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1.
Ecology ; : e4318, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38693703

RESUMO

SNAPSHOT USA is a multicontributor, long-term camera trap survey designed to survey mammals across the United States. Participants are recruited through community networks and directly through a website application (https://www.snapshot-usa.org/). The growing Snapshot dataset is useful, for example, for tracking wildlife population responses to land use, land cover, and climate changes across spatial and temporal scales. Here we present the SNAPSHOT USA 2021 dataset, the third national camera trap survey across the US. Data were collected across 109 camera trap arrays and included 1711 camera sites. The total effort equaled 71,519 camera trap nights and resulted in 172,507 sequences of animal observations. Sampling effort varied among camera trap arrays, with a minimum of 126 camera trap nights, a maximum of 3355 nights, a median 546 nights, and a mean 656 ± 431 nights. This third dataset comprises 51 camera trap arrays that were surveyed during 2019, 2020, and 2021, along with 71 camera trap arrays that were surveyed in 2020 and 2021. All raw data and accompanying metadata are stored on Wildlife Insights (https://www.wildlifeinsights.org/), and are publicly available upon acceptance of the data papers. SNAPSHOT USA aims to sample multiple ecoregions in the United States with adequate representation of each ecoregion according to its relative size. Currently, the relative density of camera trap arrays varies by an order of magnitude for the various ecoregions (0.22-5.9 arrays per 100,000 km2), emphasizing the need to increase sampling effort by further recruiting and retaining contributors. There are no copyright restrictions on these data. We request that authors cite this paper when using these data, or a subset of these data, for publication. Any use of trade, firm, or product names is for descriptive purposes only and does not imply endorsement by the US Government.

3.
Pediatrics ; 153(5)2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38660734

RESUMO

OBJECTIVES: Respiratory syncytial virus (RSV) is a common pediatric infection, with young infants being at the highest risk of hospitalization and long-term sequela. New preventive agents have been recommended to prevent severe RSV illness in infants, including a vaccine administered during pregnancy. The current rates of recommended vaccination in pregnancy are suboptimal. Our objective was to characterize interest in RSV vaccination during pregnancy among people across the United States who were pregnant or planning to become pregnant. METHODS: In March 2023, we conducted a national cross-sectional online survey of individuals 18 to 45 years old who were currently pregnant or trying to become pregnant on their perceptions of RSV-related illness and intentions to get vaccinated against RSV. We performed logistic regression analyses to determine the odds and predicted proportions of the likelihood of RSV vaccination during pregnancy, controlling for sociodemographic factors. RESULTS: Of 1619 completed surveys, 1528 were analyzed. 54% of respondents indicated that they were "very likely" to get vaccinated against RSV during pregnancy. The perception of RSV as a serious illness was the strongest predictor of vaccination likelihood. In the full regression model, predicted proportions of "very likely" to vaccinate against RSV followed a similar pattern (63% if RSV infection was perceived as serious and likely, 55% if serious and unlikely, 35% if not serious; P < .001). CONCLUSIONS: Raising awareness of RSV infection as likely and potentially serious for infants may be an influential component of targeted communications that promote RSV vaccine uptake during pregnancy.


Assuntos
Intenção , Infecções por Vírus Respiratório Sincicial , Vacinas contra Vírus Sincicial Respiratório , Humanos , Feminino , Gravidez , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Infecções por Vírus Respiratório Sincicial/epidemiologia , Estudos Transversais , Adulto , Vacinas contra Vírus Sincicial Respiratório/administração & dosagem , Adolescente , Adulto Jovem , Estados Unidos , Vacinação/estatística & dados numéricos , Vacinação/psicologia , Complicações Infecciosas na Gravidez/prevenção & controle , Pessoa de Meia-Idade , Masculino
4.
Nature ; 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38588696

