Spinal Cord Stimulation for Parkinson's Disease: A Systematic Review and Meta-Analysis of Pain and Motor Outcomes.

BACKGROUND: Spinal cord stimulation (SCS) has been investigated as a potential therapeutic option for managing refractory symptoms in patients with Parkinson's disease (PD). OBJECTIVE: This systematic review and meta-analysis aimed to evaluate the safety and efficacy of SCS in PD. METHOD: A comprehensive literature search was conducted on PubMed and Web of Science to identify SCS studies reporting Unified Parkinson Disease Rating Scale-III (UPDRS-III) or Visual Analogue Scale (VAS) score changes in PD cohorts with at least 3 patients and a follow-up period of at least 1 month. Treatment effect was measured as the mean change in outcome scores and analyzed using an inverse variance random-effects model. The risk of bias was assessed using the Newcastle-Ottawa Scale and funnel plots. RESULTS: A total of 11 studies comprising 76 patients were included. Nine studies involving 72 patients reported an estimated decrease of 4.43 points (95% confidence interval [CI]: 2.11; 6.75, p < 0.01) in UPDRS-III score, equivalent to a 14% reduction. The axial subscores in 48 patients decreased by 2.35 points (95% CI: 1.26; 3.45, p < 0.01, 20% reduction). The pooled effect size of five studies on back and leg pain VAS scores was calculated as 4.38 (95% CI: 2.67; 6.09, p < 0.001), equivalent to a 59% reduction. CONCLUSIONS: Our analysis suggests that SCS may provide significant motor and pain benefits for patients with PD, although the results should be interpreted with caution due to several potential limitations including study heterogeneity, open-label designs, small sample sizes, and the possibility of publication bias. Further research using larger sample sizes and placebo-/sham-controlled designs is needed to confirm effectiveness.

Phaneroptic characterization and zoometric indices of Creole goats in the Ayacucho Region, Peru: First step for breeding programs, selection, and conservation.

Objective: The purpose of this study is to evaluate the phenotypic characteristics and typification of Creole goats in five localities of the Ayacucho region in south-central Peru. Materials and Methods: Data from 149 goats (25 males and 124 females) were collected, excluding animals under 2 years of age, pregnant, and sick. Seven qualitative characteristics and 11 zometric measurements were evaluated, and then 9 zometric indices were estimated. Results: In the region, goats with composite colors predominated (76.50%). Additionally, supernumerary (24.20%) and divergent teats (22.60%) were observed in females, while males exhibited a scrotal bifurcation (32.00%). The origin of the flock had a significant effect (p < 0.05) on body measurements, as well as on pelvic index, transverse pelvic index, longitudinal pelvic index, compactness index, and load cannon bone index, except for body index (BOI), proportionality index, dactyl thorax index (DTI), and relative cannon bone thickness index (

0.05). In the Ayacucho region, there is a predominance of light animals (57.72%) with a significant DTI (

Reduction of alpha-synuclein oligomers in preclinical models of Parkinson's disease by electrical stimulation in vitro and deep brain stimulation in vivo.

BACKGROUND: Deep brain stimulation (DBS) has been widely used to manage debilitating neurological symptoms in movement disorders such as Parkinson's disease (PD). Despite its well-established symptomatic benefits, our understanding of the mechanisms underlying DBS and its possible effect on the accumulation of pathological proteins in neurodegeneration remains limited. Accumulation and oligomerization of the protein alpha-synuclein (α-Syn) are implicated in the loss of dopaminergic neurons in the substantia nigra in PD, making α-Syn a potential therapeutic target for disease modification. OBJECTIVE: We examined the effects of high frequency electrical stimulation on α-Syn levels and oligomerization in cell and rodent models. METHODS: High frequency stimulation, mimicking DBS parameters used for PD, was combined with viral-mediated overexpression of α-Syn in cultured rat primary cortical neurons or in substantia nigra of rats. Bimolecular protein complementation with split fluorescent protein reporters was used to detect and quantify α-Syn oligomers. RESULTS: High frequency electrical stimulation reduced the expression of PD-associated mutant α-Syn and mitigated α-Syn oligomerization in cultured neurons. Furthermore, DBS in the substantia nigra, but not the subthalamic nucleus, decreased overall levels of α-Syn, including oligomer levels, in the substantia nigra. CONCLUSIONS: Taken together, our results demonstrate that direct high frequency stimulation can reduce accumulation and pathological forms of α-Syn in cultured neurons in vitro and in substantia nigra in vivo. Thus, DBS therapy could have a role beyond symptomatic treatment, with potential disease-modifying properties that can be exploited to target pathological proteins in neurodegenerative diseases.

