Representation of Low- and Middle-Income Countries in CKD Drug Trials: A Systematic Review.

RATIONALE & OBJECTIVE: Almost 80% of individuals with chronic kidney disease (CKD) reside in low- and middle-income countries (LMICs) and are potentially underrepresented in randomized controlled clinical trials (RCTs). We assessed the global distribution of RCTs comparing pharmacological treatments for CKD over the past 2 decades, as well as the magnitude and evolution of participation by LMICs. STUDY DESIGN: Systematic review. SETTING & STUDY POPULATIONS: RCTs evaluating pharmacological interventions in adults with CKD. SELECTION CRITERIA FOR STUDIES: RCTs published between 2003-2023 and indexed in MEDLINE. DATA EXTRACTION: Each trial was reviewed and extracted independently by 2 investigators with disagreements settled by consensus or a third reviewer. ANALYTICAL APPROACH: RCT participation of World Bank-defined income groups and geographic regions were described, and the representation indices (RI) according to RCT participants and estimated CKD prevalences were calculated. RCTs were also categorized as global, regional, or national in scope. RESULTS: Among 7,760 identified studies, we included 1,366 RCTs conducted in 84 countries with 301,158 participants. National, regional, and global RCTs represented 85.4%, 3.5%, and 11.1% of studies, respectively. LMICs were included in 34.7% of RCTs. No RCTs included participants from low-income countries, and lower-middle-income countries participated in 13.2%. Of participants from RCTs with available information, 25.4% (n=64,843 of 255,237) were from LMICs. According to the RI, 6 LMICs were overrepresented (>1.25), 7 were adequately represented (0.75-1.25), and 26 were underrepresented (<0.75). Most global CKD RCTs (80.2%) included LMICs; however, LMIC participants constituted only 32.9% of the global trial population. We observed a positive trend in LMIC inclusion over time, rising from 22.9% (n=71of 310) in 2003-2007 to 45.5% (n=140of 308) in 2018-2023. LIMITATIONS: The use of an income-group dichotomy, exclusion of nonrandomized studies of intervention, and studies identified in 1 database. CONCLUSIONS: Despite an increase in participation over the past 2 decades, individuals with CKD from LMICs remain significantly underrepresented in RCTs. These findings suggest that increased efforts are warranted to increase LMIC representation in pharmacological CKD RCTs. PLAIN-LANGUAGE SUMMARY: Chronic kidney disease (CKD) substantially affects people from low- and middle-income countries (LMICs). However, the participation of these countries in randomized controlled trials (RCTs) remains uncertain. To assess the global distribution and representation of these countries in kidney disease research, we reviewed 1,366 CKD drug RCTs published from 2003-2023, conducted in 84 countries involving more than 300,000 participants. LMICs were included in approximately a third of these studies, with their participants making up approximately one-quarter of the total; lower-middle-income countries were poorly represented, and low-income countries were absent. LMICs constituted a third of participants in multinational RCTs. Most LMICs were underrepresented relative to the prevalence of CKD. We observed an increasing inclusion of LMICs, particularly in the last decade. Nonetheless, individuals with CKD from LMICs remain underrepresented in drug RCTs, suggesting that increased efforts are warranted to include representation of these populations in these studies.

Measuring contraceptive method mix, prevalence, and demand satisfied by age and marital status in 204 countries and territories, 1970-2019: a systematic analysis for the Global Burden of Disease Study 2019.

BACKGROUND: Meeting the contraceptive needs of women of reproductive age is beneficial for the health of women and children, and the economic and social empowerment of women. Higher rates of contraceptive coverage have been linked to the availability of a more diverse range of contraceptive methods. We present estimates of the contraceptive prevalence rate (CPR), modern contraceptive prevalence rate (mCPR), demand satisfied, and the method of contraception used for both partnered and unpartnered women for 5-year age groups in 204 countries and territories between 1970 and 2019. METHODS: We used 1162 population-based surveys capturing contraceptive use among women between 1970 and 2019, in which women of reproductive age (15-49 years) self-reported their, or their partner's, current use of contraception for family planning purposes. Spatiotemporal Gaussian process regression was used to generate estimates of the CPR, mCPR, demand satisfied, and method mix by age and marital status. We assessed how age-specific mCPR and demand satisfied changed with the Socio-demographic Index (SDI), a measure of social and economic development, using the meta-regression Bayesian, regularised, trimmed method from the Global Burden of Diseases, Injuries, and Risk Factors Study. FINDINGS: In 2019, 162·9 million (95% uncertainty interval [UI] 155·6-170·2) women had unmet need for contraception, of whom 29·3% (27·9-30·6) resided in sub-Saharan Africa and 27·2% (24·4-30·3) resided in south Asia. Women aged 15-19 years (64·8% [62·9-66·7]) and 20-24 years (71·9% [68·9-74·2]) had the lowest rates of demand satisfied, with 43·2 million (95% UI 39·3-48·0) women aged 15-24 years with unmet need in 2019. The mCPR and demand satisfied among women aged 15-19 years were substantially lower than among women aged 20-49 years at SDI values below 60 (on a 0-100 scale), but began to equalise as SDI increased above 60. Between 1970 and 2019, the global mCPR increased by 20·1 percentage points (95% UI 18·7-21·6). During this time, traditional methods declined as a proportion of all contraceptive methods, whereas the use of implants, injections, female sterilisation, and condoms increased. Method mix differs substantially depending on age and geography, with the share of female sterilisation increasing with age and comprising more than 50% of methods in use in south Asia. In 28 countries, one method was used by more than 50% of users in 2019. INTERPRETATION: The dominance of one contraceptive method in some locations raises the question of whether family planning policies should aim to expand method mix or invest in making existing methods more accessible. Lower rates of demand satisfied among women aged 15-24 years are also concerning because unintended pregnancies before age 25 years can forestall or eliminate education and employment opportunities that lead to social and economic empowerment. Policy makers should strive to tailor family planning programmes to the preferences of the groups with the most need, while maintaining the programmes used by existing users. FUNDING: Bill & Melinda Gates Foundation.

