After an initial Hermansky-Pudlak syndrome clinical diagnosis, molecular testing reveals variants for oculocutaneous albinism type 1B: A case report.

BACKGROUND: Albinism is a heterogeneous condition in which patients present complete absence, reduction, or normal pigmentation in skin, hair and eyes in addition to ocular defects. One of the heterogeneous forms of albinism is observed in Hermansky-Pudlak syndrome (HPS) patients. HPS is characterized by albinism and hemorrhagic diathesis due to the absence of dense bodies in platelets. METHODS: In this report, we describe a case of a pair of Puerto Rican siblings with albinism that were clinically diagnosed with HPS during childhood. Since they did not harbor the founder changes in the HPS1 and HPS3 genes common in Puerto Ricans, as adults they wanted to know the type of albinism they had. We performed exome sequencing, validation by PCR, and cloning of PCR products followed by Sanger sequencing in the family members. RESULTS: We discovered no mutations that could explain an HPS diagnosis. Instead, we found the siblings were compound heterozygotes for 4 variants in the Tyrosinase gene: c.-301C>T, c.140G>A (rs61753180; p.G47D), c.575C>A (rs1042602; p.S192Y), and c.1205G>A (rs1126809; p.R402Q). Our results show that the correct diagnosis for the siblings is OCA1B. CONCLUSION: Our study shows the importance of molecular testing when diagnosing a rare genetic disorder, especially in populations were the disease prevalence is higher.

Geriatric Syndromes and Their Relationship with Mortality in a Population of Mexican Older Adults Aged 65 and Over, Admitted to the Emergency Department of a Second-Level Care Hospital.

The main objective of this study was to analyze the relationship between Geriatric Syndromes (GSs) and in-hospital mortality in adults aged 65 and older admitted to the Emergency Department (ED). The study included 202 Older Adults (OAs) who met the inclusion criteria. We conducted a Comprehensive Geriatric Assessment and collected clinical and demographic data. A univariate analysis was carried out for each of the GSs analyzed. Those variables with p < 0.05 were entered into a multiple logistic regression using the backward stepwise entry method to analyze the independent predictor variables. The average number of GSs per individual was 4.65 (±2.76). Frailty syndrome was the most prevalent (70.2% of patients). Our study found an association between mortality and some GSs, such as frailty (p = 0.042), risk of falls (p = 0.010), delirium, cognitive impairment, dependence, and risk of ulcers (p < 0.001). We found that cognitive impairment (adjusted OR, 6.88; 95% CI, 1.41-33.5; p = 0.017) and dependence (adjusted OR, 7.52; 95% CI, 1.95-29.98; p = 0.003) were independent predictors associated with mortality in our population. It is necessary to develop new care strategies in the ED that respond to the needs of aging societies, including the use of new technologies and personnel with experience in gerontology.

Antidiabetic Effect of Passiflora ligularis Leaves in High Fat-Diet/Streptozotocin-Induced Diabetic Mice.

Type 2 diabetes mellitus (T2DM) is a major global public health concern, prompting the ongoing search for new treatment options. Medicinal plants have emerged as one such alternative. Our objective was to evaluate the antidiabetic effect of an extract from the leaves of Passiflora ligularis (P. ligularis). For this purpose, T2DM was first induced in mice using a high-fat diet and low doses of streptozotocin. Subsequently, an aqueous extract or an ethanolic extract of P. ligularis leaves was administered for 21 days. The following relevant results were found: fasting blood glucose levels were reduced by up to 41%, and by 29% after an oral glucose overload. The homeostasis model assessment of insulin resistance (HOMA-IR) was reduced by 59%. Histopathologically, better preservation of pancreatic tissue was observed. Regarding oxidative stress parameters, there was an increase of up to 48% in superoxide dismutase (SOD), an increase in catalase (CAT) activity by 35% to 80%, and a decrease in lipid peroxidation (MDA) by 35% to 80% in the liver, kidney, or pancreas. Lastly, regarding the lipid profile, triglycerides (TG) were reduced by up to 30%, total cholesterol (TC) by 35%, and low-density lipoproteins (LDL) by up to 32%, while treatments increased high-density lipoproteins (HDL) by up to 35%. With all the above, we can conclude that P. ligularis leaves showed antihyperglycemic, hypolipidemic, and antioxidant effects, making this species promising for the treatment of T2DM.

