The aim of this article is to describe the problem of pregnancy in girls under 15 years of age in the Dominican Republic in the period 2000–2021, to develop a specific indicator for this age group ...and describing the related factors.
This is an exploratory ecological study, based on secondary data sources, such as birth records from the National Statistics Office (NSO) and the Ministry of Public Health (MPH). We calculated the rates of fertility and pregnancy in early adolescence, as well as analyzed their main determining factors and consequences.
Fertility Rate in Early Adolescence (FREA) decreases from 6.27 to 1.04 per thousand in the period 2001–2021. The average FREA for 2015–2021 was 1.78. The average Estimated Rate of Pregnancy in Early Adolescence (ERPEA) for the same period was 3.39. Disability-Adjusted Life Years (DALYs) were 11,620 years. Years of Life Lost (YLL) were 9,665.9 years. The prevalence of Low Birth Weight (LBW) in the under 15-year-old age group was 14.2 %.
Pregnancy in childhood implies risks for both the mother and the child, including low birth weight. The official fertility rate is substantially underreported (2.84 vs. 1.79).
The fertility rate indicator traditionally used does not accurately measure the number of pregnancies in women, particularly in specific age groups or populations where pregnancies may be interrupted by various factors. Therefore, the use of ERPEA is recommended.
We emphasize the need for implementing the proposed indicator for the target group, as well as monitoring Sustainable Development Goal indicator 3.7.2.
The association between obstructive sleep apnea (OSA) and metabolic disorders is well-established; however, the underlying mechanisms that elucidate this relationship remain incompletely understood. ...Since the liver is a major organ in the maintenance of metabolic homeostasis, we hypothesize that liver dysfunction plays a crucial role in the pathogenesis of metabolic dysfunction associated with obstructive sleep apnea (OSA). Herein, we explored the underlying mechanisms of this association within the liver. Experiments were performed in male Wistar rats fed with a control or high fat (HF) diet (60% lipid-rich) for 12 weeks. Half of the groups were exposed to chronic intermittent hypoxia (CIH) (30 hypoxic (5% O2) cycles, 8 h/day) that mimics OSA, in the last 15 days. Insulin sensitivity and glucose tolerance were assessed. Liver samples were collected for evaluation of lipid deposition, insulin signaling, glucose homeostasis, hypoxia, oxidative stress, antioxidant defenses, mitochondrial biogenesis and inflammation. Both the CIH and HF diet induced dysmetabolism, a state not aggravated in animals submitted to HF plus CIH. CIH aggravates hepatic lipid deposition in obese animals. Hypoxia-inducible factors levels were altered by these stimuli. CIH decreased the levels of oxidative phosphorylation complexes in both groups and the levels of SOD-1. The HF diet reduced mitochondrial density and hepatic antioxidant capacity. The CIH and HF diet produced alterations in cysteine-related thiols and pro-inflammatory markers. The results obtained suggest that hepatic mitochondrial dysfunction and oxidative stress, leading to inflammation, may be significant factors contributing to the development of dysmetabolism associated with OSA.
Glycine receptors (GlyRs) are indispensable for maintaining excitatory/inhibitory balance in neuronal circuits that control reflexes and rhythmic motor behaviors. Here we have developed Glyght, a ...GlyR ligand controlled with light. It is selective over other Cys-loop receptors, is active in vivo, and displays an allosteric mechanism of action. The photomanipulation of glycinergic neurotransmission opens new avenues to understanding inhibitory circuits in intact animals and to developing drug-based phototherapies.
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•The photochromic small molecule Glyght enables control of glycine receptors with light•Glyght is active and selective in endogenous human and zebrafish receptors•Glyght is reversible in endogenous human and zebrafish receptors in vitro and in vivo•Glyght constitutes a new molecular scaffold for glycine receptor pharmacology
Gomila et al. identify the first light-controlled glycine receptor ligand, named Glyght, using in vivo behavioral screening on Danio rerio larvae, electrophysiological analysis in a heterologous system, and brain-stem slices. Moreover, Glyght is selective over other Cys-loop receptors and displays an allosteric mechanism of action.
We assessed the role of age and disease activity as new factors contributing to establish the risk of progressive multifocal leucoencephalopathy in multiple sclerosis patients treated with ...natalizumab in 36 University Hospitals in Europe. We performed the study in 1,307 multiple sclerosis patients (70.8% anti-John Cunninghan virus positive antibodies) treated with natalizumab for a median time of 3.28 years. Epidemiological, clinical, and laboratory variables were collected. Lipid-specific IgM oligoclonal band status was available in 277 patients. Factors associated with progressive multifocal leucoencephalopathy onset were explored by uni- and multivariate logistic regression.
