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1.
Development ; 149(19)2022 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-36111596

RESUMO

Larval terminal cells of the Drosophila tracheal system generate extensive branched tubes, requiring a huge increase in apical membrane. We discovered that terminal cells compromised for apical membrane expansion - mTOR-vATPase axis and apical polarity mutants - were invaded by the neighboring stalk cell. The invading cell grows and branches, replacing the original single intercellular junction between stalk and terminal cell with multiple intercellular junctions. Here, we characterize disjointed, a mutation in the same phenotypic class. We find that disjointed encodes Drosophila Archease, which is required for the RNA ligase (RtcB) function that is essential for tRNA maturation and for endoplasmic reticulum stress-regulated nonconventional splicing of Xbp1 mRNA. We show that the steady-state subcellular localization of Archease is principally nuclear and dependent upon TOR-vATPase activity. In tracheal cells mutant for Rheb or vATPase loci, Archease localization shifted dramatically from nucleus to cytoplasm. Further, we found that blocking tRNA maturation by knockdown of tRNAseZ also induced compensatory branching. Taken together, these data suggest that the TOR-vATPase axis promotes apical membrane growth in part through nuclear localization of Archease, where Archease is required for tRNA maturation.


Assuntos
Proteínas de Drosophila , RNA Ligase (ATP) , Animais , Drosophila/metabolismo , Proteínas de Drosophila/genética , RNA Ligase (ATP)/genética , RNA Ligase (ATP)/metabolismo , RNA Mensageiro/genética , RNA de Transferência/genética , Serina-Treonina Quinases TOR/genética , Traqueia/metabolismo
2.
J Antimicrob Chemother ; 79(2): 287-296, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38091580

RESUMO

BACKGROUND: Evidence on the distribution of pre-treatment HIV-1 drug resistance (HIVDR) among risk groups is limited in Africa. We assessed the prevalence, trends and transmission dynamics of pre-treatment HIVDR within and between MSM, people who inject drugs (PWID), female sex workers (FSWs), heterosexuals (HETs) and perinatally infected children in Kenya. METHODS: HIV-1 partial pol sequences from antiretroviral-naive individuals collected from multiple sources between 1986 and 2020 were used. Pre-treatment reverse transcriptase inhibitor (RTI), PI and integrase inhibitor (INSTI) mutations were assessed using the Stanford HIVDR database. Phylogenetic methods were used to determine and date transmission clusters. RESULTS: Of 3567 sequences analysed, 550 (15.4%, 95% CI: 14.2-16.6) had at least one pre-treatment HIVDR mutation, which was most prevalent amongst children (41.3%), followed by PWID (31.0%), MSM (19.9%), FSWs (15.1%) and HETs (13.9%). Overall, pre-treatment HIVDR increased consistently, from 6.9% (before 2005) to 24.2% (2016-20). Among HETs, pre-treatment HIVDR increased from 6.6% (before 2005) to 20.2% (2011-15), but dropped to 6.5% (2016-20). Additionally, 32 clusters with shared pre-treatment HIVDR mutations were identified. The majority of clusters had R0 ≥ 1.0, indicating ongoing transmissions. The largest was a K103N cluster involving 16 MSM sequences sampled between 2010 and 2017, with an estimated time to the most recent common ancestor (tMRCA) of 2005 [95% higher posterior density (HPD), 2000-08], indicating propagation over 12 years. CONCLUSIONS: Compared to HETs, children and key populations had higher levels of pre-treatment HIVDR. Introduction of INSTIs after 2017 may have abrogated the increase in pre-treatment RTI mutations, albeit in the HET population only. Taken together, our findings underscore the need for targeted efforts towards equitable access to ART for children and key populations in Kenya.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Soropositividade para HIV , HIV-1 , Profissionais do Sexo , Abuso de Substâncias por Via Intravenosa , Criança , Humanos , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Quênia/epidemiologia , Filogenia , Abuso de Substâncias por Via Intravenosa/complicações , Abuso de Substâncias por Via Intravenosa/epidemiologia , Abuso de Substâncias por Via Intravenosa/tratamento farmacológico , Farmacorresistência Viral/genética , Soropositividade para HIV/tratamento farmacológico , Inibidores da Transcriptase Reversa/uso terapêutico , Mutação , Fármacos Anti-HIV/farmacologia , Fármacos Anti-HIV/uso terapêutico
3.
Sex Transm Dis ; 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38895966

