A Systematic Review and Meta-Analysis on the Prevalence of Mild Cognitive Impairment and Dementia in Mexico.

INTRODUCTION: Age remains one of the major risk factors for the onset of mild cognitive impairment (MCI) and dementia. Studies on the prevalence of these conditions in Mexico used different methods, tools, and populations with different health statuses. All these heterogeneous results may be a problem in identifying the true prevalence of MCI and dementia in Mexico. To our knowledge, there is not a systematic review available that presents essential figures on the prevalence of these conditions in Mexico. Therefore, we intend to access the maximum number of reports published on the topic and determine the prevalence of MCI and dementia in older Mexican adults. METHODS: A systematic review using PubMed, Cochrane, Research Gate, Lilacs, and Scielo databases was performed. Meta-analysis of the prevalence of MCI and dementia was performed using a random-effects model and presented in a forest plot among cross-sectional, epidemiological, and pooled studies. RESULTS: Sixteen articles were included. The overall prevalence of MCI of 18% (95% CI 0.10-0.27) was estimated from pooled information from 12 selected studies, in women 21% (95% CI 0.08-0.38) and in men 18% (95% CI 0.06-0.33). The overall prevalence of dementia of 10% (95% CI 0.06-0.14) was estimated from pooled information from 9 selected studies, in women 14% (95% CI 0.05-0.25) and in men 10% (95% CI 0.04-0.17). CONCLUSION: Mexican older individuals have a similar prevalence of dementia and MCI as reported by international data; nevertheless, the prevalence is higher than in some Latin American countries. Mexico has particular issues that must be resolved, such as a lack of research in the southern regions of the country and the high incidence of comorbidities.

The Livestock Frontier in the Paraguayan Chaco: A Local Agent-based Perspective.

Deforestation is one of the most relevant transformations characterizing global environmental change in the tropics at present. There is wide consensus in pointing the context-dependent nature of tropical deforestation. In this sense, a better characterization of the phenomenon considering the social context could provide a more accurate picture of tropical deforestation. With this aim, a Q-methodology discourse analysis was conducted to characterise the different discourses that coexist in the particular region of the Paraguayan Chaco concerning the development of cattle ranching and derived deforestation. Four different discourses were identified as making sense the wide range of interests and values coexisting and clashing in the Paraguayan Chaco, namely: the Environmentalist discourse, the Business discourse, the Resigned discourse, and the Possibilist discourse. The results point that the fundamental differences between the discourses are largely explained by the different positions on three specific domains: (i) the socio-economic benefits the expansion of cattle ranching brings about; (ii) the environmental impacts the expansion of cattle ranching and the derived deforestation brings on; and, finally (iii) the degree to which an active intervention from the side of policy making to regulate the expansion of cattle ranching and to minimize possible detrimental effects is seen as necessary. The position of the different discourses in relation to these domains could help policy makers to make measures and regulations more widely accepted and followed.

Development and validation of a patient-reported outcome measure to assess symptom burden after chimeric antigen receptor T-cell therapy.

This cross-sectional study aimed to develop and validate a patient-reported outcomes (PROs) assessment tool to assess symptom burden and daily functioning in patients after chimeric antigen receptor (CAR) T-cell therapy, the MD Anderson Symptom Inventory (MDASI-CAR). The items were generated based on literature review, content elicitation interviews with patients, and clinician's review. The patients completed the MDASI core and module, single-item quality-of-life (QoL) measure and Patient-Reported Outcomes Measurement Information System-29 (PROMIS-29). The psychometric validation analysis was based on the acceptability after item reduction process. The final 10 MDASI-CAR module items included tremors, fever/chills, headache, balance, dizziness, attention, difficulty speaking, coughing, sexual dysfunction, and diarrhoea with high internal consistency (Cronbach's alpha: MDASI Core, 0.865; MDASI Interference, 0.915; CAR-T module, 0.746). The MDASI-CAR has excellent known-group validity that was demonstrated by differentiate patients based on patient's performance status (Cohen's d for MDASI core = -1.008, interference = -0.771, module = -0.835). Criterion validity was demonstrated by the significant correlations between the MDASI-CAR composite score, the single QoL item and the relevant domains on PROMIS-29 (all p < 0.05). This study established the MDASI-CAR module as a reliable and valid PRO tool for monitoring symptom burden after CAR T-cell therapy in patients with haematological malignancies. The findings need to be validated with a longitudinal design.