Thirty-five patients developed progressive multifocal leucoencephalopathy. The multivariate analysis identified anti-John Cunninghan virus antibody indices and relapse rate as the best predictors for the onset of this serious opportunistic infection in the whole cohort. They allowed to stratify progressive multifocal leucoencephalopathy risk before natalizumab initiation in individual patients area under the curve (AUC) = 0.85. The risk ranged from <1/3,300 in patients with anti-John Cunninghan virus antibody indices <0.9 and relapse rate >0.5, to 1/50 in the opposite case. In patients with lipid-specific IgM oligoclonal bands assessment, age at natalizumab onset, anti-John Cunninghan virus antibody indices, and lipid-specific IgM oligoclonal band status predicted progressive multifocal leucoencephalopathy risk (AUC = 0.92). The absence of lipid-specific IgM oligoclonal bands was the best individual predictor (OR = 40.94). The individual risk ranged from <1/10,000 in patients younger than 45 years at natalizumab initiation, who showed anti John Cunningham virus antibody indices <0.9 and lipid-specific IgM oligoclonal bands to 1/33 in the opposite case.
In a perspective of personalized medicine, disease activity, anti-lipid specific IgM oligoclonal bands, anti Jonh Cunninghan virus antibody levels, and age can help tailor natalizumab therapy in multiple sclerosis patients, as predictors of progressive multifocal leucoencephalopathy.
Background
Outdoor air pollution may disturb immune system development. We investigated whether gestational exposure to traffic‐related air pollutants (TRAP) is associated with unstimulated cytokine ...profiles in newborns.
Methods
Data come from 235 newborns of the NELA cohort. Innate response–related cytokines (IL‐6, IFN‐α, IL1‐β, and TNF‐α), Th1‐related (IFN‐γ and IL‐2), Th2‐related (IL‐4, IL‐5, and IL‐13), Th17‐related (IL‐17 and IL‐23), and immunomodulatory cytokine IL‐10 were quantified in the supernatant of unstimulated whole umbilical cord blood cells after 7 days of culture using the Luminex technology. Dispersion/chemical transport modeling was used to estimate long‐term (whole pregnancy and trimesters) and short‐term (15 days before delivery) residential exposures to traffic‐related nitrogen dioxide (NO2), particulate matter (PM2.5 and PM10), and ozone (O3). We fitted multivariable logistic regression, Bayesian kernel machine regression (BKMR), and weighted quantile sum (WQS) regression models.
Results
NO2 during the whole pregnancy increased the odds of detection of IL‐1β (OR per 10 µg/m3 increase = 1.37; 95% CI, 1.02, 1.85) and IL‐6 (OR per 10 µg/m3 increase = 1.32; 95% CI 1.00, 1.75). Increased odds of detected concentrations of IL‐10 was found in newborns exposed during whole pregnancy to higher levels of NO2 (OR per 10 µg/m3 increase = 1.30; 95% CI 0.99, 1.69), PM10 (OR per 10 µg/m3 increase = 1.49; 95% CI 0.95, 2.33), and PM2.5 (OR per 5 µg/m3 increase = 1.56; 95% CI 0.97, 2.51). Exposure to O3 during the whole pregnancy increased the odds of detected IL‐13 (OR per 10 µg/m3 increase = 1.22; 95% CI 1.01, 1.49). WQS model revealed first and third trimesters of gestation as windows of higher susceptibility.
Conclusions
Gestational exposure to TRAP may increase detection of pro‐inflammatory, Th2‐related, and T regulatory cytokines in newborns. These changes might influence immune system responses later in life.
This study evaluated if there is a sexual dimorphism in the acute kidney injury (AKI) to chronic kidney disease (CKD) transition and the time-course of the potential mechanisms involved in the ...dimorphic response. Female and male rats were divided into sham-operated or underwent 45-min renal ischemia (F + IR, and M + IR). All groups were studied at 24-h and 1, 2, 3, or 4-months post-ischemia. Additionally, oophorectomized rats were divided into sham or IR groups. After 24-h, AKI extent was simllar in females and males, but female rats exhibited less oxidative stress and increased renal GSH content. After 4-months and despite similar AKI, the M + IR group developed CKD characterized by proteinuria, tubulointerstitial fibrosis, glomerular hypertrophy, increased oxidative stress and a reduction in HIF1α and VEGF from the 1
-month and persisting throughout the time-course studied. Interestingly, the F + IR group did not develop CKD due to lesser oxidative stress and increased eNOS, TGFβ and HIF1α mRNA levels from the 1
-month after IR. Whereas, oophorectomized rats did develop CKD. We found a sexual dimorphic response in the AKI to CKD transition. Early antioxidant defense and higher TGFβ, HIF1α and eNOS were among the renoprotective mechanisms that the F + IR group demonstrated.
BACKGROUND
A common problem associated with toenail removal surgery is the accompanying bacterial infection that often ensues. The foot has a particularly difficult anatomy to prepare antiseptically ...for surgery, which contributes to this wide‐spread problem.