RESUMO

PARTNER is a prospective, phase II-III, randomized controlled clinical trial that recruited patients with triple-negative breast cancer1,2, who were germline BRCA1 and BRCA2 wild type3. Here we report the results of the trial. Patients (n = 559) were randomized on a 1:1 basis to receive neoadjuvant carboplatin-paclitaxel with or without 150 mg olaparib twice daily, on days 3 to 14, of each of four cycles (gap schedule olaparib, research arm) followed by three cycles of anthracycline-based chemotherapy before surgery. The primary end point was pathologic complete response (pCR)4, and secondary end points included event-free survival (EFS) and overall survival (OS)5. pCR was achieved in 51% of patients in the research arm and 52% in the control arm (P = 0.753). Estimated EFS at 36 months in the research and control arms was 80% and 79% (log-rank P > 0.9), respectively; OS was 90% and 87.2% (log-rank P = 0.8), respectively. In patients with pCR, estimated EFS at 36 months was 90%, and in those with non-pCR it was 70% (log-rank P < 0.001), and OS was 96% and 83% (log-rank P < 0.001), respectively. Neoadjuvant olaparib did not improve pCR rates, EFS or OS when added to carboplatin-paclitaxel and anthracycline-based chemotherapy in patients with triple-negative breast cancer who were germline BRCA1 and BRCA2 wild type. ClinicalTrials.gov ID: NCT03150576 .

5.
Med Teach ; : 1-3, 2024 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-38460502

RESUMO

BACKGROUND: The transition from medical school to residency is a critical developmental phase; coaching may help students prepare for this role transition. AIMS: We explored whether near-peer coaching could improve a specific workplace skill prior to residency. METHODS: A resident-as-coach program was piloted for the medicine sub-internship, an advanced acting internship rotation. Between March and June 2021, 26 students were assigned a resident coach (n = 16). Resident coaches completed one training session, and student-coach dyads met for one coaching session on 'pre-rounding'- gathering patient data before rounds. The program was evaluated through surveys and focus groups. RESULTS: 20/26 students and 14/16 residents completed the survey. 19/20 students identified a pre-rounding challenge and reported increased pre-rounding efficiency; all committed to one actionable step for improvement. All 16 residents felt their coaching skills improved. In focus groups, students valued the program's focus on honing a relevant skill in a safe, near-peer setting. Residents expressed their intent to incorporate coaching into their future work. CONCLUSIONS: A resident-as-coach model can be effective in preparing students for residency, while concurrently building residents' coaching skills.

6.
Hosp Pediatr ; 14(4): 272-280, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38449428

RESUMO

BACKGROUND: Sepsis is responsible for 75 000 pediatric hospitalizations annually, with an associated mortality rate estimated between 11% and 19%. Evidence supports the use of timely fluid resuscitation and antibiotics to decrease morbidity and mortality. Our emergency department did not meet the timeliness goals for fluid and antibiotic administration suggested by the 2012 Surviving Sepsis Campaign. METHODS: In November 2018, we implemented a sepsis response team utilizing a scripted communication tool and a dedicated sepsis supply cart to address timeliness barriers. Performance was evaluated using statistical process control charts. We conducted observations to evaluate adherence to the new process. Our aim was to meet the Surviving Sepsis Campaign's timeliness goals for first fluid and antibiotic administration (20 and 60 minutes, respectively) within 8 months of our intervention. RESULTS: We observed sustained decreases in mean time to fluids. We also observed a shift in the proportion of patients receiving fluids within 20 minutes. No shifts were observed for timely antibiotic administration. CONCLUSIONS: The implementation of a dedicated emergency department sepsis response team with designated roles and responsibilities, directed communication, and easily accessible supplies can lead to improvements in the timeliness of fluid administration in the pediatric population.