Checking the Pulse of Holistic and Culturally Competent Nursing Practice in Pennsylvania.

Traditionally, underrepresented racial and ethnic groups experience marginalization, leading to inequities and disparities in health and health care. A holistic approach to care delivery can help providers meet a culturally diverse patient population's unique healing needs. A systematic assessment of nurses' cultural competency practice was conducted in Pennsylvania to reveal opportunities and provide direction for holistic, culturally competent health care services. This exploratory cross-sectional descriptive study used the Cultural Competence Education and Awareness Survey (CCEAS) to examine cultural competence practices of registered nurses employed in the state of Pennsylvania. A total of 1246 registered nurses completed the survey. Respondents expressed a strong desire for cultural competency. Education and organizational infrastructure to facilitate cultural competency could be improved. Health care leaders and policy makers at all levels should explore opportunities to strengthen nurses' culturally competent practices through ongoing professional-development activities and enhanced organizational infrastructure.

[Resilience, anxiety and stress among formal caregivers for institutionalized older people]. / Resiliencia, estrés y ansiedad de cuidadores formales durante la pandemia por COVID-19.

BACKGROUND: Caregiver stress is a common problem observed in nursing homes. AIM: To determine the association between the level of resilience and stress, anxiety and depression in formal caregivers of older people institutionalized in long-stay establishments during the COVID-19 pandemic. MATERIAL AND METHODS: One hundred ninety eight formal caregivers working at 11 long term residences for older people in southern Chile were invited to answer the SV-RES resilience and the DASS-21 anxiety and depression scales and 102 agreed to participate. RESULTS: We observed a significant association between the resilience scale score and variables such as weekly working hours (p < 0.01), current hours of sleep (p < 0.01), self-perception of sleep (p < 0.01), anxiety level (p < 0.01) and stress level (p < 0.01). CONCLUSIONS: A higher score on the Resilience Scale was associated with the absence of anxiety and stress, working between 22 and 43 hours per week, sleeping between 7 and 8 hours of sleep and a satisfactory self-perception of sleep. Studying the factors associated with resilience in formal caregivers of the elderly allows healthcare personnel to focus preventive actions, intervening promptly in risk areas associated with the work context, and strengthening the personal resources of caregivers.

MYOD1 as a prognostic indicator in rhabdomyosarcoma.

BACKGROUND/OBJECTIVES: Rhabdomyosarcoma (RMS) is characterized by the expression of the myogenic regulatory protein MYOD1. Histologic types include alveolar, embryonal (ERMS), and spindle cell sclerosing RMS (SRMS). SRMS harbors MYOD1 mutations in a subset of adult cases in association with poor prognosis. DESIGN/METHODS: To study the level of MYOD1 protein expression and its clinical significance, we have analyzed variable numbers of pediatric (<18 years of age) and adult (age range ≥18 to 35 years) ERMS and SRMS cases for presence or absence of MYOD1 immunoreactivity in correlation with clinical outcome and MYOD1 L122R mutations. RESULTS: Lack of MYOD1 immunoreactivity, identified in 23.8% of nonalveolar RMS (non-ARMS) cases, was more prevalent in SRMS (44%) than ERMS (17.2%) and was significantly associated with low overall survival and unfavorable tumor sites (p < .05). Lack of MYOD1 immunoreactivity was not associated with MYOD1 L122R mutations, which were identified in 3/37 (8%) cases including only two of 31 (6.5%) pediatric cases, one of 11 or 9% pediatric SRMS, and one case of infant ERMS. CONCLUSION: These studies highlight the prognostic role of MYOD1 in non-ARMS. Lack of MYOD1 immunoreactivity is associated with poor prognosis in ERMS and SRMS. MYOD1 gene mutations are generally infrequent in pediatric RMS. Although mutations are predominant in SRMS, they may exceptionally occur in infantile ERMS.

