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1.
Proc Natl Acad Sci U S A ; 120(31): e2301536120, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37487069

RESUMO

Colorectal cancers (CRCs) form a heterogenous group classified into epigenetic and transcriptional subtypes. The basis for the epigenetic subtypes, exemplified by varying degrees of promoter DNA hypermethylation, and its relation to the transcriptional subtypes is not well understood. We link cancer-specific transcription factor (TF) expression alterations to methylation alterations near TF-binding sites at promoter and enhancer regions in CRCs and their premalignant precursor lesions to provide mechanistic insights into the origins and evolution of the CRC molecular subtypes. A gradient of TF expression changes forms a basis for the subtypes of abnormal DNA methylation, termed CpG-island promoter DNA methylation phenotypes (CIMPs), in CRCs and other cancers. CIMP is tightly correlated with cancer-specific hypermethylation at enhancers, which we term CpG-enhancer methylation phenotype (CEMP). Coordinated promoter and enhancer methylation appears to be driven by downregulation of TFs with common binding sites at the hypermethylated enhancers and promoters. The altered expression of TFs related to hypermethylator subtypes occurs early during CRC development, detectable in premalignant adenomas. TF-based profiling further identifies patients with worse overall survival. Importantly, altered expression of these TFs discriminates the transcriptome-based consensus molecular subtypes (CMS), thus providing a common basis for CIMP and CMS subtypes.


Assuntos
Neoplasias Colorretais , Lesões Pré-Cancerosas , Humanos , Fatores de Transcrição , Regulação da Expressão Gênica , Metilação de DNA , Epigênese Genética
2.
Epidemiol Infect ; 152: e81, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38736415

RESUMO

Nosocomial outbreak of varicella zoster virus (VZV) has been reported when susceptible individuals encounter a case of chicken pox or shingles. A suspected VZV outbreak was investigated in a 50-bedded in-patient facility of Physical Medicine and Rehabilitation in a tertiary care multispecialty hospital. A 30-year-old female patient admitted with Pott's spine was clinically diagnosed with chicken pox on 31 December 2022. The following week, four more cases were identified in the same ward. All cases were diagnosed as laboratory-confirmed varicella zoster infection by PCR. Primary case was a housekeeping staff who was clinically diagnosed with chicken pox 3 weeks prior (9 December 2022). He returned to work on eighth day of infection (17 December 2022) after apparent clinical recovery but before the lesions had crusted over. Thirty-one HCWs were identified as contacts a and three had no evidence of immunity. Two of these susceptible HCWs had onset of chickenpox shortly after first dose of VZV vaccination was inoculated. All cases recovered after treatment with no reported complications. VZV infection is highly contagious in healthcare settings with susceptible populations. Prompt identification of cases and implementation of infection prevention and control measures like patient isolation and vaccination are essential for the containment of outbreaks.


Assuntos
Infecção Hospitalar , Surtos de Doenças , Herpesvirus Humano 3 , Centros de Atenção Terciária , Humanos , Adulto , Feminino , Índia/epidemiologia , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/virologia , Herpesvirus Humano 3/isolamento & purificação , Masculino , Varicela/epidemiologia , Assistência de Longa Duração , Infecção pelo Vírus da Varicela-Zoster/epidemiologia
3.
Epidemiol Infect ; 151: e127, 2023 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-37293986

RESUMO

Evolutionary studies on Dengue virus (DENV) in endemic regions are necessary since naturally occurring mutations may lead to genotypic variations or shifts in serotypes, which may lead to future outbreaks. Our study comprehends the evolutionary dynamics of DENV, using phylogenetic, molecular clock, skyline plots, network, selection pressure, and entropy analyses based on partial CprM gene sequences. We have collected 250 samples, 161 in 2017 and 89 in 2018. Details for the 2017 samples were published in our previous article and that of 2018 are presented in this study. Further evolutionary analysis was carried out using 800 sequences, which incorporate the study and global sequences from GenBank: DENV-1 (n = 240), DENV-3 (n = 374), and DENV-4 (n = 186), identified during 1944-2020, 1956-2020, and 1956-2021, respectively. Genotypes V, III, and I were identified as the predominant genotypes of the DENV-1, DENV-3, and DENV-4 serotypes, respectively. The rate of nucleotide substitution was found highest in DENV-3 (7.90 × 10-4 s/s/y), followed by DENV-4 (6.23 × 10-4 s/s/y) and DENV-1 (5.99 × 10-4 s/s/y). The Bayesian skyline plots of the Indian strains revealed dissimilar patterns amongst the population size of the three serotypes. Network analyses showed the presence of different clusters within the prevalent genotypes. The data presented in this study will assist in supplementing the measures for vaccine development against DENV.