Assuntos
Sepse , Humanos , Criança , Estudos Retrospectivos , Sepse/terapia , Sepse/tratamento farmacológico , Antibacterianos/uso terapêutico , Serviço Hospitalar de Emergência , Tempo para o Tratamento
7.
Rev Med Interne ; 45(4): 187-193, 2024 Apr.
Artigo em Francês | MEDLINE | ID: mdl-38519305

RESUMO

INTRODUCTION: The life expectancy of ß-thalassemia patients has increased over the last 20 years. In this study, we evaluated the current health status and quality of life of these patients managed in a reference center in Marseille. METHODS: This is a single-center, descriptive study conducted between June and August 2019 in patients over 18 years of age with ß-thalassemia major or intermedia. Clinical and paraclinical data were collected retrospectively and the SF-36 health survey questionnaire was proposed to each patient. RESULTS: 43 of 64 selected patients were included and divided into 2 groups: 35 patients with transfusion-dependent ß-thalassemia and 8 patients with non-transfusion-dependent ß-thalassemia. Liver iron overload is the most frequent complication, present in 80% of transfusion-dependent and 62.5% of non-transfusion-dependent patients. Cardiac iron overload is present only in the transfusion dependent ß-thalassemia group (20%). Hypogonadotropic hypogonadism remains the most common endocrine disorder (41.9%) followed by osteoporosis (37.2%). Among the 31 patients who completed the SF-36 questionnaire, physical and mental quality of life scores were lowered in transfusion dependent (respectively 42.7 and 46.8) as in non-transfusion-dependent patients (respectively 43.8 and 28.9). CONCLUSION: Despite an improvement in medical care, our patients with ß-thalassemia show an alteration in their quality of life that will need to be characterized in the entire French cohort.


Assuntos
Nível de Saúde , Qualidade de Vida , Talassemia beta , Humanos , Talassemia beta/terapia , Talassemia beta/epidemiologia , Talassemia beta/complicações , Talassemia beta/psicologia , França/epidemiologia , Masculino , Feminino , Adulto , Estudos Retrospectivos , Adulto Jovem , Pessoa de Meia-Idade , Transfusão de Sangue/estatística & dados numéricos , Sobrecarga de Ferro/epidemiologia , Sobrecarga de Ferro/etiologia , Inquéritos e Questionários , Adolescente
8.
Adv Biol (Weinh) ; 8(4): e2300633, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38342586

RESUMO

Ceramides and cardiorespiratory (CR) fitness are both related to cardiovascular diseases. The associations of three blood plasma ceramides (C16:0, C22:0, and C24:0) with CR fitness in the population-based Study of Health in Pomerania (SHIP-START-1; n = 1,102; mean age 50.3 years, 51.5% women) are investigated. In addition, subgroup analysis according to age (

Assuntos
Aptidão Cardiorrespiratória , Doenças Cardiovasculares , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Ceramidas , Biomarcadores , Doenças Cardiovasculares/epidemiologia
9.
Future Med Chem ; 16(7): 679-688, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38390753

RESUMO

Background: The scope of the study was to analyze original preclinical studies on the antimicrobial effects of carvacrol and derivatives on the Mycobacterium genus. Materials & methods: According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, four databases (PubMed, Web of Science, SCOPUS and EMBASE) were searched. Results: The search retrieved 392 records, of which 11 papers were selected. Heterogeneity in the techniques and mycobacterial targets was observed. Carvacrol demonstrated synergistic antimycobacterial activity with rifampicin against multidrug-resistant Mycobacterium tuberculosis on membranes and biofilms. In silico approaches showed specific targets in mycobacteria, by inhibition and molecular docking assays, on the enzyme chorismate mutase and the heat shock protein 16.3. Conclusion: Carvacrol has been shown to be a scaffold candidate for future molecules with activity against mycobacteria.