CloneSifter: enrichment of rare clones from heterogeneous cell populations.

BACKGROUND: Many biological processes, such as cancer metastasis, organismal development, and acquisition of resistance to cytotoxic therapy, rely on the emergence of rare sub-clones from a larger population. Understanding how the genetic and epigenetic features of diverse clones affect clonal fitness provides insight into molecular mechanisms underlying selective processes. While large-scale barcoding with NGS readout has facilitated cellular fitness assessment at the population level, this approach does not support characterization of clones prior to selection. Single-cell genomics methods provide high biological resolution, but are challenging to scale across large populations to probe rare clones and are destructive, limiting further functional analysis of important clones. RESULTS: Here, we develop CloneSifter, a methodology for tracking and enriching rare clones throughout their response to selection. CloneSifter utilizes a CRISPR sgRNA-barcode library that facilitates the isolation of viable cells from specific clones within the barcoded population using a sequence-specific retrieval reporter. We demonstrate that CloneSifter can measure clonal fitness of cancer cell models in vitro and retrieve targeted clones at abundance as low as 1 in 1883 in a heterogeneous cell population. CONCLUSIONS: CloneSifter provides a means to track and access specific and rare clones of interest across dynamic changes in population structure to comprehensively explore the basis of these changes.

[Ernestina Pérez Barahona (1865-1951). Her medical attempt to rescue the chilean race]. / Ernestina Pérez Barahona (1865-1951): La medicina al rescate de la raza chilena.

This article analyzes some publications of Ernestina Pérez Barahona (1865-1951), the second Chilean and Latin American female physician. It exposes her concern for the public health and, more precisely, for the problem of the Chilean race. She constantly refers to hygiene in her conferences, articles and books published between 1887 and 1920. Thus, the aim of this review is to recover her production and to inform the readers about her intervention as a medical professional.

Correction to: Interaction of the heterotrimeric G protein alpha subunit SSG-1 of Sporothrix schenckii with proteins related to stress response and fungal pathogenicity using a yeast two-hybrid assay.

Following the publication of this article [1], it was brought to our attention that Fig. 7A lane 2 is identical to Fig. 7B lane 2 and Fig. 7B lane 4 is identical to Fig. 7C lane 4.

[Eloísa Díaz: between medicine, psychology and education]. / Eloísa Díaz Inzunza: entre la medicina, la psicología y la educación.

Eloísa Díaz Insunza, the first Latin American female physician, completed her studies in Medicine and Surgery at the University of Chile in 1887 and worked a large part of her life as Medical Inspector of Public Schools of Santiago, Chile. In this article, the focus is placed on her "Test Memorandum" (1886) and her first Reports to the Ministry of Public Education (1899-1905), to appreciate the hygienist perspective that characterizes her proposals. We describe her intervention project that sought to integrate medical practice with psychology and education, to solve a social problem such as the degeneration of the Chilean race.

Permanent Cerebellar Degeneration After Acute Hyperthermia with Non-toxic Lithium Levels: a Case Report and Review of Literature.

This was a study of a 33-year-old man with bipolar disorder treated with lithium who developed cerebellar atrophy after an event of extreme hyperthermia. Unlike previously reported cases of acute cerebellar atrophy after heat stroke, neuroleptic syndrome or lithium toxicity, this case was characterized by a chronic cerebellar atrophy that developed after sepsis-induced hyperthermia in the setting of non-toxic lithium levels. Unique to this case also was the early finding of cerebellar atrophy on MRI 2 weeks after the episode of hyperthermia, long-term neurotoxicity after the novo lithium therapy, and longest follow-up case of chronic cerebellar syndrome after hyperthermia with non-toxic lithium levels.