Wolbachia-carrying Aedes mosquitoes for preventing dengue infection.

BACKGROUND: Dengue is a global health problem of high significance, with 3.9 billion people at risk of infection. The geographic expansion of dengue virus (DENV) infection has resulted in increased frequency and severity of the disease, and the number of deaths has increased in recent years. Wolbachia,an intracellular bacterial endosymbiont, has been under investigation for several years as a novel dengue-control strategy. Some dengue vectors (Aedes mosquitoes) can be transinfected with specific strains of Wolbachia, which decreases their fitness (ability to survive and mate) and their ability to reproduce, inhibiting the replication of dengue. Both laboratory and field studies have demonstrated the potential effect of Wolbachia deployments on reducing dengue transmission, and modelling studies have suggested that this may be a self-sustaining strategy for dengue prevention, although long-term effects are yet to be elucidated. OBJECTIVES: To assess the efficacy of Wolbachia-carrying Aedes speciesdeployments (specifically wMel-, wMelPop-, and wAlbB- strains of Wolbachia) for preventing dengue virus infection. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, four other databases, and two trial registries up to 24 January 2024. SELECTION CRITERIA: Randomized controlled trials (RCTs), including cluster-randomized controlled trials (cRCTs), conducted in dengue endemic or epidemic-prone settings were eligible. We sought studies that investigated the impact of Wolbachia-carrying Aedes deployments on epidemiological or entomological dengue-related outcomes, utilizing either the population replacement or population suppression strategy. DATA COLLECTION AND ANALYSIS: Two review authors independently selected eligible studies, extracted data, and assessed the risk of bias using the Cochrane RoB 2 tool. We used odds ratios (OR) with the corresponding 95% confidence intervals (CI) as the effect measure for dichotomous outcomes. For count/rate outcomes, we planned to use the rate ratio with 95% CI as the effect measure. We used adjusted measures of effect for cRCTs. We assessed the certainty of evidence using GRADE. MAIN RESULTS: One completed cRCT met our inclusion criteria, and we identified two further ongoing cRCTs. The included trial was conducted in an urban setting in Yogyakarta, Indonesia. It utilized a nested test-negative study design, whereby all participants aged three to 45 years who presented at healthcare centres with a fever were enrolled in the study provided they had resided in the study area for the previous 10 nights. The trial showed that wMel-Wolbachia infected Ae aegypti deployments probably reduce the odds of contracting virologically confirmed dengue by 77% (OR 0.23, 95% CI 0.15 to 0.35; 1 trial, 6306 participants; moderate-certainty evidence). The cluster-level prevalence of wMel Wolbachia-carrying mosquitoes remained high over two years in the intervention arm of the trial, reported as 95.8% (interquartile range 91.5 to 97.8) across 27 months in clusters receiving wMel-Wolbachia Ae aegypti deployments, but there were no reliable comparative data for this outcome. Other primary outcomes were the incidence of virologically confirmed dengue, the prevalence of dengue ribonucleic acid in the mosquito population, and mosquito density, but there were no data for these outcomes. Additionally, there were no data on adverse events. AUTHORS' CONCLUSIONS: The included trial demonstrates the potential significant impact of wMel-Wolbachia-carrying Ae aegypti mosquitoes on preventing dengue infection in an endemic setting, and supports evidence reported in non-randomized and uncontrolled studies. Further trials across a greater diversity of settings are required to confirm whether these findings apply to other locations and country settings, and greater reporting of acceptability and cost are important.

Association of CYP3A4-392A/G, CYP3A5-6986A/G, and ABCB1-3435C/T Polymorphisms with Tacrolimus Dose, Serum Concentration, and Biochemical Parameters in Mexican Patients with Kidney Transplant.

