Cdk12 maintains the integrity of adult axons by suppressing actin remodeling.

The role of cyclin-dependent kinases (CDKs) that are ubiquitously expressed in the adult nervous system remains unclear. Cdk12 is enriched in terminally differentiated neurons where its conical role in the cell cycle progression is redundant. We find that in adult neurons Cdk12 acts a negative regulator of actin formation, mitochondrial dynamics and neuronal physiology. Cdk12 maintains the size of the axon at sites proximal to the cell body through the transcription of homeostatic enzymes in the 1-carbon by folate pathway which utilize the amino acid homocysteine. Loss of Cdk12 leads to elevated homocysteine and in turn leads to uncontrolled F-actin formation and axonal swelling. Actin remodeling further induces Drp1-dependent fission of mitochondria and the breakdown of axon-soma filtration barrier allowing soma restricted cargos to enter the axon. We demonstrate that Cdk12 is also an essential gene for long-term neuronal survival and loss of this gene causes age-dependent neurodegeneration. Hyperhomocysteinemia, actin changes, and mitochondrial fragmentation are associated with several neurodegenerative conditions such as Alzheimer's disease and we provide a candidate molecular pathway to link together such pathological events.

Early Release Science of the exoplanet WASP-39b with JWST NIRSpec PRISM.

Transmission spectroscopy1-3 of exoplanets has revealed signatures of water vapour, aerosols and alkali metals in a few dozen exoplanet atmospheres4,5. However, these previous inferences with the Hubble and Spitzer Space Telescopes were hindered by the observations' relatively narrow wavelength range and spectral resolving power, which precluded the unambiguous identification of other chemical species-in particular the primary carbon-bearing molecules6,7. Here we report a broad-wavelength 0.5-5.5 µm atmospheric transmission spectrum of WASP-39b8, a 1,200 K, roughly Saturn-mass, Jupiter-radius exoplanet, measured with the JWST NIRSpec's PRISM mode9 as part of the JWST Transiting Exoplanet Community Early Release Science Team Program10-12. We robustly detect several chemical species at high significance, including Na (19σ), H2O (33σ), CO2 (28σ) and CO (7σ). The non-detection of CH4, combined with a strong CO2 feature, favours atmospheric models with a super-solar atmospheric metallicity. An unanticipated absorption feature at 4 µm is best explained by SO2 (2.7σ), which could be a tracer of atmospheric photochemistry. These observations demonstrate JWST's sensitivity to a rich diversity of exoplanet compositions and chemical processes.

Adipose tissue regulatory T cells: differentiation and function.

Rising obesity levels, worldwide, are resulting in substantial increases in cardiovascular disease, diabetes, kidney disease, musculoskeletal disorders, and certain cancers, and obesity-associated illnesses are estimated to cause ∼4 million deaths worldwide per year. A common theme in this disease epidemic is the chronic systemic inflammation that accompanies obesity. CD4+ Foxp3+ regulatory T cells residing in visceral adipose tissues (VAT Tregs) are a unique immune cell population that play essential functions in restricting obesity-associated systemic inflammation through regulation of adipose tissue homeostasis. The distinct transcriptional program that defines VAT Tregs has been described, but directly linking VAT Treg differentiation and function to improving insulin sensitivity has proven more complex. Here we review new findings which have clarified how VAT Tregs differentiate, and how distinct VAT Treg subsets regulate VAT homeostasis, energy expenditure, and insulin sensitivity.

Barriers and Translational Solutions to Improving Community Living Outcomes among People of Color with Disabilities with Opioid Use Disorder: A Focus Group Perspective.

This investigation examined vocational rehabilitation, substance abuse, and mental health service providers' perceptions about barriers and potentially translational solutions to poor community living outcomes for people of color with disabilities (i.e., African Americans, Latinx, Native Americans and Alaskan Natives, Asian Americans, and Pacific islanders) who have opioid use disorder. We conducted one focus group discussion (N = 12) that identified the proliferation of opioids in the community, treatment access, employment, and transportation as community living outcome barriers. The findings point to the need for further research that address poor outcomes among target group members.

Penetrating colon trauma - outcomes related to single versus multiple colonic injuries.

