SARS-CoV-2 infection by trimester of pregnancy and adverse perinatal outcomes: a Mexican retrospective cohort study.

OBJECTIVE: Conflicting evidence for the association between COVID-19 and adverse perinatal outcomes exists. This study examined the associations between maternal COVID-19 during pregnancy and adverse perinatal outcomes including preterm birth (PTB), low birth weight (LBW), small-for-gestational age (SGA), large-for-gestational age (LGA) and fetal death; as well as whether the associations differ by trimester of infection. DESIGN AND SETTING: The study used a retrospective Mexican birth cohort from the Instituto Mexicano del Seguro Social (IMSS), Mexico, between January 2020 and November 2021. PARTICIPANTS: We used the social security administrative dataset from IMSS that had COVID-19 information and linked it with the IMSS routine hospitalisation dataset, to identify deliveries in the study period with a test for SARS-CoV-2 during pregnancy. OUTCOME MEASURES: PTB, LBW, SGA, LGA and fetal death. We used targeted maximum likelihood estimators, to quantify associations (risk ratio, RR) and CIs. We fit models for the overall COVID-19 sample, and separately for those with mild or severe disease, and by trimester of infection. Additionally, we investigated potential bias induced by missing non-tested pregnancies. RESULTS: The overall sample comprised 17 340 singleton pregnancies, of which 30% tested positive. We found that those with mild COVID-19 had an RR of 0.89 (95% CI 0.80 to 0.99) for PTB and those with severe COVID-19 had an RR of 1.53 (95% CI 1.07 to 2.19) for LGA. COVID-19 in the first trimester was associated with fetal death, RR=2.36 (95% CI 1.04, 5.36). Results also demonstrate that missing non-tested pregnancies might induce bias in the associations. CONCLUSIONS: In the overall sample, there was no evidence of an association between COVID-19 and adverse perinatal outcomes. However, the findings suggest that severe COVID-19 may increase the risk of some perinatal outcomes, with the first trimester potentially being a high-risk period.

Estimating the effect of realistic improvements of metformin adherence on COVID-19 mortality using targeted machine learning.

Background: Type 2 diabetes elevates the risk of severe outcomes in COVID-19 patients, with multiple studies reporting higher case fatality rates. Metformin is a widely used medication for glycemic management. We hypothesize that improved adherence to metformin may lower COVID-19 post-infection mortality risk in this group. Utilizing data from the Mexican Social Security Institute (IMSS), we investigate the relationship between metformin adherence and mortality following COVID-19 infection in patients with chronic metformin prescriptions. Methods: This is a retrospective cohort study consisting of 61,180 IMSS beneficiaries who received a positive polymerase chain reaction (PCR) or rapid test for SARS-CoV-2 and had at least two consecutive months of metformin prescriptions prior to the positive test. The hypothetical intervention is improved adherence to metformin, measured by proportion of days covered (PDC), with the comparison being the observed metformin adherence values. The primary outcome is all-cause mortality following COVID-19 infection. We defined the causal parameter using shift intervention, an example of modified treatment policies. We used the targeted learning framework for estimation of the target estimand. Findings: Among COVID-19 positive patients with chronic metformin prescriptions, we found that a 5% and 10% absolute increase in metformin adherence is associated with a respective 0.26% (95% CI: -0.28%, 0.79%) and 1.26% (95% CI: 0.72%, 1.80%) absolute decrease in mortality risk. Interpretation: Subject to the limitations of a real-world data study, our results indicate a causal association between improved metformin adherence and reduced COVID-19 post-infection mortality risk.

Anaplastic large cell lymphoma with ALK::ATIC fusion mimicking a histiocytic sarcoma debuting as an anterior thoracic soft tissue tumor with exceptional clinicopathological, morphological and molecular features.

A 56-year-old woman debuted with a palpable painless mass in the anterior thorax wall at the level of the second and third right parasternal intercostal space, which progressively increased in size over 5 months accompanied by localized skin rash, mild dyspnea and chest pain when changing position. Imaging studies showed a soft tissue mass measuring 75 × 62 mm and a density of 34 Hounsfield Units that had caused the lysis of the costal arches and grew expansively towards the anterior mediastinum, without identifying mediastinal adenopathies only by this imaging method. Core biopsy was performed, which was initially diagnosed as histiocytic sarcoma (HS); however, when the diagnostic panel was expanded to include molecular and NGS studies, the final diagnosis was anaplastic large cell lymphoma with ALK::ATIC fusion. Here, we report a very rare neoplasm with unusual clinical presentation, histopathology and molecular features.

Genetic parameters for different types of medullated fibre in Alpacas.