The effect of limited healthcare access on poor outcomes among hospitalized COVID-19 patients in Honduras: A single center cohort study.

Background: The COVID-19 pandemic has had a severe impact on the Latin American subcontinent, particularly in areas with limited hospital resources and a restricted Intensive Care Unit (ICU) capacity. This study aimed to provide a comprehensive description of the clinical characteristics, outcomes, and factors associated with survival of COVID-19 hospitalized patients in Honduras. Research question: What were the characteristics and outcomes of COVID-19 patients in a large referral center in Honduras? Study design and methods: This study employed a retrospective cohort design conducted in a single center in San Pedro Sula, Honduras, between October 2020 to March 2021. All hospitalized cases of confirmed COVID-19 during this timeframe were included in the analysis. Univariable and multivariable survival analysis were performed using Kaplan-Meier curves and Cox proportional hazards model aiming to identify factors associated with decreased 30 day in-hospital survival, using a priori-selected factors. Results: A total of 929 confirmed cases were identified in this cohort, with males accounting for 55.4 % of cases. The case fatality rate among the hospitalized patients was found to be 50.1 % corresponding to 466 deaths. Patients with comorbidities such as hypertension, diabetes, obesity, chronic kidney disease, chronic obstructive pulmonary disease and cardiovascular disease had a higher likelihood of mortality. Additionally, non-survivors had a significantly longer time from illness onset to hospital admission compared to survivors (8.2 days vs 4.7 days). Among the cohort, 306 patients (32.9 %) met criteria for ICU admission. However, due to limited capacity, only 60 patients (19·6 %) were admitted to the ICU. Importantly, patients that were unable to receive level-appropriate care had lower likelihood of survival compared to those who received level-appropriate care (hazard ratio: 1.84). Interpretation: This study represents, the largest investigation of in-hospital COVID-19 cases in Honduras and Central America. The findings highlight a substantial case fatality rate among hospitalized patients. In this study, patients who couldn't receive level-appropriate care (ICU admission) had a significantly lower likelihood of survival when compared to those who did. These results underscore the significant impact of healthcare access during the pandemic, particularly in low- and middle-income countries.

Diagnostic and prognostic significance of serum microRNAs in colorectal cancer.

MicroRNAs are short non-coding RNA molecules involved in the regulation of gene expression. There are few studies related to the determination of serum microRNAs in colorectal cancer. The identification of microRNAs in peripheral blood as noninvasive markers of tumor disease may lead to potential applications, although further clinical studies focusing on serum microRNAs are required to determine their clinical significance for the diagnosis and prognosis outcome of colorectal cancer.

Implications of the histological determination of microRNAs in the screening, diagnosis and prognosis of colorectal cancer.

MicroRNAs are short non-coding RNA molecules that participate in the regulation of gene expression. Several studies have demonstrated the involvement of microRNAs in oncogenesis and a variety of physiological functions. We conducted a literature review of studies that evaluated histological microRNAs in colorectal cancer. Although additional clinical studies are required to substantiate the relationship between microRNAs and colorectal cancer, there is preliminary evidence that microRNAs are related to the diagnosis and prognosis of colorectal cancer.

Prognostic implications of serum microRNA-21 in colorectal cancer.

BACKGROUND AND OBJECTIVES: MicroRNAs (miRNAs) are small, noncoding RNAs that are involved in carcinogenesis through postranscriptional gene regulatory activity. Few studies have focused on the detection of miR-21 in serum rather than in tissue. The current study aimed to measure serum miR-21 expression levels and to evaluate their association with the outcome of colorectal cancer (CRC). METHODS: Blood samples were collected from 102 CRC patients undergoing surgery with curative intent. The expression levels of miR-21 were measured using a quantitative reverse transcription polymerase chain reaction (qRT-PCR). The results were analysed to assess the relationship between serum miR-21 levels and patient survival. RESULTS: A univariate analysis revealed that lower expression levels of serum miR-21 were associated with higher local recurrence (P = 0.025) and mortality (P = 0.029). A logistic regression analysis demonstrated that the relative overexpression of miR-21 (expression > 1) was associated with a 51% reduction in the risk of recurrence. A Cox regression analysis identified miR-21 expression as an independent predictor of survival (P = 0.048); a relative increase in miR-21 expression (>1) was associated with a 50% reduction in the risk of mortality. CONCLUSION: The expression level of serum miR-21 correlates with the recurrence and mortality of CRC patients. Our results suggest that circulating serum miR-21 is a promising prognostic tumour marker, and they highlight the potential clinical utility of miR-21 expression as a prognostic marker for CRC prognosis.

