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1.
Glob Chang Biol ; 2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34553813

RESUMO

Previous studies have identified regions where the occurrence of rainfall significantly increases or decreases the probability for subsequent rainfall over periods that range from a few days to several weeks. These observable phenomena are termed "rainfall feedback" (RF). To better understand the land-atmosphere interactions involved in RF, the behavior of RF patterns was analyzed using data from 1849 to 2016 at ~3000 sites in the contiguous United States. We also considered changes in major land-use types and applied a geographically weighted regression model technique for analyzing the predictors of RF. This approach identified non-linear and spatially non-stationary relationships between RF, climate, land use, and land type. RF patterns in certain regions of the United States are predictable by modeling variables associated with climate, season, and land use. The model outputs also demonstrate the extent to which the effect of precipitation, temperature, and land use on RF depend on season and location. Specifically, major changes were observed for land use associated with agriculture in the western United States, which had negative and positive influences on RF in summer and winter, respectively. In contrast, developed land in the eastern United States correlated with positive RF values in summer but with negative ones in winter. We discuss how changes in climate and land use would be expected to affect land-atmosphere interactions, as well as the possible role that physical mechanisms and rain-enhanced bioaerosol emissions may play in the spatiotemporal changes observed for historical patterns of rainfall frequency in the United States.

2.
PLoS One ; 16(8): e0254698, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34383776

RESUMO

BACKGROUND: Pneumonia is a common and severe complication of abdominal surgery, it is associated with increased length of hospital stay, healthcare costs, and mortality. Further, pulmonary complication rates have risen during the SARS-CoV-2 pandemic. This study explored the potential cost-effectiveness of administering preoperative chlorhexidine mouthwash versus no-mouthwash at reducing postoperative pneumonia among abdominal surgery patients. METHODS: A decision analytic model taking the South African healthcare provider perspective was constructed to compare costs and benefits of mouthwash versus no-mouthwash-surgery at 30 days after abdominal surgery. We assumed two scenarios: (i) the absence of COVID-19; (ii) the presence of COVID-19. Input parameters were collected from published literature including prospective cohort studies and expert opinion. Effectiveness was measured as proportion of pneumonia patients. Deterministic and probabilistic sensitivity analyses were performed to assess the impact of parameter uncertainties. The results of the probabilistic sensitivity analysis were presented using cost-effectiveness planes and cost-effectiveness acceptability curves. RESULTS: In the absence of COVID-19, mouthwash had lower average costs compared to no-mouthwash-surgery, $3,675 (R 63,770) versus $3,958 (R 68,683), and lower proportion of pneumonia patients, 0.029 versus 0.042 (dominance of mouthwash intervention). In the presence of COVID-19, the increase in pneumonia rate due to COVID-19, made mouthwash more dominant as it was more beneficial to reduce pneumonia patients through administering mouthwash. The cost-effectiveness acceptability curves shown that mouthwash surgery is likely to be cost-effective between $0 (R0) and $15,000 (R 260,220) willingness to pay thresholds. CONCLUSIONS: Both the absence and presence of SARS-CoV-2, mouthwash is likely to be cost saving intervention for reducing pneumonia after abdominal surgery. However, the available evidence for the effectiveness of mouthwash was extrapolated from cardiac surgery; there is now an urgent need for a robust clinical trial on the intervention on non-cardiac surgery.


Assuntos
Abdome/cirurgia , Clorexidina/uso terapêutico , Modelos Teóricos , Pneumonia/prevenção & controle , COVID-19 , Análise Custo-Benefício , Humanos , Antissépticos Bucais , Pandemias , Complicações Pós-Operatórias/prevenção & controle , Cuidados Pré-Operatórios , Estudos Prospectivos , África do Sul
3.
Am Surg ; : 31348211038579, 2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34384255