Tacrolimus (TAC) is an immunosuppressant drug that prevents organ rejection after transplantation. This drug is transported from cells via P-glycoprotein (ABCB1) and is a metabolic substrate for cytochrome P450 (CYP) 3A enzymes, particularly CYP3A4 and CYP3A5. Several single-nucleotide polymorphisms (SNPs) have been identified in the genes encoding CYP3A4, CYP3A5, and ABCB1, including CYP3A4-392A/G (rs2740574), CYP3A5 6986A/G (rs776746), and ABCB1 3435C/T (rs1045642). This study aims to evaluate the association among CYP3A4-392A/G, CYP3A5-6986A/G, and ABCB1-3435C/T polymorphisms and TAC, serum concentration, and biochemical parameters that may affect TAC pharmacokinetics in Mexican kidney transplant (KT) patients. METHODS: Forty-six kidney transplant recipients (KTR) receiving immunosuppressive treatment with TAC in different combinations were included. CYP3A4, CYP3A5, and ABCB1 gene polymorphisms were genotyped using qPCR TaqMan. Serum TAC concentration (as measured) and intervening variables were assessed. Logistic regression analyses were performed at baseline and after one month to assess the extent of the association between the polymorphisms, intervening variables, and TAC concentration. RESULTS: The GG genotype of CYP3A5-6986 A/G polymorphism is associated with TAC pharmacokinetic variability OR 4.35 (95%CI: 1.13-21.9; p = 0.0458) at one month of evolution; in multivariate logistic regression, CYP3A5-6986GG genotype OR 9.32 (95%CI: 1.54-93.08; p = 0.028) and the use of medications or drugs that increase serum TAC concentration OR 9.52 (95%CI: 1.79-88.23; p = 0.018) were strongly associated with TAC pharmacokinetic variability. CONCLUSION: The findings of this study of the Mexican population showed that CYP3A5-6986 A/G GG genotype is associated with a four-fold increase in the likelihood of encountering a TAC concentration of more than 15 ng/dL. The co-occurrence of the CYP3A5-6986GG genotype and the use of drugs that increase TAC concentration correlates with a nine-fold increased risk of experiencing a TAC at a level above 15 ng/mL. Therefore, these patients have an increased susceptibility to TAC-associated toxicity.

Zika Virus: A Neurotropic Warrior against High-Grade Gliomas-Unveiling Its Potential for Oncolytic Virotherapy.

Gliomas account for approximately 75-80% of all malignant primary tumors in the central nervous system (CNS), with glioblastoma multiforme (GBM) considered the deadliest. Despite aggressive treatment involving a combination of chemotherapy, radiotherapy, and surgical intervention, patients with GBM have limited survival rates of 2 to 5 years, accompanied by a significant decline in their quality of life. In recent years, novel management strategies have emerged, such as immunotherapy, which includes the development of vaccines or T cells with chimeric antigen receptors, and oncolytic virotherapy (OVT), wherein wild type (WT) or genetically modified viruses are utilized to selectively lyse tumor cells. In vitro and in vivo studies have shown that the Zika virus (ZIKV) can infect glioma cells and induce a robust oncolytic activity. Consequently, interest in exploring this virus as a potential oncolytic virus (OV) for high-grade gliomas has surged. Given that ZIKV actively circulates in Colombia, evaluating its neurotropic and oncolytic capabilities holds considerable national and international importance, as it may emerge as an alternative for treating highly complex gliomas. Therefore, this literature review outlines the generalities of GBM, the factors determining ZIKV's specific tropism for nervous tissue, and its oncolytic capacity. Additionally, we briefly present the progress in preclinical studies supporting the use of ZIKV as an OVT for gliomas.

Association of the rs1126616 and rs9138 Variants in the SPP1 Gene among Mexican Patients with Systemic Lupus Erythematosus and Lupus Nephritis.

