Conectar
by Madoka Tonosaki, Akira Fujimori, Takeshi Yaoi, Kyoko Itoh
Abnormal spindle-like microcephaly associated (ASPM) is a causative gene of primary autosomal recessive microcephaly. Microcephaly is considered to be a consequence of a small brain, but the associated molecular mechanisms are not fully understood. In this study, we generated brain-specific Aspm knockout mice to evaluate the fetal brain phenotype and observed cortical reduction in the late stage of murine cortical development. It has been reported that the total number of neurons is regulated by the number of neural stem and progenitor cells. In the Aspm knockout mice, no apparent change was shown in the neural progenitor cell proliferation and there was no obvious effect on the number of newly generated neurons in the developing cortex. On the other hand, the knockout mice showed a constant increase in apoptosis in the cerebral cortex from the early through the late stages of cortical development. Furthermore, apoptosis occurred in the neural progenitor cells associated with DNA damage. Overall, these results suggest that apoptosis of the neural progenitor cells is involved in the thinning of the mouse cerebral cortex, due to the loss of the Aspm gene in neocortical development.by Xiaoyuan Xu, Aimin Yang, Yan Han, Wei Wang, Guimin Hao, Na Cui
Background and objectivesThis paper aimed to analyze the relationship between baseline prolactin (PRL) levels and live birth rates (LBRs) in patients undergoing embryo transfer who did not have polycystic ovarian syndrome (PCOS) using a retrospective design. Patient(s): A total of 20,877 patients who had undergone IVF/intracytoplasmic sperm injection (ICSI) between December 2014 and December 2019.
Materials and methodsWe examined the association between PRL concentrations and LBRs using multivariate regression analysis. In addition, a model for nonlinear relationships based on a two-part linear regression was developed.
ResultsFollowing adjustment for confounding factors, multivariate regression analysis confirmed a statistically significant correlation between serum PRL and LBR. Particularly, when blood PRL content was less than 14.8 ng/mL, there exists a positive relation between serum PRL and LBRs. In contrast, once PRL concentrations surpassed the inflection point at 14.8 ng/mL, a meaningful relationship could no longer be inferred between serum PRL and LBR.
ConclusionsBasal serum PRL levels were segmentally connected with LBRs.
by Ana Carolina Cavalcante Rodrigues, Caroline Vitória de Lima Moreira, Camila Carlos Prado, Luan Silvestro Bianchini Silva, Rafael Fernandes Costa, Adesina Paul Arikawe, Gustavo Rodrigues Pedrino, Elson Alves Costa, Osmar Nascimento Silva, Hamilton Barbosa Napolitano, Iranse Oliveira-Silva, James Oluwagbamigbe Fajemiroye
Profiling the variability related to the estrous cycle is essential for assessing depressive-like behavior and screening drugs. This study compares circulating plasma corticosterone levels [CORT] and behavioral alterations in mice exposed to sucrose preference, forced swimming, and tail suspension tests (SPT, FST, and TST, respectively). While SPT exposure did not significantly alter [CORT], FST and TST showed notable changes. Mice in the TST exhibited increased movement and decreased immobility time compared to FST, suggesting a lower likelihood of depressive-like behavior in male mice. Notably, during the proestrus phase, female mice displayed the highest tendency for depressive-like behavior and elevated [CORT], but similar response to antidepressants (imipramine and fluoxetine). The inherent stress of the FST and TST tasks appears to influence [CORT] as well as depressant and antidepressant effects. These comparisons provide valuable insights for further behavioral phenotyping, model sensitivity assessment, and deepen our neurobiological understanding of depression in the context of drug screening.by Sian Reece, Josie Dickerson, Brian Kelly, Rosemary R. C. McEachan, Kate E. Pickett
