbal autografts containing epithelial stem cells have been transplanted in humans for more than 20 years with great successful rates, and researchers now focus on ex vivo cultures and other cell lineages to transplant to the ocular surface. A small population of cells in the corneal endothelium was recently reported to have self-renewal capacity, although they do not proliferate in vivo. Two main obstacles have hindered endothelial cell transplantation to date: culture protocols and cell delivery methods to the posterior cornea in vivo. Human corneal stromal stem cells have been identified shortly after the recognition of precursors of endothelial cells. Stromal stem cells may have the potential to provide a direct cell-based therapeutic approach when injected to corneal scars. Furthermore, they exhibit the ability to deposit organized connective tissue in vitro and may be useful in corneal stroma engineering in the future. Recent advances and future perspectives in the field are discussed.

Anti-rods/rings autoantibody generation in hepatitis Cpatients during interferon-α/ribavirin therapy

Chronic inflammation associated with hepatitis C virus(HCV) infection can lead to disabling liver diseases with progression to liver cirrhosis and hepatocellular carcinoma. Despite the recent availability of more effective and less toxic therapeutic options, in most parts of the world the standard treatment consists of a weekly injection of pegylated interferon α(IFN-α) together with a daily dose of ribavirin. HCV patients frequently present circulating non-organ-specific autoantibodies demonstrating a variety of staining patterns in the indirect immunofluorescence assay for antinuclear antibodies(ANA). Between 20% to 40% of HCV patients treated with IFN-α and ribavirin develop autoantibodies showing a peculiar ANA pattern characterized as rods and rings(RR) structures. The aim of this article is to review the recent reports regarding RR structures and anti-rods/rings(antiRR) autoantibody production by HCV patients after IFN-α/ribavirin treatment. Anti-RR autoantibodies first appear around the sixth month of treatment and reach a plateau around the twelfth month. After treatment completion, anti-RR titers decrease/disappear in half the patients and remain steady in the other half. Some studies have observed a higher frequency of anti-RR antibodies in relapsers, i.e., patients in which circulating virus reappears after initially successful therapy. The main target of anti-RR autoantibodies in HCV patients is inosine-5'-monophosphate dehydrogenase 2(IMPDH2), the rate-limiting enzyme involved in the guanosine triphosphate biosynthesis pathway. Ribavirin is a direct IMPDH2 inhibitor and is able to induce the formation of RR structures in vitro and in vivo. In conclusion, these observations led to the hypothesis that anti-RR autoantibody production is a human model of immunologic tolerance breakdown that allows us to explore the humoral autoimmune response from the beginning of the putative triggering event: exposure to ribavirin and interferon.

Propofol vs midazolam sedation for elective endoscopy in patients with cirrhosis:A systematic review and meta-analysis of randomized controlled trials

BACKGROUND Patients with cirrhosis frequently require sedation for elective endoscopic procedures.Several sedation protocols are available,but choosing an appropriate sedative in patients with cirrhosis is challenging.AIM To conduct a systematic review and meta-analysis to compare propofol and midazolam for sedation in patients with cirrhosis during elective endoscopic procedures in an attempt to understand the best approach.METHODS This systematic review and meta-analysis was conducted using the PRISMA guidelines.Electronic searches were performed using MEDLINE,EMBASE,Central Cochrane,LILACS databases.Only randomized control trials(RCTs)were included.The outcomes studied were procedure time,recovery time,discharge time,and adverse events(bradycardia,hypotension,and hypoxemia).The risk of bias assessment was performed using the Revised Cochrane Risk-of-Bias tool for randomized trials(RoB-2).Quality of evidence was evaluated by GRADEpro.The meta-analysis was performed using Review Manager.RESULTS The search yielded 3,576 records.Out of these,8 RCTs with a total of 596 patients(302 in the propofol group and 294 in the midazolam group)were included for the final analysis.Procedure time was similar between midazolam and propofol groups(MD:0.25,95%CI:-0.64 to 1.13,P=0.59).Recovery time(MD:-8.19,95%CI:-10.59 to-5.79,P<0.00001).and discharge time were significantly less in the propofol group(MD:-12.98,95%CI:-18.46 to-7.50,P<0.00001).Adverse events were similar in both groups(RD:0.02,95%CI:0-0.04,P=0.58).Moreover,no significant difference was found for bradycardia(RD:0.03,95%CI:-0.01 to 0.07,P=0.16),hypotension(RD:0.03,95%CI:-0.01 to 0.07,P=0.17),and hypoxemia(RD:0.00,95%CI:-0.04 to 0.04,P=0.93).Five studies had low risk of bias,two demonstrated some concerns,and one presented high risk.The quality of the evidence was very low for procedure time,recovery time,and adverse events;while low for discharge time.CONCLUSION This systematic review and meta-analysis based on RCTs show that propofol has shorter recovery and patient discharge time as compared to midazolam with a similar rate of adverse events.These results suggest that propofol should be the preferred agent for sedation in patients with cirrhosis.