Quantifying the effects of the COVID-19 pandemic on gender equality on health, social, and economic indicators: a comprehensive review of data from March, 2020, to September, 2021.

BACKGROUND: Gender is emerging as a significant factor in the social, economic, and health effects of COVID-19. However, most existing studies have focused on its direct impact on health. Here, we aimed to explore the indirect effects of COVID-19 on gender disparities globally. METHODS: We reviewed publicly available datasets with information on indicators related to vaccine hesitancy and uptake, health care services, economic and work-related concerns, education, and safety at home and in the community. We used mixed effects regression, Gaussian process regression, and bootstrapping to synthesise all data sources. We accounted for uncertainty in the underlying data and modelling process. We then used mixed effects logistic regression to explore gender gaps globally and by region. FINDINGS: Between March, 2020, and September, 2021, women were more likely to report employment loss (26·0% [95% uncertainty interval 23·8-28·8, by September, 2021) than men (20·4% [18·2-22·9], by September, 2021), as well as forgoing work to care for others (ratio of women to men: 1·8 by March, 2020, and 2·4 by September, 2021). Women and girls were 1·21 times (1·20-1·21) more likely than men and boys to report dropping out of school for reasons other than school closures. Women were also 1·23 (1·22-1·23) times more likely than men to report that gender-based violence had increased during the pandemic. By September 2021, women and men did not differ significantly in vaccine hesitancy or uptake. INTERPRETATION: The most significant gender gaps identified in our study show intensified levels of pre-existing widespread inequalities between women and men during the COVID-19 pandemic. Political and social leaders should prioritise policies that enable and encourage women to participate in the labour force and continue their education, thereby equipping and enabling them with greater ability to overcome the barriers they face. FUNDING: The Bill & Melinda Gates Foundation.

A novel function of the tomato CALCINEURIN-B LIKE 10 gene as a root-located negative regulator of salt stress.

Climate change exacerbates abiotic stresses like salinization, negatively impacting crop yield, so development of strategies, like using salt-tolerant rootstocks, is crucial. The CALCINEURIN B-LIKE 10 (SlCBL10) gene has been previously identified as a positive regulator of salt tolerance in the tomato shoot. Here, we report a different function of SlCBL10 in tomato shoot and root, as disruption of SlCBL10 only induced salt sensitivity when it was used in the scion but not in the rootstock. The use of SlCBL10 silencing rootstocks (Slcbl10 mutant and RNAi line) improved salt tolerance on the basis of fruit yield. These changes were associated with improved Na+ and K+ homoeostasis, as SlCBL10 silencing reduced the Na+ content and increased the K+ content under salinity, not only in the rootstock but also in the shoot. Improvement of Na+ homoeostasis in Slcbl10 rootstock seems to be mainly due to induction of SlSOS1 expression, while the higher K+ accumulation in roots seems to be mainly determined by expression of LKT1 transporter and SlSKOR channel. These findings demonstrate that SlCBL10 is a negative regulator of salt tolerance in the root, so the use of downregulated SlCBL10 rootstocks may provide a suitable strategy to increase tomato fruit production under salinity.

Comparison of treatment and outcomes in blunt thoracic aortic injury based on different vascular surgery guidelines.