RESUMO

BACKGROUND: Estimates on sexual behavior (SB) among emerging adults (EmA) is varied in literature, which presents a challenge when designing targeted interventions. We aimed to summarize literature on prevalence and risk factors of SB among EmA in Africa. METHODS: A search for studies published in PubMed, Embase and Psych Info by March 2023 was done. Studies involving EmA (18-25 years), conducted in Africa and reporting one or more of seven SB were reviewed. Pooled prevalence estimates were summarized using forest plots. Heterogeneity in SB was explored. Risk factors were synthesized using a modified socio-ecological model. RESULTS: Overall, 143 studies were analyzed. Non-condom use had the highest pooled prevalence (47% [95% CI: 42-51]), followed by study-defined SB (37% [95% CI: 25-50]) and concurrency (37% [95% CI: 21-54]), multiple sex partners (31% [95% CI: 25-37]), younger age at sexual debut (26% [95% CI: 20-32]), age disparate relationships (24% [95% CI: 17-32]) and transactional sex (19% [95% CI: 13-26]). Heterogeneity was partially explained by sex, with female participants having higher pooled prevalence estimates compared to their male counterparts. In four of the seven outcomes, alcohol/drug use was the most common risk factor. CONCLUSIONS: SB was common among EmA and differentially higher in emerging female adults. Non-condom use had the highest pooled prevalence, which may contribute to the transmission of HIV and other sexually transmitted infections (STIs). Interventions targeting emerging female adults and alcohol/drug use may reduce SB, which may in-turn mitigate transmission of HIV and other STIs among EmA in Africa.

4.
World J Urol ; 42(1): 295, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38709300

RESUMO

PURPOSE: Selective serotonin reuptake inhibitors are associated with high rates of nonadherence and sexual dysfunction, yet the correlation between these findings in young adult men is poorly characterized. We aimed to evaluate if young adult men are less willing to adhere to antidepressant treatment due to intolerable side effects, such as sexual dysfunction. METHODS: Deidentified, compensated survey that assessed baseline demographics, PHQ-8 and GAD-7 scores, attitudes towards antidepressant medication side effects, and perceptions of antidepressant medications including selective serotonin reuptake inhibitors, bupropion, and mirtazapine. RESULTS: From 665 delivered surveys, 505 respondents completed their survey (response rate: 76%), of which 486 were included for final analysis. After seeing common side effect profiles, our sample's willingness to take sexual function-sparing agents, such as bupropion or mirtazapine, was significantly greater than selective serotonin reuptake inhibitors (p < 0.001), with no significant difference between bupropion and mirtazapine (p = 0.263). The negative influence of erectile dysfunction and anorgasmia scored significantly higher than other common antidepressant side effects like weight gain, nausea, and dry mouth (range: p < 0.001, p = 0.043). With the exception of insomnia, participants indicated that experiencing sexual dysfunction while taking an antidepressant medication would lead to nonadherence at a significantly higher frequency than any other side effect assessed (range: p < 0.001, p = 0.005). CONCLUSION: The risk of experiencing sexual side effects when taking antidepressants could lead young adult men to become nonadherent to these medications. Strategies to augment the effectiveness of antidepressants, such as shared decision-making and the use of sexual function-sparing agents, are critical.


Assuntos
Antidepressivos , Adesão à Medicação , Disfunções Sexuais Fisiológicas , Humanos , Masculino , Estudos Transversais , Adulto Jovem , Disfunções Sexuais Fisiológicas/induzido quimicamente , Adulto , Antidepressivos/efeitos adversos , Antidepressivos/uso terapêutico , Mirtazapina/uso terapêutico , Inibidores Seletivos de Recaptação de Serotonina/efeitos adversos , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Bupropiona/efeitos adversos , Bupropiona/uso terapêutico
5.
Public Health ; 233: 193-200, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38941682

RESUMO

OBJECTIVES: COVID-19 revealed major shortfalls in healthcare workers (HCWs) trained in acute and critical care worldwide, especially in low-resource settings. We aimed to assess mass online courses' efficacy in preparing HCWs to manage COVID-19 patients and to determine whether rapidly deployed e-learning can enhance their knowledge and confidence during a pandemic. STUDY DESIGN: Retrospective cohort study. METHODS: This international retrospective cohort study, led by a large Academic Medical Centre (AMC), was conducted via YouTube and the AMC's online learning platform. From 2020 to 2021, multidisciplinary experts developed and deployed six online training courses based on the latest evidence-based management guidelines. Participants were selected through a voluntary sample following an electronic campaign. Training outcomes were assessed using pre-and post-test questionnaires, evaluation forms, and post-training assessment surveys. Kirkpatrick's Model guided training evaluation to measure self-reported knowledge, clinical skills, and confidence improvement. We also captured the number and type of COVID-19 patients managed by HCWs after the trainings. RESULTS: Every 22.8 reach/impression and every 1.2 engagements led to a course registration. The 10,425 registrants (56.8% female, 43.1% male) represented 584 medical facilities across 154 cities. The largest segments of participants were students/interns (20.6%) and medical officers (13.4%). Of the 2169 registered participants in courses with tests, 66.9% completed post-tests. Test scores from all courses increased from the initial baseline to subsequent improvement post-course. Participants completing post-training assessment surveys reported that the online courses improved their knowledge and clinical skills (83.5%) and confidence (89.4%). Respondents managed over 19,720 COVID-19 patients after attending the courses, with 47.7% patients being moderately/severely ill. CONCLUSIONS: Participants' confidence in handling COVID-19 patients is increased by rapidly deploying mass training to a substantial target population through digital tools. The findings present a virtual education and assessment model that can be leveraged for future global public health issues, and estimates for future electronic campaigns to target.