Assuntos
Mycobacterium tuberculosis , Simulação de Acoplamento Molecular , Cimenos/farmacologia , Antibacterianos/farmacologia
10.
PNAS Nexus ; 3(1): pgad451, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38222467

RESUMO

Dense suspensions exhibit the remarkable ability to switch dynamically and reversibly from a fluid-like to a solid-like, shear-jammed (SJ) state. Here, we show how this transition has important implications for the propensity for forming fractures. We inject air into bulk dense cornstarch suspensions and visualize the air invasion into the opaque material using time-resolved X-ray radiography. For suspensions with cornstarch mass fractions high enough to exhibit discontinuous shear thickening and shear jamming, we show that air injection leads to fractures in the material. For high mass fractions, these fractures grow quasistatically as rough cavities with fractured interfaces. For lower mass fractions, remarkably, the fractures can relax to smooth bubbles that then rise under buoyancy. We show that the onset of the relaxation occurs as the shear rate induced by the air cavity growth decreases below the critical shear rate denoting the onset of discontinuous shear thickening, which reveals a structural signature of the SJ state.

11.
Phys Chem Chem Phys ; 26(4): 2887-2894, 2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38054479

RESUMO

Liquid-liquid phase separation (LLPS) in aerosol particles is important for the climate system due to its potential to impact heterogeneous chemistry, cloud condensation nuclei, and new particle growth. Our group and others have shown a lower separation relative humidity for submicron particles, but whether the suppression is due to thermodynamics or kinetics is unclear. Herein, we characterize the experimental LLPS phase diagram of submicron 2-methylglutaric acid and ammonium sulfate aerosol particles and compare it to that of supermicron-sized particles. Surprisingly, as the equilibration time of submicron-sized aerosol particles was increased from 20 min to 60 min, the experimental phase diagram converges with the results for supermicron-sized particles. Our findings indicate that nucleation kinetics are responsible for the observed lower separation relative humidities in submicron aerosol particles. Therefore, experiments and models that investigate atmospheric processes of organic aerosol particles may need to consider the temporal evolution of aerosol LLPS.

12.
Soc Work Health Care ; 63(1): 53-70, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37970667

RESUMO

In this article, a communication framework of Connection First is presented to help close the empathy gap in mainstream health care, including palliative and end-of-life care. Expanding beyond biomedicine, Connection First involves rethinking and restructuring business-as-usual in health care. It shifts the typical transactional process during the initial intake session into one that is transformational. Connection First is a structural intervention and skillset comprised of the following elements: disrupting diagnosis, humanizing history, and repairing ruptures. These elements combine to help close the empathy gap in health care during the initial clinical encounter, before intake, and improve outcomes.


Assuntos
Empatia , Assistência Terminal , Humanos , Atenção à Saúde , Comunicação , Cuidados Paliativos
13.
Nat Commun ; 14(1): 7809, 2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-38086838

RESUMO

Free-ranging cats (Felis catus) are globally distributed invasive carnivores that markedly impact biodiversity. Here, to evaluate the potential threat of cats, we develop a comprehensive global assessment of species consumed by cats. We identify 2,084 species eaten by cats, of which 347 (16.65%) are of conservation concern. Islands contain threefold more species of conservation concern eaten by cats than continents do. Birds, reptiles, and mammals constitute ~90% of species consumed, with insects and amphibians being less frequent. Approximately 9% of known birds, 6% of known mammals, and 4% of known reptile species are identified in cat diets. 97% of species consumed are <5 kg in adult body mass, though much larger species are also eaten. The species accumulation curves are not asymptotic, indicating that our estimates are conservative. Our results demonstrate that cats are extreme generalist predators, which is critical for understanding their impact on ecological systems and developing management solutions.


Assuntos
Biodiversidade , Mamíferos , Animais , Gatos , Ecossistema , Dieta , Répteis , Aves
14.
Support Care Cancer ; 31(12): 705, 2023 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-37975923

