Irwinottosen8406
Biochemical and biophysical analyses revealed slightly destabilized kinetic stability. T96R mutation destabilized heterozygous protein but not proteolytic degradation, explaining its pathogenicity. Inhibitory effect of small molecule drugs on T96R mutation was different, suggesting personalized treatment may be required.
A novel T96R mutation was identified for TTR protein. Biochemical and biophysical analyses revealed slightly destabilized kinetic stability. T96R mutation destabilized heterozygous protein but not proteolytic degradation, explaining its pathogenicity. Inhibitory effect of small molecule drugs on T96R mutation was different, suggesting personalized treatment may be required.Chromosome instability (CIN) is an important driver of cancer initiation, progression, drug resistance, and aging. As such, genes whose inhibition suppresses CIN are potential therapeutic targets. We report here that deletion of an accessory DNA helicase, Rrm3, suppresses high CIN caused by a wide range of genetic or pharmacological perturbations in yeast. Although this helicase mutant has altered cell cycle dynamics, suppression of CIN by rrm3∆ is independent of the DNA damage and spindle assembly checkpoints. Instead, the rrm3∆ mutant may have increased kinetochore-microtubule error correction due to an altered localization of Aurora B kinase and associated phosphatase, PP2A-Rts1.
Fitness technologies such as wearables and sit-stand desks are increasingly being used to fight sedentary lifestyles by encouraging physical activity. However, adherence to such technologies decreases over time because of apathy and increased dismissal of behavioral nudges.
To address this problem, we introduced shared autonomy in the context of sit-stand desks, where user input is integrated with robot autonomy to control the desk and reduce sedentary behavior and investigated user reactions and preferences for levels of automation with a sit-stand desk. As demographics affect user acceptance of robotic technology, we also studied how perceptions of nonvolitional behavior change differ across cultures (United States and India), sex, familiarity, dispositional factors, and health priming messages.
We conducted a web-based vignette study in the United States and India where a total of 279 participants watched video vignettes of a person interacting with sit-stand desks of various levels of automation andutcomes. Demographics such as culture and sex had significant effects on how receptive users were to autonomous intervention. As familiarity improves the likelihood of adoption, we propose a gradual behavior change intervention to increase acceptance and adherence, especially for populations with a high desire for control.
These results suggest that the shared autonomy desk is the optimal level of automation in terms of both user preferences and estimated projected health outcomes. Demographics such as culture and sex had significant effects on how receptive users were to autonomous intervention. As familiarity improves the likelihood of adoption, we propose a gradual behavior change intervention to increase acceptance and adherence, especially for populations with a high desire for control.The prevalence of multidrug-resistant bacterial infections has led to dramatically increased morbidity and mortality. Antimicrobial peptides (AMPs) have great potential as new therapeutic agents to reverse this dangerous trend. Herein, a series of novel AMP Feleucin-K3 analogues modified with unnatural peptidomimetic sulfono-γ-AA building blocks were designed and synthesized. The structure-activity, structure-toxicity, and structure-stability relationships were investigated to discover the optimal antimicrobial candidates. Among them, K122 exhibited potent and broad-spectrum antimicrobial activity and high selectivity. K122 had a rapid bactericidal effect and a low tendency to induce resistance. Surprisingly, K122 showed excellent effectiveness against bacterial pneumonia. For biofilm and local skin infections, K122 significantly decreased the bacterial load and improved tissue injury at a dose of only 0.25 mg/kg, which was 160 times lower than the concentration deemed to be safe for local dermal applications. In summary, K122 is an outstanding candidate for the treatment of multidrug-resistant bacteria and biofilm infections.Introduction Opioid use has disproportionally impacted pregnant people and their fetuses. Previous studies describing opioid use among pregnant people are limited by geographic location, type of medical coverage, and small sample size. We described characteristics of a large, diverse group of pregnant people who were enrolled in the Environmental Influences on Child Health Outcomes (ECHO) Program, and determined which characteristics were associated with opioid use during pregnancy. Materials and Methods Cross-sectional data obtained from 21,905 pregnancies of individuals across the United States enrolled in the ECHO between 1990 and 2021 were analyzed. Medical records, laboratory testing, and self-report were used to determine opioid-exposed pregnancies. Multiple imputation methods using fully conditional specification with a discriminant function accounted for missing characteristics data. Results Opioid use was present in 2.8% (n = 591) of pregnancies. The majority of people who used opioids in pregnancy wancy, while further elucidation of the reasons for use of prescription opioids during pregnancy should be further explored.
Internet-based interventions (IBIs) are effective for the prevention and treatment of mental disorders and are valuable additions for improving routine care. However, the uptake of and adherence to IBIs are often limited. To increase the actual use of IBIs, it is important to identify factors for engaging with and adhering to IBIs.