6.
Rheumatology (Oxford) ; 62(3): 1243-1247, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-35946502

RESUMO

OBJECTIVES: Rituximab (RTX) use early in the course of refractory idiopathic inflammatory myopathy (IIM) is not well studied. This study sought to determine the short-term efficacy of RTX in a registry-based cohort of refractory IIM. METHODS: Registry-based observational data about IIM patients receiving RTX between 2018 and 2021 were included. Total improvement score was calculated from the core set measures as per International Myositis Assessment and Clinical Studies group (IMACS) at baseline, 6 months and 12 months of follow-up. RESULTS: Forty-two patients (F:M, 29:13), with a mean (s.d.) age of 39.5 (11.5) years were studied. Majority of patients received RTX for refractory myositis, after a median (interquartile range) duration of 8 (4,18) months. Twenty-eight received RTX at a dosage of 1 g × two doses, while 14 received 500 mg × two doses with an interval of 15 days. At 6 months and 12 months post-RTX, the improvement was recorded in manual muscle testing (MMT-8) scores, physician global assessment (PGA), patient global assessment (PtGA) and median steroid dosage as compared with the baseline (P < 0.01 for all). A mean (s.d.) improvement of 44.5 (16) and 48.7 (19.2) in total improvement score was recorded at 6 and 12 months, respectively. The change in MMT-8, PGA and PtGA scores from baseline between the two dosage regimens of RTX were comparable at 6 and 12 months. Severe lower respiratory tract infections requiring hospitalization occurred in three patients of the cohort. CONCLUSION: RTX improved IMACS core set measures and had steroid sparing efficacy at 6 and 12 months in patients with IIM in this registry-based study. Rituximab as an induction regimen of two doses of 500 mg can be as efficacious as 1 g at 6 months and 12 months of follow-up.


Assuntos
Miosite , Humanos , Adulto , Rituximab , Resultado do Tratamento , Estudos Retrospectivos
7.
BMC Med Inform Decis Mak ; 23(1): 183, 2023 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-37715195

RESUMO

BACKGROUND: Aggregate electronic data repositories and population-level cross-sectional surveys play a critical role in HIV programme monitoring and surveillance for data-driven decision-making. However, these data sources have inherent limitations including inability to respond to public health priorities in real-time and to longitudinally follow up clients for ascertainment of long-term outcomes. Electronic medical records (EMRs) have tremendous potential to bridge these gaps when harnessed into a centralised data repository. We describe the evolution of EMRs and the development of a centralised national data warehouse (NDW) repository. Further, we describe the distribution and representativeness of data from the NDW and explore its potential for population-level surveillance of HIV testing, care and treatment in Kenya. MAIN BODY: Health information systems in Kenya have evolved from simple paper records to web-based EMRs with features that support data transmission to the NDW. The NDW design includes four layers: data warehouse application programming interface (DWAPI), central staging, integration service, and data visualization application. The number of health facilities uploading individual-level data to the NDW increased from 666 in 2016 to 1,516 in 2020, covering 41 of 47 counties in Kenya. By the end of 2020, the NDW hosted longitudinal data from 1,928,458 individuals ever started on antiretroviral therapy (ART). In 2020, there were 936,869 individuals who were active on ART in the NDW, compared to 1,219,276 individuals on ART reported in the aggregate-level Kenya Health Information System (KHIS), suggesting 77% coverage. The proportional distribution of individuals on ART by counties in the NDW was consistent with that from KHIS, suggesting representativeness and generalizability at the population level. CONCLUSION: The NDW presents opportunities for individual-level HIV programme monitoring and surveillance because of its longitudinal design and its ability to respond to public health priorities in real-time. A comparison with estimates from KHIS demonstrates that the NDW has high coverage and that the data maybe representative and generalizable at the population-level. The NDW is therefore a unique and complementary resource for HIV programme monitoring and surveillance with potential to strengthen timely data driven decision-making towards HIV epidemic control in Kenya. DATABASE LINK: ( https://dwh.nascop.org/ ).


