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1.
PLoS Pathog ; 20(10): e1012679, 2024 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-39480892

RESUMO

Salmonella enterica serovar Agona (S. Agona) has been increasingly recognised as a prominent cause of gastroenteritis. This serovar is a strong biofilm former that can undergo genome rearrangement and enter a viable but non-culturable state whilst remaining metabolically active. Similar strategies are employed by S. Typhi, the cause of typhoid fever, during human infection, which are believed to assist with the transition from acute infection to chronic carriage. Here we report S. Agona's ability to persist in people and examine factors that might be contributing to chronic carriage. A review of 2233 S. Agona isolates from UK infections (2004-2020) and associated carriage was undertaken, in which 1155 had short-read sequencing data available. A subset of 207 isolates was selected from different stages of acute and persistent infections within individual patients. The subset underwent long-read sequencing and genome structure (GS) analysis, as well as phenotyping assays including carbon source utilisation and biofilm formation. Associations between genotypes and phenotypes were investigated to compare acute infections to those which progress to chronic. GS analysis revealed the conserved arrangement GS1.0 in 195 isolates, and 8 additional GSs in 12 isolates. These rearranged isolates were typically associated with early, convalescent carriage (3 weeks- 3 months). We also identified an increase in SNP variation during this period of infection. We believe this increase in genome-scale and SNP variation reflects a population expansion after acute S. Agona infection, potentially reflecting an immune evasion mechanism which enables persistent infection to become established.

2.
Curr Opin Infect Dis ; 37(5): 413-418, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39079178

RESUMO

PURPOSE OF REVIEW: The American Academy of Pediatrics recently published guidance for the evaluation and management of febrile infants. However, guidance on testing and empiric treatment for neonatal herpes simplex virus (HSV) remains less standardized and subject to clinical practice variation. RECENT FINDINGS: Recent reports reveal that high numbers of infants presenting for sepsis evaluations need to be treated empirically with acyclovir to capture one case of neonatal HSV. Clinical and laboratory risk factors for neonatal HSV identified in the literature can be used for a targeted approach to testing and treating infants for HSV to optimize resource utilization. SUMMARY: The literature supports a targeted approach to evaluation and empiric acyclovir treatment for neonatal HSV, but additional studies are needed to validate this approach given the rarity of disease.


Assuntos
Aciclovir , Antivirais , Herpes Simples , Complicações Infecciosas na Gravidez , Humanos , Herpes Simples/tratamento farmacológico , Herpes Simples/diagnóstico , Recém-Nascido , Antivirais/uso terapêutico , Aciclovir/uso terapêutico , Complicações Infecciosas na Gravidez/tratamento farmacológico , Complicações Infecciosas na Gravidez/virologia , Complicações Infecciosas na Gravidez/diagnóstico , Sepse/tratamento farmacológico , Sepse/diagnóstico , Simplexvirus/efeitos dos fármacos , Fatores de Risco
3.
J Pediatr ; 268: 113934, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38309519

RESUMO

OBJECTIVE: The objective of this study was to determine if valganciclovir initiated after 1 month of age improves congenital cytomegalovirus-associated sensorineural hearing loss. STUDY DESIGN: We conducted a randomized, double-blind, placebo-controlled phase 2 trial of 6 weeks of oral valganciclovir at US (n = 12) and UK (n = 9) sites. Patients of ages 1 month through 3 years with baseline sensorineural hearing loss were enrolled. The primary outcome was change in total ear hearing between baseline and study month 6. Secondary outcome measures included change in best ear hearing and reduction in cytomegalovirus viral load in blood, saliva, and urine. RESULTS: Of 54 participants enrolled, 35 were documented to have congenital cytomegalovirus infection and were randomized (active group: 17; placebo group: 18). Mean age at enrollment was 17.8 ± 15.8 months (valganciclovir) vs 19.5 ± 13.1 months (placebo). Twenty (76.9%) of the 26 ears from subjects in the active treatment group did not have worsening of hearing, compared with 27 (96.4%) of 28 ears from subjects in the placebo group (P = .09). All other comparisons of total ear or best ear hearing outcomes were also not statistically significant. Saliva and urine viral loads decreased significantly in the valganciclovir group but did not correlate with change in hearing outcome. CONCLUSIONS: In this randomized controlled trial, initiation of antiviral therapy beyond the first month of age did not improve hearing outcomes in children with congenital cytomegalovirus-associated sensorineural hearing loss. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT01649869.