RESUMO

BACKGROUND: We conducted this study to compare the weight loss outcome of intragastric balloons (IGBs) in conjunction with pharmacotherapy vs IGB and intensive lifestyle changes alone. METHODS: This was a multicenter, non-randomized, retrospective study involving 4 academic hospitals. Patients underwent IGB placement with or without concomitant anti-obesity pharmacotherapy. The primary outcome was percent total weight loss (TBWL) after IGB placement at 6 and 12 months. RESULTS: This study included 102 patients, with 23 patients (mean age 46.6 years, 82.6% female) treated with IGB/pharmacotherapy and 79 patients (mean age 46.0 years, 88.6% female) treated with IGB/lifestyle modifications. Patients had a 100% follow-up rate at 6 and 12 months. At 6 months following IGB placement, both groups achieved a similar %TBWL. At 12 months, %TBWL was greater in the IGB/pharmacotherapy group (12.6% ± 1.2 vs 9.7% ± 0.7, P = .04). 65.2% of patients achieved ≥10% TBWL at 12 months in the IGB/pharmacotherapy group, compared to 38.0% in the IGB/lifestyle group (P < .05). The proportion of patients that achieved ≥15% weight loss at 12 months was also significantly different between the IGB/pharmacotherapy and IGB/lifestyle groups (30.4% vs 20.3%, P < .05). DISCUSSION: IGB with concomitant use of pharmacotherapy did not improve weight loss while the IGB was in place compared to IGB and lifestyle changes. However, patients receiving IGB with pharmacotherapy did have greater weight loss and diminished weight regain after balloon removal compared to those receiving just IGB and lifestyle changes.

4.
Mol Metab ; 53: 101289, 2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34246804

RESUMO

OBJECTIVE: ß-cell microRNA-21 (miR-21) is increased by islet inflammatory stress but it decreases glucose-stimulated insulin secretion (GSIS). Thus, we sought to define the effects of miR-21 on ß-cell function using in vitro and in vivo systems. METHODS: We developed a tetracycline-on system of pre-miR-21 induction in clonal ß-cells and human islets, along with transgenic zebrafish and mouse models of ß-cell-specific pre-miR-21 overexpression. RESULTS: ß-cell miR-21 induction markedly reduced GSIS and led to reductions in transcription factors associated with ß-cell identity and increased markers of dedifferentiation, which led us to hypothesize that miR-21 induces ß-cell dysfunction by loss of cell identity. In silico analysis identified transforming growth factor-beta 2 (Tgfb2) and Smad family member 2 (Smad2) mRNAs as predicted miR-21 targets associated with the maintenance of ß-cell identity. Tgfb2 and Smad2 were confirmed as direct miR-21 targets through RT-PCR, immunoblot, pulldown, and luciferase assays. In vivo zebrafish and mouse models exhibited glucose intolerance, decreased peak GSIS, decreased expression of ß-cell identity markers, increased insulin and glucagon co-staining cells, and reduced Tgfb2 and Smad2 expression. CONCLUSIONS: These findings implicate miR-21-mediated reduction of mRNAs specifying ß-cell identity as a contributor to ß-cell dysfunction by the loss of cellular differentiation.

5.
Psychooncology ; 30(9): 1590-1599, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34019721

RESUMO

OBJECTIVE: A new diagnosis of pediatric cancer may disrupt family functioning. The current study aimed to describe changes in family rules and routines during the first year of pediatric cancer treatment, and to explore associations with demographics, illness factors, and caregiver distress. METHODS: This exploratory mixed-methods, cross-sectional study examined 44 primary caregivers of youth in treatment for a new cancer diagnosis in 2019 and 2020, before the onset of the COVID-19 pandemic. Caregivers completed validated questionnaires assessing demographic and child illness characteristics, psychosocial distress, and cancer-related stressors, and participated in a semi-structured interview about family rules and routines. RESULTS: Caregivers reported changes in bedtime, mealtime, and school routines, relaxed behavioral expectations and rules around screen time, and new rules and routines around treatment, medications, and infection control. Caregivers with elevated levels of psychosocial distress reported more changed routines than caregivers with low levels of psychosocial distress. Caregivers who endorsed more cancer-related stressors reported more new rules and routines than those who reported fewer cancer-related stressors. Demographic and illness factors were not significantly associated with the number of changed, new, or stable family rules and routines. CONCLUSIONS: Families may relax rules and routines during the first several months of diagnosis, and this may be related to side effects of treatment and limited caregiver capacity. The long-term impact of changes in family rules and routines during cancer treatment warrants further study given that accommodating parenting strategies have been associated with adverse short- and long-term child health and behavior outcomes.