There is growing recognition that the public health measures employed to control the spread of the COVID-19 pandemic had unintended consequences on socioeconomic security and health inequalities, having the greatest impact on the most vulnerable groups. This longitudinal study aims to explore the medium to long-term impacts of the COVID-19 pandemic and subsequent public health measures on financial security for families living in the deprived and ethnically diverse city of Bradford. We collected data at four time points before and during the pandemic from mothers who participated in one of two prospective birth cohort studies in Bradford. The findings demonstrate that the risk of experiencing financial insecurity rose sharply during the pandemic and has not returned to pre-COVID-19 baseline levels. Several individual characteristics were found to be possible predictors of financial insecurity, including homeowner status, free school meal eligibility and not working. Protective factors against financial insecurity include: living in more affluent areas; greater levels of educational attainment; and families with two or more adults in the household. Notably, families of Pakistani Heritage were found to have the greatest risk of experiencing financial insecurity throughout the pandemic. Furthermore, this study demonstrated that there were strong associations between financial insecurity and maternal health and wellbeing outcomes, with mothers experiencing financial insecurity being more likely to report unsatisfactory general health and clinically important symptoms of depression and anxiety. The findings of this study highlight that the impact of financial insecurity experienced by mothers and their families throughout the pandemic was severe, wide ranging and affected the most vulnerable. In the wake of the pandemic, the emerging cost of living and energy crisis emphasises the urgent need for policy makers to act to support vulnerable families to prevent further widening of existing health and social inequalities.by Kusse Urmale Mare, Setognal Birara Aychiluhm, Kebede Gemeda Sabo, Abay Woday Tadesse, Bizunesh Fentahun Kase, Oumer Abdulkadir Ebrahim, Tsion Mulat Tebeje, Getahun Fentaw Mulaw, Beminate Lemma Seifu
BackgroundDespite the implementation of different nutritional and non-nutritional interventions, 43% of reproductive-age women in Africa suffer from anemia. Recent evidence also shows that none of the Sub-Saharan African (SSA) countries are on the track to achieve the nutrition target of 50% anemia reduction by 2030. To date, information on the level of anemia and its determinants among reproductive-age women at the SSA level is limited. Thus, this study aimed to estimate the pooled prevalence of anemia level and its determinants in SSA countries.
MethodsWe used a pooled data of 205,627 reproductive-age women from the recent demographic and health surveys of 29 SSA countries that were conducted between 2010–2021. A multilevel mixed-effects analysis with an ordered logistic regression model was fitted to identify determinants of anemia level and the deviance value was used to select the best-fitted model. First, bivariable ordinal logistic regression analysis was done and the proportional odds assumption was checked for each explanatory variable using a Brant test. Finally, in a multivariable multilevel ordinal logistic regression model, a p-value Results
The pooled prevalence of anemia among women of reproductive age in SSA was 40.5% [95% CI = 40.2%-40.7%], where 24.8% [95% CI: 24.6%-25.0%], 11.1% [95% CI = 10.9%-11.2%], and 0.8% [95% CI = 0.7%-0.8%] had mild, moderate, and severe anemia, respectively. The prevalence significantly varied from the lowest of 13% in Rwanda to the highest of 62% in Mali, and anemia was found as a severe public health problem (prevalence of ≥ 40%) in 18 countries. The regression result revealed that polygamous marriage, women and husband illiteracy, poor household wealth, shorter birth interval, non-attendance of antenatal care, underweight, unimproved toilet and water facilities, and low community-level women literacy were positively linked with high anemia level. Additionally, the likelihood of anemia was lower in women who were overweight and used modern contraception.
ConclusionsOverall results showed that anemia among women of reproductive age is a severe public health problem in SSA countries, affecting more than four in ten women. Thus, enhancing access to maternal health services (antenatal care and contraception) and improved sanitation facilities would supplement the existing interventions targeted to reduce anemia. Moreover, strengthening women’s education and policies regulating the prohibition of polygamous marriage are important to address the operational constraints.