Assuntos
Antivirais , Infecções por Citomegalovirus , Ganciclovir , Perda Auditiva Neurossensorial , Valganciclovir , Humanos , Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/congênito , Infecções por Citomegalovirus/complicações , Valganciclovir/uso terapêutico , Valganciclovir/administração & dosagem , Perda Auditiva Neurossensorial/tratamento farmacológico , Perda Auditiva Neurossensorial/virologia , Perda Auditiva Neurossensorial/etiologia , Antivirais/uso terapêutico , Antivirais/administração & dosagem , Masculino , Feminino , Método Duplo-Cego , Lactente , Administração Oral , Ganciclovir/análogos & derivados , Ganciclovir/uso terapêutico , Ganciclovir/administração & dosagem , Pré-Escolar , Resultado do Tratamento , Carga Viral , Recém-Nascido
4.
BMC Public Health ; 24(1): 410, 2024 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-38331791

RESUMO

BACKGROUND: Individuals with high social vulnerability index (SVI) have poorer outcomes with COVID-19. Masking reduces transmission of COVID-19 among children, but how SVI plays a role in masking behavior is unknown. We aimed to measure the association of SVI with masking adherence among children during the COVID-19 pandemic. METHODS: We conducted a multi-site, prospective syndromic surveillance study among children aged 2 - 17 years in the Southeastern United States by daily electronic surveys which solicited symptoms of COVID-19-like illness, infection with or exposure to SARS-CoV-2, masking habits, and any receipt of COVID-19 vaccines. Parents/guardians submitted surveys for their children; adolescents 13 years and older could opt to submit their own surveys. Multivariable and univariate linear models were used to measure the associations of different predictors such as SVI with masking adherence. RESULTS: One thousand four hundred sixty-one children from 6 states and 55 counties predominately from North and South Carolina were included in the analysis. Most children in the cohort were 5 - 11 years old, non-Hispanic White, from urban counties, and with low-moderate SVI. Overall masking adherence decreased over time, and older children had higher masking adherence throughout the study period compared with younger children. Children who resided in urban counties had greater masking adherence throughout the study period than those who resided in suburban or rural counties. Masking adherence was higher among children with both low and medium SVI than those with high SVI. CONCLUSIONS: Despite being at risk for more severe outcomes with COVID-19, children with high SVI had lower levels of masking adherence compared to those with low SVI. Our findings highlight opportunities for improved and targeted messaging in these vulnerable communities.


Assuntos
COVID-19 , Adolescente , Criança , Humanos , Estados Unidos , Pré-Escolar , COVID-19/epidemiologia , Vacinas contra COVID-19 , SARS-CoV-2 , Pandemias , Estudos Prospectivos , Vulnerabilidade Social
5.
Rev Med Suisse ; 20(888): 1707-1711, 2024 Sep 25.
Artigo em Francês | MEDLINE | ID: mdl-39323273

RESUMO

Syncope is a common reason for consultations and hospitali-zations. A diagnosis is established in 50 % of cases with the initial assessment. It can also be used to stratify the risk of cardiovascular events or recurrence, and their potentially fatal consequences. This stratification, based on European and American guidelines, is essential for guiding management. Various predictive scores exist, including the Canadian Syncope Risk Score (CSRS), which assesses the risk of serious events within 30 days. The CSRS has limitations in both emergency and outpatient settings. Current guidelines do not include specific scores, highlighting the importance of clinical judgment and the initial assessment for risk stratification.


La syncope est un motif fréquent de consultation et d'hospitalisation. Un diagnostic est établi dans 50 % des cas grâce au bilan initial. Celui-ci permet aussi de stratifier le risque d'événements cardiovasculaires ou de récidive, et leurs conséquences potentiellement fatales. Cette stratification, basée sur les recommandations européennes et américaines, est essentielle pour orienter la prise en charge. Divers scores prédictifs existent, dont le Canadian Syncope Risk Score (CSRS) qui évalue le risque d'événements graves à 30 jours. L'application de ce score comporte des limites tant dans son utilisation au service des urgences que dans la pratique en ambulatoire. Les recommandations actuelles n'incluent pas de scores spécifiques, soulignant l'importance du jugement clinique et du bilan initial pour la stratification du risque.


Assuntos
Atenção Primária à Saúde , Síncope , Humanos , Síncope/diagnóstico , Síncope/terapia , Síncope/etiologia , Guias de Prática Clínica como Assunto , Medição de Risco/métodos
6.
Br J Dermatol ; 188(4): 506-513, 2023 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-36745562