The quality of alpaca textile fibre has great potential, especially if objectionable fibres (coarse and medullated fibres) that cause itching are reduced, considering that objectionable fibres can be identified by diameter and medullation types. The objective of this study was to estimate genetic parameters for medullar types and their respective diameters to evaluate the possibility of incorporating them as selection criteria in alpaca breeding programmes. The research used 3149 alpaca fibre samples collected from 2020 to 2022, from a population of 1626 Huacaya type alpacas. The heritability and correlations of the percentages of non-medullated (NM), fragmented medulle (FM), uncontinuous medullated (UM), continuous medullated (CM), and strongly medullated (SM) fibres were analysed, also the fibre diameter (FD) for each of the medullation types. The heritability estimated for medullation types were 0.25 ± 0.01, 0.18 ± 0.01, 0.10 ± 0.01, 0.20 ± 0.01 and 0.11 ± 0.01 for NM, FM, UM, CM and SM, respectively. The genetic correlations for medullation categories ranged from 0.15 ± 0.03 to 0.66 ± 0.02 (in absolute values). The heritabilility estimated for fibre diameter (FD) of each of the medullation types were 0.29 ± 0.03, 0.27 ± 0.02, 0.35 ± 0.02, 0.30 ± 0.02, 0.25 ± 0.02 and 0.10 ± 0.02 for FD, FD_NM, FD_FM, FD_UM, FD_CM and FD_SM, respectively. The genetic correlations for fibre diameter of the medullation types ranged from 0.04 ± 0.04 to 0.97 ± 0.01. FD, NM and FM are the main traits to be used as selection criteria under a genetic index, since they would reduce fibre diameter, and also increase NM and FM, and, in addition reducing indirectly CM, SM, and SM_FD. Therefore, the quality of alpaca fibre could be improved.

Pedigree analysis in the mhorr gazelle (Nanger dama mhorr): Genetic variability evolution of the captive population.

Breeding programs have an essential role in the recovery of threatened populations through optimal genetic management and mating strategies. The dama gazelle (Nanger dama) is a North African ungulate listed as critically endangered. The mhorr subspecies is extinct in the wild and currently survives thanks to the creation in 1971 of an ex situ breeding program. The aim of the present study was to assess the evolution of genetic variability in this mhorr gazelle captive population, as well as the mating strategy used in two reference populations studied (Almeria and Europe). The entire pedigree, with 2739 animals, was analyzed to measure demographic characters, pedigree completeness level, probability of gene origin, level of relatedness and genetic structure of the population. The population size has been progressively increasing, with up to 264 individuals alive in Europe at the time of the study. The average number of equivalent complete generations was 5.55. The effective number of founders and ancestors was both 3, and the founder genome equivalent was 1.99. The genetic contributions of the four main ancestors were unbalanced. The average values of inbreeding and average relatedness for the whole pedigree were, respectively, 28.34% and 50.14%. The effective population size was 8.7 by individual increase in inbreeding and 9.8 by individual increase in coancestry. F-statistics evidenced a very small level of population subdivision (F ST = 0.033370). The mating strategy used, based on the minimum coancestry of the individuals, has minimized the losses of genetic variability and helped to balance the genetic contributions between ancestors. The strategy also avoided large subdivisions within the population and the appearance of new bottlenecks. This study shows how pedigree analysis can both be used to determine the genetic variability of the population and to assess the influence of the mating strategy used in the breeding program on such variability.

Differential patterns in runs of homozygosity in two mice lines under divergent selection for environmental variability for birth weight.

Runs of homozygosity (ROH) are defined as long continuous homozygous stretches in the genome which are assumed to originate from a common ancestor. It has been demonstrated that divergent selection for variability in mice is possible and that low variability in birth weight is associated with robustness. To analyse ROH patterns and ROH-based genomic inbreeding, two mouse lines that were divergently selected for birth weight variability for 26 generations were used, with: 752 individuals for the high variability line (H-Line), 766 individuals for the low variability line (L-Line) and 74 individuals as a reference population. Individuals were genotyped using the high density Affymetrix Mouse Diversity Genotyping Array. ROH were identified using both the sliding windows (SW) and the consecutive runs (CR) methods. Inbreeding coefficients were calculated based on pedigree (FPED ) information, on ROH identified using the SW method (FROHSW ) and on ROH identified using the CR method (FROHCR ). Differences in genomic inbreeding were not consistent across generations and these parameters did not show clear differences between lines. Correlations between FPED and FROH were high, particularly for FROHSW . Moreover, correlations between FROHSW and FPED were even higher when ROH were identified with no restrictions in the number of heterozygotes per ROH. The comparison of FROH estimates between either of the selected lines were based on significant differences at the chromosome level, mainly in chromosomes 3, 4, 6, 8, 11, 15 and 19. ROH-based inbreeding estimates that were computed using longer homozygous segments had a higher relationship with FPED . Differences in robustness between lines were not attributable to a higher homozygosis in the L-Line, but maybe to the different distribution of ROH at the chromosome level between lines. The analysis identified a set of genomic regions for future research to establish the genomic basis of robustness.

