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1.
Astrobiology ; 24(7): 669-683, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38979620

RESUMO

Mars has been exposed to ionizing radiation for several billion years, and as part of the search for life on the Red Planet, it is crucial to understand the impact of radiation on biosignature preservation. Several NASA and ESA missions are looking for evidence of ancient life in samples collected at depths shallow enough that they have been impacted by galactic cosmic rays (GCRs). In this study, we exposed a diverse set of Mars analog samples to 0.9 Megagray (MGy) of gamma radiation to mimic 15 million years of exposure on the Martian surface. We measured no significant impact of GCRs on the total organic carbon (TOC) and bulk stable C isotopes in samples with initial TOC concentration > 0.1 wt. %; however, diagnostic molecular biosignatures presented a wide range of degradation that didn't correlate to factors like mineralogy, TOC, water content, and surface area. Exposure dating suggests that the surface of Gale crater has been irradiated at more than five times our dose, yet using this relatively low dose and "best-case scenario" geologically recalcitrant biomarkers, large and variable losses were nevertheless evident. Our results empasize the importance of selecting sampling sites at depth or recently exposed at the Martian surface.


Assuntos
Biomarcadores , Argila , Radiação Cósmica , Meio Ambiente Extraterreno , Marte , Argila/química , Biomarcadores/análise , Meio Ambiente Extraterreno/química , Carbonatos/química , Carbonatos/análise , Exobiologia/métodos , Silicatos de Alumínio/química , Isótopos de Carbono/análise
2.
Front Nutr ; 11: 1415737, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38919390

RESUMO

Mounting evidence indicates that blueberry consumption is associated with a variety of health benefits. It has been suggested that regular consumption of blueberries can support and/or protect against cardiovascular disease and function, pre-diabetes and type 2 diabetes, and brain and cognitive function in individuals with health conditions and age-related decline. Further, mechanistic investigations highlight the role of blueberry anthocyanins in mediating these health benefits, in part through interactions with gut microbiota. Also, nutritional interventions with blueberries have demonstrated the ability to improve recovery following exercise-induced muscle damage, attributable to anti-inflammatory effects. Despite these advancements in blueberry health research, research gaps persist which affects the generalizability of findings from clinical trials. To evaluate the current state of knowledge and research gaps, a blueberry health roundtable with scientific experts convened in Washington, DC (December 6-7, 2022). Discussions centered around five research domains: cardiovascular health, pre-diabetes and diabetes, brain health and cognitive function, gut health, and exercise recovery. This article synthesizes the outcomes of a blueberry research roundtable discussion among researchers in these domains, offering insights into the health benefits of blueberries and delineating research gaps and future research directions.

3.
Pediatr Infect Dis J ; 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38900060

RESUMO

BACKGROUND: Although 6-month follow-up of patients with multisystem inflammatory syndrome in children (MIS-C) was reassuring, there is scant data on long-term sequelae, including whether changing variants affect clinical severity and outcomes. METHODS: Children (<18 years of age) admitted to Great Ormond Street Hospital between April 4, 2020, and January 2023, meeting diagnostic criteria for MIS-C were included. Admission and follow-up data were categorized by the predominant SARS-CoV-2 circulating variant in the United Kingdom. RESULTS: One hundred and sixty children [median age, 10.1 (interquartile range, 7.9-12.6) years] were included. There was no difference in the time of symptom onset to diagnosis between waves (P=0.23) or hospitalization days across all waves (P=0.32). Inflammatory markers were normal for up to 2 years in all patients except one. Eleven patients (6.9%) remain in follow-up: cardiology (n=5), gastroenterology (n=5) and nephrology (n=1). The main self-reported symptoms at 2 years were abdominal pain (n=5) and myalgia (n=2). Fatigue was present in approximately a quarter of patients at admission; this reduced to 14 (9%), (2%) and 1 (2%) at 6-month, 1-year and 2-year follow-ups, respectively. Chronic fatigue or long-COVID symptomatology was rare (n=1) even with high rates of concurrent Epstein-Barr virus positivity (49/134). All patients had sustained neurological recovery with no new neurological pathology observed. CONCLUSIONS: Patients with MIS-C have a sustained recovery, which is reassuring for positive long-term outcomes. Across waves, time from symptom onset to diagnosis and treatment, symptomatology and length of stay were similar. Sustained recovery is reassuring for clinicians and parents alike. Differentiating long-COVID symptomatology from that of MIS-C is important in formulating an individualized treatment plan.

