Rousesalazar7149

17.5%; p > 0.9). Critically, patients with PGVs in BRCA1, BRCA2 or TP53 did not satisfy current clinical phenotypic criteria for germline testing. Our data suggest that a personal history of multiple cancers, one being a HM, should trigger screening for PGVs.Recently, the use of antiretroviral drug tenofovir disoproxil fumarate (TDF) is increased, thanks to the new co-formulation with doravirine, the availability of booster-free regimens, and its advantageous lipid-lowering effect. The aim of our study was to identify genetic markers that contribute to assess the risk of TDF-related renal toxicity. We have retrospectively investigated, in 179 HIV positive patients treated with TDF, the association between the main variants in ABCC2, ABCC4, and ABCC10 genes and four safety endpoints, three clinically relevant as renal outcomes and a higher tenofovir plasma concentration. In patients with an annual eGFR decline >5 mL/min/1.73 m2 a difference in genotype frequencies was observed for ABCC10 c.1875 + 526 G>A (3 subjects AA vs. 44 GG + GA, p = 0.045). In patients with an eGFR decrement >25%, plus a decline in GFR category and TDF discontinuation, a difference was observed for ABCC4 c.*38T>G (35 subjects TG + GG vs. 18 TT, p = 0.052). At univariate analysis OR was 1.39 [(95% CI 1.00-1.96) p = 0.054] and at multivariate analysis OR was 1.49 [(95% CI 1.00-2.22) p = 0.049]. The stronger associations were found between the tenofovir accumulation and ABCC4 c.*38T>G and c.3348G>A the percentage of these patients was higher in the TG + GG (p = 0.011) and in the AA (p = 0.004) genotype, respectively. The logistic regression analysis confirmed these significant relationships. No significant association was observed in patients with eGFR  less then  60 mL/min/1.73m2 and with the studied ABCC2 polymorphisms. Our results show a major role for a combined determination of ABCC4/ABCC10 variants as an indicator of tenofovir toxicity in the clinical practice.The aim of this study was to perform a systematic overview of the pharmacogenetic studies conducted in Jordan. A structured search of Medline was conducted for articles over the last decade (January 2010-July 2020). Studies were classified by design, sample size, drug-gene combination, and the significance of the results. Thirty-two studies met the criteria for review. Most pharmacogenomic studies had a case-only design (n = 23). Only five studies included >500 participants. The total number of genetic variants in all studies was one hundred fifteen, which were found in forty genes, including dynamic (n = 27), and kinetic (n = 9) genes. The most commonly studied drugs were within the hematology and cardiology therapeutic areas and included statins, warfarin, aspirin, and clopidogrel. Most studies (n = 18) reported results with mixed p values [0.05]. Pharmacogenomic research in Jordan is still in its infancy and is limited mainly to replication attempts. The need for standardization is imperative, especially in developing countries with scarce funding resources.The relationship between gut microbes and COVID-19 or H1N1 infections is not fully understood. Here, we compared the gut mycobiota of 67 COVID-19 patients, 35 H1N1-infected patients and 48 healthy controls (HCs) using internal transcribed spacer (ITS) 3-ITS4 sequencing and analysed their associations with clinical features and the bacterial microbiota. Compared to HCs, the fungal burden was higher. Fungal mycobiota dysbiosis in both COVID-19 and H1N1-infected patients was mainly characterized by the depletion of fungi such as Aspergillus and Penicillium, but several fungi, including Candida glabrata, were enriched in H1N1-infected patients. The gut mycobiota profiles in COVID-19 patients with mild and severe symptoms were similar. Hospitalization had no apparent additional effects. In COVID-19 patients, Mucoromycota was positively correlated with Fusicatenibacter, Aspergillus niger was positively correlated with diarrhoea, and Penicillium citrinum was negatively correlated with C-reactive protein (CRP). In H1N1-infected patients, Aspergillus penicilloides was positively correlated with Lachnospiraceae members, Aspergillus was positively correlated with CRP, and Mucoromycota was negatively correlated with procalcitonin. Therefore, gut mycobiota dysbiosis occurs in both COVID-19 patients and H1N1-infected patients and does not improve until the patients are discharged and no longer require medical attention.The membranous receptor syndecan-4 (SDC-4) and the nuclear transcription factor hypoxia-induced factor-2α (HIF-2α) play critical roles in the pathogenesis of osteoarthritis (OA). The aim of this study was to determine whether SDC-4 inhibition downregulates HIF-2a expression by microRNA-96-5p (miR-96-5p) in murine chondrocyte and cartilage tissue. The OA model was induced surgically in mice, and SDC-4 polyclonal antibody, HIF-2α small interfering RNA (siRNA) and its control, miR-96-5p mimics and its scrambled controls or anti-miR-96-5p and its control were then injected into the knee joints. At 2 and 4 weeks after surgery, OA progression was evaluated microscopically, histologically, radiographically and immunohistochemically in these mice. Real-time polymerase chain reaction (RT-PCR) and western blotting were performed after treating with antibody and transfecting with miRNA mimic or siRNA to determine their effects on OA-related mediators. The potential miRNAs related to OA development were identified by using miRNA microarray analysis. Whether miRNAs play a pivotal role in OA development in vivo or in vitro was also investigated. MiR-96-5p expression was upregulated by SDC-4-specific antibodies in chondrocytes and cartilage tissue, and miR-96-5p directly targeted the 3'-UTR of HIF-2α to inhibit HIF-2α signaling in murine chondrocytes. Moreover, we demonstrated that anti-SDC-4-attenuated IL-1β-induced chondrocyte hypertrophy and cartilage degradation by inhibiting HIF-2α signaling by a miR-96-5p-dependent mechanism. Our study revealed that the inhibition of SDC-4 exerts its effects on both cartilage homeostasis and the chondrocyte hypertrophy phenotype by inducing miR-96-5p expression, which results in targeting HIF-2α 3'-UTR sequences and inhibiting HIF-2α in murine cartilage tissue and chondrocytes.