Assuntos
Vírus da Dengue , Dengue , Humanos , Vírus da Dengue/genética , Sorogrupo , Dengue/epidemiologia , Filogenia , Teorema de Bayes , Genótipo
4.
Curr Oncol Rep ; 25(6): 659-669, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36995533

RESUMO

PURPOSE OF REVIEW: This report aims to provide a framework for cancer rehabilitation professionals to assess social determinants of health in individuals with cancer and discuss strategies that can be implemented in practice to overcome barriers to care. RECENT FINDINGS: There has been an increased focus in improving patient conditions that can affect access to cancer rehabilitation. Along with government and world health organization initiatives, healthcare professionals and institutions continue to work towards decreasing disparities. Several disparities exist in healthcare and education access and quality, patients' social and community context, neighborhood and built environments, and economic stability. The authors emphasized the challenges that patients who require cancer rehabilitation face that healthcare providers, institutions, and governments can mitigate with outlined strategies. Education and collaboration are essential to make true progress in decreasing disparities in the populations most in need.


Assuntos
Neoplasias , Determinantes Sociais da Saúde , Humanos , Atenção à Saúde
5.
Transpl Infect Dis ; 25(1): e14011, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36602403

RESUMO

BACKGROUND: Cytomegalovirus (CMV) is one of the most common post-transplant viral infections causing significant morbidity and occasional mortality. Limited literature on the potential role of pre-transplant CMV-specific cell-mediated immunity (CMV-CMI) is available. This study aimed to evaluate the clinical utility of pre-transplant CMV-CMI monitoring in the occurrence of post-transplant CMV infection. METHODS: This was a prospective, observational study where all adult CMV seropositive patients undergoing living donor liver transplantation at a tertiary care institute were enrolled. CMV-CMI was measured using QuantiFERON-CMV (Qiagen GmbH, Hilden, Germany) and interpreted as positive if the value was ≥0.2 IU/ml, 1-2 days prior to the transplant. Based on pre-transplant CMV-CMI, cases were classified into Group 1 (n = 13, 43.3%) (positive) and Group 2 (n = 17, 56.7%) (negative). CMV infection was defined as the detection of CMV-DNA > 2.7 log10 IU/ml in plasma specimens. RESULTS: The mean age was 43 years with male (n = 29, 96.9%) predominance. Overall 40% of recipients developed post-transplant CMV infection, two (15.4%) in group 1 and 10 (58.8%) in group 2 (p-value = 0.016). Recipients in group 2 had 87% higher odds (odds ratio 0.13, confidence interval [CI] 95) of developing post-transplant CMV infection compared to group 1. The overall median duration of occurrence of post-transplant CMV infection was 26 days with the median viral load being 2.8 log10 IU/ml. The treatment duration was 13 days in group 1 and 28 days in group 2 (p = 0.003). Group 1 recipients showed rapid clearance of CMV-DNA within 7 days compared to group 2 in which it was 21 days (p = 0.004, CI 95). CONCLUSION: Pre-transplant CMV-CMI may play a protective role against post-transplant CMV infection and can serve as an adjunct for pre-transplant risk stratification.