4.
Nutrients ; 16(12)2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38931168

RESUMO

BACKGROUND: Ashwagandha has been reported to reduce stress and attenuate cognitive decline associated with inflammation and neurodegeneration in clinical populations. However, the effects as a potential nootropic nutrient in younger populations are unclear. This study examined the effects of liposomal ashwagandha supplementation on cognitive function, mood, and markers of health and safety in healthy young men and women. METHODS: 59 men and women (22.7 ± 7 yrs., 74.9 ± 16 kg, 26.2 ± 5 BMI) fasted for 12 h, donated a fasting blood sample, and were administered the COMPASS cognitive function test battery (Word Recall, Word recognition, Choice Reaction Time Task, Picture Recognition, Digit Vigilance Task, Corsi Block test, Stroop test) and profile of mood states (POMS). In a randomized and double-blind manner, participants were administered 225 mg of a placebo (Gum Arabic) or ashwagandha (Withania somnifera) root and leaf extract coated with a liposomal covering. After 60-min, participants repeated cognitive assessments. Participants continued supplementation (225 mg/d) for 30 days and then returned to the lab to repeat the experiment. Data were analyzed using a general linear model (GLM) univariate analysis with repeated measures and pairwise comparisons of mean changes from baseline with 95% confidence intervals (CI). RESULTS: Ashwagandha supplementation improved acute and/or 30-day measures of Word Recall (correct and recalled attempts), Choice Reaction Time (targets identified), Picture Recognition ("yes" correct responses, correct and overall reaction time), Digit Vigilance (correct reaction time), Stroop Color-Word (congruent words identified, reaction time), and POMS (tension and fatigue) from baseline more consistently with several differences observed between groups. CONCLUSION: Results support contentions that ashwagandha supplementation (225 mg) may improve some measures of memory, attention, vigilance, attention, and executive function while decreasing perceptions of tension and fatigue in younger healthy individuals. Retrospectively registered clinical trial ISRCTN58680760.


Assuntos
Afeto , Cognição , Suplementos Nutricionais , Extratos Vegetais , Humanos , Masculino , Feminino , Cognição/efeitos dos fármacos , Método Duplo-Cego , Adulto Jovem , Adulto , Afeto/efeitos dos fármacos , Extratos Vegetais/farmacologia , Adolescente , Tempo de Reação/efeitos dos fármacos , Biomarcadores/sangue , Lipossomos , Folhas de Planta/química , Raízes de Plantas/química
5.
J Neurosurg Spine ; : 1-11, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38728766

RESUMO

OBJECTIVE: The role of interbodies in lumbar arthrodesis has been insufficiently supported by evidence, impacting clinical decision-making and occasionally insurance coverage. This study aimed to compare clinical and radiological outcomes between lumbar arthrodesis with a synthetic interbody spacer (cage) versus structural bone graft alone (autograft or allograft) in patients with degenerative spine disease. METHODS: A systematic review of the literature was performed to identify studies directly comparing outcomes of lumbar interbody arthrodesis with and without interbody cage use. The outcomes of individual studies were synthesized in meta-analyses using random-effects models. RESULTS: Twenty studies with 1508 patients (769 with an interbody cage and 739 without an interbody cage) were included. Interbody cage placement was associated with a significantly greater increase in disc height after surgery (4.0 mm vs 3.4 mm, p < 0.01). There was a significantly greater reduction of back pain (visual analog scale [VAS] score) in cases in which an interbody cage was used (5.4 vs 4.7, p = 0.03). Fusion rates were 5.5% higher in the cage group (96.3% vs 90.8%) and reached statistical significance (p = 0.03). No statistically significant differences were identified between the two groups regarding all-cause reoperation rates, complication rates, or improvement in Oswestry Disability Index score or leg pain (VAS score). CONCLUSIONS: These results suggest that implantation of an interbody cage is associated with higher rates of fusion, more effective maintenance of disc height, and greater improvement of back pain. This study underlines the clinical value of interbody cages in lumbar arthrodesis for patients with degenerative spine disease.