How predictive of SARS-CoV-2 infection are clinical characteristics at presentation among individuals with COVID-like symptoms treated at the Mexican Institute of Social Security.

BACKGROUND: The COVID-19 pandemic has progressed rapidly, with the emergence of new virus variants that pose challenges in treating infected individuals. In Mexico, four epidemic waves have been recorded with varying disease severity. To understand the heterogeneity in clinical presentation over time and the sensitivity and specificity of signs and symptoms in identifying COVID-19 cases, an analysis of the changes in the clinical presentation of the disease was conducted. AIM: To analyze the changes in the clinical presentation of COVID-19 among 3.38 million individuals tested for SARS-CoV-2 at the Mexican Social Security Institute (IMSS) from March 2020 to October 2021 and evaluate the predictivity of signs and symptoms in identifying COVID-19 cases. METHODS: A retrospective analysis of clinical presentation patterns of COVID-19 among individuals treated at IMSS was performed, contrasting the signs and symptoms among SARS-CoV-2-positive individuals with those who tested negative for the virus but had respiratory infection symptoms. The sensitivity and specificity of each sign and symptom in identifying SARS-CoV-2 infection were estimated. RESULTS: The set of signs and symptoms reported for COVID-19-suspected patients treated at IMSS were not highly specific for SARS-CoV-2 positivity. The signs and symptoms exhibited variability based on age and epidemic wave. The area under the receiver operating characteristic (ROC) curve was 0.62 when grouping the five main symptoms (headache, dyspnea, fever, arthralgia, and cough). Most of the individual symptoms had ROC values close to 0.5 (16 out of 22 between 0.48 and 0.52), indicating non-specificity. CONCLUSIONS: The results highlight the difficulty in making a clinical diagnosis of COVID-19 due to the lack of specificity of signs and symptoms. The variability of clinical presentation over time and among age groups highlights the need for further research to differentiate whether the changes are due to changes in the virus, who is becoming infected, or the population, particularly with respect to prior infection and vaccination status.

Genomic inbreeding measures applied to a population of mice divergently selected for birth weight environmental variance.

This study aimed to compare different inbreeding measures estimated from pedigree and molecular data from two divergent mouse lines selected for environmental birth weight during 26 generations. Furthermore, the performance of different approaches and both molecular and pedigree data sources for estimating Ne were tested in this population. A total of 1,699 individuals were genotyped using a high-density genotyping array. Genomic relationship matrices were used to calculate molecular inbreeding: Nejati-Javaremi (F NEJ), Li and Horvitz (F L&H), Van Raden method 1 (F VR1) and method 2 (F VR2), and Yang (F YAN). Inbreeding based on runs of homozygosity (F ROH) and pedigree inbreeding (F PED) were also computed. F ROH, F NEJ, and F L&H were also adjusted for their average values in the first generation of selection and named F ROH0, F NEJ0, and F L&H0. ∆F was calculated from pedigrees as the individual inbreeding rate between the individual and his parents (∆F PEDt) and individual increases in inbreeding (∆F PEDi). Moreover, individual ∆F was calculated from the different molecular inbreeding coefficients (∆F NEJ0, ∆F L&H, ∆F L&H0, ∆F VR1, ∆F VR2, ∆F YAN, and ∆F ROH0). The Ne was obtained from different ∆F, such as Ne PEDt, Ne PEDi, Ne NEJ0, Ne L&H, Ne L&H0, Ne VR1, Ne VR2, Ne YAN, and Ne ROH0. Comparing with F PED , F ROH , F NEJ and F VR2 overestimated inbreeding while F NEJ0 , F L&H , F L&H0 , F VR1 and F YAN underestimated inbreeding. Correlations between inbreeding coefficients and ∆F were calculated. F ROH had the highest correlation with F PED (0.89); F YAN had correlations >0.95 with all the other molecular inbreeding coefficients. Ne PEDi was more reliable than Ne PEDt and presented similar behaviour to Ne L&H0 and Ne NEJ0. Stable trends in Ne were not observed until the 10th generation. In the 10th generation Ne PEDi was 42.20, Ne L&H0 was 45.04 and Ne NEJ0 was 45.05 and in the last generation these Ne were 35.65, 35.94 and 35.93, respectively F ROH presented the highest correlation with F PED, which addresses the identity by descent probability (IBD). The evolution of Ne L&H0 and Ne NEJ0 was the most similar to that of Ne PEDi. Data from several generations was necessary to reach a stable trend for Ne, both with pedigree and molecular data. This population was useful to test different approaches to computing inbreeding coefficients and Ne using molecular and pedigree data.