OBJECTIVE
To compare the antiseptic efficacy of two skin pretreatment methods before toenail avulsion surgery.
METHODS
Two presurgical methods were performed on 24 patients each (48 patients total). Swab samples were taken from each patient at five distinct stages (pretreatment, post‐treatment, after surgery, after saline solution irrigation of the nail bed, and after phenol application) throughout the surgical procedure, and bacterial culture analysis was performed (total inocula count and identification of specific microorganisms).
RESULTS
We found both methods to be effective at reducing the initial bacterial load when used at pretreatment, but the reduction in bacterial load was lost after the nail avulsion surgery, achieving values similar to the initial bacterial load before the presurgical scrub, from 5.17 and 5.04 log10 colony‐forming units (CFU)/cm2 to 4.86 and 5.07 log10 CFU/cm2, respectively. An interoperative irrigation step was effective in reducing the bacterial load by 95.2% and 95.3%, respectively.
STUDY LIMITATIONS
Our patients underwent phenol‐based nail avulsion, resulting in no bacterial load after complete nail removal because of the intrinsic antiseptic nature of the phenol.
CONCLUSIONS
Incorporation of intraoperative irrigation of sterile saline solution after nail avulsion surgery reduces potential bacterial load. Every effort should be made to lower the risk of contamination after nail plate avulsion.
The authors have indicated no significant interest with commercial supporters.
Administration of Hydroxychloroquine and Azithromycin in patients with coronavirus disease 2019 (COVID-19) prolongs QTc corrected interval (QTc). The effect and safety of Lopinavir/Ritonavir in ...combination with these therapies have seldom been studied.
Our aim was to evaluate changes in QTc in patients receiving double (Hydroxychloroquine + Azithromycin) and triple therapy (Hydroxychloroquine + Azithromycin + Lopinavir/Ritonavir) to treat COVID-19. Secondary outcome was the incidence of in-hospital all-cause mortality.
Patients under treatment with double (DT) and triple therapy (TT) for COVID-19 were consecutively included in this prospective observational study. Serial in-hospital electrocardiograms were performed to measure QTc at baseline and during therapy.
168 patients (±66.2 years old) were included: 32.1% received DT and 67.9% received TT. The mean baseline QTc was 410.33 ms. Patients under DT and TT prolonged QTc interval respect baseline values (p < 0.001), without significant differences between both therapy groups (p = 0.748). Overall, 33 patients (19.6%) had a peak QTc and/or an increase QTc 60 ms from baseline, with a higher prevalence among those with hypokalemia (p = 0.003). All-cause mortality was similar between both strategy groups (p = 0.093) and high risk QTc prolongation was no related to clinical events in this series.
DT and TT prolong the QTc in patients with COVID-19. Addition of Lopinavir/Ritonavir on top of Hydroxychloroquine and Azithromycin did not increase QTc compared to DT.
•What is known?.•Hydroxychloroquine and Azithromycin prolong QTc in patients with COVID-19 prompting ECG monitoring.•What is the new?•In our series, the addition of Lopinavir/ritonavir to Hydroxychloroquine and Azithromycindid not further prolong QTc interval compared to double therapy.
Prioritizing groupings of organisms or 'units' below the species level is a critical issue for conservation purposes. Several techniques encompassing different time-frames, from genetics to ...ecological markers, have been considered to evaluate existing biological diversity at a sufficient temporal resolution to define conservation units. Given that acoustic signals are expressions of phenotypic diversity, their analysis may provide crucial information on current differentiation patterns within species. Here, we tested whether differences previously delineated within dolphin species based on i) geographic isolation, ii) genetics regardless isolation, and iii) habitat, regardless isolation and genetics, can be detected through acoustic monitoring. Recordings collected from 104 acoustic encounters of Stenella coeruleoalba, Delphinus delphis and Tursiops truncatus in the Azores, Canary Islands, the Alboran Sea and the Western Mediterranean basin between 1996 and 2012 were analyzed. The acoustic structure of communication signals was evaluated by analyzing parameters of whistles in relation to the known genetic and habitat-driven population structure.
Recordings from the Atlantic and Mediterranean were accurately assigned to their respective basins of origin through Discriminant Function Analysis, with a minimum 83.8% and a maximum 93.8% classification rate. A parallel pattern between divergence in acoustic features and in the genetic and ecological traits within the basins was highlighted through Random Forest analysis. Although it is not yet possible to establish a causal link between each driver and acoustic differences between basins, we showed that signal variation reflects fine-scale diversity and may be used as a proxy for recognizing discrete units.
We recommend that acoustic analysis be included in assessments of delphinid population structure, together with genetics and ecological tracer analysis. This cost-efficient non-invasive method can be applied to uncover distinctiveness and local adaptation in other wide-ranging marine species.
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