Assuntos
Infecções por Citomegalovirus , Transplante de Fígado , Adulto , Humanos , Masculino , Citomegalovirus , Doadores Vivos , Estudos Prospectivos , Imunidade Celular , Transplantados , Antivirais/uso terapêutico
6.
Support Care Cancer ; 31(2): 122, 2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36653554

RESUMO

PURPOSE: To determine the percentage of and factors associated with unplanned transfer to the acute care service of glioblastoma multiforme acute rehabilitation inpatients. METHODS: Retrospective review of glioblastoma multiforme acute rehabilitation inpatients admitted 4/1/2016-3/31/2020 at a National Cancer Institute Comprehensive Cancer Center. RESULTS: One hundred thirty-nine consecutive admissions of unique glioblastoma multiforme acute rehabilitation inpatients were analyzed. Fifteen patients (10.7%, 95% confidence interval 6.5-17.1%) were transferred to the acute care service for unplanned reasons. The most common reasons for transfer back were neurosurgical complication 6/15(40%), neurologic decline due to mass effect 4/15(26.7%), and pulmonary embolism 2/15(13.3%). Older age (p = 0.010), infection prior to acute inpatient rehabilitation transfer (p = 0.020), and lower activity measure of post-acute care 6-click basic mobility scores (p = 0.048) were significantly associated with transfer to the acute care service. Patients who transferred to the acute care service had significantly lower overall survival than patients who did not transfer off (log-rank test p = 0.001). CONCLUSION: Acute inpatient physiatrists should closely monitor patients for neurosurgical and neurologic complications. The variables significantly associated with transfer to the acute care service may help identify patients at increased risk for medical complications who may require closer observation.


Assuntos
Glioblastoma , Pacientes Internados , Humanos , Hospitalização , Estudos Retrospectivos , Cuidados Críticos , Centros de Reabilitação
7.
Indian J Med Res ; 158(5&6): 477-482, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-38088423

RESUMO

Links between tobacco use and poor pregnancy outcomes are well established. Despite various tobacco control measures taken by the government, nearly 5-8 per cent of pregnant women consume tobacco in India. Antenatal check-ups are an opportunity to assess and assist women in quitting tobacco during pregnancy. This review highlights the challenges faced in identifying pregnant tobacco users and providing cessation counselling to them in a formal healthcare setup in the Indian context. For this narrative review, open access databases like PubMed and Google Scholar were searched, using the following search terms: challenges, quitting tobacco use, smokeless tobacco, pregnancy and India. Original articles published between 2010 and July 2022 were included in the English language with available free full text. Out of the thirty articles found to be eligible, seven were included in the review. Official websites of the National Health Mission and National Tobacco Control Programme were also searched to retrieve available data on health education and training material for healthcare workers: medical officers, Auxiliary Nurse and Midwives (ANMs), Accredited Social Health Activists (ASHAs) and list of tobacco cessation centres. This review identified the factors such as myths surrounding tobacco use, lack of targeted screening, inadequate training of healthcare workers and inaccessibility of cessation services, which are posing as challenges in controlling tobacco use in this vulnerable section of the population. Specific strategies to address these issues at the micro, meso and macro levels can prove to be vital in controlling tobacco use in pregnant women. This review also identified the vital role of gynaecologists and healthcare workers such as ANMs and ASHA in identifying and providing brief tobacco cessation counselling to pregnant users.


Assuntos
Aconselhamento , Abandono do Uso de Tabaco , Feminino , Humanos , Gravidez , Índia/epidemiologia , Uso de Tabaco
8.
Health Expect ; 2023 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-38014917

RESUMO

BACKGROUND: Citizen science is a way to democratise science by involving groups of citizens in the research process. Clinical guidelines are used to improve practice, but their implementation can be limited. Involving patients and the public can enhance guideline implementation, but there is uncertainty about the best approaches to achieve this. Citizen science is a potential way to involve patients and the public in improving clinical guideline implementation. We aimed to explore the application of citizen science methods to involve patients and the public in the dissemination and implementation of clinical guidelines in oral health and dentistry. METHODS: We developed GUIDE (GUideline Implementation in oral health and DEntistry), a citizen science online platform, using a participatory approach with researchers, oral health professionals, guideline developers and citizens. Recruitment was conducted exclusively online. The platform focused on prespecified challenges related to oral health assessment guidelines, and asked citizens to generate ideas, as well as vote and comment on other citizens' ideas to improve those challenges. Citizens also shared their views via surveys and two online synchronous group meetings. Data were collected on participant's demographics, platform engagement and experience of taking part. The most promising idea category was identified by an advisory group based on engagement, feasibility and relevance. We presented quantitative data using descriptive statistics and analysed qualitative data using inductive and deductive thematic analysis. RESULTS: The platform was open for 6 months and we recruited 189 citizens, from which over 90 citizens actively engaged with the platform. Most citizens were over 34 years (64%), female (58%) and had a university degree (50%). They generated 128 ideas, 146 comments and 248 votes. The challenge that led to most engagement was related to prevention and oral health self-care. To take this challenge forward, citizens generated a further 36 ideas to improve a pre-existing National Health Service oral care prevention leaflet. Citizens discussed motivations to take part in the platform (understanding, values, self-care), reasons to stay engaged (communication and feedback, outputs and impact, and relevance of topics discussed) and suggestions to improve future platforms. CONCLUSION: Citizen science is an effective approach to generate and prioritise ideas from a group of citizens to improve oral health and dental services. Prevention and oral health self-care were of particular interest to citizens. More research is needed to ensure recruitment of a diverse group of citizens and to improve retention in citizen science projects. PATIENT OR PUBLIC CONTRIBUTION: This project was inherently conducted with the input of public partners (citizen scientists) in all key aspects of its conduct and interpretation. In addition, two public partners were part of the research team and contributed to the design of the project, as well as key decisions related to its conduct, analysis, interpretation and dissemination and are co-authors of this manuscript.

