Impact of payment source, referral site, and place of residence on outcomes after allogeneic transplantation in Mexico

BACKGROUND The impact of social determinants of health in allogeneic transplant recipients in low-and middle-income countries is poorly described.This observational study analyzes the impact of place of residence,referring institution,and transplant cost coverage(out-of-pocket vs government-funded vs private insurance)on outcomes after allogeneic hematopoietic stem cell transplantation(alloHSCT)in two of Mexico's largest public and private institutions.AIM To evaluate the impact of social determinants of health and their relationship with outcomes among allogeneic transplant recipients in Mexico.METHODS In this retrospective cohort study,we included adolescents and adults≥16 years who received a matched sibling or haploidentical transplant from 2015-2022.Participants were selected without regard to their diagnosis and were sourced from both a private clinic and a public University Hospital in Mexico.Three payment groups were compared:Out-of-pocket(OOP),private insurance,and a federal Universal healthcare program“Seguro Popular”.Outcomes were compared between referred and institution-diagnosed patients,and between residents of Nuevo Leon and out-of-state.Primary outcomes included overall survival(OS),categorized by residence,referral,and payment source.Secondary outcomes encompassed early mortality,event-free-survival,graft-versus-host-relapse-free survival,and non-relapse-mortality(NRM).Statistical analyses employed appropriate tests,Kaplan-Meier method,and Cox proportional hazard regression modeling.Statistical software included SPSS and R with tidycmprsk library.RESULTS Our primary outcome was overall survival.We included 287 patients,n=164 who lived out of state(57.1%),and n=129 referred from another institution(44.9%).The most frequent payment source was OOP(n=139,48.4%),followed by private insurance(n=75,26.1%)and universal coverage(n=73,25.4%).No differences in OS,event-free-survival,NRM,or graft-versus-host-relapse-free survival were observed for patients diagnosed locally vs in another institution,nor patients who lived in-state vs out-of-state.Patients who covered transplant costs through private insurance had the best outcomes with improved OS(median not reached)and 2-year cumulative incidence of NRM of 14%than patients who covered costs OOP(Median OS and 2-year NRM of 32%)or through a universal healthcare program active during the study period(OS and 2-year NRM of 19%)(P=0.024 and P=0.002,respectively).In a multivariate analysis,payment source and disease risk index were the only factors associated with overall survival.CONCLUSION In this Latin-American multicenter study,the site of residence or referral for alloHSCT did not impact outcomes.However,access to healthcare coverage for alloHSCT was associated with improved OS and reduced NRM.

Unilateral rNurr1-V5 transgene expression in nigral dopaminergic neurons mitigates bilateral neuropathology and behavioral deficits in parkinsonian rats withα-synucleinopathy

Parkinsonism by unilateral,intranigralβ-sitosterolβ-D-glucoside administration in rats is distinguished in that theα-synuclein insult begins unilaterally but spreads bilaterally and increases in severity over time,thus replicating several clinical features of Parkinson’s disease,a typicalα-synucleinopathy.As Nurr1 repressesα-synuclein,we evaluated whether unilateral transfected of rNurr1-V5 transgene via neurotensin-polyplex to the substantia nigra on day 30 after unilateralβ-sitosterolβ-D-glucoside lesion could affect bilateral neuropathology and sensorimotor deficits on day 30 post-transfection.This study found that rNurr1-V5 expression but not that of the green fluorescent protein(the negative control)reducedβ-sitosterolβ-D-glucoside-induced neuropathology.Accordingly,a bilateral increase in tyrosine hydroxylase-positive cells and arborization occurred in the substantia nigra and increased tyrosine hydroxylase-positive ramifications in the striatum.In addition,tyrosine hydroxylase-positive cells displayed less senescence markerβ-galactosidase and more neuron-cytoskeleton markerβIII-tubulin and brain-derived neurotrophic factor.A significant decrease in activated microglia(positive to ionized calcium-binding adaptor molecule 1)and neurotoxic astrocytes(positive to glial fibrillary acidic protein and complement component 3)and increased neurotrophic astrocytes(positive to glial fibrillary acidic protein and S100 calcium-binding protein A10)also occurred in the substantia nigra.These effects followed the bilateral reduction inα-synuclein aggregates in the nigrostriatal system,improving sensorimotor behavior.Our results show that unilateral rNurr1-V5 transgene expression in nigral dopaminergic neurons mitigates bilateral neurodegeneration(senescence and loss of neuron-cytoskeleton and tyrosine hydroxylase-positive cells),neuroinflammation(activated microglia,neurotoxic astrocytes),α-synuclein aggregation,and sensorimotor deficits.Increased neurotrophic astrocytes and brain-derived neurotrophic factor can mediate the rNurr1-V5 effect,supporting its potential clinical use in the treatment of Parkinson’s disease.