RESUMO

PURPOSE: Bright light therapy holds promise for reducing common symptoms, e.g., fatigue, experienced by individuals with cancer. This study aimed to examine the effects of a chronotype-tailored bright light intervention on sleep disturbance, fatigue, depressive mood, cognitive dysfunction, and quality of life among post-treatment breast cancer survivors. METHODS: In this two-group randomized controlled trial (NCT03304587), participants were randomized to receive 30-min daily bright blue-green light (12,000 lx) or dim red light (5 lx) either between 19:00 and 20:00 h or within 30 min of waking in the morning. Self-reported outcomes and in-lab overnight polysomnography sleep study were assessed before (pre-test) and after the 14-day light intervention (post-test). RESULTS: The sample included 30 women 1-3 years post-completion of chemotherapy and/or radiation for stage I to III breast cancer (mean age = 52.5 ± 8.4 years). There were no significant between-group differences in any of the symptoms or quality of life (all p > 0.05). However, within each group, self-reported sleep disturbance, fatigue, depressive mood, cognitive dysfunction, and quality of life-related functioning showed significant improvements over time (all p < 0.05); the extent of improvement for fatigue and depressive mood was clinically relevant. Polysomnography sleep findings showed that a number of awakenings significantly decreased (p = 0.011) among participants who received bright light, while stage 2 sleep significantly increased (p = 0.015) among participants who received dim-red light. CONCLUSION: The findings support using light therapy to manage post-treatment symptoms in breast cancer survivors. The unexpected symptom improvements among dim-red light controls remain unexplained and require further investigation. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03304587, October 19, 2017.


Assuntos
Neoplasias da Mama , Sobreviventes de Câncer , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Neoplasias da Mama/complicações , Neoplasias da Mama/terapia , Sobreviventes de Câncer/psicologia , Cronotipo , Qualidade de Vida , Fadiga/etiologia , Fadiga/terapia , Fototerapia
15.
Front Physiol ; 14: 1266409, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37908333

RESUMO

The study objective was to evaluate the interaction between corticotrophin releasing factor (CRF) receptor signaling and prophylactic antibiotic administration on intestinal physiology in newly weaned and transported pigs. Pigs (n = 56; 5.70 ± 1.05 kg) were weaned (20.49 ± 0.64 d), a blood sample was taken, and then pigs were given an intraperitoneal injection of saline (SAL; n = 28 pigs) or a CRF receptor antagonist (CRFA; n = 28 pigs; 30 µg/kg body weight; Astressin B), and then were transported in a livestock trailer for 12 h and 49 min. A second and third intraperitoneal injection was given at 4 h 42 min and 11 h 36 min into the transport process, respectively. Following transport, 4 SAL and 4 CRFA pigs were blood sampled and euthanized. The remaining 48 pigs were individually housed and given dietary antibiotics [AB; n = 12 SAL and 12 CRFA pigs; chlortetracycline (441 ppm) + tiamulin (38.6 ppm)] or no dietary antibiotics (NAB; n = 12 SAL and 12 CRFA pigs) for 14 d post-transport. Blood was collected at 12 h and on d 3, 7, and 14, and then pigs were euthanized on d 7 (n = 24) and d 14 (n = 24) post-weaning and transport. Circulating cortisol was reduced (p = 0.05) in CRFA pigs when compared to SAL pigs post-weaning and transport. On d 7, jejunal villus height and crypt depth was greater overall (p < 0.05) in AB-fed pigs versus NAB-fed pigs. On d 14, ileal crypt depth was reduced (p = 0.02) in CRFA pigs when compared to SAL pigs. Jejunal CRF mRNA abundance tended to be reduced (p = 0.09) on d 7 in CRFA pigs versus SAL pigs. On d 14, jejunal tumor necrosis factor-alpha was reduced (p = 0.01) in AB-fed pigs versus NAB-fed pigs. On d 7, change in glucose short-circuit current tended to be increased (p = 0.07) in CRFA pigs fed the AB diet when compared to CRFA pigs fed the NAB diet. In conclusion, CRFA pigs and pigs fed AB had some similar biological intestinal function measures post-weaning and transport.

