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1.
Methods Mol Biol ; 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38976205

RESUMO

The emergence of brain organoids has revolutionized our understanding of neurodevelopment and neurological diseases by providing an in vitro model system that recapitulates key aspects of human brain development. However, conventional organoid protocols often overlook the role of microglia, the resident immune cells of the central nervous system. Microglia dysfunction is implicated in various neurological disorders, highlighting the need for their inclusion in organoid models. Here, we present a novel method for generating neuroimmune assembloids using human-induced pluripotent stem cell (iPSC)-derived cortical organoids and microglia. Building upon our previous work generating myelinating cortical organoids, we extend our methodology to include the integration of microglia, ensuring their long-term survival and maturation within the organoids. We describe two integration methods: one involving direct addition of microglia progenitors to the organoids and an alternative approach where microglia and dissociated neuronal progenitors are aggregated together in a defined ratio. To facilitate downstream analysis, we also describe a dissociation protocol for single-cell RNA sequencing (scRNA-seq) and provide guidance on fixation, cryosectioning, and immunostaining of assembloid structures. Overall, our protocol provides a comprehensive framework for generating neuroimmune assembloids, offering researchers a valuable tool for studying the interactions between neural cell types and immune cells in the context of neurological diseases.

2.
Cureus ; 15(10): e47960, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38034157

RESUMO

INTRODUCTION: Despite Indian children constituting approximately 31.4% of the population aged 0 to 14, a comprehensive exploration of childhood injuries within this demographic remains limited. This study aimed to examine the occurrence of unintentional injuries among children aged six months to 18 years in the Siddlagatta area and assess associated risk factors. METHODOLOGY: A community-based, cross-sectional study on unintentional child injuries was carried out from March 2018 to September 2020 across 11 sites in India. Employing a two-stage cluster sampling method with probability proportionate to size, 2341 urban and rural families were selected from each site. Data on unintentional injuries sustained over the past 12 months were collected using the WHO child injury questionnaire, tailored and validated for the Indian context. RESULTS: The study encompassed 10,335 individuals in households, including 2695 children aged 6 months to 18 years. Among them, 309 children experienced 390 unintentional injuries in the preceding year, excluding minor incidents. A prevalence rate of 11.5% (95% CI: 10.3-12.7) was identified for unintentional injuries among children, excluding minor cases. Falls were the most prevalent injury type (183 cases, 53.8%), while poisoning incidents were the least frequent (one case, 0.2%). More than 50% of incidents occurred within domestic settings. CONCLUSIONS: This study's outcomes underscore the prominence of fall-related injuries across all age groups and genders. Homes and schools emerged as primary settings for these injuries, highlighting the need for targeted preventive measures.

3.
Pathol Res Pract ; 248: 154651, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37390757

RESUMO

The most prevalent locations for head and neck cancer is the tongue. The surviving patients who are receiving therapy have considerably compromised speech, taste, chewing, and swallowing. CD9 is a cell surface protein that has contradictory role in cancer progression. The objective of the study is to analyze the Cluster of Differentiation 9(CD9), Epidermal Growth Factor Receptor (EGFR) and Phosphorylated Akt (p-Akt) expression in tongue cancer specimens and its clinical significance.50 tongue cancer sections were used to analyze the expression of CD9,EGFR and p-Akt by immunohistochemistry. Data regarding the histological grade of the tumor, age, sex, and habits were recorded, and relation with CD9,EGFR and p-Akt expression was assessed. Data were expressed as mean ± SEM. Categorical data was analyzed by Chi-square test. Student t-test was used to check the significance of data between two groups.A significant increase in the CD9,EGFR and p-Akt expression (1.8 ± 0.11, 2.06 ± 0.18 and 2.3 ± 0.15 respectively) was seen in the tongue cancer specimens. CD9 and p-Akt expression had a significant association with the histological grade (p < 0.004 and p < 0.006 respectively). CD9 expression was higher in patients with the combination of addiction/habit compared to patients with single addictions(1.08 ± 0.11 and 0.75 ± 0.47). Overall a poor rate of survival was observed in CD9 positive patients(p < 0.039). EGFR and p-Akt expression increased with increasing expression of CD9, suggesting its use as a biomarker to track the development of TSCC.