OBJECTIVE: Society for Vascular Surgery (SVS) recommendations for managing intimal (grade 1) blunt thoracic aortic injuries (BTAIs) include observation and medical management. University of Washington (UW) revised criteria suggest that intimal injuries with ≥1 cm flap should be upgraded to a moderate injury and treatment be considered. We sought to evaluate and compare SVS and UW criteria for BTAI and determine how discordance in grading affected treatment and outcome. METHODS: We reviewed all patients admitted with BTAI from January 1, 2011, to March 31, 2022. Data included injury grading, demographics, and concomitant traumatic injuries. Images were reviewed to categorize the injury with both grading systems. Treatment and outcomes were analyzed for concordant and discordant groups. RESULTS: Our cohort comprised 208 patients after excluding four who died upon arrival. The mean age was 45 ± 19 years, 69% were men, and the median injury severity score was 34 (interquartile range, 26-45). Strong agreement was observed between the grading systems (kappa = 0.88). All patients with concordant grade 1 injuries (n = 54) were observed. SVS grade 1/2 BTAIs were reclassified in 12 of 71 patients (16.9%). Two (28.6%) SVS grade 2 injuries were graded lower with the UW criteria; neither patient required immediate or delayed repair. Ten (15.6%) SVS grade 1 BTAIs were graded higher with UW criteria. Of these, six underwent repair (one for preoperative embolization), and four were observed without sequalae. Overall mortality was 7.7% with no difference for concordant or discordant grades (7.7% vs 8.3%; P = .99). No aneurysm-related mortalities were observed. Follow-up imaging was available for 94 survivors (49.0%) at a median of 193 days (interquartile range, 42-522 days). Two patients unrepaired at the index hospitalization (SVS grade 3/UW grade 2) underwent successful delayed repair. No patient observed for a minimal injury had BTAI progression or required treatment. CONCLUSIONS: The UW grading system may upgrade or downgrade SVS grade 1 or 2 BTAI for as many as one in six injuries. Upgraded injuries should prompt consideration of repair if there is evidence of flap progression or thromboembolic complications. Downgraded injuries suggest that treatment may not be necessary; clinical expertise is key to determine optimal management in these patients.

Tomato POLLEN DEFICIENT 2 encodes a G-type lectin receptor kinase required for viable pollen grain formation.

Pollen development is a crucial biological process indispensable for seed set in flowering plants and for successful crop breeding. However, little is known about the molecular mechanisms regulating pollen development in crop species. This study reports a novel male-sterile tomato mutant, pollen deficient 2 (pod2), characterized by the production of non-viable pollen grains and resulting in the development of small parthenocarpic fruits. A combined strategy of mapping-by-sequencing and RNA interference-mediated gene silencing was used to prove that the pod2 phenotype is caused by the loss of Solanum lycopersicum G-type lectin receptor kinase II.9 (SlG-LecRK-II.9) activity. In situ hybridization of floral buds showed that POD2/SlG-LecRK-II.9 is specifically expressed in tapetal cells and microspores at the late tetrad stage. Accordingly, abnormalities in meiosis and tapetum programmed cell death in pod2 occurred during microsporogenesis, resulting in the formation of four dysfunctional microspores leading to an aberrant microgametogenesis process. RNA-seq analyses supported the existence of alterations at the final stage of microsporogenesis, since we found tomato deregulated genes whose counterparts in Arabidopsis are essential for the normal progression of male meiosis and cytokinesis. Collectively, our results revealed the essential role of POD2/SlG-LecRK-II.9 in regulating tomato pollen development.

Evaluation of effective coverage for type 2 diabetes in Mexican primary care health information systems: a retrospective registry analysis.

BACKGROUND: As the leading cause of disability and the fourth leading cause of premature death in Mexico, type 2 diabetes (T2D) represents a serious public health concern. The incidence of diabetes has increased dramatically in recent years, and data from the Mexican National Health and Nutrition Survey (ENSANUT) indicate that many people remain undiagnosed. Persistent socioeconomic health care barriers exacerbate this situation, as T2D morbidity and mortality are worsened in vulnerable populations, such as those without social security. We evaluated the performance of public primary health centers (PHCs) in T2D medical attention through the measure of effective coverage (EC, a combined measure of health care need, use, and quality) at national, state, health jurisdiction, and municipality levels. METHODS: This retrospective analysis used blinded data recorded during 2017 in the Non-communicable Diseases National Information System (SIC) and T2D prevalence reported in 2018 ENSANUT to evaluate the EC achieved. We included individuals ≥ 20 years old without social security who did not declare the use of private health care services. Each EC component (need, use, and quality) was estimated based on the Shengelia adapted framework. The Kruskal-Wallis test was applied to evaluate the associations among EC quintiles and demographics. RESULTS: In 2017, 26.5 million individuals, aged ≥ 20 years, without social security, and without the use of private health care services, were under the care of 12,086 PHCs. The national prevalence of T2D was 10.3%, equivalent to 2.6 million people living with T2D in need of primary health care. Large contrasts were seen among EC components between and within Mexican states. We found that only 37.1% of the above individuals received health services at PHCs and of them, 25.8% improved their metabolic condition. The national EC was 9.3%, and the range (by health jurisdiction) was 0.2%-38.6%, representing a large geographic disparity in EC. We found an evident disconnect among need, utilization, and quality rates across the country. CONCLUSIONS: Expansion and improvement of EC are urgently needed to address the growing number of people living with T2D in Mexico, particularly in states with vulnerable populations.

ENO regulates tomato fruit size through the floral meristem development network.