9.
Artigo em Inglês | MEDLINE | ID: mdl-37731374

RESUMO

Anthropometric measurements like height and gender have been frequently found to be inaccurate in prediction of size of double lumen tube (DLT). A tracheal ultrasonography (TUS) is a technique that can be used to predict the size of DLT and its correct placement for lung isolation. We aim to check the accuracy of ultrasound over clinical methods. This prospective study included 68 patients undergoing elective thoracic surgery requiring one-lung ventilation (OLV) with DLT. The groups were assessed for the size of DLT by either anthropometric measurement using height and gender (Group C) or ultrasound method (Group U). Further, the accuracy of placement of DLT was assessed through, either lung auscultation in group C or various ultrasonographic and ventilatory parameters such as lung isolation in the first attempt (lung sliding and lung pulse sign), oxygenation status and peak airway pressure, in group U. Surgeon satisfaction score was also compared in both the groups. The accuracy of predicted DLT size between Group C and Group U was statistically significant (p=0.044). In Group C, 56% of patients showed a mismatch between the predicted DLT size and the actual size required, while in Group U, the mismatch was only 32.4%. The accuracy of DLT placement through group C was 41% as compared to 79% in Group U. Surgeon satisfaction score was also significantly higher in Group U as compared to Group C (p=0.0028). Thus, our study suggests that tracheal and chest ultrasonography for DLT size selection and placement for lung isolation is superior to clinical methods.

10.
Liver Int ; 42(3): 532-540, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34817928

RESUMO

BACKGROUND AND AIMS: India has a significant burden of hepatitis C virus (HCV) infection and has committed to achieving national elimination by 2030. This will require a substantial scale-up in testing and treatment. The "HEAD-Start Project Delhi" aimed to enhance HCV diagnosis and treatment pathways among the general population. METHODS: A prospective study was conducted at 5 district hospitals (Arm 1: one-stop shop), 15 polyclinics (Arm 2: referral for viral load (VL) testing and treatment) and 62 screening camps (Arm 3: referral for treatment). HCV prevalence, retention in the HCV care cascade, and turn-around time were measured. RESULTS: Between January and September 2019, 37 425 participants were screened for HCV. The median (IQR) age of participants was 35 (26-48) years, with 50.4% male and 49.6% female. A significantly higher proportion of participants in Arm 1 (93.7%) and Arm 3 (90.3%) received a VL test compared with Arm 2 (52.5%, P < .001). Of those confirmed positive, treatment was initiated at significantly higher rates for participants in both Arms 1 (85.6%) and 2 (73.7%) compared to Arm 3 (41.8%, P < .001). Arm 1 was found to be a cost-saving strategy compared to Arm 2, Arm 3, and no action. CONCLUSIONS: Delivery of all services at a single site (district hospitals) resulted in a higher yield of HCV seropositive cases and retention compared with sites where participants were referred elsewhere for VL testing and/or treatment. The highest level of retention in the care cascade was also associated with the shortest turn-around times.