We qualitatively evaluated barriers and facilitators regarding a portfolio of guided IBIs in green professions (farmers, gardeners, and foresters).
Interview participants were selected from 2 randomized controlled trials for either the prevention of depression (Prevention of Depression in Agriculturists [PROD-A]) or the reduction of pain interference (Preventive Acceptance and Commitment Therapy for Chronic Pain in Agriculturists [PACT-A]) in green professions. The intervention group in PROD-A (N=180) participated in an IBI program, receiving access to 1 of 6 symptom-tailored IBIs. The intervention group in PACT-A (N=44) received access to an IBI for chronic pain. Overall, 41in further quantitative research designs in terms of their potential to enhance intervention use in this occupational group.
German Clinical Trials Register DRKS00014000, https//tinyurl.com/3bukfr48; German Clinical Trials Register DRKS0001461, https//tinyurl.com/ebsn4sns.
German Clinical Trials Register DRKS00014000, https//tinyurl.com/3bukfr48; German Clinical Trials Register DRKS0001461, https//tinyurl.com/ebsn4sns.
The increasing number of children with cerebral palsy (CP) has a serious impact on individuals, families, and society. see more As a new technology, virtual reality (VR) has been used in the rehabilitation of children with CP.
This study aimed to systematically evaluate the effect of VR training on balance, gross motor function, and daily living ability in children with CP.
PubMed, Embase, The Cochrane Library, Web of Science, and China National Knowledge Infrastructure databases were searched by computer, with the search period being from the establishment of each database to December 25, 2021, to collect randomized controlled trials (RCTs) on the effects of VR training on balance, gross motor function, and daily living ability in children with CP. The Cochrane risk of bias assessment tool was used to conduct quality assessment on the included literature, and RevMan software (version 5.3) was used to analyze data.
A total of 16 articles were included, involving 513 children with CP. VR training can improve the balance function (Pediatric Balance Scale mean difference 2.06, 95% CI 1.15-2.97; P<.001; Berg Balance Scale mean difference 3.66, 95% CI 0.29-7.02; P=.03) and gross motor function (standardized mean difference [SMD] 0.60, 95% CI 0.34-0.87; P<.001) of children with CP. However, there is still certain disagreement on the impact on daily living ability (SMD 0.37, 95% CI -0.04 to 0.78; P=.08); after removing the source literature with heterogeneity, VR training can improve the daily living ability of children with CP (SMD 0.55, 95% CI 0.30-0.81; P<.001).
VR training can significantly improve the balance function and gross motor function of children with CP, but the effect on the daily living ability of children with CP remains controversial.
VR training can significantly improve the balance function and gross motor function of children with CP, but the effect on the daily living ability of children with CP remains controversial.Glioblastoma (GBM) is one of the most aggressive brain tumors and has a high recurrence rate, and effective treatment is urgently needed. GBM stem cells (GSCs) contribute to GBM recurrence as well as therapeutic resistance to radiation and chemotherapy. Several oncolytic viruses (OVs) have been developed and validated in clinical trials with favorable safety profiles and efficacy against GBM. Recently, Zika virus (ZIKV), a mosquito-borne flavivirus, was shown to preferentially target and kill GSCs and showed promising therapeutic effects in treating GBM in preclinical models. In this review, we summarize the known OVs for the treatment of GBM and highlight the major advantages and existing challenges for the clinical development of oncolytic ZIKV.Aim To evaluate the impact of previous infection on perioperative outcomes in patients undergoing thoracoscopic lobectomy for congenital lung anomalies. Methods This was a single-institution retrospective observational study for which patients who underwent thoracoscopic lobectomy for congenital lung disease between 2009 and 2021 were enrolled, and patients with extralobar sequestration were excluded. Patient background and data related to the surgery were compared between patients who had an infection before surgery (Group 1) and those who did not (Group 2). Results This study included 34 patients, 13 in Group 1 and 21 in Group 2. The sex-based distribution and pathological diagnosis were similar between the two groups. Malformations were prenatally diagnosed in 1 patient in Group 1 (7.7%) and 18 patients in Group 2 (86%; P less then .001). The median age and weight at the time of the procedure and procedure duration were comparable between the two groups. The amount of blood loss was significantly higher in Group 1 (60 mL) than in Group 2 (20 mL; P = .0042). Four patients in Group 2 required reoperation due to air leakage, pyothorax, and cardiac tamponade, whereas none of the Group 1 patients required reoperation (P = .12). No conversion to thoracotomy was required in either group. The duration of postoperative admission was similar between the two groups (Group 1 6 days versus Group 2 6 days; P = .14). Conclusions Preceding infection increased the amount of bleeding during thoracoscopic lobectomy but had little effect on other outcomes.