Assuntos
COVID-19 , Neoplasias , Adolescente , Cuidadores , Criança , Estudos Transversais , Família , Humanos , Neoplasias/terapia , Pandemias , Poder Familiar , SARS-CoV-2
6.
J Dev Behav Pediatr ; 42(5): 429-431, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34034293

RESUMO

CASE: Julia is a 13-year-old White adolescent girl who was referred for psychological counseling given concerns related to mood, nonadherence, and adjustment secondary to her new diagnosis of type 1 diabetes. The family lives in a rural town located several hours from the academic medical center where she was diagnosed. After several months on a waitlist, the family was contacted to schedule a telehealth appointment with a predoctoral psychology trainee. When the scheduler informed the mother that her daughter would be scheduled with Ms. Huang, the mother abruptly stopped the conversation stating, "I do not want to waste everyone's time" and initially declined the appointment offered. When the scheduler asked about her hesitance, the mother disclosed previous interactions with doctors at the hospital who were "not born in the United States" that she felt were "textbook" (e.g., smiling even when discussing a new chronic medical condition) and "hard to understand" (i.e., because of different dialect/accent). The mother shared that she found these experiences to be stressful and felt the interactions had negatively affected Julia's care. When informed about the length of the waitlist for another clinician, the mother agreed to initiate services with the trainee.The supervising psychologist shared the mother's concerns and comments with Ms. Huang. After discussion, Ms. Huang agreed to provide intervention services, "as long as the family was willing." During the initial telehealth sessions, Ms. Huang primarily focused on building rapport and strengthening the therapeutic alliance with the family. During this time, Julia's mother was reluctant to incorporate suggested parent management strategies at home. Julia also made minimal improvement in her medical management (i.e., A1c levels remained high), had difficulty using behavioral coping strategies, and experienced ongoing mood symptoms (i.e., significant irritability, sleep difficulties, and depressive symptoms). Ms. Huang began to wonder whether the family's resistance and inability to implement recommendations were in some part because of the family's initial concerns and reluctance to engage in therapy with her as a clinician.Should Ms. Huang address the previously identified concerns with the patient and her family? What should be considered when determining how to approach this situation to ensure provision of both the best care for this patient and support for this trainee?

7.
Circ Genom Precis Med ; 14(2): e003304, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33651632

RESUMO

BACKGROUND: There is considerable interest in whether genetic data can be used to improve standard cardiovascular disease risk calculators, as the latter are routinely used in clinical practice to manage preventative treatment. METHODS: Using the UK Biobank resource, we developed our own polygenic risk score for coronary artery disease (CAD). We used an additional 60 000 UK Biobank individuals to develop an integrated risk tool (IRT) that combined our polygenic risk score with established risk tools (either the American Heart Association/American College of Cardiology pooled cohort equations [PCE] or UK QRISK3), and we tested our IRT in an additional, independent set of 186 451 UK Biobank individuals. RESULTS: The novel CAD polygenic risk score shows superior predictive power for CAD events, compared with other published polygenic risk scores, and is largely uncorrelated with PCE and QRISK3. When combined with PCE into an IRT, it has superior predictive accuracy. Overall, 10.4% of incident CAD cases were misclassified as low risk by PCE and correctly classified as high risk by the IRT, compared with 4.4% misclassified by the IRT and correctly classified by PCE. The overall net reclassification improvement for the IRT was 5.9% (95% CI, 4.7-7.0). When individuals were stratified into age-by-sex subgroups, the improvement was larger for all subgroups (range, 8.3%-15.4%), with the best performance in 40- to 54-year-old men (15.4% [95% CI, 11.6-19.3]). Comparable results were found using a different risk tool (QRISK3) and also a broader definition of cardiovascular disease. Use of the IRT is estimated to avoid up to 12 000 deaths in the United States over a 5-year period. CONCLUSIONS: An IRT that includes polygenic risk outperforms current risk stratification tools and offers greater opportunity for early interventions. Given the plummeting costs of genetic tests, future iterations of CAD risk tools would be enhanced with the addition of a person's polygenic risk.