RESUMO

BACKGROUND: There is a lack of well-conducted randomized controlled trials evaluating the effectiveness of theory-based online interventions for eczema. To address these deficiencies, we previously developed and demonstrated the effectiveness of two online behavioural interventions: Eczema Care Online for parents/carers of children with eczema, and Eczema Care Online for young people with eczema. OBJECTIVES: To explore the views and experiences of people who have used the Eczema Care Online interventions to provide insights into how the interventions worked and identify contextual factors that may impede users' engagement with the interventions. METHODS: Qualitative semistructured interviews were conducted with 17 parents/carers of children with eczema and 17 young people with eczema. Participants were purposively sampled from two randomized controlled trials of the interventions and recruited from GP surgeries in England. Transcripts were analysed using inductive thematic analysis, and intervention modifications were identified using the person-based approach table of changes method. RESULTS: Both young people and parents/carers found the interventions easy to use, relatable and trustworthy, and perceived that they helped them to manage their eczema, thus suggesting that Eczema Care Online may be acceptable to its target groups. Our analysis suggested that the interventions may reduce eczema severity by facilitating empowerment among its users, specifically through improved understanding of, and confidence in, eczema management, reduced treatment concerns, and improved treatment adherence and management of irritants/triggers. Reading about the experiences of others with eczema helped people to feel 'normal' and less alone. Some (mainly young people) expressed firmly held negative beliefs about topical corticosteroids, views that were not influenced by the intervention. Minor improvements to the design and navigation of the Eczema Care Online interventions and content changes were identified and made, ready for wider implementation. CONCLUSIONS: People with eczema and their families can benefit from reliable information, specifically information on the best and safest ways to use their eczema treatments early in their eczema journey. Together, our findings from this study and the corresponding trials suggest wider implementation of Eczema Care Online (EczemaCareOnline.org.uk) is justified.


Assuntos
Eczema , Intervenção Baseada em Internet , Humanos , Criança , Adolescente , Cuidadores , Eczema/terapia , Terapia Comportamental , Pais , Ensaios Clínicos Controlados Aleatórios como Assunto
7.
Epidemiol Infect ; 151: e63, 2023 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-37009915

RESUMO

Few prospective studies have documented the seropositivity among those children infected with severe acute respiratory syndrome coronavirus 2. From 2 April 2021 to 24 June 2021, we prospectively enrolled children between the ages of 2 and 17 years at three North Carolina healthcare systems. Participants received at least four at-home serological tests detecting the presence of antibodies against, but not differentiating between, the nucleocapsid or spike antigen. A total of 1,058 participants were enrolled in the study, completing 2,709 tests between 1 May 2021 and 31 October 2021. Using multilevel regression with poststratification techniques and considering our assay sensitivity and sensitivity, we estimated that the seroprevalence of infection-induced antibodies among unvaccinated children and adolescents aged 2-17 years in North Carolina increased from 15.2% (95% credible interval, CrI 9.0-22.0) in May 2021 to 54.1% (95% CrI 46.7-61.1) by October 2021, indicating an average infection-to-reported-case ratio of 5. A rapid rise in seropositivity was most pronounced in those unvaccinated children aged 12-17 years, based on our estimates. This study underlines the utility of serial, serological testing to inform a broader understanding of the regional immune landscape and spread of infection.


Assuntos
COVID-19 , Humanos , Adolescente , Criança , Pré-Escolar , COVID-19/epidemiologia , North Carolina/epidemiologia , Estudos Prospectivos , SARS-CoV-2 , Estudos Soroepidemiológicos , Anticorpos , Anticorpos Antivirais
8.
Clin Infect Dis ; 75(10): 1792-1799, 2022 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-35363249

RESUMO

BACKGROUND: Tuberculosis (TB) elimination within the United States will require scaling up TB preventive services. Many public health departments offer care for latent tuberculosis infection (LTBI), although gaps in the LTBI care cascade are not well quantified. An understanding of these gaps will be required to design targeted public health interventions. METHODS: We conducted a cohort study through the Tuberculosis Epidemiologic Studies Consortium (TBESC) within 15 local health department (LHD) TB clinics across the United States. Data were abstracted on individuals receiving LTBI care during 2016-2017 through chart review. Our primary objective was to quantify the LTBI care cascade, beginning with LTBI testing and extending through treatment completion. RESULTS: Among 23 885 participants tested by LHDs, 46% (11 009) were male with a median age of 31 (interquartile range [IQR] 20-46). A median of 35% of participants were US-born at each site (IQR 11-78). Overall, 16 689 (70%) received a tuberculin skin test (TST), 6993 (29%) received a Quantiferon (QFT), and 1934 (8%) received a T-SPOT.TB; 5% (1190) had more than one test. Among those tested, 2877 (12%) had at least one positive test result (3% among US-born, and 23% among non-US-born, P < .01). Of 2515 (11%) of the total participants diagnosed with LTBI, 1073 (42%) initiated therapy, of whom 817 (76%) completed treatment (32% of those with LTBI diagnosis). CONCLUSIONS: Significant gaps were identified along the LTBI care cascade, with less than half of individuals diagnosed with LTBI initiating therapy. Further research is needed to better characterize the factors impeding LTBI diagnosis, treatment initiation, and treatment completion.