Aggregation kinetics of carbonyl iron based magnetic suspensions in 2D.

We investigate the (irreversible) two-dimensional aggregation kinetics of dilute non-Brownian magnetic suspensions in rectangular microchannels using video-microscopy, image analysis and particle-level dynamics simulations. Special emphasis is given to carbonyl iron suspensions that are of interest in the formulation of magnetorheological fluids. The results are compared to non-Brownian suspensions of magnetic latexes. We demonstrate that both suspensions follow a deterministic aggregation process. Furthermore, experimental and simulation aggregation curves can be collapsed onto a master curve when using the appropriate scaling time (∝λ-1ϕ2D-2.5) as a function of only two dimensionless numbers: the lambda ratio (λ) and the particle surface fraction (ϕ2D).

The influence of polymorphism on the manufacturability and in vitro dissolution of sulindac-containing hard gelatin capsules.

CONTEXT: Drug polymorphism could affect drug product dissolution, manufacturability, stability and bioavailability/bioequivalence. The impact of polymorphism on the manufacturability and in vitro dissolution profiles of sulindac capsules has not been studied yet. OBJECTIVE: To evaluate the impact of polymorphism on the manufacturability and in vitro dissolution of sulindac hard gelatin capsules. MATERIALS AND METHODS: Sulindac crystal forms I and II (SLDI and SLDII, respectively) were prepared and characterized. Powder formulations containing one of the polymorphs, lactose and magnesium stearate (at three different levels) were prepared and their flow properties determined. Hard gelatin capsules were filled with the formulations and tested for fill-weight variations. Drug dissolution for SLDI- and SLDII-containing hard gelatin capsules was determined. RESULTS: Differences in flow properties for each polymorph were observed, as well as for their formulations, which in turn affected capsule weight homogeneity. Statistically significant differences in the rate and extent of drug release were observed between SLDI- and SLDII-containing capsules. DISCUSSION: Formulations containing SLDI showed a better manufacturability and a better dissolution profile than those with SLDII. CONCLUSION: Sulindac crystalline form I was the best candidate for hard gelatin capsule formulation because of its technological and in vitro dissolution properties.

Nontuberculous Mycobacteria, Mucociliary Clearance, and Bronchiectasis.

Nontuberculous mycobacteria (NTM) are environmental and ubiquitous, but only a few species are associated with disease, often presented as nodular/bronchiectatic or cavitary pulmonary forms. Bronchiectasis, airways dilatations characterized by chronic productive cough, is the main presentation of NTM pulmonary disease. The current Cole's vicious circle model for bronchiectasis proposes that it progresses from a damaging insult, such as pneumonia, that affects the respiratory epithelium and compromises mucociliary clearance mechanisms, allowing microorganisms to colonize the airways. An important bronchiectasis risk factor is primary ciliary dyskinesia, but other ciliopathies, such as those associated with connective tissue diseases, also seem to facilitate bronchiectasis, as may occur in Lady Windermere syndrome, caused by M. avium infection. Inhaled NTM may become part of the lung microbiome. If the dose is too large, they may grow excessively as a biofilm and lead to disease. The incidence of NTM pulmonary disease has increased in the last two decades, which may have influenced the parallel increase in bronchiectasis incidence. We propose that ciliary dyskinesia is the main promoter of bronchiectasis, and that the bacteria most frequently involved are NTM. Restoration of ciliary function and impairment of mycobacterial biofilm formation may provide effective therapeutic alternatives to antibiotics.

NeuroTri2-VISDOT: An open-access tool to harness the power of second trimester human single cell data to inform models of Mendelian neurodevelopmental disorders.