8.
Am J Cardiol ; 148: 157-164, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33675770

RESUMO

The American College of Cardiology / American Heart Association pooled cohort equations tool (ASCVD-PCE) is currently recommended to assess 10-year risk for atherosclerotic cardiovascular disease (ASCVD). ASCVD-PCE does not currently include genetic risk factors. Polygenic risk scores (PRSs) have been shown to offer a powerful new approach to measuring genetic risk for common diseases, including ASCVD, and to enhance risk prediction when combined with ASCVD-PCE. Most work to date, including the assessment of tools, has focused on performance in individuals of European ancestries. Here we present evidence for the clinical validation of a new integrated risk tool (IRT), ASCVD-IRT, which combines ASCVD-PCE with PRS to predict 10-year risk of ASCVD across diverse ethnicity and ancestry groups. We demonstrate improved predictive performance of ASCVD-IRT over ASCVD-PCE, not only in individuals of self-reported White ethnicities (net reclassification improvement [NRI]; with 95% confidence interval = 2.7% [1.1 to 4.2]) but also Black / African American / Black Caribbean / Black African (NRI = 2.5% [0.6-4.3]) and South Asian (Indian, Bangladeshi or Pakistani) ethnicities (NRI = 8.7% [3.1 to 14.4]). NRI confidence intervals were wider and included zero for ethnicities with smaller sample sizes, including Hispanic (NRI = 7.5% [-1.4 to 16.5]), but PRS effect sizes in these ethnicities were significant and of comparable size to those seen in individuals of White ethnicities. Comparable results were obtained when individuals were analyzed by genetically inferred ancestry. Together, these results validate the performance of ASCVD-IRT in multiple ethnicities and ancestries, and favor their generalization to all ethnicities and ancestries.


Assuntos
Aterosclerose/epidemiologia , Predisposição Genética para Doença , Fatores de Risco de Doenças Cardíacas , Adulto , Grupo com Ancestrais do Continente Africano , Idoso , Ásia Ocidental , Grupo com Ancestrais do Continente Asiático , Aterosclerose/etnologia , Aterosclerose/genética , Estudos de Coortes , Grupo com Ancestrais do Continente Europeu , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes
9.
J Investig Med ; 69(3): 730-735, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33443058

RESUMO

Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) reduce blood pressure (BP) in obese patients with hypertension (HTN). We compared the effect of RYGB and SG on BP in obese patients with HTN at a large-volume, private bariatric surgery center using a propensity score analysis. The measurement and management of BP were exclusively left to the patient's provider without any involvement of Tulane investigators. At month 1, RYGB and SG equally decreased: (1) mean body weight: 12.7 vs 13.2 kg (p=not significant (NS)) (2) systolic/diastolic BP: 8.5/5.3 vs 8.0/4.2 mm Hg (p=NS) and (3) average number of antihypertensive medications from 1.5 to 0.8 and from 1.6 to 0.6 per patient (p=NS). From month 1 to 12, BP remained unchanged after RYGB but tended to increase from month 6 to 12 after SG. Remission of HTN occurred in 52% and 44% of patients after RYGB and SG. In contrast to the full effect of RYGB and SG on BP at 1 month, body weight decreases steadily over 12 months after RYGB and SG. In conclusion, early after surgery, RYGB and SG equally reduce BP in obese patients with HTN. Thereafter, RYGB has a more sustained effect on BP than SG.

10.
ISME J ; 15(2): 461-472, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33009511

RESUMO

The environmental sources of microbial aerosols and processes by which they are emitted into the atmosphere are not well characterized. In this study we analyzed microbial cells and biological ice nucleating particles (INPs) in smoke emitted from eight prescribed wildland fires in North Florida. When compared to air sampled prior to ignition, samples of the air-smoke mixtures contained fivefold higher concentrations of microbial cells (6.7 ± 1.3 × 104 cells m-3) and biological INPs (2.4 ± 0.91 × 103 INPs m-3 active at temperatures ≥ -15 °C), and these data significantly positively correlated with PM10. Various bacteria could be cultured from the smoke samples, and the nearest neighbors of many of the isolates are plant epi- and endophytes, suggesting vegetation was a source. Controlled laboratory combustion experiments indicated that smoke emitted from dead vegetation contained significantly higher numbers of cells, INPs, and culturable bacteria relative to the green shrubs tested. Microbial viability of smoke aerosols based on formazan production and epifluorescent microscopy revealed no significant difference in the viable fraction (~80%) when compared to samples of ambient air. From these data, we estimate each fire aerosolized an average of 7 ± 4 × 109 cells and 2 ± 1 × 108 biological INPs per m2 burned and conclude that emissions from wildland fire are sources of viable microbial aerosols to the atmosphere.