Assuntos
Tuberculose Latente , Tuberculose , Humanos , Masculino , Estados Unidos/epidemiologia , Feminino , Tuberculose Latente/diagnóstico , Tuberculose Latente/tratamento farmacológico , Tuberculose Latente/epidemiologia , Estudos de Coortes , Saúde Pública , Teste Tuberculínico , Testes de Liberação de Interferon-gama
9.
Cochrane Database Syst Rev ; 3: CD013356, 2022 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-35275399

RESUMO

BACKGROUND: Eczema is a common skin condition. Although topical corticosteroids have been a first-line treatment for eczema for decades, there are uncertainties over their optimal use. OBJECTIVES: To establish the effectiveness and safety of different ways of using topical corticosteroids for treating eczema. SEARCH METHODS: We searched databases to January 2021 (Cochrane Skin Specialised Register; CENTRAL; MEDLINE; Embase; GREAT) and five clinical trials registers. We checked bibliographies from included trials to identify further trials. SELECTION CRITERIA: Randomised controlled trials in adults and children with eczema that compared at least two strategies of topical corticosteroid use. We excluded placebo comparisons, other than for trials that evaluated proactive versus reactive treatment. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods, with GRADE certainty of evidence for key findings. Primary outcomes were changes in clinician-reported signs and relevant local adverse events. Secondary outcomes were patient-reported symptoms and relevant systemic adverse events. For local adverse events, we prioritised abnormal skin thinning as a key area of concern for healthcare professionals and patients. MAIN RESULTS: We included 104 trials (8443 participants). Most trials were conducted in high-income countries (81/104), most likely in outpatient or other hospital settings. We judged only one trial to be low risk of bias across all domains. Fifty-five trials had high risk of bias in at least one domain, mostly due to lack of blinding or missing outcome data. Stronger-potency versus weaker-potency topical corticosteroids Sixty-three trials compared different potencies of topical corticosteroids: 12 moderate versus mild, 22 potent versus mild, 25 potent versus moderate, and 6 very potent versus potent. Trials were usually in children with moderate or severe eczema, where specified, lasting one to five weeks. The most reported outcome was Investigator Global Assessment (IGA) of clinician-reported signs of eczema. We pooled four trials that compared moderate- versus mild-potency topical corticosteroids (420 participants). Moderate-potency topical corticosteroids probably result in more participants achieving treatment success, defined as cleared or marked improvement on IGA (52% versus 34%; odds ratio (OR) 2.07, 95% confidence interval (CI) 1.41 to 3.04; moderate-certainty evidence). We pooled nine trials that compared potent versus mild-potency topical corticosteroids (392 participants). Potent topical corticosteroids probably result in a large increase in number achieving treatment success (70% versus 39%; OR 3.71, 95% CI 2.04 to 6.72; moderate-certainty evidence). We pooled 15 trials that compared potent versus moderate-potency topical corticosteroids (1053 participants). There was insufficient evidence of a benefit of potent topical corticosteroids compared to moderate topical corticosteroids (OR 1.33, 95% CI 0.93 to 1.89; moderate-certainty evidence). We pooled three trials that compared very potent versus potent topical corticosteroids (216 participants). The evidence is uncertain with a wide confidence interval (OR 0.53, 95% CI 0.13 to 2.09; low-certainty evidence). Twice daily or more versus once daily application We pooled 15 of 25 trials in this comparison (1821 participants, all reported IGA). The trials usually assessed adults and children with moderate or severe eczema, where specified, using potent topical corticosteroids, lasting two to six weeks. Applying potent topical corticosteroids only once a day probably does not decrease the number achieving treatment success compared to twice daily application (OR 0.97, 95% CI 0.68 to 1.38; 15 trials, 1821 participants; moderate-certainty evidence). Local adverse events Within the trials that tested 'treating eczema flare-up' strategies, we identified only 26 cases of abnormal skin thinning from 2266 participants (1% across 22 trials). Most cases were from the use of higher-potency topical corticosteroids (16 with very potent, 6 with potent, 2 with moderate and 2 with mild). We assessed this evidence as low certainty, except for very potent versus potent topical corticosteroids, which was very low-certainty evidence.  Longer versus shorter-term duration of application for induction of remission No trials were identified. Twice weekly application (weekend, or 'proactive therapy') to prevent relapse (flare-ups) versus no topical corticosteroids/reactive application Nine trials assessed this comparison, generally lasting 16 to 20 weeks. We pooled seven trials that compared weekend (proactive) topical corticosteroids therapy versus no topical corticosteroids (1179 participants, children and adults with a range of eczema severities, though mainly moderate or severe). Weekend (proactive) therapy probably results in a large decrease in likelihood of a relapse from 58% to 25% (risk ratio (RR) 0.43, 95% CI 0.32 to 0.57; 7 trials, 1149 participants; moderate-certainty evidence). Local adverse events We did not identify any cases of abnormal skin thinning in seven trials that assessed skin thinning (1050 participants) at the end of treatment. We assessed this evidence as low certainty. Other comparisons  Other comparisons included newer versus older preparations of topical corticosteroids (15 trials), cream versus ointment (7 trials), topical corticosteroids with wet wrap versus no wet wrap (6 trials), number of days per week applied (4 trials), different concentrations of the same topical corticosteroids (2 trials), time of day applied (2 trials), topical corticosteroids alternating with topical calcineurin inhibitors versus topical corticosteroids alone (1 trial), application to wet versus dry skin (1 trial) and application before versus after emollient (1 trial). No trials compared branded versus generic topical corticosteroids and time between application of emollient and topical corticosteroids. AUTHORS' CONCLUSIONS: Potent and moderate topical corticosteroids are probably more effective than mild topical corticosteroids, primarily in moderate or severe eczema; however, there is uncertain evidence to support any advantage of very potent over potent topical corticosteroids. Effectiveness is similar between once daily and twice daily (or more) frequent use of potent topical corticosteroids to treat eczema flare-ups, and topical corticosteroids weekend (proactive) therapy is probably better than no topical corticosteroids/reactive use to prevent eczema relapse (flare-ups). Adverse events were not well reported and came largely from low- or very low-certainty, short-term trials. In trials that reported abnormal skin thinning, frequency was low overall and increased with increasing potency. We found no trials on the optimum duration of treatment of a flare, branded versus generic topical corticosteroids, and time to leave between application of topical corticosteroids and emollient. There is a need for longer-term trials, in people with mild eczema.