INTRODUCTION: There is no conclusive evidence to guide surgical management in the presence of multiple colonic injuries as opposed to a single colonic injury, and whether multiple colonic suture lines are associated with worse outcomes than single suture lines. AIM: We reviewed the outcomes of penetrating colonic trauma in relation to whether patients had single versus multiple colonic suture lines (primary repair or anastomosis) following laparotomy. METHODS: A retrospective study was conducted at a major trauma centre in South Africa from 2012-2020 for all patients over 18 years who had sustained penetrating colon injury. RESULTS: 541 cases were included: 409 with single suture line and 54 with multiple suture lines. There were no differences between groups in terms of mechanism of injury (gunshot vs stab; p = 0.328), Injury Severity Score (p = 0.071), or Penetrating Abdominal Trauma Index (p = 0.396). Admission lactate was worse for multiple suture line patients (p = 0.049), but no other blood gas parameters were different, and there was no higher incidence of damage control surgery (p = 0.558) or ICU admission (p = 0.156) for this group. There was a higher rate of diversion in the multiple suture line group (p < 0.001). Univariable logistic regression did not show an increased risk of gastro-intestinal complications, suture line leak rate, or mortality for multiple suture lines compared to single. CONCLUSION: It appears that there is no appreciable difference in outcome between patients with a single colonic suture line compared to patients with more than one suture line following trauma laparotomy. In light of this, each injury should be treated on its own merit, in the context of the patient's overall physiological condition, without undue fear of leaving the patient with more than one colonic suture line. However, judicious use of diversion remains advisable.

Penetrating Colon Trauma-the Effect of Injury Location on Outcomes.

BACKGROUND: There is limited evidence to suggest that the more distal a penetrating colonic injury, the poorer its expected outcome, prompting consideration of diversion rather than anastomosis when faced with left colonic injury. The clinical outcomes of penetrating colonic trauma in relation to their anatomical location within the colon were reviewed. METHODS: A review was performed over eight years (2012-2020) of all patients over 18 years who had sustained penetrating colon injury and presented to our trauma centre in South Africa. Direct comparison was made between right colon vs left colon injuries. RESULTS: A total of 450 patients were included; right colon: 260, left colon: 190. Gunshots predominated in the right colon, and the PATI was higher in this group. There were minimal differences in admission physiology and blood gas parameters between groups, but higher damage control surgery and ICU admission rates for the right colon group. There were similar rates of primary repair, anastomosis, and stoma between groups. Leak rates were no different between the two groups, and although overall complication rates were higher for the right colon, there was no difference with regard to gastro-intestinal and other complications, nor for mortality. While regression analysis did identify PATI to be a risk factor for overall complications and mortality, it failed to do so for anastomotic leak. CONCLUSION: Our study did not demonstrate any difference in anastomotic leak rates or mortality between right vs left colonic injury. We recommend that all colonic injuries should be treated on their own merit, balanced against the patient's condition, regardless of anatomical location within the colon.

Factors in Utilization of Telehealth Treatment by Rural African-Americans with Opioid Use Disorder and Disabilities.

This study explored factors that impact telehealth service utilization for treatment of African Americans with disabilities with opioid use disorder in rural communities. A focus group was conducted involving 12 different mental health, substance use, and rehabilitation counseling professionals. The analysis was completed using NVivo (Version 12). The results identified critical barriers that included historical distrust of technology and healthcare systems, digital divide/unavailability of Internet modems, fear of losing confidentiality, and agency non-approval. The benefits were improved communication, reduction of stigma, continuity of care, and convenience of collaboration. The findings indicate the need for additional research in this topic area.

Assistive Technology Workplace Accommodation and Employment among Diverse Populations with Disabilities: Does Race/Ethnicity Matter?

The purpose of this study was to examine the relationship between assistive technology workplace accommodation (AT-WA) usage and employment status among racial/ethnic populations with disabilities. Chi-square tests and logistic regression were used to analyze secondary data from the 2015 Kessler Foundation National Employment and Disability Survey (KFNEDS). Results indicated that significantly more consumers who used AT-WA were currently working, and a significantly greater proportion of them were White. Moreover, a significantly lower proportion of those who did not use AT-WA had less expected odds of being currently employed. Specific implications are discussed to inform practices, policy, and/or future research.

Community Living Outcome Factors for People of Color with Disabilities and Concomitant Opioid Use Disorder: A Scoping Review.

This scoping review mapped the pertinent extant published and grey literature and policy to assess factors that promote positive community living outcomes among people of color with disabilities and concomitant opioid use disorder (OUD) in the United States (U.S.). Forty-three publications covering OUD and people of color with disabilities and people of color with disabilities and community living content were reviewed. Select community living barriers and potential interventions were identified for people of color with disabilities in general; however, the review failed to classify such factors for those with OUD. Authors offered recommendations for practice, research, and policy.

The ratio of morning cortisol to CRP prospectively predicts first-onset depression in at-risk adolescents.