Boron-containing compounds as labels,drugs,and theranostic agents for diabetes and its complications

Diabetes is a disease with a high global burden.Current strategies have failed to limit the advancement and impact of the disease.Successful early diagnosis and treatment will require the development of new agents.In this sense,boroncontaining compounds have been reported as agents with the ability to reduce glycemia and lipidemia.They have also been used for labeling and measuring carbohydrates and other molecules linked to the initial stages of diabetes and its progression.In addition,certain boron compounds bind to molecules related to diabetes development and their biological activity in the regulation of elevated glycemia.Finally,it should be noted that some boron compounds appear to exert beneficial effects on diabetes complications such as accelerating wound healing while ameliorating pain in diabetic patients.

A Systematic Review of Cannabidiol Effects in Coronary Syndromes: Challenges to Clinical Translation

Background: Myocardial ischemia in addition to other several cardiac syndromes represent a pathological proinflammatory state alongside a complex cellular microenvironment that can be modified by using cannabinoids. Cannabidiol (CBD), a non-psychoactive compound of cannabis has been recently proposed as an immudomodulatory and cardioprotective drug. Objectives: In this systematic review we sought to clarify and summarize the clinical and preclinical evidence of potential benefit of the use of CBD in coronary syndromes. Methods: We conducted a systematic search and review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Review of Animal Data from Experimental Studies (CAMARADES) guidelines, in the electronic database from PubMed, Web of Science and Scopus up to April 2022 using predefined search terms. Pre-specified exclusion and inclusion criteria were considered, finally 11 articles were chosen to be included for this peer review. Results: Currently there are no good-quality clinical trials with the use of CBD in acute or chronic coronary syndromes. A total of 11 preclinical studies where prescreened and 5 demonstrated reproducible positive cardiovascular outcomes on in-vivo models treated with CBD. Mechanisms of CBD cardioprotection observed: 1) reduction in oxidative stress and inflammation, 2) activation of adenosine receptors and 3) increased expression of angiotensin type 2-receptor. Experimental models included ischemia/reperfusion injury, myocardial infarction, arrhythmias, and metabolic syndrome-like conditions. Conclusion: No clinical recommendation can be issued with the current evidence, on the use of CBD in acute and chronic coronary syndromes. Based on preclinical evidence, we considered there is enough evidence to propose the development of well-designed clinical trials that include CBD in the management of coronary syndromes.

Sound waves and solutions:Point-of-care ultrasonography for acute kidney injury in cirrhosis

This article delves into the intricate challenges of acute kidney injury(AKI)in cirrhosis,a condition fraught with high morbidity and mortality.The complexities arise from distinguishing between various causes of AKI,particularly hemodynamic AKI,in cirrhotic patients,who experience hemodynamic changes due to portal hypertension.The term"hepatocardiorenal syndrome"is introduced to encapsulate the intricate interplay among the liver,heart,and kidneys.The narrative emphasizes the often-overlooked aspect of cardiac function in AKI assessments in cirrhosis,unveiling the prevalence of cirrhotic cardiomyopathy marked by impaired diastolic function.The conventional empiric approach involving volume expansion and vasopressors for hepatorenal syndrome is critically analyzed,highlighting potential risks and variable patient responses.We advocate for a nuanced algorithm for AKI evaluation in cirrhosis,prominently featuring point-of-care ultrasonography(POCUS).POCUS applications encompass assessing fluid tolerance,detecting venous congestion,and evaluating cardiac function.