Krukenberg tumor after gastric bypass for morbid obesity. Bariatric surgery and gastric cancer.

Gastric bypass is one of the most frequently performed surgical procedures in bariatric surgery. A neoplasm within the gastric pouch is a somewhat infrequent complication but with important survival consequences. We present the case of a 51-year-old woman who developed an adenocarcinoma in the bypassed stomach three years after bariatric surgery; the tumour was incidentally discovered after gynaecological surgery for uterine myomas. Various diagnostic modalities for the excluded stomach were analysed.

[Is the claiming of costs justifiable in Jehovah's witness surgical patients after healthcare that is not part of the public health system?]. / ¿Es justificable el reintegro del gasto en enfermos quirúrgicos testigos de Jehová tras asistencia sanitaria ajena al sistema público de salud?

INTRODUCTION: Jehovah's witnesses refuse blood transfusions. The conflict arises when the patient, entitled to public health treatment, come to surgical centres without blood, to later claim the costs incurred. OBJECTIVES: To analyse the legal claims for the refunding of costs by Jehovah's witnesses treated outside the public health system. To make a cost comparison regarding this, using Diagnosis Related Groups (DRGs) in a similar hypothetical healthcare model and equal to a stay in our hospital. MATERIAL AND METHODS: A retrospective study was made of the High, Constitutional, and Supreme Court rulings. A cost analysis was made using the clinical information obtained in the rulings, to process this in the DRG in our hospital using 3MHealth Information Systems. RESULTS/CONCLUSIONS: The State is not obliged to finance religious aspects or those outside the general interest. The establishment of working protocols would avoid ethical conflicts. There are very difficult to justify differences in the costs demanded, 431,001.66 €, and compared to a model with an equal stay, 397,404.48 €.

Spatial analysis and risk mapping of Fasciola hepatica infection in dairy cattle at the Peruvian central highlands.

This study aimed to develop maps for Fasciola hepatica infection occurrence in dairy cattle in the districts of Matahuasi and Baños in the Peruvian central highlands. For this, a model based on the correlation between environmental variables and the prevalence of infection was constructed. Flukefinder® coprological test were performed in samples from dairy cattle from 8 herds, during both the rainy and wet season. Grazing plots were geo-referenced to obtain information on environmental variables. Monthly temperature, monthly rainfall, elevation, slope, normalized difference vegetation index (NDVI), enhanced vegetation index (EVI), normalized difference water index (NDWI), distance to rivers, urban areas and roads were obtained by using remote sensor images and ArcGIS®. Multilayer perceptron Artificial Neural Networks modeling were applied to construct a predictive model for the occurrence of fasciolosis, based on the relationship between environmental variables and level of infection. Kappa coefficient (k > 0.6) was used to evaluate concordance between observed and forecasted risk by the model. Coprological results demonstrated an average prevalence from 20% to 100%, in Matahuasi, and between 0 and 87.5%, in Baños. A model with a high level of concordance between predicted and observed infection risk (k = 0.77) was obtained, having as major predicting variables: slope, NDWI, NDVI and EVI. Fasciolosis risk was categorized as low (p < 20%), medium (20% < p < 50%) and high (p ≥ 50%) level. Using ArcGIS 10.4.1, risk maps were developed for each risk level of fasciolosis. Maps of fasciolosis occurrence showed that 87.2% of Matahuasi area presented a high risk for bovine fasciolosis during the dry season, and 76.6% in the wet season. In contrast, 21.9% of Baños area had a high risk of infection during the dry season and 12.1% during the wet season. In conclusion, our model showed areas with high risk for fasciolosis occurrence in both districts during both dry and rainy periods. Slope, NDWI, NDVI and EVI were the major predictors for fasciolosis occurrence.

Recharge PSYCH: A Study on Rechargeable Implantable Pulse Generators in Deep Brain Stimulation for Psychiatric Disorders.