Assuntos
Hepacivirus , Hepatite C , Adulto , Estudos de Viabilidade , Feminino , Hepatite C/diagnóstico , Hepatite C/epidemiologia , Hepatite C/terapia , Humanos , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
11.
Radiographics ; 42(2): 321-339, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35179983

RESUMO

Nipple-sparing mastectomy (NSM) is increasingly offered to patients undergoing treatment of breast cancer and prophylaxis treatment for reduction of breast cancer risk. NSM is considered oncologically safe for appropriately selected patients and is associated with improved cosmetic outcomes and quality of life. Accepted indications for NSM have expanded in recent years, and currently only inflammatory breast cancer or malignancy involving the nipple is considered an absolute contraindication. Neoplasms close to and involving the nipple areolar complex are common, and cancer of the lactiferous ducts can spread to the nipple. Therefore, accurate determination of nipple involvement at imaging examinations is critical to identifying appropriate candidates for NSM and preventing local recurrence. Multiple imaging features have been described as predictors of nipple involvement, with tumor to nipple distance, enhancement between the index malignancy and the nipple, and nipple retraction demonstrating the highest predictive values. These features can be assessed at multimodality breast imaging, particularly at breast MRI, which demonstrates high specificity and negative predictive value for determining nipple involvement in malignancy. Online supplemental material is available for this article. ©RSNA, 2022.


Assuntos
Neoplasias da Mama , Mamoplastia , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Feminino , Humanos , Mastectomia/métodos , Mamilos/diagnóstico por imagem , Mamilos/patologia , Mamilos/cirurgia , Qualidade de Vida , Radiologistas , Estudos Retrospectivos
12.
Transfus Apher Sci ; 61(1): 103293, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34686444

RESUMO

BACKGROUND: The Corona virus disease 2019 (COVID-19) pandemic caused by SARS -Corona virus-2 (SARS-CoV-2) has been a major concern the world over. Serological surveillance is an important tool to assess the spread of infection in the community. This study attempted to assess the prevalence of antibodies to SARS-CoV-2 among blood donors in Delhi, India during the pre-vaccination period. METHODS: Seroprevalence of SARS-CoV2-2 IgG antibodies were determined in blood donors reporting to the Department of Transfusion medicine at a tertiary care hepatobiliary center, in India from September to October 2020. The SARS-CoV-2 IgG antibodies against spike subunit 1 protein were measured using the enhanced chemiluminescence method. RESULTS: A total of 1066 blood donors were screened. The overall seropositivity for SARS-CoV-2 IgG antibodies was 27.57 % (294/1066). The highest seropositivity was seen in the age group 26-35 years, 46.6 % (137/492), followed by 18-25 years, 28.2 % (83/260), 36-45 years, 19.4 % (57/244), and more than 45 years, 5.8 % (17/70). The seropositivity in the donors who had donated blood previously was 26.1 % (189/723). There was no statistically significant difference amongst seroprevalence in the blood groups, AB blood group (32.6 %, 95 % CI 23.02-43.3), group B (27.2 %, 95 % CI 22.8-32.09 %), group A (27.1 %, 95 % CI 21.8-32.9 %), and group O (27.02 %, 95 % CI 22.3-32.1 %) (p 0.539). CONCLUSIONS: There was significantly higher seropositivity for SARS-CoV-2 antibodies in the voluntary healthy blood donors indicating community spread and large number of asymptomatic cases in Delhi. Higher seroprevalence in younger adults indicated increased exposure to the virus and lack of COVID appropriate behaviour.


Assuntos
COVID-19/epidemiologia , SARS-CoV-2/metabolismo , Estudos Soroepidemiológicos , Adolescente , Adulto , Doadores de Sangue , Feminino , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
13.
An Acad Bras Cienc ; 94(4): e20210202, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36102392

RESUMO

BACKGROUND: Role of Convalescent plasma (COPLA) to treat severe COVID-19 is under investigation. We compared efficacy and safety of COPLA with fresh frozen plasma (FFP) in severe COVID-19 patients. METHODS: One group received COPLA with standard medical care (n = 14), and another group received random donor FFP, as control with standard medical care (n = 15) in severe COVID-19 disease. RESULTS: The proportion of patients free of ventilation at day seven were 78.5% in COPLA group, and 93.3 % in control group were not significant (p= 0.258). However, improved respiratory rate, O2 saturation, SOFA score, and Ct value were observed in the COPLA group. No serious adverse events were noticed by plasma transfusion in both groups.