Management of nonalcoholic fatty liver disease:An evidence-based clinical practice review

AIM: To build a consensus among Chilean specialists on the appropriate management of patients with nonalcoholic fatty liver disease (NAFLD) in clinical practice.

Gastric endoscopic submucosal dissection:From animal model to patient

AIM:To assess whether the use of porcine models is useful for learning endoscopic submucosal dissection(ESD),thus contributing to its subsequent application in human patients.METHODS:This study/learning process was carried out in 3 phases:PhaseⅠ:Ex vivo animal;PhaseⅡ:In vivo animal;PhaseⅢ:Humans.One endoscopist performed 30 gastric ESDs in porcine models,and later 5gastric ESDs in 5 patients.The ESD was done following the method practiced at the National Cancer Center in Tokyo,Japan.Technical aspects,size,time and speed of ESD,as well as complications were registered.In patients,their clinical,endoscopic and histologic evolution was additionally added.RESULTS:Thirty en bloc ESDs were carried out in animal models.The mean±SD size of the pieces was of28.4±1.2 mm,and the time of ESD was 41.7±2.4min.The time of ESD in the first 15 procedures was 43.0±3.0 min whereas in the next 15 procedures,the time was 40.3±3.9 min,P=0.588.The speed in the first 15ESDs was 1.25±0.11 cm2/min vs 2.12±0.36 cm2/min in the remaining 15,P=0.028.There were no complications.In patients,5 lesions were resected en bloc.The size of the pieces was 25.2±5.1 mm and the time was85.0±25.6 min.Endoscopic and histological controls did not show evidence of residual neoplastic tissue.CONCLUSION:A sequential ESD training program of a unique endoscopist,based on the practice in porcine models,contributed to learning ESD for its subsequent application in humans,yielding good results in efficacy and safety.

Polyphenols as potential enhancers of stem cell therapy against neurodegeneration

The potential of polyphenols for treating chronic-degenerative diseases(particularly neurodegenerative diseases)is attractive.However,the selection of the best polyphenol for each treatment,the mechanisms by which they act,and their efficacy are frequently discussed.In this review,the basics and the advances in the field,as well as suggestions for using natural and synthetic polyphenols alone or in a combinatorial strategy with stem cell assays,are compiled and discussed.Thus,stem cells exhibit several responses when polyphenols are added to their environment,which could provide us with knowledge for advancing the elucidation of the origin of neurodegeneration.But also,polyphenols are being included in the innovative strategies of novel therapies for treating neurodegenerative diseases as well as metabolic diseases related to neurodegeneration.In this regard,flavonoid compounds are suggested as the best natural polyphenols due to their several mechanisms for acting in ameliorative effects;but increasing reports are involving other polyphenols.Even if some facts limiting bioactivity prevent them from conventional use,some natural polyphenols and derivatives hold the promise for being improved compounds,judged by their induced effects.The current results suggest polyphenols as enhancers of stem cell therapy against the targeted diseases.

Is the present cut-point to define type 2 diabetes appropriate in Latin-Americans?

The diagnosis of diabetes mellitus type 2(DM2) is based either on increased plasma glucose or Glycated hemoglobin levels. Since these measures are the only means for diagnosis of DM2, they must be well adapted to each population according to their metabolic characteristics, given that these may vary in each population. The World Health Organization(WHO) determined the cut-points of plasma glucose levels for the diagnosis of DM2 by associating hyperglycemia with the risk of a specific microvascular complication-retinopathy. Cardiovascular diseases are however the principal causes of mortality in patients with DM2 and we reported that in the Colombo-Ecuadorian population impaired fasting glucose and impaired glucose tolerance are both riskmarkers for myocardial infarction. We propose that the current cut-points accepted by the WHO need to be revaluated in populations such as Latin America and that there should be lower cut points for glycaemia in this population, to reduce the prevalence of cardiovascular complications associated with DM2.