Associations of diabetes, hypertension and obesity with COVID-19 mortality: a systematic review and meta-analysis.

INTRODUCTION: Despite a growing body of scholarly research on the risks of severe COVID-19 associated with diabetes, hypertension and obesity, there is a need for estimating pooled risk estimates with adjustment for confounding effects. We conducted a systematic review and meta-analysis to estimate the pooled adjusted risk ratios of diabetes, hypertension and obesity on COVID-19 mortality. METHODS: We searched 16 literature databases for original studies published between 1 December 2019 and 31 December 2020. We used the adapted Newcastle-Ottawa Scale to assess the risk of bias. Pooled risk ratios were estimated based on the adjusted effect sizes. We applied random-effects meta-analysis to account for the uncertainty in residual heterogeneity. We used contour-funnel plots and Egger's test to assess possible publication bias. RESULTS: We reviewed 34 830 records identified in literature search, of which 145 original studies were included in the meta-analysis. Pooled adjusted risk ratios were 1.43 (95% CI 1.32 to 1.54), 1.19 (95% CI 1.09 to 1.30) and 1.39 (95% CI 1.27 to 1.52) for diabetes, hypertension and obesity (body mass index ≥30 kg/m2) on COVID-19 mortality, respectively. The pooled adjusted risk ratios appeared to be stronger in studies conducted before April 2020, Western Pacific Region, low- and middle-income countries, and countries with low Global Health Security Index scores, when compared with their counterparts. CONCLUSIONS: Diabetes, hypertension and obesity were associated with an increased risk of COVID-19 mortality independent of other known risk factors, particularly in low-resource settings. Addressing these chronic diseases could be important for global pandemic preparedness and mortality prevention. PROSPERO REGISTRATION NUMBER: CRD42021204371.

Genome-Wide Association Study of Fiber Diameter in Alpacas.

The aim of this study was the identification of candidate genomic regions associated with fiber diameter in alpacas. DNA samples were collected from 1011 female Huacaya alpacas from two geographical Andean regions in Peru (Pasco and Puno), and three alpaca farms within each region. The samples were genotyped using an Affymetrix Custom Alpaca genotyping array containing 76,508 SNPs. After the quality controls, 960 samples and 51,742 SNPs were retained. Three association study methodologies were performed. The GWAS based on a linear model allowed us to identify 11 and 35 SNPs (-log10(p-values) > 4) using information on all alpacas and alpacas with extreme values of fiber diameter, respectively. The haplotype and marker analysis method allowed us to identify nine haplotypes with standardized haplotype heritability higher than six standard deviations. The selection signatures based on cross-population extended haplotype homozygosity (XP-EHH) allowed us to identify 180 SNPs with XP-EHH values greater than |3|. Four candidate regions with adjacent SNPs identified via two association methods of analysis are located on VPA6, VPA9, VPA29 and one chromosomally unassigned scaffold. This study represents the first analysis of alpaca whole genome association with fiber diameter, using a recently assembled alpaca SNP microarray.

Differential sensitivity of climate conditions on birth weight genetic values in mice divergently selected for birth weight residual variance.

After 32 generations of a divergent selection experiment for residual variance of birth weight in mice, two divergent lines were thus obtained: the heterogeneous line (H-line) and the homogeneous line (L-line). Throughout the generations, differences were observed between the two lines in traits such as litter size, survival at weaning, and birth weight variability caused by unidentified environmental conditions. The L-line exhibited advantages in terms of higher survival rates, larger litter sizes, and less sensitivity to changes in food intake. The study is an examination of the effects of climate as an environmental factor on the performance of these animals. Climate factors including maximum, minimum, and mean temperature (T), humidity (H), and TH index; at three stages (the fecundation, a week before the parturition and the parturition), were linked to a birth weight dataset consisting of 22,614 records distributed as follows: 8,853 corresponding to the H-line, 12,649 to the L-line, and 1,112 to the initial population. Out of the 27 analyzed climatic variables, the maximum temperature 1 wk before parturition (MXTW) was identified as the most influential when comparing heteroscedastic models with the deviance information criterion. The order of Legendre polynomial to apply in the following random regression model was tested by a cross-validation using homoscedastic models. Finally, MXTW was compared on how it affected the two divergent lines by analyzing predicted breeding values (PBV) obtained from a random regression heteroscedastic model. The mean PBV of the H-line in the first generation showed a range of 0.070 g with a negative slope, which was 35 times higher than the range obtained for the L-line, which varied within 0.002 g. In the last generation of selection, the H-line exhibited greater instability of PBV across temperatures, with a difference of 0.101 g between the maximum and minimum mean PBV, compared to 0.017 g for the L-line. The standard deviations of the slopes in the H-line were more dispersed than in the L-line. Unlike the H-line, the L-line had slopes that were not significantly different from 0 throughout the generations of selection, indicating greater stability in response to MXTW variations. The H-line exhibited a higher sensitivity to changes in MXTW, particularly in birth weight, with the L-line being more stable. The selection for uniformity of birth weight could lead to less sensitive animals under environmental changes.