A dramatic evolution of fruit size has accompanied the domestication and improvement of fruit-bearing crop species. In tomato (Solanum lycopersicum), naturally occurring cis-regulatory mutations in the genes of the CLAVATA-WUSCHEL signaling pathway have led to a significant increase in fruit size generating enlarged meristems that lead to flowers with extra organs and bigger fruits. In this work, by combining mapping-by-sequencing and CRISPR/Cas9 genome editing methods, we isolated EXCESSIVE NUMBER OF FLORAL ORGANS (ENO), an AP2/ERF transcription factor which regulates floral meristem activity. Thus, the ENO gene mutation gives rise to plants that yield larger multilocular fruits due to an increased size of the floral meristem. Genetic analyses indicate that eno exhibits synergistic effects with mutations at the LOCULE NUMBER (encoding SlWUS) and FASCIATED (encoding SlCLV3) loci, two central players in the evolution of fruit size in the domestication of cultivated tomatoes. Our findings reveal that an eno mutation causes a substantial expansion of SlWUS expression domains in a flower-specific manner. In vitro binding results show that ENO is able to interact with the GGC-box cis-regulatory element within the SlWUS promoter region, suggesting that ENO directly regulates SlWUS expression domains to maintain floral stem-cell homeostasis. Furthermore, the study of natural allelic variation of the ENO locus proved that a cis-regulatory mutation in the promoter of ENO had been targeted by positive selection during the domestication process, setting up the background for significant increases in fruit locule number and fruit size in modern tomatoes.

Caloric adequacy of parenteral nutrition and its influence on the clinical outcome of hospitalised patients.

Background: The adaptation of Parenteral Nutrition (PN) to actual energy requirements of hospitalised patients is essential, since excessive and insufficient nutritional intake have been associated with poor clinical outcomes. Aim: To evaluate the adaptation of prescribed PN to the estimated nutritional requirements using three predictive equations and the influence of excessive/insufficient nutrient intake on patient clinical outcomes (nutritional parameters, metabolic and infectious complications). Methods: Prospective, observational study in hospitalised patients nutritionally assessed. Data was collected the first and fifth/sixth day of PN with clinical (infection, length of hospital stay), biochemical (visceral proteins, cholesterol, glucose, triglycerides, lymphocytes, CRP) and anthropometric parameters (skin folds, height, weight). Theoretical requirements were calculated using Harris-Benedict (HB), Mifflin-St Jeor (MF) and 25 Kcal/Kg/day formulas. The HB formula was used to compare estimated and provided requirements. Results: A total of 94 patients (mean: 72 ± 13.7 years old) were included with initial mean weight and height of 69.2 Kg and 162.8 cm, respectively (mean BMI: 26.1 Kg/m2). No statistically significant differences were found between the actual (1620 Kcal/day) and estimated caloric mean calculated with HB (1643 Kcal/day) and MF (1628 Kcal/day). When comparing with the caloric estimation, 31.9% of patients were underfed, while 14.9% were overfed. Intergroup analysis demonstrated significant variations in albumin, prealbumin, glucose, cholesterol, triglycerides and MUAC, with a significant increase of hyperglycaemia (+37.86; p < 0.05) and hypertriglyceridemia (+63.10; p < 0.05), being higher in overfed patients. Conclusion: In our study, inadequate nutrient intake was associated with a higher degree of hyperglycaemia and hypertriglyceridemia, without positive impact on anthropometric parameters.

The burden of disease, injuries, and risk factors in Mexico: 1990-2021 update.

BACKGROUND: For thirty years, Mexico has studied the burden of disease in order to inform health decisions. OBJECTIVE: To analyze the burden of disease, injuries, and risk factors in Mexico between 1990 and 2021. MATERIAL AND METHODS: Estimates from the Global Burden of Disease 2021 study were used to analyze mortality, years of life lost due to premature mortality, years lived with disability and disability-adjusted life years, as well as the burden attributable to risk factors by sex, age and state of the country. RESULTS: Infant mortality decreased by 39.4% from 1990 to 2000 and by 49.0% from 2000 to 2013. At the national level, mortality decreased by 27.5% between 1990 and 2019, but increased in 2020 and 2021 across all states, especially in adults aged from 35 to 64 years due to the COVID-19 pandemic, which contributed with 24.3% of deaths in 2021. Significant differences in mortality were observed according to age and sex. The burden attributable to metabolic risk factors did increase, while alcohol and tobacco consumption decreased. Access to drinking water and sanitation showed improvements. CONCLUSIONS: Assessing the burden of disease is crucial in order to design effective strategies to address current health needs and future healthcare challenges.