Whole exome and genome sequencing, coupled with refined bioinformatic pipelines, have enabled improved diagnostic yields for individuals with Mendelian conditions and have led to the rapid identification of novel syndromes. For many Mendelian neurodevelopmental disorders (NDDs), there is a lack of pre-existing model systems for mechanistic work. Thus, it is critical for translational researchers to have an accessible phenotype- and genotype-informed approach for model system selection. Single-cell RNA sequencing data can be informative in such an approach, as it can indicate which cell types express a gene of interest at the highest levels across time. For Mendelian NDDs, such data for the developing human brain is especially useful. A valuable single-cell RNA sequencing dataset of the second trimester developing human brain was produced by Bhaduri et al in 2021, but access to these data can be limited by computing power and the learning curve of single-cell data analysis. To reduce these barriers for translational research on Mendelian NDDs, we have built the web-based tool, Neurodevelopment in Trimester 2 - VIsualization of Single cell Data Online Tool (NeuroTri2-VISDOT), for exploring this single-cell dataset, and we have employed it in several different settings to demonstrate its utility for the translational research community.

Genetic Mapping of prod E.3.3 , a New Lethal Allele of prod.

The E.3.3 mutation was generated in a Flp/FRT EMS screen for conditional mutations that cause growth and developmental defects in a genetic background that blocks apoptosis. The mutations were conditional, based on the Dark 82 allele being present on the starting chromosome, and blocking canonical apoptosis in a homozygous state. The E.3.3 mosaic eyes exhibit defects in eye development including patches of rough eye and irregular surface structure. Whole Genome Sequencing and complementation mapping revealed E.3.3 as an allele of prod . Prod is a DNA-binding protein that binds satellite repeats and is involved in chromocenter formation during mitosis. Here we present a novel allele of prod , prod E.3.3 , that disrupts the functional region of the Prod protein resulting in disruption of typical eye structure, likely due to disruption of chromatid separation during development.

Expanded phenotypic spectrum of neurodevelopmental and neurodegenerative disorder Bryant-Li-Bhoj syndrome with 38 additional individuals.

Bryant-Li-Bhoj syndrome (BLBS), which became OMIM-classified in 2022 (OMIM: 619720, 619721), is caused by germline variants in the two genes that encode histone H3.3 (H3-3A/H3F3A and H3-3B/H3F3B) [1-4]. This syndrome is characterized by developmental delay/intellectual disability, craniofacial anomalies, hyper/hypotonia, and abnormal neuroimaging [1, 5]. BLBS was initially categorized as a progressive neurodegenerative syndrome caused by de novo heterozygous variants in either H3-3A or H3-3B [1-4]. Here, we analyze the data of the 58 previously published individuals along 38 unpublished, unrelated individuals. In this larger cohort of 96 people, we identify causative missense, synonymous, and stop-loss variants. We also expand upon the phenotypic characterization by elaborating on the neurodevelopmental component of BLBS. Notably, phenotypic heterogeneity was present even amongst individuals harboring the same variant. To explore the complex phenotypic variation in this expanded cohort, the relationships between syndromic phenotypes with three variables of interest were interrogated: sex, gene containing the causative variant, and variant location in the H3.3 protein. While specific genotype-phenotype correlations have not been conclusively delineated, the results presented here suggest that the location of the variants within the H3.3 protein and the affected gene (H3-3A or H3-3B) contribute more to the severity of distinct phenotypes than sex. Since these variables do not account for all BLBS phenotypic variability, these findings suggest that additional factors may play a role in modifying the phenotypes of affected individuals. Histones are poised at the interface of genetics and epigenetics, highlighting the potential role for gene-environment interactions and the importance of future research.

Pilot scale production of the vaccine adjuvant Proteoliposome derived Cochleates (AFCo1) from Neisseria meningitidis serogroup B.