by Philomina Afful, Godwin Adjei Vechey, Peter Kipo Leta, Foster Bediako Gbafu, Fortress Yayra Aku
Multidrug-resistant Tuberculosis (MDR-TB) remains a global health concern. The disease results in a prolonged treatment and hence, poses a financial burden to affected individuals and their families. The Ghana National TB Control Programme (NTP) has made extensive efforts to control the menace, however, it remains a concern. This study, therefore, aimed to determine the predictors of multidrug-resistant TB in the Cape Coast Teaching Hospital of Ghana. An unmatched case-control study involving 37 cases and 111 controls was conducted using data of TB cases registered for treatment between January 2018 and December 2020 at the Cape Coast Teaching Hospital. Socio-demographic, individual level and social characteristics information were collected from respondents through telephone surveys, face-to-face interviews and review of records using a structured questionnaire built in the Kobo Collect Toolbox. The data was exported to Stata version 16.0 for analysis. Chi-square test and multiple logistic regression were used to determine the predictors of MDR-TB. Associations were considered statistically significant at a 95% confidence interval with a p-value of less than 0.05. The results revealed that the majority (25 [67.6%]) of MDR-TB cases and controls (76 [68.5%]) were aged 30 years and above with a median age of 36.5 (IQR: 28–50) years for all respondents, while 20 (54.1%) of MDR-TB cases and 33 (29.7%) of controls lived in households with one room residences for their families. The following predictors for MDR-TB were identified: BCG vaccination status (AOR = 0.17,95% CI:0.07–0.45), long distance to health facility (AOR = 4.11, 95% CI: 1.55–10.87), number of rooms in residence (AOR = 0.37,95% CI: 0.14–0.99) and first place of visit upon noticing TB symptom (AOR = 4.22,95% CI:1.31–13.64). Predictors of MDR-TB in the current study were multi-faceted. Measures to control MDR-TB should target socio-demographic, health-seeking behaviour and social-related concerns.by Carlos Ignacio Reyes-Farias, Marcelo Reategui-Diaz, Franco Romani-Romani, Larry Prokop
BackgroundSodium-glucose cotransporter 2 (SGLT-2) inhibitors have shown a favorable effect on cardiovascular and renal outcomes in patients with type 2 diabetes mellitus (T2DM). However, their efficacy in patients with chronic kidney disease (CKD) with or without T2DM has not yet been analyzed.
ObjectiveTo assess the cardiovascular and renal effects of SGLT-2 inhibitors in patients with CKD with and without T2DM, including all CKD patients in the current literature.
MethodsWe searched MEDLINE, EMBASE, CENTRAL and Scopus for randomized controlled trials of SGLT-2 inhibitors that evaluated cardiovascular and kidney outcomes in patients with CKD, or trials in which these patients were a subgroup. We defined 2 primary outcomes: a composite of cardiovascular death or hospitalization for heart failure, and a composite renal outcome. For each outcome, we obtained overall hazard ratios with 95% confidence intervals by using a random effects model.
ResultsWe included 14 randomized controlled trials. SGLT-2 inhibitors decreased the hazard for the primary cardiovascular outcome (HR 0.76; [95% CI 0.72–0.79]) and the primary renal outcome (HR 0.69; [95% CI 0.61–0.79]) in patients with CKD with or without T2DM. We did not find significant differences in the subgroup analyses according to diabetes status, baseline eGFR values or the type of SGLT-2 inhibitor used.
ConclusionIn patients with CKD, treatment with SGLT-2 inhibitors in addition to standard therapy conferred protection against cardiovascular and renal outcomes. Further research on patients with non-diabetic CKD should be done to confirm the utility of these medications in this population. (PROSPERO ID: CRD42021275012).
by Weiyi Huang, Robin L. Page, Theresa Morris, Susan Ayres, Alva O. Ferdinand, Samiran Sinha
BackgroundThe association of maternal exposure to selective serotonin reuptake inhibitors (SSRIs) or serotonin and norepinephrine reuptake inhibitors (SNRIs) with the risk of system-specific congenital malformations in offspring remains unclear. We conducted a meta-analysis to examine this association and the risk difference between these two types of inhibitors.
MethodsA literature search was performed from January 2000 to May 2023 using PubMed and Web of Science databases. Cohort and case-control studies that assess the association of maternal exposure to SSRIs or SNRIs with the risk of congenital abnormalities were eligible for the study.