ANTECEDENTES: Desde hace treinta años, México ha estudiado la carga de la enfermedad para sustentar decisiones en salud. OBJETIVO: Analizar la carga de enfermedad, lesiones y factores de riesgo en México entre 1990 y 2021. MATERIAL Y MÉTODOS: Se utilizaron las estimaciones del Global Burden of Disease 2021 para analizar la mortalidad, los años de vida perdidos por muerte prematura, los años vividos con discapacidad y los años de vida saludable perdidos, así como la carga atribuible a los factores de riesgos por sexo, edad y entidad federativa. RESULTADOS: La mortalidad infantil disminuyó 39.4 % de 1990 a 2000, y 49.0 % de 2000 a 2019. En el ámbito nacional, la mortalidad decreció 27.5 % entre 1990 y 2019, pero ascendió en 2020 y 2021 en todos los estados, especialmente en adultos de 35 a 64 años, debido a la pandemia de COVID-19, que contribuyó con 24.3 % de las defunciones en 2019. Se observaron diferencias significativas en la mortalidad según la edad y el sexo. La carga atribuible a los factores de riesgo metabólicos se incrementó, mientras que la atribuible el consumo de alcohol y tabaco disminuyó. El acceso al agua potable y saneamiento mejoró. CONCLUSIONES: Evaluar la carga de enfermedad es crucial para diseñar estrategias eficaces para abordar las necesidades actuales y los futuros desafíos en salud.

COVID-19 impact on life expectancy in Mexico. An analysis based on the Global Burden of Disease 2021 study.

BACKGROUND: Between 2020 and 2021, Mexico documented 2.21 million fatalities, out of which 25.3% were attributable to SARS-COV-2 infection. OBJECTIVES: To evaluate COVID-19 mortality during 2020-2021, determine its impact on national- and state-level life expectancy at birth, and in a group of selected countries of the region, as well as to analyze it according to sociodemographic profiles. MATERIAL AND METHODS: Data from the Global Burden of Disease 2021 study were used to report mortality, the impact on life expectancy and underlying causes between 2019 and 2021. These data were evaluated from the perspective of response to the pandemic and according to the sociodemographic structure based on a quadratic regression model. RESULTS: Between 2020 and 2021, 708,971 excess deaths were recorded, which decreased life expectancy at birth by 4.6 years; 76% of this reduction was attributed to COVID-19. The COVID-19 mortality rate was higher than expected according to the sociodemographic conditions of the states. CONCLUSIONS: In Mexico and the countries of the region, the pandemic was devastating and generated regressions in life expectancy at birth, which varied from two to nine years. It is not clear why the effect was so different between countries and within Mexico.

ANTECEDENTES: Entre 2020 y 2021, México experimentó 2.21 millones de defunciones, de las cuales 25.3 % estuvo relacionado con infección por SARS-COV-2. OBJETIVOS: Evaluar la mortalidad por COVID-19 en 2020-2021, determinar su influencia en la esperanza de vida al nacer a nivel nacional, estatal y en países seleccionados de la región, así como analizarla en función del perfil sociodemográfico. MATERIAL Y MÉTODOS: Se utilizaron datos del Global Burden of Disease 2021 para reportar la mortalidad, el impacto en la esperanza de vida y las causas subyacentes entre 2019 y 2021. Se usó una regresión cuadrática para evaluar la mortalidad en exceso como indicador de la respuesta de los estados a la pandemia, considerando su estructura sociodemográfica. RESULTADOS: Entre 2020 y 2021, se registraron 708 971 muertes en exceso, que disminuyeron la esperanza de vida al nacer en 4.6 años; 76 % de esta reducción se atribuyó a COVID-19. La tasa de mortalidad por COVID-19 fue superior a la esperada conforme a las condiciones sociodemográficas de las entidades. CONCLUSIONES: En México y los países de la región, la pandemia fue devastadora y generó regresiones en la esperanza de vida al nacer, que variaron de dos a nueve años. Se requiere más investigación para entender las variaciones en sus efectos.

Tomato CRABS CLAW paralogues interact with chromatin remodelling factors to mediate carpel development and floral determinacy.

CRABS CLAW (CRC) orthologues play a crucial role in floral meristem (FM) determinacy and gynoecium formation across angiosperms, the key developmental processes for ensuring successful plant reproduction and crop production. However, the mechanisms behind CRC mediated FM termination are far from fully understood. Here, we addressed the functional characterization of tomato (Solanum lycopersicum) paralogous CRC genes. Using mapping-by-sequencing, RNA interference and CRISPR/Cas9 techniques, expression analyses, protein-protein interaction assays and Arabidopsis complementation experiments, we examined their potential roles in FM determinacy and carpel formation. We revealed that the incomplete penetrance and variable expressivity of the indeterminate carpel-inside-carpel phenotype observed in fruit iterative growth (fig) mutant plants are due to the lack of function of the S. lycopersicum CRC homologue SlCRCa. Furthermore, a detailed functional analysis of tomato CRC paralogues, SlCRCa and SlCRCb, allowed us to propose that they operate as positive regulators of FM determinacy by acting in a compensatory and partially redundant manner to safeguard the proper formation of flowers and fruits. Our results uncover for the first time the physical interaction of putative CRC orthologues with members of the chromatin remodelling complex that epigenetically represses WUSCHEL expression through histone deacetylation to ensure the proper termination of floral stem cell activity.