Assuntos
Fármacos Dermatológicos , Eczema , Corticosteroides/uso terapêutico , Adulto , Criança , Fármacos Dermatológicos/efeitos adversos , Eczema/tratamento farmacológico , Emolientes/uso terapêutico , Glucocorticoides/uso terapêutico , Humanos , Imunoglobulina A , Recidiva
10.
MMWR Recomm Rep ; 69(1): 1-11, 2020 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-32053584

RESUMO

Comprehensive guidelines for treatment of latent tuberculosis infection (LTBI) among persons living in the United States were last published in 2000 (American Thoracic Society. CDC targeted tuberculin testing and treatment of latent tuberculosis infection. Am J Respir Crit Care Med 2000;161:S221-47). Since then, several new regimens have been evaluated in clinical trials. To update previous guidelines, the National Tuberculosis Controllers Association (NTCA) and CDC convened a committee to conduct a systematic literature review and make new recommendations for the most effective and least toxic regimens for treatment of LTBI among persons who live in the United States.The systematic literature review included clinical trials of regimens to treat LTBI. Quality of evidence (high, moderate, low, or very low) from clinical trial comparisons was appraised using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria. In addition, a network meta-analysis evaluated regimens that had not been compared directly in clinical trials. The effectiveness outcome was tuberculosis disease; the toxicity outcome was hepatotoxicity. Strong GRADE recommendations required at least moderate evidence of effectiveness and that the desirable consequences outweighed the undesirable consequences in the majority of patients. Conditional GRADE recommendations were made when determination of whether desirable consequences outweighed undesirable consequences was uncertain (e.g., with low-quality evidence).These updated 2020 LTBI treatment guidelines include the NTCA- and CDC-recommended treatment regimens that comprise three preferred rifamycin-based regimens and two alternative monotherapy regimens with daily isoniazid. All recommended treatment regimens are intended for persons infected with Mycobacterium tuberculosis that is presumed to be susceptible to isoniazid or rifampin. These updated guidelines do not apply when evidence is available that the infecting M. tuberculosis strain is resistant to both isoniazid and rifampin; recommendations for treating contacts exposed to multidrug-resistant tuberculosis were published in 2019 (Nahid P, Mase SR Migliori GB, et al. Treatment of drug-resistant tuberculosis. An official ATS/CDC/ERS/IDSA clinical practice guideline. Am J Respir Crit Care Med 2019;200:e93-e142). The three rifamycin-based preferred regimens are 3 months of once-weekly isoniazid plus rifapentine, 4 months of daily rifampin, or 3 months of daily isoniazid plus rifampin. Prescribing providers or pharmacists who are unfamiliar with rifampin and rifapentine might confuse the two drugs. They are not interchangeable, and caution should be taken to ensure that patients receive the correct medication for the intended regimen. Preference for these rifamycin-based regimens was made on the basis of effectiveness, safety, and high treatment completion rates. The two alternative treatment regimens are daily isoniazid for 6 or 9 months; isoniazid monotherapy is efficacious but has higher toxicity risk and lower treatment completion rates than shorter rifamycin-based regimens.In summary, short-course (3- to 4-month) rifamycin-based treatment regimens are preferred over longer-course (6-9 month) isoniazid monotherapy for treatment of LTBI. These updated guidelines can be used by clinicians, public health officials, policymakers, health care organizations, and other state and local stakeholders who might need to adapt them to fit individual clinical circumstances.