16.
Environ Monit Assess ; 195(11): 1398, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37910273

RESUMO

As climate change strains the world's freshwater resources, access to safe and clean water becomes limited. The use of alternative water sources, such as rooftop-harvested rainwater, has become one mechanism to address freshwater scarcity in the American Southwest, particularly when it comes to home gardening. The University of Arizona's Project Harvest, in partnership with the Sonora Environmental Research Institute, Inc., is a multi-year, co-created citizen science project aimed at increasing current understanding of harvested rainwater quality. Citizens in four Arizona, USA, communities (Hayden/Winkelman, Globe/Miami, Dewey-Humboldt, and Tucson) submitted harvested rainwater samples over 3 years. The harvested rainwater samples were then analyzed using IDEXX Colilert® for total coliforms and E. coli and using Hach PathoScreen™ test for sulfate-reducing bacteria (SRB). This study design allows for the validation of a low-cost, at-home alternative methodology for testing rainwater for bacteria that may indicate fecal contamination. In total, 226 samples were tested using both methodologies, revealing a positive correlation (r=0.245; p<0.002) between total coliform MPN and SRB MPN, but no discernable correlation between E. coli MPN and SRB MPN. This work indicates a potential value of SRB testing for harvested rainwater if cost, laboratory access, and fecal contamination are of concern.


Assuntos
Sulfeto de Hidrogênio , Abastecimento de Água , Monitoramento Ambiental/métodos , Escherichia coli , Chuva , Água , Microbiologia da Água
17.
J Clin Invest ; 134(3)2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-38032734

RESUMO

Pancreatic ß cells are specialized for coupling glucose metabolism to insulin peptide production and secretion. Acute glucose exposure robustly and coordinately increases translation of proinsulin and proteins required for secretion of mature insulin peptide. By contrast, chronically elevated glucose levels that occur during diabetes impair ß cell insulin secretion and have been shown experimentally to suppress insulin translation. Whether translation of other genes critical for insulin secretion is similarly downregulated by chronic high glucose is unknown. Here, we used high-throughput ribosome profiling and nascent proteomics in MIN6 insulinoma cells to elucidate the genome-wide impact of sustained high glucose on ß cell mRNA translation. Before induction of ER stress or suppression of global translation, sustained high glucose suppressed glucose-stimulated insulin secretion and downregulated translation of not only insulin, but also mRNAs related to insulin secretory granule formation, exocytosis, and metabolism-coupled insulin secretion. Translation of these mRNAs was also downregulated in primary rat and human islets following ex vivo incubation with sustained high glucose and in an in vivo model of chronic mild hyperglycemia. Furthermore, translational downregulation decreased cellular abundance of these proteins. Our study uncovered a translational regulatory circuit during ß cell glucose toxicity that impairs expression of proteins with critical roles in ß cell function.


Assuntos
Hiperglicemia , Células Secretoras de Insulina , Ilhotas Pancreáticas , Neoplasias Pancreáticas , Ratos , Humanos , Animais , Secreção de Insulina , RNA Mensageiro/metabolismo , Insulina/metabolismo , Hiperglicemia/genética , Hiperglicemia/metabolismo , Glucose/metabolismo , Células Secretoras de Insulina/metabolismo , Peptídeos/metabolismo , Neoplasias Pancreáticas/metabolismo , Ilhotas Pancreáticas/metabolismo
18.
Periodontol 2000 ; 2023 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-37845800

RESUMO

Noncommunicable diseases (NCDs) are multifactorial, long-term, chronic conditions that represent a burden to health-care systems worldwide as they can only be controlled rather than cured; hence, they require long-term care. With the exponential increase in NCDs, the occurrence of individuals presenting with more than one chronic disease is also rapidly rising. "Multimorbidity," defined as the presence of two or more long-term physical or mental disorders, is now considered a worldwide epidemic, affecting around 20% of the adult population. Periodontitis, diabetes, and obesity, all chronic inflammatory diseases, are an example of multimorbidity highly relevant to dental practitioners. Over the last three decades, the three-way relationship among the diseases has been vastly researched and accepted, with important contributions by European researchers. The interplay among periodontitis, diabetes, and obesity is sustained by shared biological mechanisms, such as systemic inflammation, insulin resistance, and metabolic dysfunction, as well as common lifestyle-related risk factors. As such, unhealthy lifestyles were found to generally increase systemic inflammation and insulin resistance and decrease immune function, hence, eventually increasing the risk of NCDs onset and the development of multimorbidity. This narrative review of the evidence supports the need for a paradigm shift from a "single-disease" to a "multiple-disease" framework, characterized by an integrated multidisciplinary approach, which should include lifestyle modification interventions to successfully tackle multimorbid periodontitis and metabolic diseases (diabetes and obesity). A multidisciplinary integrated care pathway in both dental and medical settings should be considered to further tackle the global health challenge of multimorbidity.