Intergenerational Replication of Teenage Pregnancy and Educational Attainment in Mexico.

Mexico ranks among the OECD countries with the highest prevalence of teenage pregnancies, exhibiting a fertility rate of 70.6 births for every 1000 adolescents. Mexican adolescents with a history of pregnancy are twice as likely to lag behind in their studies as those who have not been pregnant. Research on adolescent maternity and its explanatory mechanisms is required as a basis for implementing policies and programs that effectively curb teenage pregnancy-related behaviors, prevent educational gaps, and reduce the intergenerational transmission of poverty. Based on quasi-experimental methodology and a non-recursive structural equation model with instrumental variables, this paper analyzed the intergenerational transmission of teenage pregnancy from mothers to daughters, as well as the relationship between teenage pregnancy and educational attainment. Using data from the 2009 National Survey of Demographic Dynamics in Mexico, our estimated model indicated a unidirectional relationship from teenage pregnancy to educational attainment. An association was observed between teenage pregnancy and an increased probability of a moderate or severe educational gap (≥ 1 year) by 21% ± 5 and a severe educational gap (≥ 2 years) by 33% ± 8. Adolescents whose mothers reported teenage pregnancy at < 15 years of age were approximately 84% more likely to experience teenage pregnancy themselves than other adolescents. Relevant explanatory mechanisms included low socioeconomic status and a low level of education in the household. Mexico needs to formulate, implement, and expand comprehensive and early prevention strategies as well as teenage pregnancy care throughout its most vulnerable regions. Efforts should be made at the individual, family, and community levels; incorporate alliances with teenage networks; actively engage parents, teachers, and health care providers; and reinforce educational initiatives on sexual and reproductive health for adolescents. It would be convenient for the Government to implement public policies that emphasize the results obtained. There is no better instrument than to show the evidence of the gradual deterioration of human capital in Mexico associated with adolescent pregnancy.

Decoding Gene Expression Signatures Underlying Vegetative to Inflorescence Meristem Transition in the Common Bean.

The tropical common bean (Phaseolus vulgaris L.) is an obligatory short-day plant that requires relaxation of the photoperiod to induce flowering. Similar to other crops, photoperiod-induced floral initiation depends on the differentiation and maintenance of meristems. In this study, the global changes in transcript expression profiles were analyzed in two meristematic tissues corresponding to the vegetative and inflorescence meristems of two genotypes with different sensitivities to photoperiods. A total of 3396 differentially expressed genes (DEGs) were identified, and 1271 and 1533 were found to be up-regulated and down-regulated, respectively, whereas 592 genes showed discordant expression patterns between both genotypes. Arabidopsis homologues of DEGs were identified, and most of them were not previously involved in Arabidopsis floral transition, suggesting an evolutionary divergence of the transcriptional regulatory networks of the flowering process of both species. However, some genes belonging to the photoperiod and flower development pathways with evolutionarily conserved transcriptional profiles have been found. In addition, the flower meristem identity genes APETALA1 and LEAFY, as well as CONSTANS-LIKE 5, were identified as markers to distinguish between the vegetative and reproductive stages. Our data also indicated that the down-regulation of the photoperiodic genes seems to be directly associated with promoting floral transition under inductive short-day lengths. These findings provide valuable insight into the molecular factors that underlie meristematic development and contribute to understanding the photoperiod adaptation in the common bean.

Crossroads in Liver Transplantation: Is Artificial Intelligence the Key to Donor-Recipient Matching?

Liver transplantation outcomes have improved in recent years. However, with the emergence of expanded donor criteria, tools to better assist donor-recipient matching have become necessary. Most of the currently proposed scores based on conventional biostatistics are not good classifiers of a problem that is considered "unbalanced." In recent years, the implementation of artificial intelligence in medicine has experienced exponential growth. Deep learning, a branch of artificial intelligence, may be the answer to this classification problem. The ability to handle a large number of variables with speed, objectivity, and multi-objective analysis is one of its advantages. Artificial neural networks and random forests have been the most widely used deep classifiers in this field. This review aims to give a brief overview of D-R matching and its evolution in recent years and how artificial intelligence may be able to provide a solution.

Global, regional, and national sepsis incidence and mortality, 1990-2017: analysis for the Global Burden of Disease Study.