Assuntos
Tuberculose Latente/tratamento farmacológico , Guias de Prática Clínica como Assunto , Centers for Disease Control and Prevention, U.S. , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Estados Unidos
11.
Invest New Drugs ; 39(1): 98-110, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32856275

RESUMO

Two novel chemotherapeutic chalcones were synthesized and their structures were confirmed by different spectral tools. Theoretical studies such as molecular modeling were done to detect the mechanism of action of these compounds. In vitro cytotoxicity showed a strong effect against all tested cell lines (MCF7, A459, HepG2, and HCT116), and low toxic effect against normal human melanocytes (HFB4). The lung carcinoma cell line was chosen for further molecular studies. Real-time PCR demonstrated that the two compounds upregulated gene expression of (BAX, p53, casp-3, casp-8, casp-9) genes and decreased the expression of anti-apoptotic genes bcl2, CDK4, and MMP1. Flow-cytometry indicated that cell cycle arrest of A459 was induced at the G2/M phase and the apoptotic percentage increased significantly compared to the control sample. Cytochrome c oxidase and VEGF enzyme activity were detected by ELISA assay. SEM tool was used to follow the morphological changes that occurred on the cell surface, cell granulation, and average roughness of the cell surface. The change in the number and morphology of mitochondria, cell shrinkage, increase in the number of cytoplasmic organelles, membrane blebbing, chromatin condensation, and apoptotic bodies were observed using TEM. The obtained data suggested that new chalcones exerted their pathways on lung carcinoma through induction of two pathways of apoptosis. Graphical abstract Novel chalcones were prepared and confirmed by different spectral tools. Docking simulations were done to detect the mechanism of action. In vitro cytotoxicity indicated a strong effect against different cancer cell lines and low toxic effects against normal human melanocytes (HFB4). The lung carcinoma cell line was chosen for further molecular studies that include Real-time PCR, Flow-cytometry, Cytochrome c oxidase, and ELISA assay. SEM and TEM tool were used to follow the morphological changes occurred on the cell surface.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Chalconas/farmacologia , Proteínas Tirosina Quinases/antagonistas & inibidores , Caspases/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Chalconas/química , Expressão Gênica/efeitos dos fármacos , Humanos , Simulação de Acoplamento Molecular , Proteína Supressora de Tumor p53/efeitos dos fármacos , Proteína X Associada a bcl-2/efeitos dos fármacos
12.
J Infect Dis ; 219(9): 1398-1406, 2019 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-30535363

RESUMO

BACKGROUND: Viral loads (VLs) frequently are followed during treatment of symptomatic congenital cytomegalovirus disease, but their predictive value is unclear. METHODS: Post hoc analysis of 2 antiviral studies was performed. Seventy-three subjects were treated for 6 weeks and 47 subjects were treated for 6 months. Whole blood VL was determined by real-time polymerase chain reaction before and during therapy. RESULTS: Higher baseline VL was associated with central nervous system involvement (3.82 log, range 1-5.65 vs 3.32 log, range 1-5.36; P = .001), thrombocytopenia (3.68 log, range 1-5.65 vs 3.43 log, range 1-5.36; P = .03), and transaminitis at presentation (3.73 log, range 1-5.60 vs 3.39 log, range 1-5.65; P = .009), but with overlap in the amount of virus detected between groups. In subjects treated for 6 months, lower VL at presentation correlated with better hearing outcomes at 12 months, but VL breakpoints predictive of hearing loss were not identified. Sustained viral suppression during 6 months of therapy correlated with better hearing outcomes at 6, 12, and 24 months (P = .01, P = .0007, P = .04), but a majority without viral suppression still had improved hearing. CONCLUSIONS: In infants with symptomatic congenital cytomegalovirus disease, higher whole blood VL before initiation of antiviral therapy has no clinically meaningful predictive value for long-term outcomes.


Assuntos
Antivirais/uso terapêutico , Infecções por Citomegalovirus/sangue , Infecções por Citomegalovirus/tratamento farmacológico , Citomegalovirus/genética , DNA Viral/sangue , Carga Viral , Administração Intravenosa , Administração Oral , Antivirais/administração & dosagem , Doenças do Sistema Nervoso Central/virologia , Desenvolvimento Infantil , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/congênito , Feminino , Ganciclovir/uso terapêutico , Audição , Perda Auditiva/virologia , Humanos , Lactente , Recém-Nascido , Masculino , Valor Preditivo dos Testes , Resposta Viral Sustentada , Trombocitopenia/virologia , Valganciclovir/uso terapêutico , Carga Viral/efeitos dos fármacos
14.
J Infect Dis ; 217(10): 1612-1615, 2018 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-29401303

RESUMO

Real-time polymerase chain reaction (PCR) of saliva is highly sensitive for newborn congenital cytomegalovirus (CMV) screening. This study uses nationally published CMV seroprevalence and breastfeeding rates to estimate the contribution of CMV DNA in breast milk to false-positive saliva PCR results. The false-positive rates adjusted for breastfeeding ranged from 0.03% in white Hispanic persons to 0.14% in white non-Hispanic persons. Saliva CMV PCR for newborn screening is highly sensitive, and the low false-positive rates in this study suggest that saliva PCR results are unlikely to be significantly influenced by breastfeeding or other perinatal exposures.


