Laserlight heat on the Two opposites Beamline P02Two PETRA III

Median age at time of confirmation of the diagnosis was 9.95 days (range 0-39d). In the univariate analysis, male sex, preterm birth, hypoxia and related indicators (umbilical artery pH <7.1; 5-minute Apgar score <7; intubation/mask ventilation; perinatal asphyxia), operative vaginal delivery, emergency Caesarean section, and pathological fetal Doppler sonography were associated (p<0.05) with neonatal CSVT. Multivariable regression yielded hypoxia (odds ratio=20.3; 95% CI 8.1-50.8) as the independent risk factor.
Incidence of neonatal CSVT was within the range of other population-based studies. The results suggest that hypoxia is an important perinatal risk factor for the aetiology of neonatal CSVT.
Incidence of neonatal CSVT was within the range of other population-based studies. The results suggest that hypoxia is an important perinatal risk factor for the aetiology of neonatal CSVT.High-quality data are needed to guide interventions aimed at improving breast cancer outcomes in sub-Saharan Africa. We present data from an institutional breast cancer database to create a framework for cancer policy and development in Nigeria. An institutional database was queried for consecutive patients diagnosed with breast cancer between January 2010 and December 2018. Sociodemographic, diagnostic, histopathologic, treatment and outcome variables were analyzed. Of 607 patients, there were 597 females with a mean age of 49.8 ± 12.2 years. Most patients presented with a palpable mass (97%) and advanced disease (80.2% ≥ Stage III). Immunohistochemistry was performed on 21.6% (131/607) of specimens. Forty percent were estrogen receptor positive, 32.8% were positive for HER-2 and 43.5% were triple negative. Surgery was performed on 49.9% (303/607) of patients, while 72% received chemotherapy and 7.9% had radiotherapy. At a median follow-up period of 20.5 months, the overall survival was 43.6% (95% CI -37.7 to 49.5). Among patients with resectable disease, 18.8% (57/303) experienced a recurrence. Survival was significantly better for early-stage disease (I and II) compared to late-stage disease (III or IV) (78.6% vs 33.3%, P  less then  .001). Receipt of adjuvant radiotherapy after systemic chemotherapy was associated with improved survival in patients with locally advanced disease (68.5%, CI -46.3 to 86 vs 51%, CI 38.6 to 61.9, P  less then  .001). This large cohort highlights the dual burden of advanced disease and inadequate access to comprehensive breast cancer care in Nigeria. There is a significant potential for improving outcomes by promoting early diagnosis and facilitating access to multimodality treatment.Smith-Kingsmore syndrome (SKS) is a rare autosomal dominant disorder caused by heterozygous germline activating pathogenic variants in mammalian target of rapamycin (MTOR) on chromosome 1p36. A few patients with disseminated mosaicism have been described so far and they seem to display a different phenotype when compared to germline cases. Here we report the sixth case with a disseminated mosaic MTOR pathogenic variant, a 7-year-old boy with hemimegalencephaly, epilepsy, developmental delay, hypomelanosis of Ito, and lateralized overgrowth. Genetic testing revealed a pathogenic variant (c.4448G > A, p.Cys1483Tyr) in MTOR with a frequency of 32% in the DNA extracted from a skin sample, 3% in saliva and 0.46% in blood. The clinical features observed in our patient further corroborate the existence of differences in phenotypic presentation of germline and mosaic SKS cases. Moreover, lateralized overgrowth, a finding never described so far in SKS, further expands the phenotypic spectrum of SKS and allows the inclusion of MTOR pathogenic variants among the several causes of asymmetric body overgrowth.The intestinal environment is unique because it supports the intestinal epithelial cells under a normal oxygen environment and the microbiota under an anoxic environment. Due to importance of understanding the interactions between the epithelium and the microbiota, there is a strong need for developing representative and simple experimental models. Current approaches do not capture the partitioned oxygen environment, require external anaerobic chambers, or are complex. Another major limitation is that with the solutions that can mimic this oxygen environment, the oxygenation level of the epithelial cells is not known, raising the question whether the cells are hypoxic or not. We report standalone microfluidic devices that form a partitioned oxygen environment without the use of an external anaerobic chamber or oxygen scavengers to coculture intestinal epithelial and bacterial cells. By changing the thickness of the device cover, the oxygen tension in the chamber was modulated. We verified the oxygen levels using several tests microscale oxygen sensitive sensors which were integrated within the devices, immunostaining of Caco-2 cells to determine hypoxia levels, and genetically encoded bacteria to visualize the growth. Collectively, these methods monitored oxygen concentrations in the devices more comprehensively than previous reports and allowed for control of oxygen tension to match the requirements of both intestinal cells and anaerobic bacteria. Our experimental model is supported by the mathematical model that considered diffusion of oxygen into the top chamber. This allowed us to experimentally determine the oxygen consumption rate of the intestinal epithelial cells under perfusion.