Systemic lupus erythematosus (SLE) is a multisystem disease considered a prototype of the main autoimmune disease and presents serious complications, such as lupus nephritis (LN), which generates a significant impact on morbidity and mortality. The SPP1 gene encodes the osteopontin (OPN) protein, which plays a crucial role in the regulation of inflammation and immunity. The variants rs1126616 and rs9138 of this gene have been associated with the inflammatory response. The study aims to analyze the association of the rs1126616 and rs9138 variants of the SPP1 gene in SLE Mexican-Mestizo patients without LN (SLE-LN). In this cross-sectional study, a total of 171 genomic DNA samples from SLE patients were clinically confirmed, of which 111 were SLE without LN, 60 were SLE with LN, and 100 healthy individuals were included as reference group. The rs1126616 variant was genotyped using PCR-RFLPs, and the rs9138 variant was genotyped using qPCR TaqMan. The TT genotype, the recessive model [OR 2.76 (95% CI 1.31-5.82), p = 0.011], and the T allele [OR 2.0 (95% CI 1.26-3.16), p = 0.003] of the rs1126616 variant are risk factors for SLE with LN. By contrast, the rs9138 variant did not show statistically significant differences among SLE patients stratified by LN. In our study of SLE Mexican-Mestizo patients with and without NL, demographic and clinical characteristics do not differ from other SLE populations, and the TT genotype of the rs1126616 variant of the SPP1 gene confers a risk factor for the presentation of LN. Otherwise, the rs9138 variant did not show association with NL.

Sex Differences in the Atherogenic Risk Index in Healthy Mexican Population and Its Relationship with Anthropometric and Psychological Factors.

Dyslipidemia is a risk factor for cardiovascular disease and mortality; however, the association of this variable with a wide range of personal and psychological variables has not been researched. Therefore, the aim of this study was to compare lipid levels and anthropometric measures between sexes and to determine the association between personal and psychological variables with the atherogenic risk index (ARI). An adult population which auto-reported as healthy was invited to participate via social media and in person. They filled out a questionnaire with personal and psychological variables; in addition, the body mass index (BMI) and waist-to-hip ratio (WHR) were measured, and a blood sample was obtained to determine serum lipids. A total of 172 participants were included, from which 92 (53.49%) were women; both sexes were comparable in age and most sociodemographic values. Men showed significantly higher levels of total cholesterol, LDL cholesterol, triglycerides, ARI, and lower levels of HDL cholesterol. The men also showed higher values of WHR than the women. In the bivariate analysis, ARI showed the highest correlation with WHR (r = 0.664) in the men and with BMI (r = 0.619) in the women. In the multivariate analysis, the quality of food intake was negatively correlated with ARI in the global and women's samples, and the psychological variables of assertiveness and positive relations with others were negatively correlated with ARI in women, while purpose in life was negatively correlated with ARI in men. In conclusion, the higher levels of serum lipids and ARI in men can be explained by the higher values of WHR in this sex. Behavioral and psychological variables could be protective factors for high ARI.

Photocatalytic and Photothermal Antimicrobial Mussel-Inspired Nanocomposites for Biomedical Applications.

Bacterial infection has traditionally been treated with antibiotics, but their overuse is leading to the development of antibiotic resistance. This may be mitigated by alternative approaches to prevent or treat bacterial infections without utilization of antibiotics. Among the alternatives is the use of photo-responsive antimicrobial nanoparticles and/or nanocomposites, which present unique properties activated by light. In this study, we explored the combined use of titanium oxide and polydopamine to create nanoparticles with photocatalytic and photothermal antibacterial properties triggered by visible or near-infrared light. Furthermore, as a proof-of-concept, these photo-responsive nanoparticles were combined with mussel-inspired catechol-modified hyaluronic acid hydrogels to form novel light-driven antibacterial nanocomposites. The materials were challenged with models of Gram-negative and Gram-positive bacteria. For visible light, the average percentage killed (PK) was 94.6 for E. coli and 92.3 for S. aureus. For near-infrared light, PK for E. coli reported 52.8 and 99.2 for S. aureus. These results confirm the exciting potential of these nanocomposites to prevent the development of antibiotic resistance and also to open the door for further studies to optimize their composition in order to increase their bactericidal efficacy for biomedical applications.

Basal procalcitonin, C-reactive protein, interleukin-6, and presepsin for prediction of mortality in critically ill septic patients: a systematic review and meta-analysis.