Assuntos
Data Warehousing , Registros Eletrônicos de Saúde , Humanos , Estudos Transversais , Quênia/epidemiologia , Teste de HIV
8.
J Oral Rehabil ; 50(5): 351-359, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36704914

RESUMO

BACKGROUND: Mouth breathing (MB) can affect morphological changes in the craniofacial structures, electromyography is widely used for quantitative analysis of muscle function. OBJECTIVE: The aim was to evaluate the electromyographic (EMG) activities of the anterior temporalis (TA), masseter muscle (MM), orbicularis oris superior (OOS) and mentalis muscle (MT) in children with different vertical skeletal patterns and breathing modes during rest and various functional mandibular movements. METHODS: BioEMG III was used to measure the variations in EMG activities of TA, MM, OOS, and MT in 185 subjects aged 6-12 years during continuous clenching, rest, maximal intercuspation, lips closed lightly and swallowing. RESULTS: The results of logistic regression analysis showed that the model with vertical skeletal patterns as the dependent variable was ineffective (p = .106), while the model with breathing modes as the dependent variable was effective (p = .000). When considering both vertical skeletal patterns and breathing modes, the following significant differences were found. (1) In the normal-angle group, the EMG ratio in OOS with lips closed lightly of MB was significantly higher than NB (p = .005). (2) In the low-angle group, EMG ratios in TA and MM during the swallowing of MB were significantly lower than NB (p = .020, p = .040, respectively). (3) In the high-angle group, EMG ratios of MB were significantly higher in MT during continuous clenching, rest, lips closed lightly and swallowing (p = .038, p = .036, p = .005, p = .028, respectively), and OOS with lips closed lightly compared to NB (p = .005). CONCLUSION: Breathing modes and vertical skeletal patterns interacted to alter maxillofacial EMG activities, with breathing modes having a greater effect.


Assuntos
Músculos Faciais , Lábio , Criança , Humanos , Músculos Faciais/fisiologia , Lábio/fisiologia , Músculo Masseter/fisiologia , Mandíbula , Músculo Temporal/fisiologia , Eletromiografia/métodos , Respiração Bucal
9.
BMC Public Health ; 22(1): 280, 2022 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-35148720

RESUMO

BACKGROUND: HIV testing is the first step to stop transmission. We aimed to evaluate HIV testing history and new diagnoses among adult outpatients in Kenya aged 18-39 years seeking care for symptoms of acute HIV infection (AHI). METHODS: The Tambua Mapema Plus study, a stepped-wedge trial, enrolled patients presenting to care at six primary care facilities with symptoms of AHI for a targeted HIV-1 nucleic acid (NA) testing intervention compared with standard provider-initiated testing using rapid antibody tests. Intervention participants underwent a questionnaire and NA testing, followed by rapid tests if NA-positive. Multinomial logistic regression was used to analyse factors associated with never testing or testing > 1 year ago ("late retesting") relative to testing ≤ 1 year ago ("on-time testers"). Logistic regression was used to analyse factors associated with new diagnosis. All analyses were stratified by sex. RESULTS: Of 1,500 intervention participants, 613 (40.9%) were men. Overall, 250 (40.8%) men vs. 364 (41.0%) women were late retesters, and 103 (16.8%) men vs. 50 (5.6%) women had never tested prior to enrolment. Younger age, single status, lower education level, no formal employment, childlessness, sexual activity in the past 6 weeks, and > 1 sexual partner were associated with testing history among both men and women. Intimate partner violence > 1 month ago, a regular sexual partner, and concurrency were associated with testing history among women only. New diagnoses were made in 37 (2.5%) participants (17 men and 20 women), of whom 8 (21.6%) had never tested and 16 (43.2%) were late retesters. Newly-diagnosed men were more likely to have symptoms for > 14 days, lower education level and no religious affiliation and less likely to be young, single, and childless than HIV-negative men; newly-diagnosed women were more likely to report fever than HIV-negative women. Among men, never testing was associated with fivefold increased odds (95% confidence interval 1.4-20.9) of new diagnosis relative to on-time testers in adjusted analyses. CONCLUSION: Most new HIV diagnoses were among participants who had never tested or tested > 1 year ago. Strengthening provider-initiated testing targeting never testers and late retesters could decrease time to diagnosis among symptomatic adults in coastal Kenya. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03508908 registered on 26/04/2018.


Assuntos
Infecções por HIV , Adulto , Estudos Transversais , Feminino , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Teste de HIV , Humanos , Lactente , Quênia/epidemiologia , Masculino , Pacientes Ambulatoriais
10.
Ir Med J ; 115(7): 635, 2022 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-36300768

RESUMO

Introduction In the Republic of Ireland, there are no tuberous sclerosis complex (TSC) specialist clinics. Methods A clinical audit was carried out to assess the care received by patients attending two specialist adult epilepsy specialist centres, measuring their care against the UK guidelines. Results Although many baseline investigations are carried out, only one-third of patients had diagnostic genetic testing results available. Neuropsychiatry is largely neglected, and the completion of neuropsychiatric assessments checklists is inadequate. Discussions concerning SUDEP are not happening and access to treatment is limited. Reporting of radiological findings in TSC is inconsistent and the number of adults with TSC accessing specialist epilepsy services appear to be low. Discussion TSC care in the Republic of Ireland is fragmented, difficult to navigate and wasteful of resources due to the complex nature of the disease and no formal clinical setting to manage it. The service gaps echo the demand for an improved care system including consistent radiological reporting of TSC pathology. The absence of a specialist TSC clinic compounds the complexity of navigating care for individuals with TSC, families and healthcare professionals. Extending this audit nationally will give a more complete picture and highlight the resources required to bring care of these patients in line with recommended guidelines.