Assuntos
COVID-19 , Plasma , Transfusão de Componentes Sanguíneos/efeitos adversos , COVID-19/terapia , Humanos , Imunização Passiva/efeitos adversos , Soroterapia para COVID-19
14.
J Anaesthesiol Clin Pharmacol ; 38(1): 143-147, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35706650

RESUMO

Blind nasal intubation (BNI) has been around for over a century now. Many clinicians advocate it as an "old-is-gold" skill, which can be performed without any adjuncts in cases where visualization of larynx is a problem. Even today, BNI not only comes handy in resource-limited centers, it may also come to the rescue of airway managers in well-equipped centers. However, in the century since it was first described, there have been other major developments in the field of airway management and BNI as a skill has taken a backseat when it comes to a priority order. More so because it is limited by modalities to teach and train as most of the available manikins, which are otherwise phenomenal when it comes to imitating anatomy and overall attention to detail of a human airway, suffer terribly in one basic aspect needed to teach, train, and learn BNI-"they" cannot breathe! Attempts have been made to fabricate some manikins on these lines. But what if they can not only breathe but breathe out CO2 as well! We describe a simple method whereby we created a "CO2 breathing" manikin and tested it in an Airway Management Workshop with 105 participants, and then evaluated it under controlled conditions in 20 volunteers. We got very encouraging results and realized that our manikin makes the teaching and training of BNI very interesting and attractive by simulating the actual clinical scenario. We feel that it has the potential of reinventing the valuable skill of BNI.

15.
Beilstein J Org Chem ; 18: 217-224, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35280951

RESUMO

A practical enantioselective N-selective nitroso aldol reaction of α-methylmalonamates with a nitrosoarene is reported. The reaction employs the Takemoto thiourea catalyst for the induction of enantioselectivity, and the corresponding optically active oxyaminated malonamates were obtained in reasonably good yields.

16.
Am J Respir Cell Mol Biol ; 65(1): 41-53, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33784482

RESUMO

Coronavirus disease (COVID-19) is an acute infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Human SP-D (surfactant protein D) is known to interact with the spike protein of SARS-CoV, but its immune surveillance against SARS-CoV-2 is not known. The current study aimed to examine the potential of a recombinant fragment of human SP-D (rfhSP-D) as an inhibitor of replication and infection of SARS-CoV-2. The interaction of rfhSP-D with the spike protein of SARS-CoV-2 and human ACE-2 (angiotensin-converting enzyme 2) receptor was predicted via docking analysis. The inhibition of interaction between the spike protein and ACE-2 by rfhSP-D was confirmed using direct and indirect ELISA. The effect of rfhSP-D on replication and infectivity of SARS-CoV-2 from clinical samples was assessed by measuring the expression of RdRp gene of the virus using quantitative PCR. In silico interaction studies indicated that three amino acid residues in the receptor-binding domain of spike protein of SARS-CoV-2 were commonly involved in interacting with rfhSP-D and ACE-2. Studies using clinical samples of SARS-CoV-2-positive cases (asymptomatic, n = 7; symptomatic, n = 8) and negative control samples (n = 15) demonstrated that treatment with 1.67 µM rfhSP-D inhibited viral replication by ∼5.5-fold and was more efficient than remdesivir (100 µM) in Vero cells. An approximately two-fold reduction in viral infectivity was also observed after treatment with 1.67 µM rfhSP-D. These results conclusively demonstrate that the rfhSP-D mediated calcium independent interaction between the receptor-binding domain of the S1 subunit of the SARS-CoV-2 spike protein and human ACE-2, its host cell receptor, and significantly reduced SARS-CoV-2 infection and replication in vitro.