BACKGROUND: Numerous biomarkers have been proposed for diagnosis, therapeutic, and prognosis in sepsis. Previous evaluations of the value of biomarkers for predicting mortality due to this life-threatening condition fail to address the complexity of this condition and the risk of bias associated with prognostic studies. We evaluate the predictive performance of four of these biomarkers in the prognosis of mortality through a methodologically sound evaluation. METHODS: We conducted a systematic review a systematic review and meta-analysis to determine, in critically ill adults with sepsis, whether procalcitonin (PCT), C-reactive protein (CRP), interleukin-6 (IL-6), and presepsin (sCD14) are independent prognostic factors for mortality. We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials up to March 2023. Only Phase-2 confirmatory prognostic factor studies among critically ill septic adults were included. Random effects meta-analyses pooled the prognostic association estimates. RESULTS: We included 60 studies (15,681 patients) with 99 biomarker assessments. Quality of the statistical analysis and reporting domains using the QUIPS tool showed high risk of bias in > 60% assessments. The biomarker measurement as a continuous variable in models adjusted by key covariates (age and severity score) for predicting mortality at 28-30 days showed a null or near to null association for basal PCT (pooled OR = 0.99, 95% CI = 0.99-1.003), CRP (OR = 1.01, 95% CI = 0.87 to 1.17), and IL-6 (OR = 1.02, 95% CI = 1.01-1.03) and sCD14 (pooled HR = 1.003, 95% CI = 1.000 to 1.006). Additional meta-analyses accounting for other prognostic covariates had similarly null findings. CONCLUSION: Baseline, isolated measurement of PCT, CRP, IL-6, and sCD14 has not been shown to help predict mortality in critically ill patients with sepsis. The role of these biomarkers should be evaluated in new studies where the patient selection would be standardized and the measurement of biomarker results. TRIAL REGISTRATION: PROSPERO (CRD42019128790).

Detection of variable genotypes in common human papillomavirus-associated invasive penile squamous cell carcinomas: a study of 177 human papillomavirus-positive cases.

Human papillomavirus (HPV) is detected in 30-50% of invasive penile carcinomas, and it is frequently associated with basaloid and warty morphological features. Based on this heterogeneity and different clinical behaviors, we hypothesized a variation in their HPV genotypic composition. To test this, we evaluated 177 HPV-positive cases: basaloid (114), warty-basaloid (28), and warty (condylomatous) (35) invasive carcinomas. HPV DNA detection and genotyping was performed using the SPF-10/DEIA/LiPA25 system. Nineteen HPV genotypes were detected. High-risk HPVs predominated (96%), and low-risk HPVs were rarely present. Most common genotype was HPV16 followed by HPVs 33 and 35. According to the genotypes identified, 93% of the cases would be covered with current vaccination programs. There was a significant variation in the distribution of HPV16 and non-HPV16 genotypes according to histological subtype. HPV16 was significantly frequent in basaloid (87%) and was less frequent in warty carcinomas (61%). This molecular difference, along with their distinctive macro-microscopic and prognostic features, makes basaloid and warty carcinomas unique. The gradual decreasing frequency of HPV16 demonstrated in basaloid, warty-basaloid, and warty carcinomas suggest that the basaloid cell, present in those types in decreasing proportions, may be responsible for the differences.

Incidence and Mortality Rates for Childhood Acute Lymphoblastic Leukemia in Puerto Rican Hispanics, 2012-2016.

BACKGROUND: Acute lymphoblastic leukemia (ALL) accounts for 80% of all leukemias diagnosed in children. Although ALL age patterns are consistent across racial/ethnic groups, their incidence and mortality rates are highly variable. We assessed the age-standardized ALL incidence and mortality rates of Puerto Rican Hispanic (PRH) children and compared them with those of US mainland Hispanics (USH), non-Hispanic Whites (NHW), non-Hispanic Blacks (NHB), and Non-Hispanic Asian or Pacific Islanders (NHAPI). METHODS: Differences between racial/ethnic groups were assessed by estimating the standardized rate ratio (SRR) for 2010 to 2014. Secondary data analyses of the Puerto Rico Central Cancer Registry and the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) databases were performed for the 2001 to 2016 period. RESULTS: PRH children had 31% lower incidence rates than USH, but 86% higher incidence rates than NHB. In addition, the incidence trends of ALL increased significantly from 2001 to 2016 among PRH and USH, with 5% and 0.9% per year, respectively. Moreover, PRH have a lower 5-year overall survival (81.7%) when compared with other racial/ethnic groups. CONCLUSIONS: PRH children were found to have disparities in ALL incidence and mortality rates compared with other racial/ethnic groups in the US. Additional research is warranted to identify the genetic and environmental risk factors that may be associated with the disparities observed. IMPACT: This is the first study reporting the incidence and mortality rates of childhood ALL for PRH and making comparisons with other racial/ethnic groups in the US. See related commentary by Mejía-Aranguré and Núñez-Enríquez, p. 999.