ResultsTwenty-one cohort studies and seven case-control studies were included in the meta-analysis. Compared to non-exposure, maternal exposure to SNRIs is associated with a higher risk of congenital cardiovascular abnormalities (pooled OR: 1.64 with 95% CI: 1.36, 1.97), anomalies of the kidney and urinary tract (pooled OR: 1.63 with 95% CI: 1.21, 2.20), malformations of nervous system (pooled OR: 2.28 with 95% CI: 1.50, 3.45), anomalies of digestive system (pooled OR: 2.05 with 95% CI: 1.60, 2.64) and abdominal birth defects (pooled OR: 2.91 with 95%CI: 1.98, 4.28), while maternal exposure to SSRIs is associated with a higher risk of congenital cardiovascular abnormalities (pooled OR: 1.25 with 95%CI: 1.20, 1.30), anomalies of the kidney and urinary tract (pooled OR: 1.14 with 95%CI: 1.02, 1.27), anomalies of digestive system (pooled OR: 1.11 with 95%CI: 1.01, 1.21), abdominal birth defects (pooled OR: 1.33 with 95%CI: 1.16, 1.53) and musculoskeletal malformations (pooled OR: 1.44 with 95%CI: 1.32, 1.56).
ConclusionsSSRIs and SNRIs have various teratogenic risks. Clinicians must consider risk-benefit ratios and patient history when prescribing medicines.
by Young Min Hur, Jae Young Yoo, Young Ah You, Sunwha Park, Soo Min Kim, Gain Lee, Young Ju Kim
Preterm birth (PTB) refers to delivery before 37 weeks of gestation. Premature neonates exhibit higher neonatal morbidity and mortality rates than term neonates; therefore, it is crucial to predict and prevent PTB. Advancements enable the prediction and prevention of PTB using genetic approaches, especially by investigating its correlation with single nucleotide polymorphisms (SNPs). We aimed to identify impactive and relevant SNPs for the prediction of PTB via whole–genome sequencing analyses of the blood of 31 pregnant women with PTB (n = 13) and term birth (n = 18) who visited the Ewha Womans University Mokdong Hospital from November 1, 2018 to February 29, 2020. A genome-wide association study was performed using PLINK 1.9 software and 256 SNPs were selected and traced through protein-protein interactions. Moreover, a validation study by genotyping was performed on 60 other participants (preterm birth, n = 30; term birth, n = 30) for 25 SNPs related to ion channel binding and receptor complex pathways. Odds ratios were calculated using additive, dominant, and recessive genetic models. The risk of PTB in women with the AG allele of rs2485579 (gene name: RYR2) was significantly 4.82-fold increase, and the risk of PTB in women with the AG allele of rs7903957 (gene name: TBX5) was significantly 0.25-fold reduce. Our results suggest that rs2485579 (in RYR2) can be a genetic marker of PTB, which is considered through the association with abnormal cytoplasmic Ca2+ concentration and dysfunctional uterine contraction due to differences of RYR2 in the sarcoplasmic reticulum.by Philipp D. Koellinger, Aysu Okbay, Hyeokmoon Kweon, Annemarie Schweinert, Richard Karlsson Linnér, Jan Goebel, David Richte, Lisa Reiber, Bettina Maria Zweck, Daniel W. Belsky, Pietro Biroli, Rui Mata, Elliot M. Tucker-Drob, K. Paige Harden, Gert Wagner, Ralph Hertwig
The German Socio-Economic Panel (SOEP) serves a global research community by providing representative annual longitudinal data of respondents living in private households in Germany. The dataset offers a valuable life course panorama, encompassing living conditions, socioeconomic status, familial connections, personality traits, values, preferences, health, and well-being. To amplify research opportunities further, we have extended the SOEP Innovation Sample (SOEP-IS) by collecting genetic data from 2,598 participants, yielding the first genotyped dataset for Germany based on a representative population sample (SOEP-G). The sample includes 107 full-sibling pairs, 501 parent-offspring pairs, and 152 triads, which overlap with the parent-offspring pairs. Leveraging the results from well-powered genome-wide association studies, we created a repository comprising 66 polygenic indices (PGIs) in the SOEP-G sample. We show that the PGIs for height, BMI, and educational attainment capture 22∼24%, 12∼13%, and 9% of the variance in the respective phenotypes. Using the PGIs for height and BMI, we demonstrate that the considerable increase in average height and the decrease in average BMI in more recent birth cohorts cannot be attributed to genetic shifts within the German population or to age effects alone. These findings suggest an important role of improved environmental conditions in driving these changes. Furthermore, we show that higher values in the PGIs for educational attainment and the highest math class are associated with better self-rated health, illustrating complex relationships between genetics, cognition, behavior, socio-economic status, and health. In summary, the SOEP-G data and the PGI repository we created provide a valuable resource for studying individual differences, inequalities, life-course development, health, and interactions between genetic predispositions and the environment.by Hong Gyu Yoon, Jin Hwan Cheong, Je Il Ryu, Yu Deok Won, Kyueng-Whan Min, Myung-Hoon Han
Background and purposeGlioblastoma multiforme (GBM) is the most devastating brain tumor with less than 5% of patients surviving 5 years following diagnosis. Many studies have focused on the genetics of GBM with the aim of improving the prognosis of GBM patients. We investigated specific genes whose expressions are significantly related to both the length of the overall survival and the progression-free survival in patients with GBM.