Assuntos
Poluentes Atmosféricos , Incêndios , Incêndios Florestais , Aerossóis , Atmosfera , Florida , Gelo/análise
11.
J Marital Fam Ther ; 47(1): 150-165, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32652676

RESUMO

Lesbian, gay, bisexual, and queer (LGBQ) young people from religious families are at increased risk of family rejection, poor mental health outcomes, and are overrepresented in mental health services. This article describes a two-part qualitative study aimed at exploring the experiences of LGBQ young adults from religious families in psychotherapy, identifying positive and negative psychotherapy experiences, and understanding the influence of family and religion on the psychotherapy experience. Data were collected through a web-based survey (n = 77) and interviews (n = 7) with LGBQ young adults (ages 18-25) from religious families. The study followed an interpretative phenomenological approach. Integrated results found often invisible, relational therapy processes, and religious discourses as significant to LGBQ young people who seek psychotherapy. Implications for future research, effective systemic family therapy practices with LGBQ young people from religious families, and a critique on ethical and legal limits of confidentiality with policy implications are outlined.

12.
Infect Dis Health ; 26(1): 72-80, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33071208

RESUMO

BACKGROUND: Vulnerable patients being cared for in hospital-at-home settings require safe disinfection of their medical devices, including nebulisers and other respiratory equipment. The scale of patients now being cared for in hospital-at-home settings as a result of COVID19 places huge pressure on hospital central sterile services departments (CSSDs) to provide consumable items to safely support such patients' care. This places new importance on the disinfection of mundane objects, including crockery, cutlery and frequently touched objects in the home environment. This study examined temperature performance of steam disinfectors and the consequences of potential operator misuse on the survival of 62 bacteria and yeast organisms. METHODS: Thermal performance of steam disinfectors was evaluated using calibrated thermocouple probes in multiple permutations of device usage with 62 test organisms. RESULTS: Thermocouple data demonstrated disinfection A0 values of 6000 (upper layer) and 60 (lower layer). Steam disinfection of baby bottles had a thermal lethality of at least A0 = 600. Variation in disinfector temperatures were noted, depending on the geometric location of thermocouples. Additional notable temperature reductions occurred with device underfilling with suboptimal water volumes. Steam disinfection eradicated all 62 non-spore-forming Gram-positive, Gram-negative and yeast organisms tested and eradicated all organisms in the inner teat space of contaminated babies' dummies, rendering safe steam disinfection of babies' dummies. CONCLUSION: Domestic steam disinfection offers an inexpensive, simple, versatile and widely available technology for the elimination of common non-spore-forming nosocomial pathogens and safe disinfection of medical devices, fomites and other mundane objects within the hospital-at-home scenario, thereby enhancing patient safety.

13.
Obes Surg ; 31(1): 451-456, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32740826

RESUMO

The purpose of this study was to achieve consensus amongst a global panel of expert bariatric surgeons on various aspects of resuming Bariatric and Metabolic Surgery (BMS) during the Coronavirus Disease-2019 (COVID-19) pandemic. A modified Delphi consensus-building protocol was used to build consensus amongst 44 globally recognised bariatric surgeons. The experts were asked to either agree or disagree with 111 statements they collectively proposed over two separate rounds. An agreement amongst ≥ 70.0% of experts was construed as consensus as per the predetermined methodology. We present here 38 of our key recommendations. This first global consensus statement on the resumption of BMS can provide a framework for multidisciplinary BMS teams planning to resume local services as well as guide future research in this area.