6.
J Neurosurg Spine ; : 1-14, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38701518

RESUMO

OBJECTIVE: Use of bone morphogenetic protein (BMP)-an osteoinductive agent commonly used in lumbar arthrodesis-is off-label for cervical arthrodesis. This study aimed to identify the effect of BMP use on clinical and radiological outcomes in instrumented cervical arthrodesis. METHODS: A comprehensive systematic review of the literature was performed to identify studies directly comparing outcomes between cervical arthrodeses with and without using BMP. Outcomes were analyzed separately for cases of anterior cervical discectomy and fusion (ACDF) and posterior cervical fusion (PCF). RESULTS: A total of 20 studies with 5828 patients (1948 with BMP and 3880 without BMP) were included. In the ACDF cases, BMP use was associated with higher fusion rates (98.9% vs 93.6%, risk difference [RD] 8%; risk ratio [RR] 1.12, p = 0.02), lower reoperation rates (2.2% vs 3.1%, RD 3%; RR 0.48, p = 0.04), and higher risk of dysphagia (24.7% vs 8.1%, RD 11%; RR 1.93, p = 0.02). No significant differences in the Neck Disability Index, neck pain, or arm pain scores were associated with the use of BMP. On subgroup meta-analysis of ACDF cases, older age (≥ 50 years) and higher BMP dose (≥ 0.9 mg/level) were associated with significantly higher fusion rates and relatively lower risk for dysphagia, whereas arthrodesis of fewer segments (< 2 levels) showed significantly higher dysphagia rates without a significant increase in fusion rates. In the PCF cases, the use of BMP was not associated with significant differences in fusion (p = 0.38) or reoperation (p = 0.61) rates but was associated with significantly higher blood loss during surgery (mean difference 146.7 ml, p ≤ 0.01). CONCLUSIONS: Use of BMP in ACDF offers higher rates of augmented fusion and lower rates of all-cause reoperation but with an increased risk of dysphagia. The benefit of fusion outweighs the risk of dysphagia with a higher BMP dose in older patients being operated on for < 2 levels. The use of BMP in PCF seems to have a less important effect on clinical and radiological outcomes.

7.
Sch Psychol ; 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38753396

RESUMO

We explored associations among teachers' self-reported enjoyment for teaching mathematics, science, and English language arts and their students' self-reported behavioral engagement in each content area, and how these associations varied depending on student sex and socioeconomic status. Participants included 33 fourth-grade teachers and 443 students from 14 schools in the Southwestern United States. Multiple regression models with cluster robust standard errors was used. Models regressed students' content-area engagement on teachers' content-area enjoyment, controlling for students' initial engagement in that content area and other relevant covariates. Teachers' English language arts and mathematics enjoyment were each positively associated with students' engagement in each content area, and an interaction effect was detected in mathematics whereby lower socioeconomic status students with low-mathematics-enjoyment teachers reported lower mathematics engagement. Findings extend recent research highlighting teachers' emotions, and more specifically positive emotions, as factors that can be leveraged to support student learning, as well as provide more nuanced information about the contexts and student groups for whom these processes may be most relevant. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

8.
J Sch Health ; 94(8): 777-785, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38684235

RESUMO

BACKGROUND: Since returning to in-person instruction after the emergence of COVID-19 schools have seen a dramatic increase in the number of students chronically absent, with data indicating a greater increase for low-income, Black, and Hispanic students. Given the role of school attendance in both promoting positive educational outcomes as well as providing students with physical and mental health supports, it is critical to identify ways to re-engage families in a manner that is culturally responsive and equitable. CONTRIBUTIONS TO THEORY: Current attendance interventions focus primarily on school-based academic and behavioral supports for students while excluding the family. Additionally, traditional family engagement models do not address the sociocultural realities of low-income and/or minoritized families. We present a strengths-based model of family engagement to support attendance. IMPLICATIONS FOR SCHOOL HEALTH POLICY, PRACTICE, AND EQUITY: Along with our model, we provide concrete supports that schools can provide, including example measurement items. In this way, schools and districts can self-assess as well as identify action steps to promote positive school-family partnerships for equitable family engagement. CONCLUSIONS: Without consistent attendance, schools cannot support positive educational outcomes nor provide important safety net services for students. Attendance is a family engagement challenge, which addressing holistically can reduce racial and socioeconomic educational and health disparities.