MethodsWe obtained data for 12,042 gene mRNA expressions in 525 GBM tissues from the Cancer Genome Atlas (TCGA) database. Among those genes, we identified independent genes significantly associated with the prognosis of GBM. Receiver operating characteristic (ROC) curve analysis was performed to determine the genes significant for predicting the long-term survival of patients with GBM. Bioinformatics analysis was also performed for the significant genes.
ResultsWe identified 33 independent genes whose expressions were significantly associated with the prognosis of 525 patients with GBM. Among them, the expressions of five genes were independently associated with an improved prognosis of GBM, and the expressions of 28 genes were independently related to a poorer prognosis of GBM. The expressions of the ADAM22, ATP5C1, RAC3, SHANK1, AEBP1, C1RL, CHL1, CHST2, EFEMP2, and PGCP genes were either positively or negatively related to the long-term survival of GBM patients.
ConclusionsUsing a large-scale and open database, we found genes significantly associated with both the prognosis and long-term survival of patients with GBM. We believe that our findings may contribute to improving the understanding of the mechanisms underlying GBM.
by Casper Worm Hansen, Carl-Johan Dalgaard, Holger Strulik
We construct a cohort-based frailty index for 180 countries over the period 1990-2019. We use this measure of physiological aging to estimate the impact of deteriorating health on labor force participation. Our three-dimensional panel framework, in which the unit of observation is a cohort in a given country at a given age, allows us to control for a range of unobserved factors. Our identification strategy further exploits a compensating law of physiological aging to account for reverse causality. We find a negative effect of physiological aging on labor market participation: an increase of the frailty index by one percent leads to a reduction of labor force participation of about 0.6 (±0.2) percentage points. Since health deficits (in the frailty index) are accumulated at a rate of about 3 percent per year of life, almost all of the age-related decline in labor force participation can be motivated by deteriorating health.by Chao Li, Zhong Liu, Justin Anderson, Zhongyu Liu, Liping Tang, Yao Li, Ning Peng, Jianguo Chen, Xueming Liu, Lianwu Fu, Tim M. Townes, Steven M. Rowe, David M. Bedwell, Jennifer Guimbellot, Rui Zhao
A major unmet need in the cystic fibrosis (CF) therapeutic landscape is the lack of effective treatments for nonsense CFTR mutations, which affect approximately 10% of CF patients. Correction of nonsense CFTR mutations via genomic editing represents a promising therapeutic approach. In this study, we tested whether prime editing, a novel CRISPR-based genomic editing method, can be a potential therapeutic modality to correct nonsense CFTR mutations. We generated iPSCs from a CF patient homozygous for the CFTR W1282X mutation. We demonstrated that prime editing corrected one mutant allele in iPSCs, which effectively restored CFTR function in iPSC-derived airway epithelial cells and organoids. We further demonstrated that prime editing may directly repair mutations in iPSC-derived airway epithelial cells when the prime editing machinery is efficiently delivered by helper-dependent adenovirus (HDAd). Together, our data demonstrated that prime editing may potentially be applied to correct CFTR mutations such as W1282X.by Yanhong Wang, Weiran Zhou, Lin Wang, Qianbing Ying
The Yangtze River Economic Belt, as a globally important economic growth pole and population concentration area, has always received attention to its ecological and environmental issues. Currently, there is little research on the synergy among the ecological environment risk prevention and control mechanisms in this region. Strengthening research in this area has important scientific value for improving the effectiveness of ecological risk prevention and control and the sustainable development of the Yangtze River Economic Belt. Based on the data from 11 provinces and cities in the Yangtze River Economic Belt from 2017 to 2021, this study establishes an indicator system with benefit incentive mechanisms, risk regulatory mechanisms, and risk governance