Molecular and Sociodemographic Colorectal Cancer Disparities in Latinos Living in Puerto Rico.

BACKGROUND: The incidence of sporadic colorectal cancer (CRC) among individuals <50 years (early-onset CRC) has been increasing in the United States (U.S.) and Puerto Rico. CRC is currently the leading cause of cancer death among Hispanic men and women living in Puerto Rico (PRH). The objective of this study was to characterize the molecular markers and clinicopathologic features of colorectal tumors from PRH to better understand the molecular pathways leading to CRC in this Hispanic subpopulation. METHODS: Microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and KRAS and BRAF mutation status were analyzed. Sociodemographic and clinicopathological characteristics were evaluated using Chi-squared and Fisher's exact tests. RESULTS: Of the 718 tumors analyzed, 34.2% (n = 245) were early-onset CRC, and 51.7% were males. Among the tumors with molecular data available (n = 192), 3.2% had MSI, 9.7% had BRAF, and 31.9% had KRAS mutations. The most common KRAS mutations observed were G12D (26.6%) and G13D (20.0%); G12C was present in 4.4% of tumors. A higher percentage of Amerindian admixture was significantly associated with early-onset CRC. CONCLUSIONS: The differences observed in the prevalence of the molecular markers among PRH tumors compared to other racial/ethnic groups suggest a distinct molecular carcinogenic pathway among Hispanics. Additional studies are warranted.

Molecular profiling of colorectal cancer in a genetically admixed Hispanic population.

BACKGORUND: Colorectal cancer (CRC) is among the leading causes of cancer-related deaths among Hispanics living in the United States (USH). Understanding the most common carcinogenic molecular pathways that affect Hispanics with CRC is crucial to guide research efforts in developing new therapeutic modalities incorporating genomically diverse populations. Tumor profiling techniques help identify actionable alternatives to recommend treatment and improve survival in cancer patients. METHODS: We conducted a secondary data analysis to evaluate the mutational profile of 218 CRC tumors in Hispanics living in Puerto Rico (PRH) who underwent next-generation sequencing (NGS) testing from 2015 to 2020. We compared the prevalence of CRC tumor somatic mutations in PRHs with the mutational profiles reported for CRC from The Cancer Genome Atlas (TCGA) Pan-Cancer Clinical Data, the AACR Project Genomics Evidence Neoplasia Information Exchange (GENIE)-Non-Hispanic, and GENIE-Hispanic datasets. RESULTS: Among the top mutated genes in CRC tumors in PRHs were APC, TP53, and KRAS, which had significantly higher mutational frequencies in PRH compared to the examined datasets, including GENIE-Hispanics. The most frequent gene amplifications for PRH were CDX2, CDKN1B, and HNRNPA2B1. Targetable biomarkers for CRC, such as microsatellite instability-high (MSI), wild-type KRAS, wild-type NRAS, V600E BRAF, and ERBB2 gene amplifications were found in 2.0%, 43.8%, 97.8%, 3.9%, and 2.3%, respectively, of PRH patients. CONCLUSION: This is the first study to report the mutational profile of CRC tumors in PRHs and make comparisons to other non-Hispanic and USH populations.

Immunomodulation in age-related disorders and nanotechnology interventions.