Two mice lines obtained by divergent selection for birth weight residual variance were used to determine whether environmental factors could differently affect the homogeneous and heterogeneous lines. The maximum temperature 1 wk before parturition (MXTW) had the higher impact on the birth weight of the animals. A random regression model showed the individual trajectory of birth weight throughout the changes in MXTW. It was evident that the homogeneous line is less susceptible to changes in climate. This result, therefore, supports the hypothesis that the selection for homogeneity in production animals is more advantageous. More robust animals are obtained that can better cope with changes in climate without compromising their productive traits.

Approaching autozygosity in a small pedigree of Gochu Asturcelta pigs.

BACKGROUND: In spite of the availability of single nucleotide polymorphism (SNP) array data, differentiation between observed homozygosity and that caused by mating between relatives (autozygosity) introduces major difficulties. Homozygosity estimators show large variation due to different causes, namely, Mendelian sampling, population structure, and differences among chromosomes. Therefore, the ascertainment of how inbreeding is reflected in the genome is still an issue. The aim of this research was to study the usefulness of genomic information for the assessment of genetic diversity in the highly endangered Gochu Asturcelta pig breed. Pedigree depth varied from 0 (founders) to 4 equivalent discrete generations (t). Four homozygosity parameters (runs of homozygosity, FROH; heterozygosity-rich regions, FHRR; Li and Horvitz's, FLH; and Yang and colleague's FYAN) were computed for each individual, adjusted for the variability in the base population (BP; six individuals) and further jackknifed over autosomes. Individual increases in homozygosity (depending on t) and increases in pairwise homozygosity (i.e., increase in the parents' mean) were computed for each individual in the pedigree, and effective population size (Ne) was computed for five subpopulations (cohorts). Genealogical parameters (individual inbreeding, individual increase in inbreeding, and Ne) were used for comparisons. RESULTS: The mean F was 0.120 ± 0.074 and the mean BP-adjusted homozygosity ranged from 0.099 ± 0.081 (FLH) to 0.152 ± 0.075 (FYAN). After jackknifing, the mean values were slightly lower. The increase in pairwise homozygosity tended to be twofold higher than the corresponding individual increase in homozygosity values. When compared with genealogical estimates, estimates of Ne obtained using FYAN tended to have low root-mean-squared errors. However, Ne estimates based on increases in pairwise homozygosity using both FROH and FHRR estimates of genomic inbreeding had lower root-mean-squared errors. CONCLUSIONS: Parameters characterizing homozygosity may not accurately depict losses of variability in small populations in which breeding policy prohibits matings between close relatives. After BP adjustment, the performance of FROH and FHRR was highly consistent. Assuming that an increase in homozygosity depends only on pedigree depth can lead to underestimating it in populations with shallow pedigrees. An increase in pairwise homozygosity computed from either FROH or FHRR is a promising approach for characterizing autozygosity.

Who is most at risk of dying if infected with SARS-CoV-2? A mortality risk factor analysis using machine learning of patients with COVID-19 over time: a large population-based cohort study in Mexico.

OBJECTIVE: COVID-19 would kill fewer people if health programmes can predict who is at higher risk of mortality because resources can be targeted to protect those people from infection. We predict mortality in a very large population in Mexico with machine learning using demographic variables and pre-existing conditions. DESIGN: Cohort study. SETTING: March 2020 to November 2021 in Mexico, nationally represented. PARTICIPANTS: 1.4 million laboratory-confirmed patients with COVID-19 in Mexico at or over 20 years of age. PRIMARY AND SECONDARY OUTCOME MEASURES: Analysis is performed on data from March 2020 to November 2021 and over three phases: (1) from March to October in 2020, (2) from November 2020 to March 2021 and (3) from April to November 2021. We predict mortality using an ensemble machine learning method, super learner, and independently estimate the adjusted mortality relative risk of each pre-existing condition using targeted maximum likelihood estimation. RESULTS: Super learner fit has a high predictive performance (C-statistic: 0.907), where age is the most predictive factor for mortality. After adjusting for demographic factors, renal disease, hypertension, diabetes and obesity are the most impactful pre-existing conditions. Phase analysis shows that the adjusted mortality risk decreased over time while relative risk increased for each pre-existing condition. CONCLUSIONS: While age is the most important predictor of mortality, younger individuals with hypertension, diabetes and obesity are at comparable mortality risk as individuals who are 20 years older without any of the three conditions. Our model can be continuously updated to identify individuals who should most be protected against infection as the pandemic evolves.

