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MicroRNAs (miRNAs) play a crucial role in regulating gene expression and influence many biological processes. Despite their importance, understanding of how genetic variation affects miRNA expression in the brain and how this relates to brain disorders remains limited. Here we investigated these questions by identifying microRNA expression quantitative trait loci (miR-QTLs), or genetic variants associated with brain miRNA levels, using genome-wide small RNA sequencing profiles from dorsolateral prefrontal cortex samples of 604 older adult donors of European ancestry. Here we show that nearly half (224 of 470) of the analyzed miRNAs have associated miR-QTLs, many of which fall in regulatory regions such as brain promoters and enhancers. We also demonstrate that intragenic miRNAs often have genetic regulation independent from their host genes. Furthermore, by integrating our findings with 16 genome-wide association studies of psychiatric and neurodegenerative disorders, we identified miRNAs that likely contribute to bipolar disorder, depression, schizophrenia and Parkinsons disease. These findings advance understanding of the genetic regulation of miRNAs and their role in brain health and disease.

BackgroundWeb-based time-use diaries for schoolchildren are limited, and existing studies focus mostly on capturing physical activities and sedentary behaviors but less comprehensively on dietary behaviors. ObjectiveThis study aims to describe the development of My E-Diary for Activities and Lifestyle (MEDAL)—a self-administered, web-based time-use application to assess diet and movement behavior—and to evaluate its usability in schoolchildren in Singapore. MethodsMEDAL was developed through formative research and an iterative user-centric design approach involving small groups of schoolchildren (ranging from n=5 to n=15, aged 7-13 years). To test the usability, children aged 10-11 years were recruited from 2 primary schools in Singapore to complete MEDAL for 2 weekdays and 2 weekend days and complete a 10-item usability questionnaire. ResultsThe development process revealed that younger children (aged

Meloxicam is a nonsteroidal anti-inflammatory analgesic drug that is often used in mice. However, doses of 1 to 5 mg/kg given twice daily were recently reported to provide inadequate analgesia. Some studies suggest that doses of up to 20 mg/kg may be necessary for adequate pain management. We investigated the analgesia provided by a high-dose of meloxicam in female CD1 mice. Pharmacokinetic analyses demonstrated that a subcutaneous injection of 10 mg/kg or 20 mg/kg of meloxicam produced therapeutic plasma concentrations for at least 12 h. Ovariectomies via ventral laparotomy were performed to assess analgesic efficacy. Mice were treated immediately before surgery with a high-dose of 10 mg/kg, a low-dose of 2.5 mg/kg, or saline, followed by every 12 h for 36 h. At 3, 6, 12, 24, and 48 h after surgery, mice were assessed for pain based on the following behaviors: distance traveled, time mobile, grooming, rearing, hunched posture, orbital tightening, and von Frey. Initially, some mice received a 20-mg/kg loading dose followed by 10 mg/kg every 12 h. This regimen caused severe morbidity and mortality in 2 mice. Subsequently, this regimen was abandoned, and mice assigned to the high-dose group received 10 mg/kg every 12 h. Mice that received the 10-mg/kg dose after surgery showed less orbital tightening between 3 to 6 h and reduced frequency of hunched posture for 48 h compared with mice that received either the low-dose or saline. However, mice were significantly less mobile for 6 to 12 h after surgery regardless of treatment. These data indicate that a meloxicam dose of 10 mg/kg every 12 h provides better analgesia than a 2.5-mg/kg dose but does not completely alleviate pain.

Buprenorphine (Bup) is an opioid analgesic that is commonly used in laboratory rodents to provide postoperative analgesia. However, dosing every 4 to 6 h is necessary to maintain an analgesic plasma concentration of the drug. A long lasting, highly concentrated veterinary formulation of Bup (LHC-Bup) has been used to provide prolonged analgesia in cats and nonhuman primates. In the current study, we evaluated the duration of efficacy of LHC-Bup to determine if this formulation would provide a similarly prolonged analgesia in rats. Drug concentrations were measured after subcutaneous injection of 0.5 mg/kg LHC-Bup in both male and female rats. Plasma levels were measured at 0.25, 0.5, 1, 2, 4, 8, 12, 24, 36, 48, and 72 h. Male and female rats had peak plasma levels of LHC-Bup at 90 ng/mL and 34 ng/mL, respectively, at 15 min after administration, with a steady decrease by 24 h to 0.7 ng/mL in males and 1.3 ng/mL in females. Mechanical pain tolerance was evaluated after LHC-Bup administration using a Randall-Selitto analgesiometer to assess paw withdrawal. Male rats had a significantly longer paw withdrawal time for up to 12 h after administration, and females had longer paw withdrawal times for up to 24 h. An experimental laparotomy model was then used to assess the clinical efficacy of LHC-Bup at 0.5 mg/kg. LHC-Bup treatment was associated with a greater total distance traveled, reduced time to retrieve a food treat, and reduced grooming from 3 to 12 h after surgery as compared with saline controls. Groups receiving LHC-Bup showed coprophagy whereas other rats did not. These results suggest that administering LHC-Bup at 0.5 mg/kg provides therapeutic plasma concentrations for 12 to 24 h after administration and analgesic efficacy for at least 12 h after dosing. As such, LHC-Bup is a suitable alternative to Bup-HCl.