BACKGROUND: Rechargeable implantable pulse generators (r-IPGs) for deep brain stimulation (DBS) promise longer battery life and fewer replacement surgeries versus non-rechargeable systems. Long-term data on the effects of recharging in patients who received DBS for psychiatric indications is limited. The Recharge PSYCH trial is the first study that included DBS patients with psychiatric disorders treated with different r-IPG models. METHODS: Standardized questionnaires were sent to all psychiatric DBS patients with an r-IPG implanted at the time of the study. The primary endpoint was convenience of recharging. Secondary endpoints were rate of user confidence and rate of usage-related complications, as well as charge burden (defined as minutes per week needed to recharge). RESULTS: Data sets of n = 21 patients were eligible for data analysis. At the time of the survey patients were implanted with the r-IPG for a mean 31.8 ± 22.4 months. Prior to being implanted with an r-IPG, patients had undergone a median of 3 IPG replacements. The overall convenience of the charging process was rated as "easy" with a median of 8.0 out of 10.0 points. 33.3% of patients experienced situations in which the device could not be successfully recharged. In 38.1% of patients, therapy with the r-IPG was interrupted unintentionally. The average charge burden was 286 ± 22.4 minutes per week. CONCLUSIONS: Patients with psychiatric disorders rated the recharging process as "easy", but with a significantly higher charge burden and usage-related complication rates compared to published data on movement disorder DBS patients.

Trends and disparities in deep brain stimulation utilization in the United States: a Nationwide Inpatient Sample analysis from 1993 to 2017.

Background: Deep brain stimulation (DBS) is an approved treatment option for Parkinson's Disease (PD), essential tremor (ET), dystonia, obsessive-compulsive disorder and epilepsy in the United States. There are disparities in access to DBS, and clear understanding of the contextual factors driving them is important. Previous studies aimed at understanding these factors have been limited by single indications or small cohort sizes. The aim of this study is to provide an updated and comprehensive analysis of DBS utilization for multiple indications to better understand the factors driving disparities in access. Methods: The United States based National Inpatient Sample (NIS) database was utilized to analyze the surgical volume and trends of procedures based on indication, using relevant ICD codes. Predictors of DBS use were analyzed using a logistic regression model. DBS-implanted patients in each indication were compared based on the patient-, hospital-, and outcome-related variables. Findings: Our analysis of 104,356 DBS discharges from 1993 to 2017 revealed that the most frequent indications for DBS were PD (67%), ET (24%), and dystonia (4%). Although the number of DBS procedures has consistently increased over the years, radiofrequency ablation utilization has significantly decreased to only a few patients per year since 2003. Negative predictors for DBS utilization in PD and ET cohorts included age increase and female sex, while African American status was a negative predictor across all cohorts. Significant differences in patient-, hospital-, and outcome-related variables between DBS indications were also determined. Interpretation: Demographic and socioeconomic-based disparities in DBS use are evident. Although racial disparities are present across all indications, other disparities such as age, sex, wealth, and insurance status are only relevant in certain indications. Funding: This work was supported by Alan & Susan Hudson Cornerstone Chair in Neurosurgery at University Health Network.

The targeted delivery of multicomponent cargos to cancer cells by nanoporous particle-supported lipid bilayers.

Encapsulation of drugs within nanocarriers that selectively target malignant cells promises to mitigate side effects of conventional chemotherapy and to enable delivery of the unique drug combinations needed for personalized medicine. To realize this potential, however, targeted nanocarriers must simultaneously overcome multiple challenges, including specificity, stability and a high capacity for disparate cargos. Here we report porous nanoparticle-supported lipid bilayers (protocells) that synergistically combine properties of liposomes and nanoporous particles. Protocells modified with a targeting peptide that binds to human hepatocellular carcinoma exhibit a 10,000-fold greater affinity for human hepatocellular carcinoma than for hepatocytes, endothelial cells or immune cells. Furthermore, protocells can be loaded with combinations of therapeutic (drugs, small interfering RNA and toxins) and diagnostic (quantum dots) agents and modified to promote endosomal escape and nuclear accumulation of selected cargos. The enormous capacity of the high-surface-area nanoporous core combined with the enhanced targeting efficacy enabled by the fluid supported lipid bilayer enable a single protocell loaded with a drug cocktail to kill a drug-resistant human hepatocellular carcinoma cell, representing a 10(6)-fold improvement over comparable liposomes.

Biogeographical patterns and co-occurrence of pathogenic infection across island populations of Berthelot's pipit (Anthus berthelotii).