RATIONALE: Early-onset adolescent depression is related to poor prognosis and a range of psychiatric and medical comorbidities later in life, making the identification of a priori risk factors for depression highly important. Increasingly, dysregulated levels of immune and neuroendocrine markers, such as C-reactive protein (CRP) and cortisol, have been demonstrated as both precursors to and consequences of depression. However, longitudinal research with adolescent populations is limited and demonstrates mixed immuno-endocrine-depression links. OBJECTIVE: This study explored the putative bidirectional relationship between salivary measures of cortisol (Cort) and CRP, including the novel Cort:CRP ratio and depression. METHODS: Participants from the randomized control trial 'Sleep and Education: learning New Skills Early' (SENSE) Study were 122 adolescents at risk for depression (73 females) aged 12-16 years (M = 12.71 years, SD = 1.01 years) assessed at baseline (T1), post-intervention (T2), and a two-year follow-up (T3). RESULTS: Logistic regression results demonstrated that adolescents with higher T1 Cort:CRPmorn ratio levels were two-fold more likely to develop a first-onset depressive disorder from T2 to T3 as compared to adolescents with lower Cort:CRPmorn ratio levels, ß = 0.73, t (36) = 2.15, p = .04, OR = 2.08. This effect was not moderated by treatment condition (ß = -1.38, t (13) = -1.33, p = .20) and did not change when controlling for known risk factors for depression, including sex, age, body-mass index, socio-economic status, T1 anxiety disorder, nor T1 sleep disturbance, anxiety, or depressive symptoms (ß = 0.91, t (31) = 2.14, p = .04). CONCLUSION: Results highlight potential immuno-endocrine dysregulation as an underlying risk factor for adolescent first-onset depression, and may inform the development of targeted, preventative biobehavioral treatment strategies for youth depression.

Unilateral Verrucous Psoriasis.

Verrucous psoriasis is a variant of psoriasis that presents with wartlike clinical features and overlapping histologic features of verruca and psoriasis. The disease typically arises in patients with established psoriasis but can occur de novo. We report the case of an 80-year-old man with a history of hypertension and coronary artery disease who presented with a rash characterized by multiple asymptomatic plaques with overlying verrucous nodules on the left side of the body. The lesions appeared shortly after coronary artery bypass surgery with a saphenous vein graft.

T Regulatory Cells in the Visceral Adipose Tissues.

CD4+ Foxp3+ T regulatory cells (Tregs) residing in the visceral adipose tissues (VAT) have profound effects on local and systemic metabolism. Although many of the molecular characteristics of VAT resident Tregs have been identified, how these cells promote metabolic homeostasis is still unclear. Several new publications help to illuminate the molecular mechanisms that underpin VAT resident Treg function and will be discussed here.

Tregs facilitate obesity and insulin resistance via a Blimp-1/IL-10 axis.

Interleukin-10 (IL-10) is a critical cytokine used by immune cells to suppress inflammation. Paradoxically, immune cell-derived IL-10 can drive insulin resistance in obesity by suppressing adipocyte energy expenditure and thermogenesis. However, the source of IL-10 necessary for the suppression of adipocyte thermogenesis is unknown. We show here that CD4+Foxp3+ regulatory T cells (Tregs) are a substantial source of IL-10 and that Treg-derived IL-10 can suppress adipocyte beiging. Unexpectedly, Treg-specific loss of IL-10 resulted in increased insulin sensitivity and reduced obesity in high-fat diet-fed male mice. Mechanistically, we determined that Treg-specific loss of the transcription factor Blimp-1, a driver of IL-10 expression by Tregs, phenocopied the Treg-specific IL-10-deficient mice. Loss of Blimp-1 expression in Tregs resulted in reduced ST2+KLRG1+, IL-10-secreting Tregs, particularly in the white adipose tissue. Blimp-1-deficient mice were protected from glucose intolerance, insulin resistance, and diet-induced obesity, through increased white adipose tissue browning. Taken together, our data show that Blimp-1-regulated IL-10 secretion by Tregs represses white adipose tissue beiging to maintain adipose tissue homeostasis.

The most influential papers in mitral valve surgery; a bibliometric analysis.

This study is an analysis of the 100 most cited articles in mitral valve surgery. A bibliometric analysis is a tool to evaluate research performance in a given field. It uses the number of times a publication is cited by others as a proxy marker of its impact. The most cited paper Carpentier et al. discusses mitral valve repair in terms of restoring the geometry of the entire valve rather than simply narrowing the annulus (Carpentier, J Thorac Cardiovasc Surg 86:23-37, 1983). The first successful mitral valve repair was performed by Elliot Cutler at Brigham and Women's Hospital in 1923 (Cohn et al., Ann Cardiothorac Surg 4:315, 2015). More recently percutaneous and minimally invasive techniques that were originally designed as an option for high risk patients are being trialled in other patient groups (Hajar, Heart Views 19:160-3, 2018). Comparison of percutaneous method with open repair represents an expanding area of research (Hajar, Heart Views 19:160-3, 2018). This study will analyse the top 100 cited papers relevant to mitral valve surgery, identifying the most influential papers that guide current management, the institutions that produce them and the authors involved.