Carcinoma de células grandes de pulmón con inmunofenotipo nulo: reporte de caso y revisión breve de la literatura / Large cell carcinoma of the lung with null immunophenotype: Case report & brief review

El carcinoma de células grandes de pulmón con inmunofenotipo nulo (LCC-NI) constituye una entidad diagnóstica que hoy en día es especialmente infrecuente ya que no cuenta con ningún tipo de diferenciación celular o alteraciones moleculares propias. Representa un reto diagnóstico excepcional, el cual solo es posible realizar por exclusión contando con la resección quirúrgica, estudios de inmunohistoquímica y moleculares adecuados. Presentamos el caso de un varón de 69años de edad, con antecedente de alto índice tabáquico, que debuta con dolor pleurítico y tumor en el lóbulo pulmonar superior derecho, el cual se retira mediante lobectomía. A la evaluación patológica muestra una morfología de células grandes sin ningún inmunofenotipo, alteraciones moleculares o genómicas mediante estudios de secuenciación de siguiente generación (NGS), diagnosticándose como un LCC-NI.(AU)

Large cell carcinoma of the lung with null-immunophenotype (LCC-NI) is a diagnostic entity that is especially uncommon now as it does not have any type of cell differentiation or its own molecular alterations. It presents an exceptional diagnostic challenge; indeed, the diagnosis is only possible with complete surgical excision and adequate immunohistochemical and molecular studies. We report the case of a 69-year-old male, with a history of long-term smoking who presented with pleuritic pain. A tumor in the upper lobe of the right lung was detected and removed by lobectomy. Histopathology revealed a neoplasm with large cell morphology without any specific immunophenotype, molecular or genomic rearrangements through next-generation sequencing (NGS) studies, which was diagnosed as LCC-NI.(AU)

[Trend in inequities in homicides in Mexico, 2000-2021: longitudinal ecological studyDesigualdades nas taxas de homicídios do México no período de 2000 a 2021: estudo ecológico longitudinal]. / Tendencia de las inequidades en homicidios en México para el periodo de 2000 a 2021: análisis ecológico longitudinal.

Objective: To document trends in inequity in homicide rates in Mexico for the period 2000-2021, at the state and national levels. Methods: An observational, longitudinal ecological study was conducted in which standardized homicide mortality rates were estimated, by municipality and sex. Municipalities were classified in five groups, according to the Social Lag Index. The absolute inequality gap was obtained, as well as differences between groups with very high and very low social lag, for each year of the study period. Results: In the 32 states, an increase was observed in the rate of death by homicide, with higher rates among men but a greater relative increase among women (+127.86% vs. +110.03%). The absolute gap between municipalities with very high and very low social lag narrowed in the period, due to higher homicide rates in municipalities with low social lag and a modest reduction in municipalities with very high social lag. Conclusions: In Mexico, between 2000 and 2021, the absolute gap in deaths by homicide between municipalities with very high and very low social lag declined due to higher homicide rates in municipalities with lower social lag. It is necessary to strengthen policies and actions aimed at addressing the social determinants of interpersonal violence.

Objetivo: Documentar as tendências de desigualdade nas taxas de homicídio do México no período de 2000 a 2021 em nível estadual e nacional. Métodos: Foi realizado um estudo ecológico observacional e longitudinal no qual se estimaram taxas padronizadas de mortalidade por homicídio por município e sexo. Os municípios foram classificados em cinco grupos conforme o índice de defasagem social. Calculou-se a diferença absoluta de desigualdade como a diferença entre os grupos com defasagem social muito alta e muito baixa, para cada ano do período estudado. Resultados: Em todos os 32 municípios, observou-se aumento na taxa de mortalidade por homicídio; as taxas foram mais altas entre homens, embora o aumento relativo tenha sido maior entre as mulheres (variação percentual: 127,86% comparado a 110,03%). A diferença absoluta entre municípios com defasagem social muito alta e muito baixa diminuiu no período estudado devido ao aumento na taxa de mortalidade por homicídio nos municípios com defasagem social baixa e uma certa redução nos que tinham defasagem social muito alta. Conclusões: No México, entre 2000 e 2021, a diferença absoluta nas mortes por homicídio entre municípios com defasagem social muito alta e muito baixa diminuiu devido ao aumento na taxa de homicídios nos municípios com uma menor defasagem social. É necessário reforçar políticas e iniciativas que abordam os determinantes sociais da violência interpessoal.