To assess tidal volume (Vt) and minute ventilation (MV) during cardiopulmonary resuscitation (CPR) with two different chest compressions techniques two-finger (TFT) or two-thumb technique (TTT) in a neonatal model.

Vt and MV were continuously measured during consecutive periods of resuscitation in an intubated manikin. Aprotinin concentration Thirty participants performed the two compression techniques in a random order for 2-min periods while performing positive pressure ventilation using a T-piece resuscitator (TPR) or a self-inflating bag (SIB).

Vt during CPR with TFT was significantly higher than TTT with either TPR 44.9 ± 4.3 vs 39.2 ± 5.4 ml (p < 0.001) or SIB 39.2 ± 5.7 vs 35.6 ± 6.5 ml (p < 0.023). Similarly MV was significantly higher in TFT than TTT with either mode 1346 ± 130 vs 1175 ± 162 ml/min, respectively, with TPR (p < 0.001) and 1177 ± 170 vs 1069 ± 196 ml/min with SIB (p < 0.03).

Chest compressions during CPR using the TFT achieved higher Vt and MV than TTT in this model of neonatal resuscitation.

Chest compressions during CPR using the TFT achieved higher Vt and MV than TTT in this model of neonatal resuscitation.

The objective of this study is to analyze the effect of adjusting for body measures on the association between small for gestational age (SGA) and overweight at 3 years.

Data were obtained from the Preterm Infant Multicenter Growth Study (n = 1089). Logistic regression was used, to adjust for confounders with additional adjustments separately for weight and height at 21 months. Marginal structural models (MSMs) estimated the direct effect of SGA on overweight.

The crude and adjusted for confounders models yielded null associations between SGA and overweight. Adjusting for height yielded a positive association (odds ratio (OR) 2.31, 95% CI 0.52-10.26) and adjusting for weight provided a significantly positive association (OR 6.60, 95% CI 1.10-37.14). The MSMs, with height and weight held constant, provided no evidence for a direct effect of SGA on overweight (OR 0.83, 95% CI 0.14-5.01, OR 0.71, 95% CI 0.18-2.81, respectively).

Adjusting for body measures can change the association between SGA and overweight, providing spurious estimates.

Adjusting for body measures can change the association between SGA and overweight, providing spurious estimates.

Characterize the impact of milrinone on arterial pressure of neonates with persistent hypoxemic respiratory failure (HRF) and hypoxic ischemic encephalopathy (HIE) treated with inhaled nitric oxide and therapeutic hypothermia (TH).

Retrospective cohort study. Arterial pressure was assessed hourly for 24 h. The primary outcome was change in diastolic arterial pressure (DAP).

56 patients were included [(i) cases HIE/TH who received milrinone (n = 9), (ii) Milrinone controls (n = 17), (iii) HIE controls (n = 30)]. Baseline demographics, severity of HRF and arterial pressure were comparable between groups. Only milrinone treated patients with HIE/TH had a marked drop in DAP in the first hour, which persisted for more than 12 h despite escalation in inotropes (p = 0.008).

Milrinone treated patients with HRF and HIE/TH develop profound reduction in DAP and require escalation of cardiovascular support. The risk benefit profile of milrinone should be considered and pharmacological studies are warranted to evaluate drug metabolism and clearance in this population.

Milrinone treated patients with HRF and HIE/TH develop profound reduction in DAP and require escalation of cardiovascular support. The risk benefit profile of milrinone should be considered and pharmacological studies are warranted to evaluate drug metabolism and clearance in this population.Placental transfusion results in a significant decrease in the risk of death for extremely preterm infants. With immediate cord clamping (ICC), these infants can leave up to one-half of their normal circulating in utero blood volume in the placenta. Extremely preterm infants are at highest risk of harm from ICC yet are currently the most likely to receive ICC. Receiving a placenta transfusion provides infants with life-saving components and enhanced perfusion. We present some lesser-known but important effects of placental transfusion. New research reveals that enhanced vascular perfusion causes an organ's endothelial cells to release angiocrine responses to guide essential functions. High progesterone levels and pulmonary artery pressure in the first few hours of life assist with neonatal adaptation. We propose that lack of essential blood volume may be a major factor contributing to inflammation, morbidities, and mortality that preterm infants frequently encounter.There is a large body of evidence demonstrating that delaying clamping of the umbilical cord provides benefits for term and preterm infants. These benefits include reductions in mortality in preterm infants and improved developmental scores at 4 years of age in term infants. However, non-breathing or non-vigorous infants at birth are excluded due to the perceived need for immediate resuscitation. Recent studies have demonstrated early physiological benefits in both human and animal models if resuscitation is performed with an intact cord, but this is still an active area of research. Given the large number of ongoing and planned trials, we have brought together an international group that have been intimately involved in the development or use of resuscitation equipment designed to be used while the cord is still intact. In this review, we will present the benefits and limitations of devices that have been developed or are in use. Published trials or ongoing studies using their respective devices will also be reviewed.