Barrisaksen7872

There was no association between asthma and death in patients admitted to the intensive care unit (ICU), however, asthma significantly reduced the risk of death in the hospitalized patients who did not require ICU.

Our results suggest that patients with asthma are less likely to require hospitalization, develop pneumonia, need tracheal intubation or die from COVID-19 as compared to patients without asthma.

Our results suggest that patients with asthma are less likely to require hospitalization, develop pneumonia, need tracheal intubation or die from COVID-19 as compared to patients without asthma.

To identify regional differences in, and determinants of dental caries among children in western Norway.

We studied dental caries in 705 children aged 12 years and 18 years living in the southern region (

 = 403) and other parts of Hordaland County (

 = 302) in Norway. Information on oral hygiene, fluoride intake, and sugar consumption was collected using questionnaires. We also collected information from the Public Dental Service (PDS) on the history of decayed, missing, or filled teeth; professional fluoride application; recall and regular check-up intervals and treatment visits. Residence (southern region versus the rest of Hordaland, the reference) was the independent variable. We analysed regional differences in (i) caries prevalence and severity, (ii) potential contributors to caries, and (iii) procedures and routines in PDS.

Caries prevalence and severity were higher in the southern region (67% and 24%, respectively). Self-reported brushing habits, fluoride use, and sugar consumption patterns were similar between regions. We observed more frequent application of professional fluoride (incidence rate ratio [IRR] = 3.05, 95% CI 1.99-4.66], fewer check-ups [IRR = 0.88, 95% CI 0.81-0.95], and fewer treatment visits [IRR = 0.77, 95% CI 0.60-0.98] among participants in the southern region, compared to the rest of Hordaland. The recall intervals in the southern region were 10% longer among 12-year-olds and 10% shorter among 18-year-olds, compared to their respective counterparts in Hordaland.

The observed regional gradients in caries experience mirrored regional differences in dental routines and procedures. Caries-related risk behaviours did not explain the observed differences in caries experience.

The observed regional gradients in caries experience mirrored regional differences in dental routines and procedures. Caries-related risk behaviours did not explain the observed differences in caries experience.

Sodium oxybate (SXB) is a standard of care for cataplexy, excessive daytime sleepiness, and disrupted nighttime sleep in narcolepsy. At recommended dosages in adults (6-9g/night), SXB increases daily dietary intake of sodium by 1100-1640 mg. Because excess sodium intake is associated with increased blood pressure and cardiovascular risk, an oxybate formulation containing 92% less sodium than SXB (lower-sodium oxybate; LXB) was developed to provide an alternative oxybate treatment option. In 2020, LXB was approved for treatment of cataplexy or excessive daytime sleepiness in patients 7years of age and older with narcolepsy, and in 2021, for treatment of idiopathic hypersomnia in adults.

Development of LXB from initial concept to regulatory approval is described, including formulation development and preclinical and clinical studies. Pharmacokinetic parameters and bioequivalence evaluations from phase 1 clinical trials are detailed. Efficacy and safety results from phase 3 clinical trials of LXB in patientsum, and potassium ions in addition to a small amount of sodium to make a new oxybate medication, called Xywav®, that has 92% less sodium than Xyrem. Xywav and Xyrem were similar in laboratory and animal studies. In people, the body absorbs and processes Xywav slightly differently than Xyrem, but Xywav treatment has been shown to work the same to reduce symptoms of cataplexy and EDS in people with narcolepsy and is approved by the US Food and Drug Administration. Another neurological disorder with EDS is called idiopathic hypersomnia. Based on a clinical study, Xywav also reduced EDS and other symptoms in people with idiopathic hypersomnia. Side effects with Xywav are similar to those seen in previous studies with Xyrem.

Succinic acid and irbesartan are commonly used drugs in cardiovascular disease treatment. The interaction might occur during their co-administration, which was still unclear.

To reveal the effect of succinic acid on the metabolism of irbesartan and its potential mechanism.

The Sprague-Dawley rats (

 = 6) were treated with a single dose of 30 mg/kg irbesartan (control) or the co-administration with the pre-treatment of 200 mg/kg succinic acid for 7 d. The effect of succinic acid on the metabolic stability and the activity of CYP2C9 was evaluated in rat liver microsomes.

Succinic acid increased the AUC (5328.71 ± 959.31 μg/L × h vs. 3340.23 ± 737.75 μg/L × h) and prolonged the half-life of irbesartan (from 12.79 ± 0.73 h to 20.59 ± 6.35 h). The



(2.83 ± 0.75 h vs. 3.83 ± 1.10 h) and clearance rate (3.46 ± 1.13 L/h/kg vs. 6.91 ± 1.65 L/h/kg) of irbesartan was reduced by succinic acid. Consistently, succinic acid improved the metabolic stability (half-life from 23.32 ± 3.46 to 27.35 ± 2.15 min, intrinsic clearance rate from 59.43 ± 6.12 to 50.68 ± 5.64 μL/min/mg protein). Succinic acid was also found to inhibit the activity of CYP2C9 with the IC

value of 13.87 μM.

Succinic acid increased the system exposure of irbesartan via inhibiting CYP2C9. The experiment design of this study also provides a reference for the further validation of this interaction in humans.

Succinic acid increased the system exposure of irbesartan via inhibiting CYP2C9. The experiment design of this study also provides a reference for the further validation of this interaction in humans.