Aim: Determining specific causes of allograft failure allows a focus on understanding and treating these conditions. Previous studies highlight chronic antibody‐mediated rejection as a leading cause of late allograft failure. We sought to define causes of allograft failure in a large cohort of kidney transplant recipients across multiple centres in Australia and New Zealand, including cases previously attributed to chronic allograft nephropathy (CAN). Methods: All death‐censored allograft failures at 9 participating centres between 1 January 2014 to 31 December 2018 were included. Available clinical and biopsy data were reviewed and the "most likely" cause assigned. Results: There were 642 death‐censored allograft failures in the study period. Of these, 495 (77.1%) had an informative biopsy performed a median of 13.4 months (IQR 2.5–39.1 months) prior to allograft failure. Rejection of any type was the leading cause of allograft failure (47.5%), comprised chiefly of chronic antibody‐mediated rejection (37.4%) and chronic T‐cell mediated rejection (6.4%). Other leading causes were undifferentiated interstitial fibrosis and tubular atrophy (10.8%), late medical and surgical complications (8.1%) and recurrent or de novo glomerulonephritis (7.0%). Polyoma viral nephropathy and calcineurin inhibitor toxicity each contributed to <2%. Causes of allograft failure previously attributed to CAN (n = 419, 65.3%) had a similar distribution to the overall cohort, with 43.9% attributed to chronic antibody‐mediated rejection. Conclusion: To prolong allograft survival, improved strategies are needed to curtail alloimmune responses. Greater understanding of the causes of undifferentiated interstitial fibrosis and tubular atrophy and potential treatments would also be of considerable benefit. Summary at a Glance: In a multicentre, 5‐year, cross‐sectional analysis, rejection, particularly chronic antibody mediated rejection was the leading cause of allograft failure. Further efforts to prevent allo‐immune injury are therefore needed. Interstitial fibrosis and tubular atrophy not due to rejection was also common and requires further exploration into causation and prevention. [ABSTRACT FROM AUTHOR]

Background: Having a brother or sister who has a chronic illness (lasting >6 months and requiring long-term care) or life-limiting condition (LLC; where cure is highly unlikely and the child is expected to die) has major impacts on siblings. Parent–sibling illness-related communication may contribute to siblings' capacity to cope. Objectives: In this study, we aimed to explore parent–sibling illness-related communication, from the perspectives of parents and siblings. We also aimed to qualitatively compare participants' responses according to illness group (chronic illness vs. LLCs). Methods: We collected qualitative data from siblings (32 with a brother/sister with a chronic illness, 37 with a brother/sister with an LLC) and parents of a child with a chronic illness (n = 86) or LLC (n = 38) using purpose-designed, open-ended survey questions regarding illness-related communication. We used an inductive qualitative content analysis and matrix coding to explore themes and compare across illness groups. Results: Two-thirds of siblings expressed satisfaction with their family's illness-related communication. Siblings typically reported satisfaction with communication when it was open and age-appropriate, and reported dissatisfaction when information was withheld or they felt overwhelmed with more information than they could manage. Parents generally favored an open communication style with the siblings, though this was more common among parents of children with an LLC than chronic illness. Significance of results: Our findings show that while many siblings shared that they felt satisfied with familial illness-related communication, parents should enquire with the siblings about their communication preferences in order to tailor illness-related information to the child's maturity level, distress, and age. [ABSTRACT FROM AUTHOR]

The present study set out to examine students' preferences for lecturers' personality as a function of their classroom behaviour, core self-evaluations and self-rated character strengths. Various hypotheses were tested: first, students' Big Five traits would significantly predict corresponding personality preferences for lecturers (the matching hypothesis); second, students' core self-evaluation scores would significantly predict preferences for extraverted, agreeable and conscientious lecturers; and third, self-rated character strengths would also significantly predict extraverted, agreeable and conscientious lecturers. We also investigated difference in preferences among two ethnic groups (South East Asian/Chinese versus Caucasian/British). In all, 264 British students completed four questionnaires. Conscientiousness was the most desired trait in lecturers, followed by agreeableness, extraversion and openness; neuroticism was the least desired trait. Preference for agreeable lecturers was best predicted by all individual difference variables. Caucasian students had a stronger dislike for neurotic lecturers, while Asians had higher preferences for extraverted, open and agreeable lecturers. There was some evidence of the student-lecturer personality match. Limitations and further research options were discussed.