BACKGROUND: Sepsis is life-threatening organ dysfunction due to a dysregulated host response to infection. It is considered a major cause of health loss, but data for the global burden of sepsis are limited. As a syndrome caused by underlying infection, sepsis is not part of standard Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) estimates. Accurate estimates are important to inform and monitor health policy interventions, allocation of resources, and clinical treatment initiatives. We estimated the global, regional, and national incidence of sepsis and mortality from this disorder using data from GBD 2017. METHODS: We used multiple cause-of-death data from 109 million individual death records to calculate mortality related to sepsis among each of the 282 underlying causes of death in GBD 2017. The percentage of sepsis-related deaths by underlying GBD cause in each location worldwide was modelled using mixed-effects linear regression. Sepsis-related mortality for each age group, sex, location, GBD cause, and year (1990-2017) was estimated by applying modelled cause-specific fractions to GBD 2017 cause-of-death estimates. We used data for 8·7 million individual hospital records to calculate in-hospital sepsis-associated case-fatality, stratified by underlying GBD cause. In-hospital sepsis-associated case-fatality was modelled for each location using linear regression, and sepsis incidence was estimated by applying modelled case-fatality to sepsis-related mortality estimates. FINDINGS: In 2017, an estimated 48·9 million (95% uncertainty interval [UI] 38·9-62·9) incident cases of sepsis were recorded worldwide and 11·0 million (10·1-12·0) sepsis-related deaths were reported, representing 19·7% (18·2-21·4) of all global deaths. Age-standardised sepsis incidence fell by 37·0% (95% UI 11·8-54·5) and mortality decreased by 52·8% (47·7-57·5) from 1990 to 2017. Sepsis incidence and mortality varied substantially across regions, with the highest burden in sub-Saharan Africa, Oceania, south Asia, east Asia, and southeast Asia. INTERPRETATION: Despite declining age-standardised incidence and mortality, sepsis remains a major cause of health loss worldwide and has an especially high health-related burden in sub-Saharan Africa. FUNDING: The Bill & Melinda Gates Foundation, the National Institutes of Health, the University of Pittsburgh, the British Columbia Children's Hospital Foundation, the Wellcome Trust, and the Fleming Fund.

Fertility, mortality, migration, and population scenarios for 195 countries and territories from 2017 to 2100: a forecasting analysis for the Global Burden of Disease Study.

BACKGROUND: Understanding potential patterns in future population levels is crucial for anticipating and planning for changing age structures, resource and health-care needs, and environmental and economic landscapes. Future fertility patterns are a key input to estimation of future population size, but they are surrounded by substantial uncertainty and diverging methodologies of estimation and forecasting, leading to important differences in global population projections. Changing population size and age structure might have profound economic, social, and geopolitical impacts in many countries. In this study, we developed novel methods for forecasting mortality, fertility, migration, and population. We also assessed potential economic and geopolitical effects of future demographic shifts. METHODS: We modelled future population in reference and alternative scenarios as a function of fertility, migration, and mortality rates. We developed statistical models for completed cohort fertility at age 50 years (CCF50). Completed cohort fertility is much more stable over time than the period measure of the total fertility rate (TFR). We modelled CCF50 as a time-series random walk function of educational attainment and contraceptive met need. Age-specific fertility rates were modelled as a function of CCF50 and covariates. We modelled age-specific mortality to 2100 using underlying mortality, a risk factor scalar, and an autoregressive integrated moving average (ARIMA) model. Net migration was modelled as a function of the Socio-demographic Index, crude population growth rate, and deaths from war and natural disasters; and use of an ARIMA model. The model framework was used to develop a reference scenario and alternative scenarios based on the pace of change in educational attainment and contraceptive met need. We estimated the size of gross domestic product for each country and territory in the reference scenario. Forecast uncertainty intervals (UIs) incorporated uncertainty propagated from past data inputs, model estimation, and forecast data distributions. FINDINGS: The global TFR in the reference scenario was forecasted to be 1·66 (95% UI 1·33-2·08) in 2100. In the reference scenario, the global population was projected to peak in 2064 at 9·73 billion (8·84-10·9) people and decline to 8·79 billion (6·83-11·8) in 2100. The reference projections for the five largest countries in 2100 were India (1·09 billion [0·72-1·71], Nigeria (791 million [594-1056]), China (732 million [456-1499]), the USA (336 million [248-456]), and Pakistan (248 million [151-427]). Findings also suggest a shifting age structure in many parts of the world, with 2·37 billion (1·91-2·87) individuals older than 65 years and 1·70 billion (1·11-2·81) individuals younger than 20 years, forecasted globally in 2100. By 2050, 151 countries were forecasted to have a TFR lower than the replacement level (TFR <2·1), and 183 were forecasted to have a TFR lower than replacement by 2100. 23 countries in the reference scenario, including Japan, Thailand, and Spain, were forecasted to have population declines greater than 50% from 2017 to 2100; China's population was forecasted to decline by 48·0% (-6·1 to 68·4). China was forecasted to become the largest economy by 2035 but in the reference scenario, the USA was forecasted to once again become the largest economy in 2098. Our alternative scenarios suggest that meeting the Sustainable Development Goals targets for education and contraceptive met need would result in a global population of 6·29 billion (4·82-8·73) in 2100 and a population of 6·88 billion (5·27-9·51) when assuming 99th percentile rates of change in these drivers. INTERPRETATION: Our findings suggest that continued trends in female educational attainment and access to contraception will hasten declines in fertility and slow population growth. A sustained TFR lower than the replacement level in many countries, including China and India, would have economic, social, environmental, and geopolitical consequences. Policy options to adapt to continued low fertility, while sustaining and enhancing female reproductive health, will be crucial in the years to come. FUNDING: Bill & Melinda Gates Foundation.