Recently, the aging population has increased exponentially around the globe bringing more challenges to improve quality of life in those populations while reducing the economic burden on healthcare systems. Aging is associated with changes in the immune system culminating in detrimental effects such as immune dysfunction, immunosenescence, and chronic inflammation. Age-related decline of immune functions is associated with various pathologies including cardiovascular, autoimmune, neurodegenerative, and infectious diseases to name a few. Conventional treatment addresses the onset of age-related diseases by early detection of risk factors, administration of vaccines as preventive care, immunomodulatory treatment, and other dietary supplements. However, these approaches often come with systemic side-effects, low bioavailability of therapeutic agents, and poor outcomes seen in the elderly. Recent innovations in nanotechnology have led to the development of novel biomaterials/nanomaterials, which explore targeted drug delivery and immunomodulatory interactions in vivo. Current nanotechnology-based immunomodulatory approaches that have the potential to be used as therapeutic interventions for some prominent age-related diseases are discussed here. Finally, we explore challenges and future aspects of nanotechnology in the treatments of age-related disorders to improve quality of life in the elderly. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Cardiovascular Disease Therapeutic Approaches and Drug Discovery > Nanomedicine for Neurological Disease Therapeutic Approaches and Drug Discovery > Emerging Technologies.

Extract of Calyces from Physalis peruviana Reduces Insulin Resistance and Oxidative Stress in Streptozotocin-Induced Diabetic Mice.

Diabetes mellitus is a metabolic disorder mainly characterized by obesity, hyperglycemia, altered lipid profile, oxidative stress, and vascular compromise. Physalis peruviana is a plant used in traditional Colombian medicine for its known activities of glucose regulation. This study aimed to evaluate the anti-diabetic activity of the butanol fraction from an extract of Physalis peruviana calyces in two doses (50 mg/kg and 100 mg/kg) in induced type 2 diabetic mice. Blood glucose levels were evaluated once a week, demonstrating that a dose of 100 mg/kg resulted in greater regulation of blood glucose levels in mice throughout the experiment. The same overall result was found for the oral glucose tolerance test (OGTT) and the homeostatic model assessment for insulin resistance (HOMA- IR). The lipid profile exhibited improvement compared to the non-treated group, a dose of 100 mg/kg having greater protection against oxidative stress (catalase, superoxide dismutase, and malondialdehyde levels). Histopathological findings in several tissues showed structure preservation in most of the animals treated. The butanol fraction from Physalis peruviana at 100 mg/kg showed beneficial results in improving hyperglycemia, lipidemia, and oxidative stress status, and can therefore be considered a beneficial coadjuvant in the therapy of diabetes mellitus.

The dual pathogenesis of penile neoplasia: The heterogeneous morphology of human papillomavirus-related tumors.

Objective: Penile neoplasia, usually of squamous histogenesis, is currently classified into human papillomavirus (HPV)-related or -dependent and non-HPV-related or -independent. There are distinct morphological differences among the two groups. New research studies on penile cancer from Northern countries showed that the presence of HPV is correlated with a better prognosis than virus negative people, while studies in Southern countries had not confirmed, perhaps due to differences in staging or treatment. Methods: We focused on the description of the HPV-related carcinomas of the penis. The approach was to describe common clinical features followed by the pathological features of each entity or subtype stressing the characteristics for differential diagnosis, HPV genotypes, and prognostic features of the invasive carcinomas. Similar structure was followed for penile intraepithelial neoplasia, except for prognosis because of the scant evidence available. Results: Most of HPV-related lesions can be straightforwardly recognized by routine hematoxylin and eosin stains, but in some cases surrogate p16 immunohistochemical staining or molecular methods such as in situ hybridization or polymerase chain reaction can be utilized. Currently, there are eight tumor invasive variants associated with HPV, as follows: basaloid, warty, warty-basaloid, papillary basaloid, clear cell, medullary, lymphoepithelioma-like, and giant condylomas with malignant transformation. Conclusion: This review presents and describes the heterogeneous clinical, morphological, and genotypic features of the HPV-related subtypes of invasive and non-invasive penile neoplasia.

Meta-DiSc 2.0: a web application for meta-analysis of diagnostic test accuracy data.