Assuntos
COVID-19/metabolismo , Proteína D Associada a Surfactante Pulmonar , SARS-CoV-2/fisiologia , Glicoproteína da Espícula de Coronavírus , Replicação Viral , Adulto , Animais , Chlorocebus aethiops , Feminino , Humanos , Masculino , Ligação Proteica , Proteína D Associada a Surfactante Pulmonar/química , Proteína D Associada a Surfactante Pulmonar/metabolismo , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/metabolismo , Células Vero
17.
Transpl Infect Dis ; 23(4): e13644, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33999511

RESUMO

INTRODUCTION: The role of HLA compatibility in kidney, heart, and stem cell transplantation is well known, but with regard to living donor liver transplantation (LDLT), there is a different scenario. In the present study, we aim to examine the effects of donor-recipient HLA mismatches at A, B, and DR loci on various outcomes of LDLT-like graft survival, early allograft dysfunction (EAD), acute rejection, length of hospital (LOH) stay, sepsis, and cytomegalovirus (CMV) reactivation. METHODS: This is a retrospective single center study of a cohort of adult patients who underwent first time ABO-compatible (ABOc) LDLT between January 2010 and December 2018. Transplants with incomplete records or without HLA typing data were excluded. Donor-recipient HLA-A, B, and DR mismatches were assessed in the host versus graft (HVG) direction and were correlated with various post-transplant outcomes. RESULTS: Among 140 transplants being evaluated, approximately two third had total HLA mismatches between 2 and 3. HLA mismatches at each locus as well as cumulative HLA mismatches did not show any association with overall graft survival, EAD, acute rejection episodes, and LOH stay. However, the presence of minimum one mismatch at HLA-A and DR loci was associated with the development of CMV reactivation (P = .03) and sepsis (P = .02) post-LDLT respectively. CONCLUSION: HLA mismatch is not associated with acute rejection, early graft dysfunction, and overall survival in LDLT. Its impact on CMV reactivation and sepsis needs further evaluation.


Assuntos
Transplante de Fígado , Rejeição de Enxerto/epidemiologia , Sobrevivência de Enxerto , Antígenos HLA/genética , Humanos , Transplante de Fígado/efeitos adversos , Doadores Vivos , Estudos Retrospectivos , Centros de Atenção Terciária
18.
BMC Oral Health ; 21(1): 336, 2021 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-34243733

RESUMO

BACKGROUND: Dental caries is one of the most prevalent non-communicable disease globally and can have serious health sequelae impacting negatively on quality of life. In the UK most adults experience dental caries during their lifetime and the 2009 Adult Dental Health Survey reported that 85% of adults have at least one dental restoration. Conservative removal of tooth tissue for both primary and secondary caries reduces the risk of failure due to tooth-restoration, complex fracture as well as remaining tooth surfaces being less vulnerable to further caries. However, despite its prevalence there is no consensus on how much caries to remove prior to placing a restoration to achieve optimal outcomes. Evidence for selective compared to complete or near-complete caries removal suggests there may be benefits for selective removal in sustaining tooth vitality, therefore avoiding abscess formation and pain, so eliminating the need for more complex and costly treatment or eventual tooth loss. However, the evidence is of low scientific quality and mainly gleaned from studies in primary teeth. METHOD: This is a pragmatic, multi-centre, two-arm patient randomised controlled clinical trial including an internal pilot set in primary dental care in Scotland and England. Dental health professionals will recruit 623 participants over 12-years of age with deep carious lesions in their permanent posterior teeth. Participants will have a single tooth randomised to either the selective caries removal or complete caries removal treatment arm. Baseline measures and outcome data (during the 3-year follow-up period) will be assessed through clinical examination, patient questionnaires and NHS databases. A mixed-method process evaluation will complement the clinical and economic outcome evaluation and examine implementation, mechanisms of impact and context. The primary outcome at three years is sustained tooth vitality. The primary economic outcome is net benefit modelled over a lifetime horizon. Clinical secondary outcomes include pulp exposure, progession of caries, restoration failure; as well as patient-centred and economic outcomes. DISCUSSION: SCRiPT will provide evidence for the most clinically effective and cost-beneficial approach to managing deep carious lesions in permanent posterior teeth in primary care. This will support general dental practitioners, patients and policy makers in decision making. Trial Registration Trial registry: ISRCTN. TRIAL REGISTRATION NUMBER: ISRCTN76503940. Date of Registration: 30.10.2019. URL of trial registry record: https://www.isrctn.com/ISRCTN76503940?q=ISRCTN76503940%20&filters=&sort=&offset=1&totalResults=1&page=1&pageSize=10&searchType=basic-search .