Assuntos
Epilepsia , Esclerose Tuberosa , Adulto , Humanos , Epilepsia/etiologia , Epilepsia/tratamento farmacológico , Doenças Raras , Esclerose , Esclerose Tuberosa/genética , Esclerose Tuberosa/terapia , Esclerose Tuberosa/diagnóstico
11.
BMC Oral Health ; 22(1): 228, 2022 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-35681197

RESUMO

BACKGROUND: This retrospective study investigated the effect of breathing pattern, skeletal class (Class I, Class II), and age on the hyoid bone position (HBP) in normodivergent subjects. METHODS: A total of 126 subjects (61 males, 65 females) aged 7-9 years and 10-12 years were scanned using cone-beam computed tomography (CBCT). All participants were classified according to the anteroposterior skeletal pattern into (Class I, Class II). Each skeletal group was further divided according to the breathing mode into mouth breathers (MB) and nasal breathers (NB). The HBP was measured accordingly. Independent sample t-test and Mann Whitney U test were used to detect significant differences between the groups, and binary logistic regression was used to identify MB predictive indicators. RESULTS: The breathing mode and skeletal class affected the vertical HBP in subjects with 7-9 years, while they affected the anteroposterior HBP in subjects with 10-12 years. Regarding the age effect, hyoid bone was located more anteriorly in the older NB subjects, and hyoid bone was more inferiorly in the older age group. A regression equation of the significant variables was formulated, C3-Me (P: 001, OR: 2.27), and H-EB (P: 0.046, OR: 1.16) were positively correlated with occurrence of MB. CONCLUSION: There were significantly different HBPs among subjects with different anteroposterior skeletal classes, breathing modes, and age cohorts. Moreover, C3-Me, and H-EB were significant predictors and correlated with increased likelihood of being MB subject.


Assuntos
Osso Hioide , Respiração Bucal , Idoso , Cefalometria/métodos , Tomografia Computadorizada de Feixe Cônico/métodos , Feminino , Humanos , Osso Hioide/diagnóstico por imagem , Masculino , Mandíbula , Respiração Bucal/diagnóstico por imagem , Estudos Retrospectivos
12.
BMC Oral Health ; 22(1): 320, 2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-35915494

RESUMO

OBJECTIVE: This study aimed to investigate whether the subjects with mouth breathing (MB) or nasal breathing (NB) with different sagittal skeletal patterns showed different maxillary arch and pharyngeal airway characteristics. METHODS: Cone-beam computed tomography scans from 70 children aged 10 to 12 years with sagittal skeletal Classes I and II were used to measure the pharyngeal airway, maxillary width, palatal area, and height. The independent t-test and the Mann-Whitney U test were used for the intragroup analysis of pharyngeal airway and maxillary arch parameters. RESULTS: In the Skeletal Class I group, nasopharyngeal airway volume (P < 0.01), oropharyngeal airway volume (OPV), and total pharyngeal airway volume (TPV) (all P < 0.001) were significantly greater in subjects with NB than in those with MB. Furthermore, intermolar width, maxillary width at the molars, intercanine width, maxillary width at the canines, and palatal area were significantly larger in subjects with NB than in those with MB (all P < 0.001). In the Skeletal Class II group, OPV, TPV (both P < 0.05) were significantly greater in subjects with NB than in those with MB. No significant differences in pharyngeal airway parameters in the MB group between subjects with Skeletal Class I and those with Skeletal Class II. CONCLUSION: Regardless of sagittal Skeletal Class I or II, the pharyngeal airway and maxillary arch in children with MB differ from those with NB. However, the pharyngeal airway was not significantly different between Skeletal Class I and II in children with MB.