Assuntos
Instituições Acadêmicas , Humanos , Instituições Acadêmicas/organização & administração , COVID-19 , Família , Serviços de Saúde Escolar/organização & administração , Criança , SARS-CoV-2 , Estudantes/psicologia , Adolescente
9.
Curr Cardiol Rep ; 26(6): 483-495, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38568339

RESUMO

PURPOSE OF REVIEW: Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder in women of reproductive age. It has been associated with metabolic, reproductive, and psychiatric disorders. Despite its association with insulin resistance (IR) and cardiovascular disease (CVD) risk factors, the association between PCOS and CVD outcomes has been conflicting. This review reports the updated evidence between PCOS, insulin resistance, and CVD events. RECENT FINDINGS: IR is highly prevalent occurring in 50 to 95% of general and obese PCOS women. The etiology of PCOS involves IR and hyperandrogenism, which lead to CVD risk factors, subclinical CVD, and CVD outcomes. Multiple studies including meta-analysis confirmed a strong association between PCOS and CVD events including ischemic heart disease, stroke, atrial fibrillation, and diabetes, particularly among premenopausal women, and these associations were mediated by metabolic abnormalities. PCOS is highly familial and has substantial CVD risk and transgenerational effects regardless of obesity. A personalized approach to the CVD risk assessment and management of symptom manifestations should be conducted according to its phenotypes. Lifestyle modifications and reduction in environmental stressors should be encouraged for CVD prevention among PCOS women.


Assuntos
Doenças Cardiovasculares , Resistência à Insulina , Síndrome do Ovário Policístico , Humanos , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/fisiopatologia , Feminino , Doenças Cardiovasculares/etiologia , Obesidade/complicações , Obesidade/fisiopatologia , Fatores de Risco , Medição de Risco , Fatores de Risco de Doenças Cardíacas , Prevalência , Hiperandrogenismo/complicações , Hiperandrogenismo/fisiopatologia
10.
Transl Androl Urol ; 13(3): 406-413, 2024 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-38590963

RESUMO

Background: Firearm injuries increased significantly during the coronavirus disease 2019 (COVID-19) pandemic. We aimed to describe our experience with patients admitted to a level 1 trauma center with gunshot-related trauma to the genitourinary (GU) tract before and during COVID-19 pandemic. Methods: Patients sustaining gunshot-related trauma to the adrenals, kidneys, ureters, bladder, scrotum, testicles, penis, and urethra between January 1, 2018 and December 31, 2021 were identified from our institutional trauma database. Patient charts were queried to extract demographic information, management, and follow-up. Results: A total of 117 patients met inclusion criteria with 39 (33%) of GU injuries occurring pre-COVID, and 78 (67%) occurring during or post-COVID. Seventy-two (62%) presented with kidney injury. Patients injured in the pre-COVID period were more likely to participate in a follow-up visit by 2.17 times at 60 days (P=0.017), 1.98 times at 90 days (P=0.030), and 2.04 times at 1-year (P=0.014) than during COVID. Pre-COVID, 46% of patients were injured in the city's northwestern region and 54% from other areas, during COVID 24% of patients came from the northwestern region compared to 76% from other areas (P=0.029). Conclusions: Gunshot wounds (GSW) involving the GU tract increased during the COVID-19 pandemic, with renal injury most frequent. Follow-up visits declined by around half during the pandemic, primarily at 60 days, 90 days, and 1 year post-injury. The number of patients admitted with urologic injuries pre-COVID versus during COVID was significantly different depending on the patient's area of residence. More work is needed to evaluate the outcomes of traumatic GU injuries due to GSW pre- and post-pandemic.