Assuntos
Aleitamento Materno/efeitos adversos , Infecções por Citomegalovirus/diagnóstico , Citomegalovirus/genética , Saliva/virologia , DNA Viral/genética , Feminino , Humanos , Recém-Nascido , Masculino , Triagem Neonatal/métodos , Reação em Cadeia da Polimerase em Tempo Real/métodos
15.
J Food Sci Technol ; 56(1): 253-261, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30728567

RESUMO

The investigation studied the effect of sour fruit juices as coagulants on the physico-chemical properties, phytonutrients, sensory scores, texture profile analysis (TPA) and microstructure using scanning electron microscopy (SEM) of paneer. Paneer was coagulated using citric acid solution (control), lemon or amla juice. The total solids and protein recovery were higher using amla juice while fat recovery was more in control than with the other two coagulants. The mineral profile indicated that calcium content was higher in lemon and amla paneer than citric whereas sodium was highest in citric sample. Paneer collected using fruit juices exhibited higher quantity of functional components studied i.e. antioxidant activity, ascorbic acid, total phenols and tannins than control. Also, it scored high for sensory attributes of appearance/color, body and texture, mouthfeel, flavor and overall acceptability but exhibited disparate values for TPA (hardness, adhesiveness, gumminess and resilience) and discrete structures under SEM.

16.
N Engl J Med ; 372(10): 933-43, 2015 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-25738669

RESUMO

BACKGROUND: The treatment of symptomatic congenital cytomegalovirus (CMV) disease with intravenous ganciclovir for 6 weeks has been shown to improve audiologic outcomes at 6 months, but the benefits wane over time. METHODS: We conducted a randomized, placebo-controlled trial of valganciclovir therapy in neonates with symptomatic congenital CMV disease, comparing 6 months of therapy with 6 weeks of therapy. The primary end point was the change in hearing in the better ear ("best-ear" hearing) from baseline to 6 months. Secondary end points included the change in hearing from baseline to follow-up at 12 and 24 months and neurodevelopmental outcomes, with each end point adjusted for central nervous system involvement at baseline. RESULTS: A total of 96 neonates underwent randomization, of whom 86 had follow-up data at 6 months that could be evaluated. Best-ear hearing at 6 months was similar in the 6-month group and the 6-week group (2 and 3 participants, respectively, had improvement; 36 and 37 had no change; and 5 and 3 had worsening; P=0.41). Total-ear hearing (hearing in one or both ears that could be evaluated) was more likely to be improved or to remain normal at 12 months in the 6-month group than in the 6-week group (73% vs. 57%, P=0.01). The benefit in total-ear hearing was maintained at 24 months (77% vs. 64%, P=0.04). At 24 months, the 6-month group, as compared with the 6-week group, had better neurodevelopmental scores on the Bayley Scales of Infant and Toddler Development, third edition, on the language-composite component (P=0.004) and on the receptive-communication scale (P=0.003). Grade 3 or 4 neutropenia occurred in 19% of the participants during the first 6 weeks. During the next 4.5 months of the study, grade 3 or 4 neutropenia occurred in 21% of the participants in the 6-month group and in 27% of those in the 6-week group (P=0.64). CONCLUSIONS: Treating symptomatic congenital CMV disease with valganciclovir for 6 months, as compared with 6 weeks, did not improve hearing in the short term but appeared to improve hearing and developmental outcomes modestly in the longer term. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT00466817.).


Assuntos
Antivirais/administração & dosagem , Infecções por Citomegalovirus/congênito , Infecções por Citomegalovirus/tratamento farmacológico , Ganciclovir/análogos & derivados , Perda Auditiva Neurossensorial/prevenção & controle , Antivirais/efeitos adversos , Audiometria , Desenvolvimento Infantil , Infecções por Citomegalovirus/complicações , Método Duplo-Cego , Esquema de Medicação , Potenciais Evocados Auditivos do Tronco Encefálico , Ganciclovir/administração & dosagem , Ganciclovir/efeitos adversos , Idade Gestacional , Perda Auditiva Neurossensorial/virologia , Humanos , Recém-Nascido , Neutropenia/induzido quimicamente , Valganciclovir
17.
J Pediatr ; 200: 196-201.e1, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29784513