Therapeutic alternatives for the treatment of type 1 hepatorenal syndrome: A Delphi technique-based consensus

AIM To propose several alternatives treatment of type 1 hepatorenal syndrome(HRS-1) what is the most severe expression of circulatory dysfunction on patients with portal hypertension.METHODS A group of eleven gastroenterologists and nephrologists performed a structured analysis of available literature.Each expert was designated to review and answer a question.They generated draft statements for evaluation by all the experts.Additional input was obtained from medical community.In order to reach consensus,a modified three-round Delphi technique method was used.According to United States Preventive Services Task Force criteria,the quality of the evidence and level of recommendation supporting each statement was graded.RESULTS Nine questions were formulated.The available evidence was evaluated considering its quality,number of patients included in the studies and the consistency of its results.The generated questions were answered by the expert panel with a high level of agreement.Thus,a therapeutic algorithm was generated.The role of terlipressin and norepinephrine was confirmed as the pharmacologic treatment of choice.On the other hand the use of the combination of octreotide,midodrine and albumin without vasoconstrictors was discouraged.The role of several other options was also evaluated and the available evidence was explored and discussed.Liver transplantation is considered the definitive treatment for HRS-1.The present consensus is an important effort that intends to organize the available strategies based on the available evidence in the literature,the quality of the evidence and the benefits,adverse effects and availability of the therapeutic tools described.CONCLUSION Based on the available evidence the expert panel was able to discriminate the most appropriate therapeutic alternatives for the treatment of HRS-1.

Global longitudinal strain is superior to ejection fraction for detecting myocardial dysfunction in end-stage renal disease with hyperparathyroidism

BACKGROUND The estimation of left ventricular ejection fraction(LVEF)by 2D echocardiography(2D-ECHO)is the most used tool to assess LV systolic function(LVSF).Global longitudinal strain(GLS)has recently been suggested as a superior method for several evaluations.This study explored the association and prevalence of LV systolic dysfunction(LVSD)by using these methods in patients with end-stage renal disease(ESRD)and severe hyperparathyroidism(SHPTH);both associated with cardiovascular events(CEs).AIM To evaluate the myocardial function in patients with ESRD and SHPTH by using the GLS and LVEF measured through conventional 2D-ECHO.METHODS In 62 patients with ESRD and SHPTH,asymptomatic,and without a history of CEs,LVSF was evaluated by 2D-ECHO,obtaining the EF,by the Simpson biplane method,and GLS by speckle tracking.RESULTS The total patients with ESRD had a preserved LVEF(>50%)but abnormal GLS(<13.55%).Additionally,multivariate analysis showed an independent association of GLS and serum parathyroid hormone(PTH),LV mass index,and hemoglobin.Also,PTH was independently associated with lateral e'wave and tricuspid regurgitation velocity.CONCLUSION In patients with SHPTH linked to ESRD,the use of GLS by 2D-ECHO is a more sensitive tool than LVEF for detecting LVSD.

Hepatoprotective effect of Geranium schiedeanum against ethanol toxicity during liver regeneration