12.
Nutrients ; 16(7)2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38613023

RESUMO

BACKGROUND: Microalgae like Phaeodactylum tricornutum (PT) contain the carotenoid, fucoxanthin, which has been purported to promote fat loss, lower blood lipids, and improve glucose management. This study examined whether dietary supplementation with microalgae extracts from PT containing 4.4 mg/d of fucoxanthin affects changes in body composition or health markers in overweight women during an exercise and diet intervention. MATERIALS AND METHODS: A total of 37 females (28.6 ± 7.9 years, 80.2 ± 14.9 kg, 29.6 ± 3.8 kg/m², 41.4 ± 4.2% fat) fasted for 12 h, donated a fasting blood sample, completed health and mood state inventories, and undertook body composition, health, and exercise assessments. In a counterbalanced, randomized, and double-blind manner, participants ingested a placebo (PL), or microalgae extract of Phaeodactylum tricornutum standardized to 4.4 mg of fucoxanthin (FX) for 12 weeks while participating in a supervised exercise program that included resistance-training and walking (3 days/week) with encouragement to accumulate 10,000 steps/day on remaining days of the week. The diet intervention involved reducing energy intake by about -300 kcal/d (i.e., ≈1400-1600 kcals/d, 55% carbohydrate, 30% fat, 15% protein) to promote a -500 kcal/d energy deficit with exercise. Follow-up testing was performed at 6 and 12 weeks. A general linear model (GLM) with repeated measures statistical analysis was used to analyze group responses and changes from baseline with 95% confidence intervals. RESULTS: Dietary supplementation with microalgae extract from PT containing fucoxanthin for 12 weeks did not promote additional weight loss or fat loss in overweight but otherwise healthy females initiating an exercise and diet intervention designed to promote modest weight loss. However, fucoxanthin supplementation preserved bone mass, increased bone density, and saw greater improvements in walking steps/day, resting heart rate, aerobic capacity, blood lipid profiles, adherence to diet goals, functional activity tolerance, and measures of quality of life. Consequently, there appears to be some benefit to supplementing microalgae extract from PT containing fucoxanthin during a diet and exercise program. Registered clinical trial #NCT04761406.


Assuntos
Microalgas , Xantofilas , Feminino , Humanos , Suplementos Nutricionais , Sobrepeso/terapia , Qualidade de Vida , Redução de Peso , Adulto Jovem , Adulto
13.
Blood ; 2024 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-38643491

RESUMO

Post-transplant lymphoproliferative disorder (PTLD) is a rare complication of solid organ transplantation, and cytotoxic chemotherapy is associated with treatment-related morbidity and mortality. Current treatment takes a sequential, risk-stratified approach, patients with low-risk disease following initial immunotherapy can avoid escalation to immunochemotherapy. TIDaL is a prospective, single-arm phase 2 trial investigating the activity and tolerability of ibrutinib combined with risk-stratified therapy for first-line treatment of PTLD. Eligible patients were adults with newly-diagnosed CD20-positive B-cell PTLD after solid organ transplant and performance status 0 to 2. Initial treatment comprised 49 days of ibrutinib 560mg once daily, with 4 doses of weekly rituximab. Treatment response on interim scan and baseline international prognostic index were used to allocate patients to either a low-risk arm (who continued ibrutinib, alongside 4 further doses of 3-weekly rituximab) or high-risk (escalation to R-CHOP immunochemotherapy, ibrutinib continuing in patients aged <65 years). The primary outcome was complete response on interim scan, achieved by 11/38 patients (29%, 95% confidence interval (CI) 15% - 46%). This did not reach the pre-specified threshold for clinically significant activity. Secondary outcomes included allocation to the low-risk arm (41% of patients), 2-year progression-free survival (58%, 95% CI 44% - 76%), and 2-year overall survival (76%, 95% CI 63% - 91%). Adverse events were mostly haematological, gastrointestinal and infective. Whilst TIDaL does not support adding ibrutinib into first-line treatment of PTLD, increasing the proportion of patients who can be treated without cytotoxic chemotherapy remains an important aim of future research. This trial was registered as ISRCTN32667607.