BACKGROUND: Diagnostic evidence of the accuracy of a test for identifying a target condition of interest can be estimated using systematic approaches following standardized methodologies. Statistical methods for the meta-analysis of diagnostic test accuracy (DTA) studies are relatively complex, presenting a challenge for reviewers without extensive statistical expertise. In 2006, we developed Meta-DiSc, a free user-friendly software to perform test accuracy meta-analysis. This statistical program is now widely used for performing DTA meta-analyses. We aimed to build a new version of the Meta-DiSc software to include statistical methods based on hierarchical models and an enhanced web-based interface to improve user experience. RESULTS: In this article, we present the updated version, Meta-DiSc 2.0, a web-based application developed using the R Shiny package. This new version implements recommended state-of-the-art statistical models to overcome the limitations of the statistical approaches included in the previous version. Meta-DiSc 2.0 performs statistical analyses of DTA reviews using a bivariate random effects model. The application offers a thorough analysis of heterogeneity, calculating logit variance estimates of sensitivity and specificity, the bivariate I-squared, the area of the 95% prediction ellipse, and the median odds ratios for sensitivity and specificity, and facilitating subgroup and meta-regression analyses. Furthermore, univariate random effects models can be applied to meta-analyses with few studies or with non-convergent bivariate models. The application interface has an intuitive design set out in four main menus: file upload; graphical description (forest and ROC plane plots); meta-analysis (pooling of sensitivity and specificity, estimation of likelihood ratios and diagnostic odds ratio, sROC curve); and summary of findings (impact of test through downstream consequences in a hypothetical population with a given prevalence). All computational algorithms have been validated in several real datasets by comparing results obtained with STATA/SAS and MetaDTA packages. CONCLUSION: We have developed and validated an updated version of the Meta-DiSc software that is more accessible and statistically sound. The web application is freely available at www.metadisc.es .

Bioinformatic Characterization and Molecular Evolution of the Lucina pectinata Hemoglobins.

(1) Introduction: Lucina pectinata is a clam found in sulfide-rich mud environments that has three hemoglobins believed to be responsible for the transport of hydrogen sulfide (HbILp) and oxygen (HbIILp and HbIIILp) to chemoautotrophic endosymbionts. The physiological roles and evolution of these globins in sulfide-rich environments are not well understood. (2) Methods: We performed bioinformatic and phylogenetic analyses with 32 homologous mollusk globin sequences. Phylogenetics suggests a first gene duplication resulting in sulfide binding and oxygen binding genes. A more recent gene duplication gave rise to the two oxygen-binding hemoglobins. Multidimensional scaling analysis of the sequence space shows evolutionary drift of HbIILp and HbIIILp, while HbILp was closer to the Calyptogena hemoglobins. Further corroboration is seen by conservation in the coding region of hemoglobins from L. pectinata compared to those from Calyptogena. (3) Conclusions: Presence of glutamine in position E7 in organisms living in sulfide-rich environments can be considered an adaptation to prevent loss of protein function. In HbILp a substitution of phenylalanine in position B10 is accountable for its unique reactivity towards H2S. It appears that HbILp has been changing over time, apparently not subject to functional constraints of binding oxygen, and acquired a unique function for a specialized environment.

Prevalence of Sexual Dysfunction in Mexican Women with Rheumatoid Arthritis.

We estimate the prevalence and identified the associated factors of sexual dysfunction in Mexican women with rheumatoid arthritis (RA). A cross-sectional survey was applied to 100 women with RA and compared with 100 healthy, sexually active, adult women. Assessments included an interview using the Female Sexual Function Index (FSFI). Assessment of factors related to sexual dysfunction included gynecologic characteristics, disease activity (DAS-28), and functioning questionnaire (HAQ-DI). Mann-Whitney U test and the Chi-square test were used to compare medians and proportions between the groups. A multivariate logistic regression was performed using sexual dysfunction according to impairments shown by the FSFI. A higher proportion of RA patients had sexual dysfunction compared with controls. Domains with higher impairment in RA patients were desire, arousal, lubrication, and orgasm. A decrease in sexual function correlated with age (r = −0.365 p < 0.001) and higher scores in HAQ-DI (r = −0.261 p = 0.009). Those patients with a higher disability had higher impairments in desire, arousal, lubrication, and satisfaction. In the multivariate analysis, menopause was associated with sexual dysfunction (OR: 10.02; 95% CI: 1.05−95.40, p = 0.04), whereas use of methotrexate was a protective factor (OR: 0.32; 95% CI: 0.11−0.92, p = 0.03). Sexual dysfunction is highly prevalent in Mexican women with RA. Clinicians should systematically evaluate the impairment in sexual function in women with RA.