AIM: To evaluate the effect of an extract of Geranium schiedeanum(Gs) as a hepatoprotective agent against ethanol(Et OH)-induced toxicity in rats. METHODS: Male Wistar rats weighing 200-230 g were subjected to a 70% partial hepatectomy(PH); they were then divided into three groups(groups 1-3). During the experiment, animals in group 1 drank only water. The other two groups(2-3) drank an aqueous solution of Et OH(40%, v/v). Additionally, rats in group 3 received a Gs extract daily at a dose of 300 mg/kg body weight intragastically. Subsequently, to identify markers of liver damage in serum, alanine aminotransferase, aspartate aminotransferase, albumin and bilirubin were measured by colorimetric methods. Glucose, triglyceride and cholesterol concentrations were also determined. In addition, oxidative damage was estimated by measuring lipid peroxidation [using thiobarbituric-acid reactive substances(TBARS)] in both plasma and the liver and by measuring the total concentration of antioxidants in serum and the total antioxidant capacity in the liver. In addition, a liver mass gain assessment, total DNA analysis and a morpho-histological analysis of the liver from animals in all three groups were performed and compared. Finally, the number of deaths observed in the three groups was analyzed.RESULTS: Administration of the Geranium shiedeanum extract significantly reduced the unfavorable effect of ethanol on liver regeneration(restitution liver mass: PHEt OH group 60.68% vs PH-Gs-Et OH group 69.22%). This finding was congruent with the reduced levels of hepatic enzymes and the sustained or increased levels of albumin and decreased bilirubin in serum. The extract also modified the metabolic processes that regulate glucose and lipid levels, as observed from the serum measurements. Lower antioxidant levels and the liver damage induced by Et OH administration appeared to be mitigated by the extract, as observed from the TBARs(PH-Et OH group 200.14 mmol/mg vs PH-Gs-Et OH group 54.20 mmol/mg; P < 0.05), total status of antioxidants(PH-Et OH group 1.43 mmol/L vs PH-Gs-Et OH group 1.99 mmol/L; P < 0.05), total antioxidant capacity values, liver mass gain and total DNA determination(PH-Et OH group 4.80 mg/g vs PH-Gs-Et OH 9.10 mg/g; P < 0.05). Overall, these processes could be related to decreased mortality in these treated animals.CONCLUSION: The administered extract showed a hepatoprotective effect, limiting the Et OH-induced hepatotoxic effects. This effect can be related tomodulating oxido-reduction processes.

Safety and Efficacy of Oral Mirodenafil in Mexican with Erectile Dysfunction

Erectile dysfunction is treated with 5-phospodiesterase inhibitors as Mirodenafil, which has shown its efficacy and safety in Koreans, however;no information in other populations is available. An open clinical trial study was designed to evaluate the efficacy and safety in real life of a fixed-dose of Mirodenafil in Mexican patients with erectile dysfunction. Forty-seven male patients received a 100 mg tablet of Mirodenafil, during 12 weeks. Primary outcome efficacy measure was the percentage of male patients with successful intercourse. Secondary outcomes measures included patient satisfaction, mood and self-esteem level. Safety assessments included laboratory tests, vital signs, physical examination, 12-lead electrocardiogram recordings, and incidence of adverse events by patients. Oral administration of Mirodenafil improved in an 80% - 90% the number of successful intercourses from 7 to 84 days of treatment. Moreover, patients reported a significant increment in their sexual satisfaction, mood and self-esteem. Mirodenafil treatment did not modify vital signs nor anthropometric parameters during 84 days. Mild headache was the most frequent adverse event (17.0%) and there were no severe adverse events during pharmacological treatment. Data suggest that oral Mirodenafil is safety, well tolerated and effective in the Mexican population with erectile dysfunction.

Insights into the structural biology of G-protein coupled receptors impacts drug design for central nervous system neurodegenerative processes

In the last few years, there have been important new insights into the structural biology of G-protein coupled receptors. It is now known that allosteric binding sites are involved in the affinity and selec- tivity of ligands for G-protein coupled receptors, and that signaling by these receptors involves both G-protein dependent and independent pathways. The present review outlines the physiological and pharmacological implications of this perspective for the design of new drugs to treat disorders of the central nervous system. Specifically, new possibilities are explored in relation to allosteric and or- thosteric binding sites on dopamine receptors for the treatment of Parkinson＇s disease, and on muscarinic receptors for Alzheimer＇s disease. Future research can seek to identify ligands that can bind to more than one site on the same receptor, or simultaneously bind to two receptors and form a dimer. For example, the design of bivalent drugs that can reach homo/hetero-dimers of D2 dopa- mine receptor holds promise as a relevant therapeutic strategy for Parkinson＇s disease. Regarding the treatment of Alzheimer＇s disease, the design of dualsteric ligands for mono-oligomeric mus- carinic receptors could increase therapeutic effectiveness by generating potent compounds that could activate more than one signaling pathway.