14.
Prev Sci ; 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38653943

RESUMO

Service engagement is critical when working with children and families experiencing chronic adversities because of their socially marginalized status. Further, sociodemographic disparities exist in service engagement within service systems including Community-Based Behavioral Health; likely in part, a result of structural issues driving unresponsive service systems. Despite this knowledge, a large proportion of the family engagement literature continues to be approached through a deficit-based and family-centric lens leaving out important systemic considerations and furthering health inequities. Drawing from a Socio-Ecological Framework (Stokols, 1996), this study focuses on exploring the value of peer support providers (PSPs) to understand how sociocultural responsiveness functions under this service model. Individual interviews and focus group data were collected from both families and PSPs. Thematic analysis (Braun & Clarke in Qualitative Research in Psychology, 3(2), 77-101, 2006) was utilized to code and synthetize the data collected. Findings highlight the importance of capitalizing on meaningful and trusting relationships to foster family engagement in services. These findings solidify the understanding that family engagement is a function of crucial relationships between family, provider, and systems. This work also illustrates how PSPs organic embodiment of sociocultural responsiveness through cultural humility is an avenue through which family engagement can be sustained.

15.
Laryngoscope ; 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38554009

RESUMO

OBJECTIVE: To evaluate the literature and summarize cochlear implantation (CI) outcomes after intralabyrinthine schwannoma (ILS) excision and tumor observation with CI. DATA SOURCES: OVID Medline, Embase, Web of Science; conception to 2024. REVIEW METHODS: A literature review was performed using subject headings, MeSH terms, and keywords. Abstracts and full texts were reviewed by two independent reviewers and adjudicated by a third. Inclusion criteria included studies with ILS and CI with reported audiologic outcomes. Subjects were analyzed into two groups, ILS resection with CI and in situ ILS with CI. Patients with NF2 were included. The main outcome of interest was CI audiometric performance level, with secondary outcomes of CI user status and open-set speech attainment. RESULTS: There were 29 articles with a total of 93 patients who met inclusion criteria. The resection group had 17% low performers, 44% intermediate performers, and 38% high performers. The in situ group had 40% low performers, 32% intermediate performers, 27% high performers. The resection group had 69 patients with 97% maintaining user status and 92% with open-set speech recognition. The observation group had 24 patients, with 87% user rate and 86% achieving open-set speech recognition. There was a greater percentage of NF2 diagnosis seen in the in situ group. CONCLUSION: There is a paucity of literature on CI and ILS. Patients are managed with both resection of tumor and implantation in situ. Early data are limited, with improvement in hearing outcomes and high user rates in both populations. LEVEL OF EVIDENCE: N/A Laryngoscope, 2024.

16.
Sci Rep ; 14(1): 7303, 2024 03 27.
Artigo em Inglês | MEDLINE | ID: mdl-38538642

RESUMO

Ex vivo drug screening is a potentially powerful tool for the future of cancer care, but the accuracy of results is contingent on the culture model. Both monolayer (2D) and spheroid (3D) culture systems offer advantages, but given the differences in mechanical environment, we hypothesized that that the suitability of one system over another would be critical for screening drugs with mechanical targets in mechanical tissues. HCC827 lung adenocarcinoma cells were challenged with EGFR tyrosine kinase inhibitors in monolayer and spheroid culture. RNA sequencing was performed on cells in both conditions to assess culture-induced transcriptional changes that could account for differences in drug response and differences in EGFR expression detected by immunostain. A microRNA microarray was performed to assess culture-induced differences in regulation of microRNA, and the impact of miR-146a-5p on drug response was verified by inhibition. Results were confirmed in human lung adenocarcinoma tissue. HCC827 spheroids were resistant to erlotinib and gefitinib, but significantly more sensitive in 2D culture. RNA-seq and immunostaining show a discrepancy in EGFR transcript and protein expression between the two conditions, which we attribute to miR-146a-5p. This microRNA targets EGFR and is differentially expressed between 2D and 3D culture. Inhibition of miR-146a-5p significantly increased erlotinib cytotoxicity, but validation in patient-derived spheroids suggests that the effect may be mutation-specific. Analysis of RNA-seq data suggests that cells in 2D culture become highly dependent on EGFR signaling to drive proliferation and cell spreading, resulting in a misleading level of sensitivity to EGFR TKIs, while the same cells in spheroid culture retain microRNA-driven EGFR feedback regulation that leaves them less vulnerable to EGFR inhibition. These findings underscore the need for close scrutiny of culture-induced effects on drug target regulation in model design for ex vivo drug screening.