Assuntos
Imageamento Tridimensional , Maxila , Respiração Bucal , Faringe , Cefalometria/métodos , Tomografia Computadorizada de Feixe Cônico/métodos , Humanos , Imageamento Tridimensional/métodos , Mandíbula , Maxila/diagnóstico por imagem , Palato , Faringe/diagnóstico por imagem
13.
Clin Infect Dis ; 73(5): 832-841, 2021 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-33588436

RESUMO

BACKGROUND: Acute retroviral syndrome (ARS) is associated with human immunodeficiency virus type 1 (HIV-1) subtype and disease progression, but the underlying immunopathological pathways are poorly understood. We aimed to elucidate associations between innate immune responses during hyperacute HIV-1 infection (hAHI) and ARS. METHODS: Plasma samples obtained from volunteers (≥18.0 years) before and during hAHI, defined as HIV-1 antibody negative and RNA or p24 antigen positive, from Kenya, Rwanda, Uganda, Zambia, and Sweden were analyzed. Forty soluble innate immune markers were measured using multiplexed assays. Immune responses were differentiated into volunteers with stronger and comparatively weaker responses using principal component analysis. Presence or absence of ARS was defined based on 11 symptoms using latent class analysis. Logistic regression was used to determine associations between immune responses and ARS. RESULTS: Of 55 volunteers, 31 (56%) had ARS. Volunteers with stronger immune responses (n = 36 [65%]) had increased odds of ARS which was independent of HIV-1 subtype, age, and risk group (adjusted odds ratio, 7.1 [95% confidence interval {CI}: 1.7-28.8], P = .003). Interferon gamma-induced protein (IP)-10 was 14-fold higher during hAHI, elevated in 7 of the 11 symptoms and independently associated with ARS. IP-10 threshold >466.0 pg/mL differentiated stronger immune responses with a sensitivity of 84.2% (95% CI: 60.4-96.6) and specificity of 100.0% (95% CI]: 90.3-100.0). CONCLUSIONS: A stronger innate immune response during hAHI was associated with ARS. Plasma IP-10 may be a candidate biomarker of stronger innate immunity. Our findings provide further insights on innate immune responses in regulating ARS and may inform the design of vaccine candidates harnessing innate immunity.


Assuntos
Síndrome Retroviral Aguda , Infecções por HIV , HIV-1 , Quimiocina CXCL10 , Humanos , Imunidade Inata
14.
World J Urol ; 39(9): 3399-3405, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33710425

RESUMO

PURPOSE: Increasing use and resolution of testicular ultrasound imaging has resulted in a greater diagnosis of non-palpable small testicular masses and subsequent over-treatment with orchiectomy. Our aim was to determine the diagnostic accuracy of testicular ultrasound to accurately determine the pathologic size of small testicular masses (SMTMs) and to evaluate the association of various measurements with benign pathology. METHODS: Retrospectively, an institutional testicular cancer database was reviewed to evaluate the patients who underwent an orchiectomy for a testicular mass seen on ultrasound from 2003 to 2017. Three-dimensional measurements were compared from the ultrasound and pathology specimens, including other measures such as tumor volume and percentage of testicular volume. Finally, the predictive accuracy of maximum diameter and tumor volume to predict benign pathology was evaluated using receiver-operating curve analysis. RESULTS: We identified 208 patients and showed that ultrasound significantly underestimated sub-centimeter testicular masses (mean difference 0.56 cm, 95%CI 0.89-0.14, p = 0.004) and testicular masses between 1 and < 2 cm (mean difference 0.50 cm, 95%CI 0.97-0.15, p = 0.009). Tumor volume measured on ultrasound was consistently similar to pathologic tumor volume across all sizes and was significantly correlated (Spearman's Rho = 0.81). Mass volume had a greater predictive accuracy for benign pathology than maximum diameter using a 1 cm cut-off (AUC 0.65 vs 0.60). CONCLUSION: Using the maximal diameter, testicular ultrasound significantly miscalculated the pathologic dimensions of masses less than 2 cm compared to orchiectomy specimens. Volumetric measurements may better represent actual tumor sizes for SMTMs and may be a more useful measure for identifying those a higher risk for benign pathology, however, further studies are required.


Assuntos
Precisão da Medição Dimensional , Neoplasias Testiculares/diagnóstico por imagem , Neoplasias Testiculares/patologia , Carga Tumoral , Adulto , Correlação de Dados , Humanos , Masculino , Estudos Retrospectivos , Ultrassonografia
15.
Nature ; 522(7554): 98-101, 2015 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-26017307

RESUMO

Interactions between primary producers and bacteria impact the physiology of both partners, alter the chemistry of their environment, and shape ecosystem diversity. In marine ecosystems, these interactions are difficult to study partly because the major photosynthetic organisms are microscopic, unicellular phytoplankton. Coastal phytoplankton communities are dominated by diatoms, which generate approximately 40% of marine primary production and form the base of many marine food webs. Diatoms co-occur with specific bacterial taxa, but the mechanisms of potential interactions are mostly unknown. Here we tease apart a bacterial consortium associated with a globally distributed diatom and find that a Sulfitobacter species promotes diatom cell division via secretion of the hormone indole-3-acetic acid, synthesized by the bacterium using both diatom-secreted and endogenous tryptophan. Indole-3-acetic acid and tryptophan serve as signalling molecules that are part of a complex exchange of nutrients, including diatom-excreted organosulfur molecules and bacterial-excreted ammonia. The potential prevalence of this mode of signalling in the oceans is corroborated by metabolite and metatranscriptome analyses that show widespread indole-3-acetic acid production by Sulfitobacter-related bacteria, particularly in coastal environments. Our study expands on the emerging recognition that marine microbial communities are part of tightly connected networks by providing evidence that these interactions are mediated through production and exchange of infochemicals.