The article discusses a case study of a 32-year-old woman with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). The patient presented with recurrent strokes, migraines, and large- and medium-artery aneurysms, along with a NOTCH3 mutation. While CADASIL is typically associated with small-vessel arteriopathy, this case highlights the rare occurrence of large artery involvement. The study emphasizes the importance of vascular evaluation in patients with CADASIL due to potential medium-to-large artery abnormalities. [Extracted from the article]

This correction notice addresses errors in Figures 2, 3, and S3 of the article titled "Dynein and Dynactin Leverage Their Bivalent Character to Form a High-Affinity Interaction." The correction provides updated versions of the figures to address the issues. The corresponding author stated that the individual-level quantitative data underlying the article are no longer available. The authors acknowledge the errors, apologize, and are grateful for the opportunity to correct them. [Extracted from the article]

Fulminant type 1 diabetes (FT1D) is a unique subtype of type 1 diabetes, characterized by acute absolute insulin deficiency, severe ketosis, and increased risk of hypoglycemia, glycemic variability and microvascular complications. Seven people with FT1D were identified from two tertiary centers in Singapore. Six were Chinese, the mean age was 35 years and all were lean (mean body mass index 20.3 kg/m2). All presented with diabetes ketosis or ketoacidosis and low C‐peptide. All but one had low glutamic acid decarboxylase antibodies. Nearly half had a missed/delayed diagnosis of FT1D. Three had frequent hypoglycemia, which improved after transition to continuous subcutaneous insulin infusion therapy. Individuals with FT1D experience unique diagnostic and management challenges associated with rapid absolute insulin deficiency. Greater awareness about this clinical entity is required. [ABSTRACT FROM AUTHOR]

Summary: Obstructive sleep apnea (OSA) is a prevalent complication that affects up to 60% of children and adolescents with obesity. It is associated with poorer cardiometabolic outcomes and neurocognitive deficits. Appropriate screening and intervention for OSA are crucial in the management of children with obesity. We performed a scoping review of international and national pediatric obesity (n = 30) and pediatric OSA (n = 10) management guidelines to evaluate the recommendations on OSA screening in pediatric obesity. Sixteen (53%) of the pediatric obesity guidelines had incorporated OSA screening to varying extents, with no consistent recommendations on when and how to screen for OSA, and subsequent management of OSA in children with obesity. We provide our recommendations that are based on the strength and certainty of evidence presented. These include a clinical‐based screening for OSA in all children with body mass index (BMI) ≥ 85th percentile or those with rapid BMI gain (upward crossing of 2 BMI percentiles) and the use of overnight polysomnography to confirm the diagnosis of OSA in those with high clinical suspicion. We discuss further management of OSA unique to children with obesity. An appropriate screening strategy for OSA would facilitate timely intervention that has been shown to improve cardiometabolic and neurocognitive outcomes. [ABSTRACT FROM AUTHOR]

'Collegiality' comes from the Latin term 'Collegium', which essentially refers to a community of individuals bounded by their collective pursuit of a common goal. The concept has historical roots in both organised religion and academia, with its use subsequently extended to various industrial and corporate settings including healthcare. Nowadays, 'collegiality' has become a common buzzword adopted by the medical fraternity – often deemed as having a polite and respectful demeanour, maintaining cordial work relationships and being a team player who demonstrates willingness to help others and avoid speaking ill of fellow colleagues. While it is true that workplace incivility, aggression, bullying and verbal abuse are not uncommonly reported in highly stressful healthcare settings, which are concerning phenomena that should be addressed and prevented, the concept of 'medical collegiality' is, in reality, a rich and multi-faceted concept that is not limited to behavioural attributes, but extends to larger cultural principles and organisational constructs. In this article, we herein define 'medical collegiality' as 'a collective manifestation of respect, empathy and solidarity within the medical fraternity, driven by a common pursuit of clinical excellence in patient care, demonstrated through interpersonal/work relationships and organisational culture', by referencing historical origins of 'collegiality' in organised religion and academia. We further review the concept of 'medical collegiality' through three core lenses of cultural, behavioural and structural collegiality. Finally, we discuss the importance of medical collegiality for physician mental health and well-being, and quality of clinical care. [ABSTRACT FROM AUTHOR]