During endoscopic submucosal dissection for superficial esophageal cancer, patient body movement can sometimes occur, which may cause discontinuation of the procedure. Propofol and dexmedetomidine have recently been found to be useful sedatives for endoscopic submucosal dissection. This study investigated whether sedation using propofol plus dexmedetomidine can suppress the patient's body movements during esophageal endoscopic submucosal dissection and compared this combination with sedation using propofol alone.
This was a prospective double-blind randomized controlled trial. Patients with superficial esophageal cancers who underwent esophageal endoscopic submucosal dissection at Yokohama City University Hospital were prospectively enrolled and were randomly assigned to the propofol and the propofol plus dexmedetomidine groups. The primary endpoint was the incidence of restlessness. The secondary endpoints were the satisfaction score, maintenance dose of propofol, and number of rescue propofol injections.
Sixty-six patients (propofol group n=33; combination group n=33) were included. The combination group had a significantly lower incidence of restlessness than the propofol group (3.0% vs 27.3%, P=0.02). In the combination group, the satisfaction scores of the endoscopists were significantly higher, the maintenance dose of propofol was significantly lower, and the number of rescue propofol injections was lower than those in the propofol group (3.0% vs 18.2%, P<0.001). Although the incidence of bradycardia was significantly higher in the combination group (30.3% vs 3.0%, P<0.01), no serious adverse effects occurred.
The propofol plus dexmedetomidine combination provided excellent sedation that effectively suppressed the patient's body movements during esophageal endoscopic submucosal dissection.
The propofol plus dexmedetomidine combination provided excellent sedation that effectively suppressed the patient's body movements during esophageal endoscopic submucosal dissection.For the development of coronavirus disease 2019 (COVID-19) drugs during the ongoing pandemic, speed is of essence whereas quality of evidence is of paramount importance. Although thousands of COVID-19 trials were rapidly started, many are unlikely to provide robust statistical evidence and meet regulatory standards (e.g., because of lack of randomization or insufficient power). This has led to an inefficient use of time and resources. With more coordination, the sheer number of patients in these trials might have generated convincing data for several investigational treatments. Collaborative platform trials, comparing several drugs to a shared control arm, are an attractive solution. Those trials can utilize a variety of adaptive design features in order to accelerate the finding of life-saving treatments. In this paper, we discuss several possible designs, illustrate them via simulations, and also discuss challenges, such as the heterogeneity of the target population, time-varying standard of care, and the potentially high number of false hypothesis rejections in phase II and phase III trials. We provide corresponding regulatory perspectives on approval and reimbursement, and note that the optimal design of a platform trial will differ with our societal objective and by stakeholder. Hasty approvals may delay the development of better alternatives, whereas searching relentlessly for the single most efficacious treatment may indirectly diminish the number of lives saved as time is lost. We point out the need for incentivizing developers to participate in collaborative evidence-generation initiatives when a positive return on investment is not met.
Targeting macrophage but not hepatocyte liver X receptors (LXRs) can reduce atherosclerosis without effect on hepatic lipogenesis. In this study, we encapsulated LXR ligands with D-Nap-GFFY to form a nanofibre hydrogel (D-Nap-GFFY-T0901317 or GFFY-T0901317) and determined its effect on atherosclerosis, hepatic lipogenesis and the underlying mechanisms involved.
D-Nap-GFFY-T0901317 was subcutaneously injected to proatherogenic diet-fed apoE-deficient (Apoe
) mice, followed by determination of the development of atherosclerosis, liver steatosis and the involved mechanisms, with comparison of T0901317 oral administration.
Subcutaneous injection of D-Nap-GFFY-T0901317 to Apoe
mice inhibited atherosclerosis at a comparable level as T0901317 oral administration without effect on hepatic lipogenesis. More importantly, D-Nap-GFFY-T0901317 regressed the advanced lesions. In arterial wall, D-Nap-GFFY-T0901317 reduced macrophage/foam cells, necrotic cores and calcification and increased collagen content. It acicating its potential application for atherosclerosis treatment.
The α7 and α4β2* ("*" denotes possibly assembly with another subunit) nicotinic acetylcholine receptors (nAChRs) are the most abundant nAChRs in the mammalian brain. These receptors are the most targeted nAChRs in drug discovery programmes for brain disorders. However, the development of subtype-specific agonists remains challenging due to the high degree of sequence homology and conservation of function in nAChRs. We have developed C(10) variants of cytisine, a partial agonist of α4β2 nAChR that has been used for smoking cessation. read more The C(10) methyl analogue used in this study displays negligible affinity for α7 nAChR, while retaining high affinity for α4β2 nAChR.
The structural underpinning of the selectivity of 10-methylcytisine for α7 and α4β2 nAChRs was investigated using molecular dynamic simulations, mutagenesis and whole-cell and single-channel current recordings.
We identified a conserved arginine in the β3 strand that exhibits a non-conserved function in nAChRs. In α4β2 nAChR, the arginine forms a salt bridge with an aspartate residue in loop B that is necessary for receptor expression, whereas in α7 nAChR, this residue is not stabilised by electrostatic interactions, making its side chain highly mobile.