The use of new adjuvants in vaccine formulations is a subject of current research. Only few parenteral adjuvants have been licensed. We have developed a mucosal and parenteral adjuvant known as AFCo1 (Adjuvant Finlay Cochleate 1, derived from proteoliposomes of N. meningitidis B) using a dialysis procedure to produce them on lab scale. The immunogenicity of the AFCo1 produced by dialysis has been already evaluated, but it was necessary to demonstrate the feasibility of a larger-scale manufacturing process. Therefore, we used a crossflow diafiltration system (CFS) that allows easy scale up to obtain large batches in an aseptic environment. The aim of this work was to produce AFCo1 on pilot scale, while conserving the adjuvant properties. The proteoliposomes (raw material) were resuspended in a buffer containing sodium deoxycholate and were transformed into AFCo1 under the action of a calcium forming buffer. The detergent was removed from the protein solution by diafiltration to a constant volume. In this CFS, we used a hollow fiber cartridge from Amicon (polysulfona cartridge of 10 kDa porosity, 1mm channel diameter of fiber and 0.45 m² area of filtration), allowing production of a batch of up to 20 L. AFCo1 were successfully produced by tangential filtration to pilot scale. The batch passed preliminary stability tests. Nasal immunization of BALB/c mice, induced specific saliva IgA and serum IgG. The induction of Th1 responses were demonstrated by the induction of IgG2a, IFNγ and not IL-5. The adjuvant action over Neisseria (self) antigens and with co-administered (heterologous) antigens such as ovalbumin and a synthetic peptide from haemolytic Streptococcus B was also demonstrated.

Polypyrimidine Tract Binding Protein: A Universal Player in Cancer Development.

OBJECTIVES: Polypyrimidine tract binding protein is a 57-Kda protein located in the perinucleolar compartment where it binds RNA and regulates several biological functions through the regulation of RNA splicing. Numerous research articles have been published that address the cellular network and functions of PTB and its isoforms in various disease states. METHODOLOGY: Through an extensive PubMed search, we attempt to summarize the relevant research into this biomolecule. RESULTS: Besides its roles in embryonic development, neuronal cell growth, RNA metabolism, apoptosis, and hematopoiesis, PTB can affect cancer growth via several metabolic, proliferative, and structural mechanisms. PTB overexpression has been documented in several cancers where it plays a role as a novel prognostic factor. CONCLUSION: The diverse carcinogenic effect opens an argument into its potential role in inhibitory targeted therapy.

Wastewater surveillance of SARS-CoV-2 genomic populations on a country-wide scale through targeted sequencing.

SARS-CoV-2 surveillance of viral populations in wastewater samples is recognized as a useful tool for monitoring epidemic waves and boosting health preparedness. Next generation sequencing of viral RNA isolated from wastewater is a convenient and cost-effective strategy to understand the molecular epidemiology of SARS-CoV-2 and provide insights on the population dynamics of viral variants at the community level. However, in low- and middle-income countries, isolated groups have performed wastewater monitoring and data has not been extensively shared in the scientific community. Here we report the results of monitoring the co-circulation and abundance of variants of concern (VOCs) of SARS-CoV-2 in Uruguay, a small country in Latin America, between November 2020-July 2021 using wastewater surveillance. RNA isolated from wastewater was characterized by targeted sequencing of the Receptor Binding Domain region within the spike gene. Two computational approaches were used to track the viral variants. The results of the wastewater analysis showed the transition in the overall predominance of viral variants in wastewater from No-VOCs to successive VOCs, in agreement with clinical surveillance from sequencing of nasal swabs. The mutations K417T, E484K and N501Y, that characterize the Gamma VOC, were detected as early as December 2020, several weeks before the first clinical case was reported. Interestingly, a non-synonymous mutation described in the Delta VOC, L452R, was detected at a very low frequency since April 2021 when using a recently described sequence analysis tool (SAM Refiner). Wastewater NGS-based surveillance of SARS-CoV-2 is a reliable and complementary tool for monitoring the introduction and prevalence of VOCs at a community level allowing early public health decisions. This approach allows the tracking of symptomatic and asymptomatic individuals, who are generally under-reported in countries with limited clinical testing capacity. Our results suggests that wastewater-based epidemiology can contribute to improving public health responses in low- and middle-income countries.