Different kinds of stem cells in the development of SARS-CoV-2 treatments

On February 11,2020,the World Health Organization officially announced the coronavirus disease 2019(COVID-19)caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),as an emerging recent pandemic illness,which currently has approximately taken the life of two million persons in more than 200 countries.Medical,clinical,and scientific efforts have focused on searching for new prevention and treatment strategies.Regenerative medicine and tissue engineering focused on using stem cells(SCs)have become a promising tool,and the regenerative and immunoregulatory capabilities of mesenchymal SCs(MSCs)and their exosomes have been demonstrated.Moreover,it has been essential to establishing models to reproduce the viral life cycle and mimic the pathology of COVID-19 to understand the virus's behavior.The fields of pluripotent SCs(PSCs),induced PSCs(iPSCs),and artificial iPSCs have been used for this purpose in the development of infection models or organoids.Nevertheless,some inconveniences have been declared in SC use;for example,it has been reported that SARS-CoV-2 enters human cells through the angiotensin-converting enzyme 2 receptor,which is highly expressed in MSCs,so it is important to continue investigating the employment of SCs in COVID-19,taking into consideration their advantages and disadvantages.In this review,we expose the use of different kinds of SCs and their derivatives for studying the SARS-CoV-2 behavior and develop treatments to counter COVID-19.

Artificial intelligence model validation before its application in clinical diagnosis assistance

The process of selecting an artificial intelligence(AI)model to assist clinical diagnosis of a particular pathology and its validation tests is relevant since the values of accuracy,sensitivity and specificity may not reflect the behavior of the method in a real environment.Here,we provide helpful considerations to increase the success of using an AI model in clinical practice.

Incidence, prevalence, and demographic characteristics of ocular cicatricial pemphigoid in Colombia: data from the National Health Registry 2009-2019

AIM:To provide an epidemiological characterization of ocular cicatricial pemphigoid(OCP)in Colombia.METHODS:We conducted a cross-sectional study using SISPRO.We applied the specific code of the International Classification of Diseases for Ocular Pemphigoid,from 2009-2019 to estimate prevalence,incidence,and the demographic status of the disease in Colombia.RESULTS:The estimated average prevalence was 0.22 per 1000000 inhabitants,and the estimated average incidence was 0.24 per 1000000 inhabitants.With a female predominance of 62.5%,and a male/female ratio of 1:1.6.The group of patients diagnosed with the disease after the age of 80 presented the highest prevalence.The departments with the highest prevalence were Antioquia,Bogotá,and Santander.CONCLUSION:There are important differences between worldwide and Colombian prevalence and incidence data,which may be related to genetic and epigenetic factors,and the possible underdiagnosis of the disease.According to the results,OCP is an extremely rare disease in Colombia.Nevertheless,it is important to encourage awareness of the disease due to its devastating consequences.

Hepatitis C virus infection in Argentina: Burden of chronic disease

AIM: To estimate the progression of the hepatitis C virus(HCV) epidemic and measure the burden of HCVrelated morbidity and mortality. METHODS: Age- and gender-defined cohorts were used to follow the viremic population in Argentina and estimate HCV incidence, prevalence, hepatic complications, and mortality. The relative impact of two scenarios on HCV-related outcomes was assessed:(1) increased sustained virologic response(SVR); and(2) increased SVR and treatment.RESULTS: Under scenario 1, SVR raised to 85%-95% in 2016. Compared to the base case scenario, there was a 0.3% reduction in prevalent cases and liverrelated deaths by 2030. Given low treatment rates, cases of hepatocellular carcinoma and decompensated cirrhosis decreased < 1%, in contrast to the base case in 2030. Under scenario 2, the same increases in SVR were modeled, with gradual increases in the annual diagnosed and treated populations. This scenario decreased prevalent infections 45%, liver-related deaths 55%, liver cancer cases 60%, and decompensated cirrhosis 55%, as compared to the base case by 2030. CONCLUSION: In Argentina, cases of end stage liver disease and liver-related deaths due to HCV are still growing, while its prevalence is decreasing. Increasing in SVR rates is not enough, and increasing in the number of patients diagnosed and candidates for treatment is needed to reduce the HCV disease burden. Based on this scenario, strategies to increase diagnosis and treatment uptake must be developed to reduce HCV burden in Argentina.