Assuntos
Cirurgia Bariátrica , COVID-19 , Consenso , Técnica Delfos , Humanos , Obesidade Mórbida/cirurgia , Pandemias , SARS-CoV-2
14.
Front Cell Dev Biol ; 8: 579073, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33134296

RESUMO

During brain development, the tissue pattern and specification are the foundation of neuronal circuit formation. Contact-mediated lateral inhibition is well known to play an important role in determining cell fate decisions in the nervous system by either regulating tissue boundary formation or the classical salt-and-pepper pattern of differentiation that results from direct neighboring cell contacts. In many systems, however, such as the Drosophila notum, Drosophila wing, zebrafish pigmented cells, and zebrafish spinal cord, the differentiation pattern occurs at multiple-cell diameter distances. In this review, we discuss the evidence and characteristics of long-distance patterning mechanisms mediated by cellular protrusions. In the nervous system, cellular protrusions deliver the Notch ligand Delta at long range to prevent cells from differentiating in their vicinity. By temporal control of protrusive activity, this mechanism can pattern differentiation in both space and time.

15.
J Opioid Manag ; 16(5): 317-328, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33226089

RESUMO

OBJECTIVE: Insomnia commonly co-occurs with depression, chronic pain, and opioid use. Both insomnia and chronic opioid analgesic use (OAU) are independent risk factors for a new depression episode (NDE). This study determined if the association between longer OAU duration and NDE was stronger in those with versus without insomnia. DESIGN: Retrospective cohort. SETTING: Veterans Health Administration electronic medical records (2000-2012). PARTICIPANTS: New opioid users in follow-up (2002-2012), free of depression for two years prior to follow-up, and aged 18-80 (n = 70,997). METHODS: NDE was ≥ 2 ICD-9 codes in a 12-month period. Insomnia before OAU initiation was ≥1 ICD-9 code. Cox proportional hazard models stratified on insomnia assessed the relationship between initiating a 1-30, 31-90, or > 90 day period of OAU and NDE while controlling for confounders using inverse probability of treatment-weighted propensity scores (PS). RESULTS: Compared to 1-30 day OAU, 31-90 day was associated with NDE in those without (HR = 1.20; 95 percent CI: 1.12-1.28) but not with insomnia (HR = 1.06; 95 percent CI: 0.86-1.32). Results showed a stronger effect of chronic (>90) OAU in those with insomnia (HR = 1.59; 95 percent CI: 1.27-1.98) compared to those without (HR = 1.31; 95 percent CI: 1.21-1.42). However, all stratum-specific effects were not significantly different (p = 0.136). CONCLUSIONS: Although stratum-specific risks were statistically similar, there was evidence for a trend that chronic OAU is a stronger risk factor for NDE in those with versus without insomnia. Providers are encouraged to monitor sleep impairment among patients on opioid therapy, as sleep may be associated with greater risk for NDE in patients with chronic OAU.


Assuntos
Analgésicos Opioides/efeitos adversos , Depressão/induzido quimicamente , Depressão/psicologia , Medicamentos sob Prescrição/efeitos adversos , Distúrbios do Início e da Manutenção do Sono/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Analgésicos Opioides/uso terapêutico , Estudos de Coortes , Depressão/epidemiologia , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Estados Unidos/epidemiologia , United States Department of Veterans Affairs , Veteranos/psicologia , Serviços de Saúde para Veteranos Militares , Adulto Jovem
17.
J Cell Sci ; 133(19)2020 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-32917740

RESUMO

The JAK/STAT pathway is an essential signalling cascade required for multiple processes during development and for adult homeostasis. A key question in understanding this pathway is how it is regulated in different cell contexts. Here, we have examined how endocytic processing contributes to signalling by the single cytokine receptor in Drosophila melanogaster cells, Domeless. We identify an evolutionarily conserved di-leucine (di-Leu) motif that is required for Domeless internalisation and show that endocytosis is required for activation of a subset of Domeless targets. Our data indicate that endocytosis both qualitatively and quantitatively regulates Domeless signalling. STAT92E, the single STAT transcription factor in Drosophila, appears to be the target of endocytic regulation, and our studies show that phosphorylation of STAT92E on Tyr704, although necessary, is not always sufficient for target transcription. Finally, we identify a conserved residue, Thr702, which is essential for Tyr704 phosphorylation. Taken together, our findings identify previously unknown aspects of JAK/STAT pathway regulation likely to play key roles in the spatial and temporal regulation of signalling in vivo.