To assess the relation between socioeconomic status and achievement of target blood pressure in hypertension.

Retrospective longitudinal cohort study between 2001 and 2014.

Primary health care in Skaraborg, Sweden.

48,254 patients all older than 30 years, and 53.3% women, with diagnosed hypertension.

Proportion of patients who achieved a blood pressure target <140/90 mmHg in relation to the country of birth, personal disposable income, and educational level.

Patients had a lower likelihood of achieving the blood pressure target if they were born in a Nordic country outside Sweden [risk ratio 0.92; 95% confidence interval (CI) 0.88-0.97], or born in Europe outside the Nordic countries (risk ratio 0.87; 95% CI 0.82-0.92), compared to those born in Sweden. Patients in the lowest income quantile had a lower likelihood to achieve blood pressure target, as compared to the highest quantile (risk ratio 0.93; 95% CI 0.90-0.96). Educational level was not associated with outcome. Women but not men in the income were factors associated with poorer blood pressure control.KEY POINTSThe association between socioeconomic status and achieving blood pressure targets in hypertension has been ambiguous.•In this study of 48,254 patients with hypertension, lower income was associated with a reduced likelihood to achieve blood pressure control.•Being born in a foreign European country is associated with a lower likelihood to achieve blood pressure control.•We found no association between educational level and achieved blood pressure control.The V-domain Ig Suppressor of T-cell Activation (VISTA) is an immune checkpoint regulator that suppresses immune responses and is readily expressed on human and murine myeloid cells and T cells. This immunosuppressive pathway can be activated using VISTA agonists. Here, we report the development of murine anti-human VISTA (anti-hVISTA) monoclonal antibodies (mAbs), anti-hVISTA nanobodies (Nbs), and cross-reactive rat anti-murine/human VISTA (anti-hmVISTA) mAbs. All mAbs and Nbs generated bound to VISTA (human and/or murine) with dissociation constants in the sub-nanomolar or low nanomolar range. Competition analysis revealed that the selected Nbs bound the same or a nearby epitope(s) as the human VISTA-specific mAbs. However, the cross-reactive mAbs only partially competed with Nbs for binding to hVISTA. All mAbs and one Nb (hVISTANb7) were able to strongly detect VISTA expression on primary human monocytes. Importantly, the murine anti-hVISTA mAbs 7E12 and 7G5 displayed strong agonistic activity in human peripheral blood mononuclear cell cultures, while Nb7 and rat anti-hmVISTA mAbs 3C3, 7C6, 7C7, and 7G1 also behaved as hVISTA agonists, albeit to a lesser extent. Cross-reactive mAbs 7C7 and 7G1 further displayed agonistic potential in murine splenocyte assays. Importantly, mAb 7G1 significantly reduced inflammation associated with the murine model of imiquimod-induced psoriasis. These agonistic VISTA mAbs may represent therapeutic leads to treat inflammatory disorders.Severe acute respiratory syndrome coronavirus 2 variants have continued to emerge in diverse geographic locations with a temporal distribution. The Lambda variant containing multiple mutations in the spike protein, has thus far appeared mainly in South America. The variant harbours two mutations in the receptor binding domain, L452Q and F490S, which may change its infectivity and antigenicity to neutralizing antibodies. In this study, we constructed 10 pseudoviruses to study the Lambda variant and each individual amino acid mutation's effect on viral function, and used eight cell lines to study variant infectivity. In total, 12 monoclonal antibodies, 14 convalescent sera, and 23 immunized sera induced by mRNA vaccines, inactivated vaccine, and adenovirus type 5 vector vaccine were used to study the antigenicity of the Lambda variant. We found that compared with the D614G reference strain, Lambda demonstrated enhanced infectivity of Calu-3 and LLC-MK2 cells by 3.3-fold and 1.6-fold, respectively. Notably, the sensitivity of the Lambda variant to 5 of 12 neutralizing monoclonal antibodies, 9G11, AM180, R126, X593, and AbG3, was substantially diminished. Furthermore, convalescent- and vaccine-immunized sera showed on average 1.3-2.5-fold lower neutralizing titres against the Lambda variant. Single mutation analysis revealed that this reduction in neutralization was caused by L452Q and F490S mutations. Collectively, the reduced neutralization ability of the Lambda variant suggests that the efficacy of monoclonal antibodies and vaccines may be compromised during the current pandemic.WDR45-related neurodevelopmental disorder (NDD) is a clinically-heterogenous congenital disorder of macroautophagy/autophagy. The natural history of this ultra-orphan disease remains incompletely understood, leading to delays in diagnosis and lack of quantifiable outcome measures. In this cross-sectional study, we model quantitative natural history data for WDR45-related NDD using a standardized analysis of 160 published cases, representing the largest cohort to date. The primary outcome of this study was survival. Age at disease onset, diagnostic delay and geographic distribution were quantified as secondary endpoints. Our tertiary aim was to explore and quantify the spectrum of WDR45-related phenotypes. Survival estimations showed low mortality until 39 years of age. check details Median age at onset was 10 months, with a median diagnostic delay of 6.2 years. Geographic distribution appeared worldwide with clusters in North America, East Asia, Western Europe and the Middle East. The clinical spectrum was highly variable with a bi-phasic evolution characterized by early-onset developmental and epileptic encephalopathy during childhood followed by a progressive dystonia-parkinsonism syndrome along with cognitive decline during early adulthood.