Assuntos
Adenocarcinoma de Pulmão , Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , MicroRNAs , Humanos , MicroRNAs/metabolismo , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Cloridrato de Erlotinib/farmacologia , Cloridrato de Erlotinib/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Antineoplásicos/farmacologia , Retroalimentação , Receptores ErbB/metabolismo , Linhagem Celular Tumoral , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/genética , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Mutação
17.
Acta Trop ; 253: 107162, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38428628

RESUMO

OBJECTIVES: During the COVID-19 pandemic, the risk of childhood infectious diseases was increased. Post-COVID-19 escalation of chickenpox cases, becoming an emerging public health concern. Thus, the study was designed to compare chickenpox prevalence and Varicella zoster virus (VZV) genotypes circulating before, during, and post-COVID-19 in Pakistan. METHODS: A total of 267 lesion specimens collected from tertiary care hospitals, and chickenpox outbreaks from Pakistan were analysed by a two-amplicon approach with phylogenetic analysis. RESULTS: Among suspected cases, overall 178/267 were VZV positive. Majority (84.2 %; 150/178) cases were of post-COVID-19 pandemic time. Small outbreaks occurred soon after COVID-19 in Rawalpindi and Islamabad (Pakistan), 40 positive cases out of 178 cases were outbreak cases. There was first time detection of the M4 genotype, which was significantly associated with disease severity (p = 0.0006) and post-COVID-19 chickenpox outbreaks in 2021 (77.9 %; 46/59; p < 0.00001). However, in pre-COVID-19 only M2 genotype was detected. The M2 prevalence varied from 2019 (100 %; 19/19) to 2022 (3.2 %; 3/91). However, the most prevalent strain of 2022 belonged to the M1 genotype (64.8 %; 59/91). CONCLUSION: A significant rise in chickenpox cases detected soon after COVID-19 in Pakistan, and oscillation of different VZV genotypes with first time detection of M4 genotype is an alarming situation. This demands further detailed genotypic studies on transmission dynamics of a rare M4 with other genotypes to protect the local population and restrict spread in other regions.


Assuntos
COVID-19 , Varicela , Herpes Zoster , Humanos , Varicela/epidemiologia , Varicela/diagnóstico , Paquistão/epidemiologia , Filogenia , Pandemias , COVID-19/diagnóstico , COVID-19/epidemiologia , Herpesvirus Humano 3/genética , Genótipo , Herpes Zoster/diagnóstico , Herpes Zoster/epidemiologia
18.
Patient Educ Couns ; 123: 108237, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38461793

RESUMO

OBJECTIVE: Given the importance of unhurried conversations for providing careful and kind care, we sought to create, test, and validate the Unhurried Conversations Assessment Tool (UCAT) for assessing the unhurriedness of patient-clinician consultations. METHODS: In the first two phases, the unhurried conversation dimensions were identified and transformed into an assessment tool. In the third phase, two independent raters used UCAT to evaluate the unhurriedness of 100 randomly selected consultations from 184 videos recorded for a large research trial. UCAT's psychometric properties were evaluated using this data. RESULTS: UCAT demonstrates content validity based on the literature and expert review. EFA and reliability analyses confirm its construct validity and internal consistency. The seven formative dimensions account for 89.93% of the variance in unhurriedness, each displaying excellent internal consistency (α > 0.90). Inter-rater agreement for the overall assessment item was fair (ICC = 0.59), with individual dimension ICCs ranging from 0.26 (poor) to 0.95 (excellent). CONCLUSION: UCAT components comprehensively assess the unhurriedness of consultations. The tool exhibits content and construct validity and can be used reliably. PRACTICE IMPLICATIONS: UCAT's design and psychometric properties make it a practical and efficient tool. Clinicians can use it for self-evaluations and training to foster unhurried conversations.