Tendencia de las inequidades en homicidios en México para el periodo de 2000 a 2021: análisis ecológico longitudinal

[RESUMEN]. Objetivo. Documentar las tendencias de la inequidad en las tasas de homicidio en México para el periodo 2000-2021, a nivel estatal y nacional. Métodos. Se realizó un estudio ecológico observacional y longitudinal en el cual se estimaron las tasas estandarizadas de mortalidad de homicidios por municipio y sexo. Clasificando a los municipios de acuerdo con el Índice de Rezago Social en cinco grupos. Se obtuvo la brecha absoluta de desigualdad, así como la diferencia entre los grupos de muy alto y muy bajo rezago social para cada año del periodo estudiado. Resultados. En las 32 entidades se observa un incremento en la tasa de mortalidad por homicidios, con tasas mayores entre hombres, pero un incremento relativo mayor entre mujeres (porcentaje de cambio: 127,86 vs 110,03). La brecha absoluta entre municipios de muy alto y muy bajo rezago social se ha cerrado en el periodo por el incremento en la tasa de mortalidad por homicidios en los municipios de bajo rezago social y por una cierta reducción en los de muy alto rezago social. Conclusiones. En México, entre 2000 y 2021 se redujo la brecha absoluta en las defunciones por homicidios entre municipios de muy alto y muy bajo rezago social debido al incremento en la tasa de homicidios en los municipios de menor rezago social. Es necesario reforzar políticas y acciones encaminadas a atender los determinantes sociales de la violencia interpersonal.

[ABSTRACT]. Objective. To document trends in inequity in homicide rates in Mexico for the period 2000–2021, at the state and national levels. Methods. An observational, longitudinal ecological study was conducted in which standardized homicide mortality rates were estimated, by municipality and sex. Municipalities were classified in five groups, accor- ding to the Social Lag Index. The absolute inequality gap was obtained, as well as differences between groups with very high and very low social lag, for each year of the study period. Results. In the 32 states, an increase was observed in the rate of death by homicide, with higher rates among men but a greater relative increase among women (+127.86% vs. +110.03%). The absolute gap between municipalities with very high and very low social lag narrowed in the period, due to higher homicide rates in municipalities with low social lag and a modest reduction in municipalities with very high social lag. Conclusions. In Mexico, between 2000 and 2021, the absolute gap in deaths by homicide between municipa- lities with very high and very low social lag declined due to higher homicide rates in municipalities with lower social lag. It is necessary to strengthen policies and actions aimed at addressing the social determinants of interpersonal violence.

[RESUMO]. Objetivo. Documentar as tendências de desigualdade nas taxas de homicídio do México no período de 2000 a 2021 em nível estadual e nacional. Métodos. Foi realizado um estudo ecológico observacional e longitudinal no qual se estimaram taxas padroni- zadas de mortalidade por homicídio por município e sexo. Os municípios foram classificados em cinco grupos conforme o índice de defasagem social. Calculou-se a diferença absoluta de desigualdade como a diferença entre os grupos com defasagem social muito alta e muito baixa, para cada ano do período estudado. Resultados. Em todos os 32 municípios, observou-se aumento na taxa de mortalidade por homicídio; as taxas foram mais altas entre homens, embora o aumento relativo tenha sido maior entre as mulheres (variação per- centual: 127,86% comparado a 110,03%). A diferença absoluta entre municípios com defasagem social muito alta e muito baixa diminuiu no período estudado devido ao aumento na taxa de mortalidade por homicídio nos municípios com defasagem social baixa e uma certa redução nos que tinham defasagem social muito alta. Conclusões. No México, entre 2000 e 2021, a diferença absoluta nas mortes por homicídio entre municí- pios com defasagem social muito alta e muito baixa diminuiu devido ao aumento na taxa de homicídios nos municípios com uma menor defasagem social. É necessário reforçar políticas e iniciativas que abordam os determinantes sociais da violência interpessoal.

Evaluating the design of the Integrated Care for Older People: a theory of change approach.