mechanisms as frameworks. By employing a composite system synergy model, this study utilizes the entropy weight method to assign weights to each indicator and calculates the orderliness and synergy of the three mechanisms separately. The results show that: (1) There are differences in the orderliness of mechanisms among the regions. The downstream area has the highest orderliness of the three mechanisms, with the middle stream area higher than the upstream area in terms of incentive mechanisms and risk governance mechanisms. (2) The orderliness of each mechanism has slight fluctuations but shows an overall upward trend, with the orderliness of regulatory mechanisms significantly higher than that of incentive mechanisms and governance mechanisms. (3) In terms of synergy, the three major mechanisms show a stable upward trend in synergy but with a relatively low degree of synergy. Based on these findings, future efforts should focus on optimizing mechanism construction and information sharing, improving incentive mechanisms, strengthening risk regulatory mechanisms, and consolidating the effectiveness of risk governance mechanisms.by Roya Haghiri-Vijeh, Kat Newman-Seymour, Daniel Huizenga, Aidan Hung
ObjectiveThe objective of this scoping review protocol is to review what has been reported on the development and the use of gender-affirming online resources and games for gender-independent, intersex, non-binary, and transgender (GIaNT) youth (aged 9–26).
IntroductionGIaNT youth and their specialized health care needs are mostly exempt from curriculums. There is limited information on the specific online sources available for GIaNT children and youth.
Inclusion criteriaThe inclusion criteria are sources that include GIaNT children and youth and focus on online spaces and games for the identified population.
MethodsThe Joanna Briggs Institute (JBI) method for scoping reviews has guided the development of this protocol. Databases to be searched include CINAHL, Cochrane, Epistemonikos, ERIC, Gender Studies Database, GenderWatch, LGBTQ+ Source, ProQuest, PyscInfo, and Scopus. Unpublished studies and gray literature searches will be undertaken in ProQuest thesis and dissertation and a limited number of relevant websites. No limit on date or region will be applied. Records will be screened and extracted by two independent reviewers. Results will be presented as tables with accompanying narrative summary.
ConclusionThis scoping review protocol will guide the review and mapping of literature on available sources for online spaces and games for GIaNT children and youth.
Sedentary behaviour is associated with a variety of adverse health outcomes, including obesity, oestrogen metabolism and chronic inflammation, all of which are related to the pathogenesis of uterine fibroids (UFs). This study aimed to explore the relationship between leisure sedentary time (LST) and UFs.
Cross-sectional.
We conducted a cross-sectional analysis of data from patients from the Yunnan region in the China Multi-Ethnic Cohort Study.
A total of 6623 non-menopausal women aged 30–55 years old were recruited. Menstrual status was self-reported. Participants who lacked a unique national identity card, suffered from serious mental illness, did not have a clear diagnosis of UFs, or provided incomplete information were excluded.
UFs were diagnosed by abdominal B-ultrasound. Leisure sedentary behaviour was assessed by using a face-to-face questionnaire interview. Logistic regression and restricted cubic spline were employed to explore the relationship between LST and UFs.
A total of 562 participants had UFs, with a prevalence rate of 8.5% (7.8%, 9.2%). Multivariate adjusted logistic regression analysis showed that the risk of UFs in women with LST≥6 hour/day was 2.008 times that in women with LST0.05). According to the results of the stratified analysis for menstrual status and body mass index (BMI), there was a correlation between LST and the prevalence of UFs only in women with a BMI2 or perimenopause.
LST was independently associated with the prevalence of UFs, and a linear dose-response relationship was observed. Our study provides evidence on the factors influencing UFs, and further research is needed to propose feasible measures for UFs prevention.
FreshRSS 