RESUMO

OBJECTIVE: To evaluate the impact of race and ethnicity upon the prevalence and clinical spectrum of congenital cytomegalovirus infection (cCMV). STUDY DESIGN: From 2007 to 2012, 100 332 infants from 7 medical centers were screened for cCMV while in the hospital. Ethnicity and race were collected and cCMV prevalence rates were calculated. RESULTS: The overall prevalence of cCMV in the cohort was 4.5 per 1000 live births (95% CI, 4.1-4.9). Black infants had the highest cCMV prevalence (9.5 per 1000 live births; 95% CI, 8.3-11.0), followed by multiracial infants (7.8 per 1000 live births; 95% CI, 4.7-12.0). Significantly lower prevalence rates were observed in non-Hispanic white infants (2.7 per 1000 live births; 95% CI, 2.2-3.3), Hispanic white infants (3.0 per 1000 live births; 95% CI, 2.4-3.6), and Asian infants (1.0 per 1000 live births; 95% CI, 0.3-2.5). After adjusting for socioeconomic status and maternal age, black infants were significantly more likely to have cCMV compared with non-Hispanic white infants (adjusted prevalence OR, 1.9; 95% CI, 1.4-2.5). Hispanic white infants had a slightly lower risk of having cCMV compared with non-Hispanic white infants (adjusted prevalence OR, 0.7; 95% CI, 0.5-1.0). However, no significant differences in symptomatic cCMV (9.6%) and sensorineural hearing loss (7.8%) were observed between the race/ethnic groups. CONCLUSIONS: Significant racial and ethnic differences exist in the prevalence of cCMV, even after adjusting for socioeconomic status and maternal age. Although once infected, the newborn disease and rates of hearing loss in infants are similar with respect to race and ethnicity.


Assuntos
Infecções por Citomegalovirus/etnologia , Etnicidade , Programas de Rastreamento/métodos , Grupos Raciais , Adulto , Infecções por Citomegalovirus/congênito , Feminino , Seguimentos , Humanos , Recém-Nascido , Masculino , Prevalência , Estudos Retrospectivos , Estados Unidos/epidemiologia
18.
Gynecol Oncol ; 150(2): 300-305, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29807694

RESUMO

INTRODUCTION: CC-002 is a prospective cooperative group study conducted by NRG Oncology to evaluate whether a pre-operative GA-GYN score derived from a predictive model utilizing components of an abbreviated geriatric assessment (GA) is associated with major post-operative complications in elderly women with suspected ovarian, fallopian tube, primary peritoneal or advanced stage papillary serous uterine (GYN) carcinoma undergoing primary open cytoreductive surgery. METHODS: Patients 70 years or older with suspected advanced gynecologic cancers undergoing evaluation for surgery were eligible. A GA-GYN score was derived from a model utilizing the GA as a pre-operative tool. Patients were followed for six weeks post-operatively or until start of chemotherapy. Post-operative events were recorded either directly as binary occurrence (yes or no) using CTCAE version 4.0. RESULTS: There were 189 eligible patients, 117 patients with primary surgical intervention and 37 patients undergoing interval cytoreduction surgery. The association between higher GA-GYN score and major postoperative complications in patients undergoing primary surgery was not significant (p = 0.1341). In a subgroup analysis of patients with advanced staged malignant disease who underwent primary cytoreductive surgery, there was a trend towards an association with the GA-GYN score and post-operative complications. CONCLUSION: The pre-operative GA-GYN score derived from a predictive model utilizing components of an abbreviated geriatric assessment was not predictive of major post-operative complications in elderly patients undergoing primary open cytoreductive surgery. However, there was an association between GA-GYN score and post-operative complications in a subgroup of patients with advanced staged malignant disease.


Assuntos
Neoplasias dos Genitais Femininos/diagnóstico , Neoplasias dos Genitais Femininos/cirurgia , Avaliação Geriátrica/métodos , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Neoplasias dos Genitais Femininos/patologia , Humanos , Cuidados Pós-Operatórios/métodos , Cuidados Pré-Operatórios/métodos , Estudos Prospectivos
19.
Pak J Med Sci ; 34(2): 405-411, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29805417

RESUMO

BACKGROUND AND OBJECTIVE: Workplace based assessment has a strong educational impact in terms of student's clinical performance by steering their learning towards the desired learning outcomes. Educational impact is hardly measured in the sphere of medical education and this study is an attempt to measure educational impact of post graduate residents. The aim of this study was "To explore educational impact of Minicex (Mini-clinical evaluation exercise) on residents with respect to their learning". METHODS: A mixed convergent parallel method was selected, participants were identified through non-probability convenience sampling, total 10 participants were chosen for data collection, all of them experienced four minicex encounters which generated their scores (the quantitative data), after first two Minicex encounters each participant was interviewed using a structured interview technique, similarly, after 3rd and 4th Minicex encounters. Data was entered in the SPSS version -21 to calculate descriptive statistics. Inferential statistics were determined using ANOVA to calculate improvement in score over time and P-value to report statistical significance. Qualitative analysis was done using thematic analysis approach with the help of themes based on interview questions: priori theme. NVIVO was used for triangulation of themes accordingly. RESULTS: The results indicate statistically significant improvement in scores and p values were considered significant at 0.05. Also, qualitative analysis provided reasons for improvement in scores and residents' satisfaction such as feedback, motivation, self-directed learning, peer assisted learning. CONCLUSION: The study concluded that residents learning behavior and, their satisfaction from assessment method can be enhanced through work place based assessment particularly in context of minicex (mini-clinical evaluation exercise) so encouraging its use in similar situations. However, the scope for generalization of results remains limited owing to a small sample size.

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