Introduction: Given the progressive aging of the population, there is an urgent need at the health system level to implement effective models to care for older people (OP). Healthy aging is imperative to reach the Sustainable Development Goals. The World Health Organization (WHO) developed the Integrated Care for Older People (ICOPE) strategy to address this challenge. Implementing ICOPE requires its adaption to a specific context. We propose a pathway for such adaptation through an evaluation of the design of ICOPE; thus, we aim to describe the Theory of Change (ToC) of ICOPE and evaluate it for its implementation in Mexico City. Methods: Based on the WHO and published literature documentation, we drafted an initial ToC for ICOPE. Then, we validated the ToC with experts in ICOPE, after which we evaluated and refined it by discussing the causal pathway, intervention required to activate it, rationale, and assumptions in consecutive workshops with 91 stakeholders and healthcare workers, using the nominal group technique to reach a consensus. Results: The resulting ToC has the potential to contribute to healthy aging by three expected impacts: (1) prevention, reversal, or delaying of the decline of intrinsic capacity (IC) in OP; (2) improvement of the quality of life of OP; and (3) increase of disability-free life expectancy. The ICOPE causal pathway had ten preconditions, including the availability of resources, identifying at-risk individuals, available treatments, and evaluating results. Discussion: We adapted ICOPE to a specific implementation context by evaluating its ToC in a participatory process that allows us to identify challenges and address them, at least in terms of the guidelines to operate the strategy. As ICOPE is an approach for a primary healthcare system, its adoption in a community healthcare program is promising and feasible. Evaluation as a tool could contribute to the design of effective interventions. The evaluation of the design of ICOPE for its implementation contributes to the strength of its potential to improve care for OP. This design for implementing ICOPE has the potential to be applied to similar contexts, for example, in other lower-middle-income countries.

Copy Number Variation Regions Differing in Segregation Patterns Span Different Sets of Genes.

Copy number variations regions (CNVRs) can be classified either as segregating, when found in both parents, and offspring, or non-segregating. A total of 65 segregating and 31 non-segregating CNVRs identified in at least 10 individuals within a dense pedigree of the Gochu Asturcelta pig breed was subjected to enrichment and functional annotation analyses to ascertain their functional independence and importance. Enrichment analyses allowed us to annotate 1018 and 351 candidate genes within the bounds of the segregating and non-segregating CNVRs, respectively. The information retrieved suggested that the candidate genes spanned by segregating and non-segregating CNVRs were functionally independent. Functional annotation analyses allowed us to identify nine different significantly enriched functional annotation clusters (ACs) in segregating CNVR candidate genes mainly involved in immunity and regulation of the cell cycle. Up to five significantly enriched ACs, mainly involved in reproduction and meat quality, were identified in non-segregating CNVRs. The current analysis fits with previous reports suggesting that segregating CNVRs would explain performance at the population level, whereas non-segregating CNVRs could explain between-individuals differences in performance.

[Large cell carcinoma of the lung with null immunophenotype: Case report & brief review]. / Carcinoma de células grandes de pulmón con inmunofenotipo nulo: reporte de caso y revisión breve de la literatura.

Large cell carcinoma of the lung with null-immunophenotype (LCC-NI) is a diagnostic entity that is especially uncommon now as it does not have any type of cell differentiation or its own molecular alterations. It presents an exceptional diagnostic challenge; indeed, the diagnosis is only possible with complete surgical excision and adequate immunohistochemical and molecular studies. We report the case of a 69-year-old male, with a history of long-term smoking who presented with pleuritic pain. A tumor in the upper lobe of the right lung was detected and removed by lobectomy. Histopathology revealed a neoplasm with large cell morphology without any specific immunophenotype, molecular or genomic rearrangements through next-generation sequencing (NGS) studies, which was diagnosed as LCC-NI.

Genetic parameters for fleece uniformity in alpacas.

Fiber diameter is the main selection objective and criterion in alpaca breeding programs, but it can vary across anatomic regions of the animal. As fiber diameter is usually registered from a unique sample from the mid side of the body, fiber diameter variability within fleece is never addressed and phenotypic and genetic differences may exist for fleece uniformity in alpaca populations. The objective of this work was to estimate the genetic parameters of fleece uniformity in an alpaca population. Fiber diameters measured in three different locations were used as repeated records of the same animal and studied for fitting a model that considers heterogeneous the residual variance of the model. Also, the logarithm of the standard deviation of the three measures was used as a measure of the fleece variability. Estimate of the additive genetic variance of the environmental variability was 0.43±0.14, enough high to suggest the existence of wide room to select for fleece uniformity. Genetic correlation of the trait with its environmental variability was 0.76±0.13 showing that fleece uniformity will be indirectly selected when aiming to reduce the fiber diameter. In the light of these parameters, and due to the cost of registering and the cost of opportunity, it looks no worthy to include uniformity as a selection criterion in alpaca breeding programs.

The quality of alpaca fiber is mainly assessed by a low fiber diameter. However, the fiber diameter can greatly vary along the different body locations of the animal, the industry demands not only the fineness of the fiber but also the fleece uniformity. This work studied the genetic parameters related to fleece uniformity by analyzing the diameter of three samples from different body locations (mid side, shoulder, and thigh) under two different models of analysis. The results showed variability between sampling locations and the existence of important genetic variability susceptible to being used in alpaca selection. Nevertheless, selection based on a single measurement could be used as the high correlations between locations and between the trait and its variability, saving the cost of sample analyses, being the fleece uniformity indirectly selected.