Assuntos
Comunicação , Avaliação Educacional , Humanos , Reprodutibilidade dos Testes , Avaliação Educacional/métodos , Psicometria , Competência Clínica
19.
PLoS One ; 19(3): e0295639, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38502654

RESUMO

INTRODUCTION: Complex challenges amongst ageing cohorts of adolescents and adults living with perinatally acquired HIV (PaHIV) may impact on hospitalisation. We report hospitalisation rates and explored predictive factors for hospitalisation in adolescents and adults (10-35 years) living with PaHIV in England. METHOD: Retrospective observational cohort study over a three-year period 2016-2019. Data collected included cause and duration of hospitalisation, HIV viral load and CD4 lymphocyte count. The primary outcome was overnight hospitalisation. Patients exited at study end/ transfer of care (TOC)/ loss to follow up (LTFU) or death. Maternity/hospital admissions at other centres were excluded. Admission rates per 100 person-years (95% CI) were calculated by age group. Negative binomial regression with generalized estimating equations was performed. RESULTS: 255 patients contributed 689 person-years of follow up. 56% were female and 83% were of a Black, Black British, Caribbean or African ethnicity. At baseline, the median age was 19 years (IQR 16-22). 36 individuals experienced a total of 62 admissions which resulted in 558 overnight stays (median stay was 5 nights). One person died (lymphoma), six had TOC and one was LTFU by the end of the three-year study period. Crude incidence of admission for the whole cohort was 9.0 per 100 PY (6.9-11.6). The respective crude incidence rates were 1.5 PY (0.0-8.2) in those aged 10-14 years and 3.5 PY (1.5-7.0) in the 15-19-year-olds. In those aged 20-24 years it was 14.5 PY (10.1-20.2) and in those >25 years the crude incidence rate was 11.7 PY (6.9-18.5). Factors significantly associated with admission were a CD4 lymphocyte count <200 cells/uL, adjusted IRR 4.0 (1.8-8.8) and a history of a CDC-C diagnosis, adjusted IRR 2.9 (1.6-5.3). 89% admissions were HIV-related: 45% new/current CDC-C diagnoses, 76% due to infection. CONCLUSIONS: Hospitalisation rates were four-fold higher in adults (>20 years of age) compared to adolescents (10-19-year-olds). The continuing challenges experienced by PaHIV youth require enhanced multidisciplinary support throughout adulthood.


Assuntos
Infecções por HIV , HIV , Adolescente , Adulto , Feminino , Humanos , Masculino , Adulto Jovem , Contagem de Linfócito CD4 , Hospitalização , Estudos Retrospectivos , Criança , População Negra , População do Caribe , População Africana
20.
J Occup Environ Med ; 66(6): 475-480, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38471807

RESUMO

OBJECTIVE: This study assessed firefighters' physiological stress response to a live fire training evolution (LFTE). METHODS: Seventy-six ( n = 76) firefighters completed an LFTE. Salivary samples were collected pre-, immediately post, and 30-min post-LFTE and analyzed for α-amylase (AA), cortisol (CORT), and secretory immunoglobulin-A (SIgA). RESULTS: Concentrations of AA, CORT, and SIgA were elevated immediately post LFTE versus pre (P<0.001) and 30-min post (P<0.001). Cohen's d effect size comparing pre and immediately-post means were 0.83, 0.77, and 0.61 for AA, CORT, and SIgA and were 0.54, 0.44, and 0.69 for AA, CORT, and SIgA, comparing immediately-post and 30-min post, respectively. CONCLUSIONS: These data demonstrate the stress response and activation of the hypothalamic-pituitary-adrenal/sympathetic-adreno-medullar axis and immune system immediately after real-world firefighting operations. Future work is needed to understand the impact of elevated stress biomarkers on firefighter performance and disease risk.


Assuntos
Bombeiros , Hidrocortisona , Saliva , alfa-Amilases , Humanos , Masculino , Hidrocortisona/análise , Hidrocortisona/metabolismo , Adulto , Saliva/química , Feminino , alfa-Amilases/análise , alfa-Amilases/metabolismo , Estresse Fisiológico/fisiologia , Imunoglobulina A Secretora/análise , Imunoglobulina A Secretora/metabolismo , Pessoa de Meia-Idade , Estresse Ocupacional , Sistema Hipotálamo-Hipofisário/fisiologia , Sistema Hipófise-Suprarrenal/fisiologia
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