Assessing the continuum of care for maternal health in Mexico, 1994-2018.

OBJECTIVE: To describe the temporal and geographical patterns of the continuum of maternal health care in Mexico, as well as the sociodemographic characteristics that affect the likelihood of receiving this care. METHODS: We conducted a pooled cross-sectional analysis using the 1997, 2009, 2014 and 2018 waves of the National Survey of Demographic Dynamics, collating sociodemographic and obstetric characteristics of 93 745 women aged 12-54 years at last delivery. We defined eight variables along the antenatal-postnatal continuum, both independently and conditionally. We used a pooled fixed-effects multivariable logistic model to determine the likelihood of receiving the continuum of care for various properties. We also mapped the quintiles of adjusted state-level absolute change in continuum of care coverage during 1994-2018. FINDINGS: We observed large absolute increases in the proportion of women receiving timely antenatal and postnatal care (from 48.9% to 88.2% and from 39.1% to 68.7%, respectively). In our conditional analysis, we found that the proportion of women receiving adequate antenatal care doubled over this period. We showed that having social security and a higher level of education is positively associated with receiving the continuum of care. We observed the largest relative increases in continuum of care coverage in Chiapas (181.5%) and Durango (160.6%), assigned human development index categories of low and medium, respectively. CONCLUSION: Despite significant progress in coverage of the continuum of maternal health care, disparities remain. While ensuring progress towards achievement of the health-related sustainable development goal, government intervention must also target underserved populations.

The res (restored cell structure by salinity) tomato mutant reveals the role of the DEAD-box RNA helicase SlDEAD39 in plant development and salt response.

Increasing evidences highlight the importance of DEAD-box RNA helicases in plant development and stress responses. In a previous study, we characterized the tomato res mutant (restored cell structure by salinity), showing chlorosis and development alterations that reverted under salt-stress conditions. Map-based cloning demonstrates that RES gene encodes SlDEAD39, a chloroplast-targeted DEAD-box RNA helicase. Constitutive expression of SlDEAD39 complements the res mutation, while the silencing lines had a similar phenotype than res mutant, which is also reverted under salinity. Functional analysis of res mutant proved SlDEAD39 is involved in the in vivo processing of the chloroplast, 23S rRNA, at the hidden break-B site, a feature also supported by in vitro binding experiments of the protein. In addition, our results show that other genes coding for chloroplast-targeted DEAD-box proteins are induced by salt-stress, which might explain the rescue of the res mutant phenotype. Interestingly, salinity restored the phenotype of res adult plants by increasing their sugar content and fruit yield. Together, these results propose an unprecedented role of a DEAD-box RNA helicase in regulating plant development and stress response through the proper ribosome and chloroplast functioning, which, in turn, represents a potential target to improve salt tolerance in tomato crops.

Monitoring the progress of health-related sustainable development goals (SDGs) in Brazilian states using the Global Burden of Disease indicators.

BACKGROUND: Measuring the Global Burden of Disease (GBD) has been the key to verifying the evolution of health indicators worldwide. We analyse subnational GBD data for Brazil in order to monitor the performance of the Brazilian states in the last 28 years on their progress towards meeting the health-related SDGs. METHODS: As part of the GBD study, we assessed the 41 health-related indicators from the SDGs in Brazil at the subnational level for all the 26 Brazilian states and the Federal District from 1990 to 2017. The GBD group has rescaled all worldwide indicators from 0 to 100, assuming that for each one of them, the worst value among all countries and overtime is 0, and the best is 100. They also estimate the overall health-related SDG index as a function of all previously estimated health indicators and the SDI index (Socio-Demographic Index) as a function of per capita income, average schooling in the population aged 15 years or over, and total fertility rate under the age of 25 (TFU25). RESULTS: From 1990 to 2017, most subnational health-related SDGs, the SDG and SDI indexes improved considerable in most Brazilian states. The observed differences in SDG indicators within Brazilian states, including HIV incidence and health worker density, increased over time. In 2017, health-related indicators that achieved good results globally included the prevalence of child wasting, NTD, household air pollution, conflict mortality, skilled birth attendance, use of modern contraceptive methods, vaccine coverage, and health worker density, but poor results were observed for child overweight and homicide rates. The high rates of overweight, alcohol consumption, and smoking prevalence found in the historically richest regions (i.e., the South and Southeast), contrast with the high rates of tuberculosis, maternal, neonatal, and under-5 mortality and WASH-related mortality found in the poorer regions (i.e., the North and Northeast). CONCLUSIONS: The majority of Brazil's health-related SDG indicators have substantially improved over the past 28 years. However, inequalities in health among the Brazilian states and regions remain noticeable negatively affecting the Brazilian population, which can contribute to Brazil not achieving the SDG 2030 targets.