Assuntos
Cárie Dentária , Adulto , Assistência Odontológica , Cárie Dentária/terapia , Suscetibilidade à Cárie Dentária , Odontólogos , Inglaterra , Humanos , Atenção Primária à Saúde , Papel Profissional , Qualidade de Vida , Escócia , Dente Decíduo
19.
Indian J Public Health ; 64(2): 161-167, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32584299

RESUMO

BACKGROUND: Nutrition epidemiology initially focused on few nutrients thought to be responsible for noncommunicable diseases (NCDs). The database of Indian Nutrition Survey is based majorly on calorie intake. OBJECTIVE: The objective was to compare the change in the average calorie intake from 1990 to 2012 with the emerging epidemic of diabetes and hypertension (HTN) in India since 1990. METHODS: A comprehensive search was made in National Library of Medicine's PubMed database and Google Scholar from March to August 2018, on the above-mentioned subjects. Reports of national surveys (National Sample Survey Office and National Nutrition Monitoring Bureau) were included for average calorie intake among different states from year 1990 onward. Region-wise search depicted by national nutrition surveys resulted in 277 and 587 abstracts on the prevalence of HTN and diabetes mellitus, respectively. There were 51 full-text articles and abstracts on the prevalence of HTN and diabetes from the above regions. RESULTS: The average calorie intake per capita per day in the four zones of country in rural areas decreased from 1990 to 2012. An increasing trend in the prevalence of diabetes from rural areas was observed from 1994 to 2012. The per capita average calorie intake per day in urban areas from 1999 through 2011 in all zones except the eastern part of country was on rise. There was no consistent trend in the prevalence of HTN in any of the zones. CONCLUSION: It is not just an increase in calories, but a trade-off between the demand for calories and the demand for healthy lifestyles determines the prevalence of NCDs.


Assuntos
Diabetes Mellitus/epidemiologia , Ingestão de Energia , Hipertensão/epidemiologia , Estilo de Vida Saudável , Humanos , Índia/epidemiologia , Doenças não Transmissíveis/epidemiologia , Características de Residência , Fatores de Risco
20.
J Clin Gastroenterol ; 53(9): e382-e386, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-30789854

RESUMO

GOALS: The goal of this study was to identify factors impacting the quality of bowel preparation in an urban tertiary care setting. BACKGROUND: Inadequate bowel preparation is encountered in 17% to 32% of colonoscopies performed in the United States. Suboptimal colonic visualization reduces the yield of screening colonoscopies and increases healthcare costs because of longer procedure times and aborted procedures. STUDY: We performed a cross-sectional survey in patients undergoing outpatient colonoscopy within the Johns Hopkins Health System. A Boston Bowel Preparation Score (BBPS) score of <5 was considered inadequate. Fisher's exact, χ tests and univariate and multivariate binary logistic regression were performed to assess the strength of the association for selected factors with a BBPS<5. RESULTS: In total, 467 patients (76.3% response rate) completed the survey between August 2017 and October 2017. The median BBPS score was 7, and 81.4% of patients had an adequate bowel preparation (BBPS≥5). There was significant association between bowel preparation adequacy and level of education, health literacy, functional status, income, and medication burden. When adjusted for other factors, poor confidence in filling forms (OR, 24.1; P<0.001), multiple daily prescription medications (OR, 12.49; P=0.02) and poor functional status (OR, 2.82; P=0.03) had the highest odds of predicting inadequate bowel preparation. CONCLUSIONS: Inadequate bowel preparation is a significant problem accounting for reduced yield of screening and increased health care costs. Poor health literacy, functional status, and number of daily medications are significant factors predicting inadequate bowel preparation in the tertiary care setting.


Assuntos
Catárticos/administração & dosagem , Colonoscopia/métodos , Letramento em Saúde/estatística & dados numéricos , Programas de Rastreamento/métodos , Idoso , Idoso de 80 Anos ou mais , Colonoscopia/economia , Estudos Transversais , Feminino , Custos de Cuidados de Saúde/estatística & dados numéricos , Humanos , Masculino , Programas de Rastreamento/economia , Pessoa de Meia-Idade , Inquéritos e Questionários , Atenção Terciária à Saúde , Fatores de Tempo
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