Pathogens can exert strong selective forces upon host populations. However, before we can make any predictions about the consequences of pathogen-mediated selection, we first need to determine whether patterns of pathogen distribution are consistent over spatiotemporal scales. We used molecular techniques to screen for a variety of blood pathogens (avian malaria, pox and trypanosomes) over a three-year time period across 13 island populations of the Berthelot's pipit (Anthus berthelotii). This species has only recently dispersed across its range in the North Atlantic, with little subsequent migration, providing an ideal opportunity to examine the causes and effects of pathogenic infection in populations in the early stages of differentiation. We screened 832 individuals, and identified two strains of Plasmodium, four strains of Leucocytozoon, and one pox strain. We found strong differences in pathogen prevalence across populations, ranging from 0 to 65%, and while some fluctuations in prevalence occurred, these differences were largely stable over the time period studied. Smaller, more isolated islands harboured fewer pathogen strains than larger, less isolated islands, indicating that at the population level, colonization and extinction play an important role in determining pathogen distribution. Individual-level analyses confirmed the island effect, and also revealed a positive association between Plasmodium and pox infection, which could have arisen due to dual transmission of the pathogens by the same vectors, or because one pathogen lowers resistance to the other. Our findings, combined with an effect of infection on host body condition, suggest that Berthelot's pipits are subject to different levels of pathogen-mediated selection both across and within populations, and that these selective pressures are consistent over time.

Does bariatric surgery decrease gastric cancer risk?

BACKGROUND/AIMS: In the attempt to establish the different incidence between cancer in anatomically whole stomachs and cancer in patients who have undergone a surgical procedure for morbid obesity, a review on the epidemiology of bariatric surgery and stomach cancer and a correlation with the global incidence of stomach cancer (comparing it with the median age of patients who developed neoplasms after bariatric surgery) have been conducted. METHODOLOGY: This was a descriptive study of the gastric neoplasms located at the gastric pouch, bypassed stomach or in the esophagogastric junction, following bariatric surgery described in the medical literature. RESULTS: Twenty-one cases of gastric neoplasm located at the gastric pouch, in the bypassed stomach or in the esophagogastric junction were described after bariatric surgery. CONCLUSIONS: Bariatric surgery seems to produce a decrease in the incidence of cancer when comparing obese patients who were operated and obese patients who have not, so additional studies are needed to compare the cancer incidence between the general population and patients undergoing bariatric surgery. New studies will determine if it is necessary to focus on the early detection of pathological processes at the excluded digestive tract.

[Pneumoperitoneum, pneumoretroperitoneum, bilateral pneumothorax, pneumomediastinum and subcutaneous emphysema due ERCP]. / Neumoperitoneo, neumoretroperitoneo, neumotórax bilateral, neumomediastino y enfisema subcutáneo secundario a CPRE.

Endoscopic retrograde cholangiopancreatography (ERCP) has become an essential procedure in the diagnosis and treatment of biliopancreatic diseases. Complications of this procedure are potentially serious, being necessary to know how to recognize them for the application of the appropriate treatment. We report the case of a 79-year-old woman who developed a massive subcutaneous emphysema, bilateral pneumothorax, retropneumomediastinum, retropneumoperitoneum and pneumoperitoneum due to iatrogenic duodenal injury secondary to ERCP. The clinical suspicion for early diagnosis of iatrogenic injury after ERCP will determine the correct treatment of this complication and will achieve better outcomes.

[Epigenetics and colorectal cancer]. / Epigenética y cáncer colorrectal.

The epigenetic and physiological mechanisms that alter the structure of chromatin include the methylation of DNA, changes in the histones, and changes in RNA. A literature review has been carried out using PubMed on the evidence published on the association between epigenetics and colorectal cancer. The scientific literature shows that epigenetic changes, such as genetic modifications may be very significant in the origin of neoplastic disease, contributing both to the development and progression of the disease.

Functionalization of Poly(styrene-co-methyl methacrylate) Particles for Selective Removal of Bilirubin.

Hyperbilirubinemia is one of the main causes of death in patients with severe hepatic problems, which justifies the research for bilirubin removal solutions. In this study, St-MMA particles with PEGMA and/or GMA brushes were synthesized. First, the recipe for St-MMA was optimized and then adapted for PEGMA and GMA incorporation. Different solvents were then assayed to improve the BSA immobilization capacity of the particles. Ethyl lactate proved to be the best solvent, reaching a BSA immobilization capacity improvement of up to 60% for St-MMA-GMA-PEGMA particles. These particles also presented the best results for BR removal from PBS. No significant differences in the final capacity for BR removal from PBS media were observed when BSA was attached to the particles; however, the kinetics were greatly improved, requiring half the time. Finally, St-MMA-GMA-PEGMA particles that were wetted in EL with BSA reduced the bilirubin concentration in plasma from levels that threaten the survival of critical patients to levels close to those of healthy individuals in less than 30 min. On the contrary, particles without BSA were unable to remove bilirubin from plasma. Thus, the attachment of albumin to the particles plays a key role in selectively reducing bilirubin levels.