Assuntos
Diatomáceas/metabolismo , Diatomáceas/microbiologia , Ecossistema , Ácidos Indolacéticos/metabolismo , Fitoplâncton/metabolismo , Fitoplâncton/microbiologia , Rhodobacteraceae/metabolismo , Diatomáceas/citologia , Diatomáceas/genética , Metabolômica , Dados de Sequência Molecular , Oceanos e Mares , Fotossíntese , Fitoplâncton/citologia , Fitoplâncton/genética , Rhodobacteraceae/genética , Água do Mar/química , Transcriptoma , Triptofano/metabolismo
16.
BMC Psychiatry ; 21(1): 90, 2021 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-33568115

RESUMO

BACKGROUND: In sub-Saharan Africa, common mental disorders (CMDs) like depression and anxiety are under-investigated amongst young people living with HIV (YLWH). To address the gap, in Kenya we: a) determined the prevalence of CMDs among YLWH compared to their uninfected peers; b) investigated HIV status as an independent predictor of CMDs in young people; c) investigated CMDs risk and protective indicators with more focus on YLWH. METHODS: Between November 2018 and September 2019, 819 young people aged 18-24 years (407 HIV-infected) were recruited from two Counties on the Kenyan coast. Locally adapted pre-existing mental health measures, Patient Health Questionnaire (9-item) and Generalized Anxiety Disorder scale (7-item), were administered among other questionnaires via audio computer-assisted self-interview. Logistic regression was used to determine the correlates of CMDs. RESULTS: Prevalence of CMDs was significantly elevated among YLWH compared to their uninfected peers i.e. 29% vs. 12%; p < 0.001 for depressive symptoms, 19% vs. 8%; p < 0.001 for anxiety symptoms, and 16% vs. 5%; p < 0.001 for comorbid depressive and anxiety symptoms. HIV status independently predicted depressive symptoms and its co-occurrence with anxiety symptoms. Among YLWH, negative life events, higher perceived HIV-related stigma and low adherence to antiretroviral therapy were the risk indicators for elevated CMDs. Among HIV-uninfected youths, death of both parents was a risk indicator for elevated depressive symptoms. Protective indicators against CMDs among youths with and without HIV included higher social support and health-related quality of life. CONCLUSION: At the Kenyan coast, YLWH have significantly higher burden of CMDs compared to their uninfected peers. Being HIV-positive as a youth in this setting is predictive of more depressive symptoms and its comorbidity with anxiety symptoms. YLWH at high risk of CMDs in coastal Kenya can benefit from early detection, referral and treatment if routine screening for CMDs is integrated in their care package. The mental wellbeing of bereaving HIV-unaffected youths could be improved through continued support to help them come to terms with their loss. At the community level, programmes strengthening the social capital or improving the overall quality of life of youths with or without HIV may be beneficial to their mental health.


Assuntos
Infecções por HIV , Transtornos Mentais , Adolescente , Adulto , Estudos Transversais , Depressão/epidemiologia , Infecções por HIV/epidemiologia , Humanos , Quênia/epidemiologia , Transtornos Mentais/epidemiologia , Prevalência , Qualidade de Vida , Adulto Jovem
17.
PLoS Genet ; 14(1): e1007146, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29309404

RESUMO

During sprouting angiogenesis in the vertebrate vascular system, and primary branching in the Drosophila tracheal system, specialized tip cells direct branch outgrowth and network formation. When tip cells lumenize, they form subcellular (seamless) tubes. How these seamless tubes are made, shaped and maintained remains poorly understood. Here we characterize a Drosophila mutant called ichor (ich), and show that ich is essential for the integrity and shape of seamless tubes in tracheal terminal cells. We find that Ich regulates seamless tubulogenesis via its role in promoting the formation of a mature apical extracellular matrix (aECM) lining the lumen of the seamless tubes. We determined that ich encodes a zinc finger protein (CG11966) that acts, as a transcriptional activator required for the expression of multiple aECM factors, including a novel membrane-anchored trypsin protease (CG8213). Thus, the integrity and shape of seamless tubes are regulated by the aECM that lines their lumens.