Assuntos
Proteínas de Drosophila , Drosophila melanogaster , Animais , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Expressão Gênica , Janus Quinases/genética , Janus Quinases/metabolismo , Ligantes , Fatores de Transcrição STAT/genética , Fatores de Transcrição STAT/metabolismo
19.
J Sch Health ; 90(10): 771-778, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32812237

RESUMO

BACKGROUND: Lesbian, gay, bisexual, and questioning (LGBQ) adolescents are at increased risk of poor mental health due to minority stress, a chronic stress associated discrimination, social rejection, and victimization brought on by prejudicial attitudes towards LGBQ individuals. To improve understanding of the differential impact of various kinds of victimization on mental health outcomes for LGBQ adolescents, we analyzed data from the 2015 Youth Risk Behavior Survey (YRBS) for victimization and mental health symptom clusters and associations high school youth and compared by sexual orientation and gender. METHODS: Separate Latent Class Analysis (LCA) was conducted to identify profiles of both victimization and mental health symptoms for participants (N = 15,624). Subsequently, stratified weighted logistic regression models were used on an eligible analytic sample of 11,458 to assess differences in the association of victimization and mental health between LGBQ and heterosexual high school students. RESULTS: In each LCA, participants were assigned to one of 3 classes for victimization (minimal, 81.3%; bullying, 12.5%; or physical/sexual violence, 6.2%) and 1 of 2 classes for mental health symptoms (minimal, 81.2%; severe, 18.8%). LGBQ participants were overrepresented in physical/sexual violence and bullying victimization profiles. Both bullying and physical/sexual violence profiles were associated with almost 5 times the odds of endorsing severe mental health symptoms. CONCLUSIONS: This study expands our understanding of the relationship between types and effect of peer victimization for LGBQ and heterosexual youth with implications for school health and prevention efforts through increased positive school climate for LGBQ students.

20.
Pediatr Pulmonol ; 55(11): 3012-3020, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32729958

RESUMO

BACKGROUND: Patients with cystic fibrosis have increased morbidity/mortality due to chronic respiratory infections, which primarily originate from the environment. Infection prevention and control emphasize the importance of cleaning and disinfection of respiratory devices, however, there is a paucity of guidance on toothbrush hygiene, which have been shown to be a source of cystic fibrosis (CF) pathogens. METHODS: This study examined steam disinfection of toothbrushes contaminated with clinically significant CF isolates (n = 80; Gram positive = 33; Gram negative = 32, and non-tuberculous mycobacteria = 6) and yeasts (n = 9), as well as oral streptococci (n = 26) and environmental Pseudomonas aeruginosa (n = 12). RESULTS: Steam disinfection eradicated all organisms tested, as well as all organisms in CF sputum applied to toothbrushes. CONCLUSIONS: Steam disinfection offers a relatively simple, cheap and available method of eliminating non-spore-forming CF pathogens on toothbrushes. Toothbrushes should be thoroughly rinsed after each use before steam disinfection, to remove plaque, epithelial cells, and residual toothpaste. Toothbrushes should be steam disinfected after each use employing a baby bottle steam disinfector, adhering to manufacturers' operating instructions and stored in the disinfector until next used within 12 to 24 hours. Toothbrushes should be replaced every 3 to 4 months, or sooner if the bristles look worn out, as well as every time a pulmonary exacerbation occurs or every time the patient is treated for a pulmonary/throat infection. Steam disinfection of toothbrushes is crucial when the patient is undergoing eradication regimes for P. aeruginosa and methicillin-resistant Staphylococcus aureus, so that the patient does not become reinfected from this source, thereby aiding eradication and enhancing patient safety.


Assuntos
Fibrose Cística , Desinfecção/métodos , Infecções por Bactérias Gram-Negativas/prevenção & controle , Infecções por Bactérias Gram-Positivas/prevenção & controle , Micoses/prevenção & controle , Vapor , Bactérias/isolamento & purificação , Fibrose Cística/microbiologia , Humanos , Escarro/microbiologia , Leveduras/isolamento & purificação
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