19.
Open Forum Infect Dis ; 10(10): ofad485, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37869403

RESUMO

Background: To assist clinicians with identifying children at risk of severe outcomes, we assessed the association between laboratory findings and severe outcomes among severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected children and determined if SARS-CoV-2 test result status modified the associations. Methods: We conducted a cross-sectional analysis of participants tested for SARS-CoV-2 infection in 41 pediatric emergency departments in 10 countries. Participants were hospitalized, had laboratory testing performed, and completed 14-day follow-up. The primary objective was to assess the associations between laboratory findings and severe outcomes. The secondary objective was to determine if the SARS-CoV-2 test result modified the associations. Results: We included 1817 participants; 522 (28.7%) SARS-CoV-2 test-positive and 1295 (71.3%) test-negative. Seventy-five (14.4%) test-positive and 174 (13.4%) test-negative children experienced severe outcomes. In regression analysis, we found that among SARS-CoV-2-positive children, procalcitonin ≥0.5 ng/mL (adjusted odds ratio [aOR], 9.14; 95% CI, 2.90-28.80), ferritin >500 ng/mL (aOR, 7.95; 95% CI, 1.89-33.44), D-dimer ≥1500 ng/mL (aOR, 4.57; 95% CI, 1.12-18.68), serum glucose ≥120 mg/dL (aOR, 2.01; 95% CI, 1.06-3.81), lymphocyte count <1.0 × 109/L (aOR, 3.21; 95% CI, 1.34-7.69), and platelet count <150 × 109/L (aOR, 2.82; 95% CI, 1.31-6.07) were associated with severe outcomes. Evaluation of the interaction term revealed that a positive SARS-CoV-2 result increased the associations with severe outcomes for elevated procalcitonin, C-reactive protein (CRP), D-dimer, and for reduced lymphocyte and platelet counts. Conclusions: Specific laboratory parameters are associated with severe outcomes in SARS-CoV-2-infected children, and elevated serum procalcitonin, CRP, and D-dimer and low absolute lymphocyte and platelet counts were more strongly associated with severe outcomes in children testing positive compared with those testing negative.

20.
bioRxiv ; 2023 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-37808767

RESUMO

Pancreatic ß-cells are specialized for coupling glucose metabolism to insulin peptide production and secretion. Acute glucose exposure robustly and coordinately increases translation of proinsulin and proteins required for secretion of mature insulin peptide. By contrast, chronically elevated glucose levels that occur during diabetes impair ß-cell insulin secretion and have been shown experimentally to suppress insulin translation. Whether translation of other genes critical for insulin secretion are similarly downregulated by chronic high glucose is unknown. Here, we used high-throughput ribosome profiling and nascent proteomics in MIN6 insulinoma cells to elucidate the genome-wide impact of sustained high glucose on ß-cell mRNA translation. Prior to induction of ER stress or suppression of global translation, sustained high glucose suppressed glucose-stimulated insulin secretion and downregulated translation of not only insulin, but also of mRNAs related to insulin secretory granule formation, exocytosis, and metabolism-coupled insulin secretion. Translation of these mRNAs was also downregulated in primary rat and human islets following ex-vivo incubation with sustained high glucose and in an in vivo model of chronic mild hyperglycemia. Furthermore, translational downregulation decreased cellular abundance of these proteins. Our findings uncover a translational regulatory circuit during ß-cell glucose toxicity that impairs expression of proteins with critical roles in ß-cell function.

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