Assuntos
Proteínas de Drosophila/fisiologia , Matriz Extracelular/fisiologia , Morfogênese/genética , Proteínas Nucleares/fisiologia , Junções Íntimas/genética , Fatores de Transcrição/fisiologia , Animais , Animais Geneticamente Modificados , Vasos Sanguíneos/embriologia , Células Cultivadas , Proteínas de Drosophila/genética , Drosophila melanogaster/embriologia , Drosophila melanogaster/genética , Embrião não Mamífero , Matriz Extracelular/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Vasos Linfáticos/embriologia , Neovascularização Fisiológica/genética , Proteínas Nucleares/genética , Tamanho do Órgão , Junções Íntimas/metabolismo , Traqueia/embriologia , Traqueia/metabolismo , Fatores de Transcrição/genética , Dedos de Zinco
18.
Community Dent Health ; 38(3): 161-164, 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34369114

RESUMO

This paper aims to explore the outcome of a telephone triage system used by different team members to run an Urgent Dental Care Hub (UDCH) during the first wave of the COVID-19 pandemic. It will also look at the adjustments made to the system because of the challenges faced. Data were collected from the telephone triage proforma and clinical notes of patients that were triaged from 2nd April to 10th June 2020. With 65% of telephone triaged and accepted patients receiving definitive treatment that alleviated the presenting complaint, the value of telephone triage is highlighted in streamlining an urgent dental care service during a viral pandemic. Public health competencies being illustrated: Dental public health intelligence, Developing and monitoring quality dental services.


Assuntos
COVID-19 , Pandemias , Assistência Odontológica , Humanos , Saúde Pública , SARS-CoV-2 , Telefone , Triagem
19.
J Assoc Physicians India ; 69(1): 36-40, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34227774

RESUMO

There is a need to understand the clinical and antibody associations in patients with IIM in various ethnicities and geographical areas. Patients who fulfilled Bohan's and Peter criteria of IIM and seen between October 2017 through Jan 2020 were enrolled in this study at 3 centres. Clinical and relevant laboratory parameters were recorded in a pre designed case record form. MSA and MAA to 16 antigens were performed by line blot assay using Euroimmun (Luebec, Germany) as per manufacturer's instruction. Of the 150 patients, 13 were juvenile onset. Ninety sera had either one MSA or MAA. Sixty sera had neither MSA/MAA. anti-Ro 52 were the commonest antibody and anti-Mi-2α and b the commonest MSA. Novel associations identified were severe myositis with anti-Ro 52, cutaneous ulcerations with anti-MDA5 and anti-PM-Scl and calcinosis with anti-PM-Scl. One-third sera had no MSA or MAA. Larger sample size and use of antibody assays together with muscle biopsy will improve subtyping and phenotype associations in IIM.


Assuntos
Autoanticorpos , Miosite , Alemanha , Humanos , Índia/epidemiologia , Miosite/epidemiologia , Prevalência
20.
Malays J Pathol ; 43(2): 261-268, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34448790

RESUMO

INTRODUCTION: Continuous ambulatory peritoneal dialysis (CAPD)-associated peritonitis remains a major complication in patients on CAPD leading to increased morbidity and mortality. Successful therapy of peritonitis is highly dependent on a positive microbiological culture because narrow spectrum antibiotics are essential to efficiently combat infection. Therefore, this study evaluated the performance of Tween 80 containing media at three different concentrations (0.1%, 1.0% and 2.0%) to increase the pathogen yield from peritoneal fluid in comparison with the standard culture media. MATERIALS AND METHODS: Peritoneal fluid samples (n=121) obtained from CAPD patients suspected of peritonitis at Hospital Kuala Lumpur were analysed macroscopically and microscopically prior to culture. All samples were cultured on seven different culture media, including sheep blood agar, MacConkey agar, Sabouraud dextrose agar, brain heart infusion agar and Tween 80 incorporated blood agar. All plates were incubated at an optimum temperature up to 48 hours. RESULTS AND CONCLUSION: Among all the culture media investigated, 0.1% to 2.0% Tween 80 incorporated blood agar yielded the highest positive culture (23/121) in comparison with all other standard media, thus lowering the negative culture rate among CAPD patients. Statistical analysis by Chi Square revealed significant differences (p <0.001) between the three concentrations of Tween 80 tested in this study. Among the three different concentrations of Tween 80 optimised in this study, blood agar containing 0.1% Tween 80 generated the best results, achieved by optimum growth of all Gram-positive organisms, Gram-negative organisms and yeast cells simultaneously. Using a small amount of detergent at low cost significantly increased the pathogen yield during CAPD-associated peritonitis.


Assuntos
Diálise Peritoneal Ambulatorial Contínua , Ágar , Líquido Ascítico , Meios de Cultura , Hospitais , Humanos , Diálise Peritoneal Ambulatorial Contínua/efeitos adversos , Peritonite/etiologia , Polissorbatos/efeitos adversos
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