Cerebral dopamine neurotrophic factor transfection in dopamine neurons using neurotensin-polyplex nanoparticles reverses 6-hydroxydopamine-induced nigrostriatal neurodegeneration

Overexpression of neurotrophic factors in nigral dopamine neurons is a promising approach to reverse neurodegeneration of the nigrostriatal dopamine system,a hallmark in Parkinson's disease.The human cerebral dopamine neurotrophic factor(h CDNF)has recently emerged as a strong candidate for Parkinson's disease therapy.This study shows that h CDNF expression in dopamine neurons using the neurotensinpolyplex nanoparticle system reverses 6-hydroxydopamine-induced morphological,biochemical,and behavioral alterations.Three independent electron microscopy techniques showed that the neurotensin-polyplex nanoparticles containing the h CDNF gene,ranging in size from 20 to 150 nm,enabled the expression of a secretable h CDNF in vitro.Their injection in the substantia nigra compacta on day 21 after the 6-hydroxydopamine lesion resulted in detectable h CDNF in dopamine neurons,whose levels remained constant throughout the study in the substantia nigra compacta and striatum.Compared with the lesioned group,tyrosine hydroxylase-positive(TH^(+))nigral cell population and TH+fiber density rose in the substantia nigra compacta and striatum after h CDNF transfection.An increase inβIII-tubulin and growth-associated protein 43 phospho-S41(GAP43 p)followed TH^(+)cell recovery,as well as dopamine and its catabolite levels.Partial reversal(80%)of drugactivated circling behavior and full recovery of spontaneous motor and non-motor behavior were achieved.Brain-derived neurotrophic factor recovery in dopamine neurons that also occurred suggests its participation in the neurotrophic effects.These findings support the potential of nanoparticle-mediated h CDNF gene delivery to develop a disease-modifying treatment against Parkinson's disease.The Institutional Animal Care and Use Committee of Centro de Investigación y de Estudios Avanzados approved our experimental procedures for animal use(authorization No.162-15)on June 9,2019.

Evaluation of a Voluntary Control Program for the Detection of Bovine Leukemia Virus Antibodies Based on Agar Gel Immunodiffusion Test in Dairy Farms in Costa Rica

Cattle from 20 dairy farms were serologically tested over a five-year period using agar gel immunodiffusion test (AGIDT) as part of a voluntary Bovine Leukemia Virus (BLV) control program. After five years of removing infected animals from the herds based on BLV-AGIDT serological status, blood samples from 332 cattle in these farms were collected and analyzed side by side by AGIDT and enzyme-linked immunosorbent assay (ELISA) to detect antibodies against BLV. AGIDT detected 29.2% (97) and 16.0% (53) of the animals as positive and weak positive respectively, whereas ELISA detected 58.2% (193) cattle as positive. The prevalence of BLV-antibodies determined with AGIDT in the dairy farms oscillated between 0% and 86%, whereas prevalence determined by ELISA ranged between 28% and 100% in the same farms. Although both techniques showed similarly results in farms with high BLV-prevalence, ELISA detected a larger proportion of BLV-positive, especially in farms with low or no BLV-prevalence based on AGIDT, leading to wrong assumptions in terms of farm level control efforts. Our results strongly suggest that AGIDT alone is inadequate to implement BLV control programs and ELISA is a more adequate test for BLV surveillance and control programs.