Assuntos
Carcinoma de Células Escamosas , Neoplasias da Língua , Humanos , Carcinoma de Células Escamosas/patologia , Receptores ErbB/metabolismo , Prognóstico , Proteínas Proto-Oncogênicas c-akt , Tetraspanina 29 , Tetraspaninas , Língua/metabolismo , Língua/patologia , Neoplasias da Língua/patologia
4.
Hum Reprod ; 37(11): 2672-2689, 2022 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-36112004

RESUMO

STUDY QUESTION: Is there an association between fertility status, method of conception and the risks of birth defects and childhood cancer? SUMMARY ANSWER: The risk of childhood cancer had two independent components: (i) method of conception and (ii) presence, type and number of birth defects. WHAT IS KNOWN ALREADY: The rarity of the co-occurrence of birth defects, cancer and ART makes studying their association challenging. Prior studies have indicated that infertility and ART are associated with an increased risk of birth defects or cancer but have been limited by small sample size and inadequate statistical power, failure to adjust for or include plurality, differences in definitions and/or methods of ascertainment, lack of information on ART treatment parameters or study periods spanning decades resulting in a substantial historical bias as ART techniques have improved. STUDY DESIGN, SIZE, DURATION: This was a population-based cohort study linking ART cycles reported to the Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) from 1 January 2004 to 31 December 2017 that resulted in live births in 2004-2018 in Massachusetts and North Carolina and live births in 2004-2017 in Texas and New York. A 10:1 sample of non-ART births were chosen within the same time period as the ART birth. Non-ART siblings were identified through the ART mother's information. Children from non-ART births were classified as being born to women who conceived with ovulation induction or IUI (OI/IUI) when there was an indication of infertility treatment on the birth certificate, and the woman did not link to the SART CORS; all others were classified as being naturally conceived. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study population included 165 125 ART children, 31 524 non-ART siblings, 12 451 children born to OI/IUI-treated women and 1 353 440 naturally conceived children. All study children were linked to their respective State birth defect registries to identify major defects diagnosed within the first year of life. We classified children with major defects as either chromosomal (i.e. presence of a chromosomal defect with or without any other major defect) or nonchromosomal (i.e. presence of a major defect but having no chromosomal defect), or all major defects (chromosomal and nonchromosomal), and calculated rates per 1000 children. Logistic regression models were used to generate adjusted odds ratios (AORs) and 95% CIs of the risk of birth defects by conception group (OI/IUI, non-ART sibling and ART by oocyte source and embryo state) with naturally conceived children as the reference, adjusted for paternal and maternal ages; maternal race and ethnicity, education, BMI, parity, diabetes, hypertension; and for plurality, infant sex and State and year of birth. All study children were also linked to their respective State cancer registries. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% CIs of cancer by birth defect status (including presence of a defect, type and number of defects), and conception group. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 29 571 singleton children (2.0%) and 3753 twin children (3.5%) had a major birth defect (chromosomal or nonchromosomal). Children conceived with ART from autologous oocytes had increased risks for nonchromosomal defects, including blastogenesis, cardiovascular, gastrointestinal and, for males only, genitourinary defects, with AORs ranging from 1.22 to 1.85; children in the autologous-fresh group also had increased risks for musculoskeletal (AOR 1.28, 95% CI 1.13, 1.45) and orofacial defects (AOR 1.40, 95% CI 1.17, 1.68). Within the donor oocyte group, the children conceived from fresh embryos did not have increased risks in any birth defect category, whereas children conceived from thawed embryos had increased risks for nonchromosomal defects (AOR 1.20, 95% CI 1.03, 1.40) and blastogenesis defects (AOR 1.74, 95% CI 1.14, 2.65). The risk of cancer was increased among ART children in the autologous-fresh group (HR 1.31, 95% CI 1.08, 1.59) and non-ART siblings (1.34, 95% CI 1.02, 1.76). The risk of leukemia was increased among children in the OI/IUI group (HR 2.15, 95% CI 1.04, 4.47) and non-ART siblings (HR 1.63, 95% CI 1.02, 2.61). The risk of central nervous system tumors was increased among ART children in the autologous-fresh group (HR 1.68, 95% CI 1.14, 2.48), donor-fresh group (HR 2.57, 95% CI 1.04, 6.32) and non-ART siblings (HR 1.84, 95% CI 1.12, 3.03). ART children in the autologous-fresh group were also at increased risk for solid tumors (HR 1.39, 95% CI 1.09, 1.77). A total of 127 children had both major birth defects and cancer, of which 53 children (42%) had leukemia. The risk of cancer had two independent components: (i) method of conception (described above) and (ii) presence, type and number of birth defects. The presence of nonchromosomal defects increased the cancer risk, greater for two or more defects versus one defect, for all cancers and each type evaluated. The presence of chromosomal defects was strongly associated with cancer risk (HR 8.70 for all cancers and HR 21.90 for leukemia), further elevated in the presence of both chromosomal and nonchromosomal defects (HR 21.29 for all cancers, HR 64.83 for leukemia and HR 4.71 for embryonal tumors). Among the 83 946 children born from ART in the USA in 2019 compared to their naturally conceived counterparts, these risks translate into an estimated excess of 761 children with major birth defects, 31 children with cancer and 11 children with both major birth defects and cancer. LIMITATIONS, REASONS FOR CAUTION: In the SART CORS database, it was not possible to differentiate method of embryo freezing (slow freezing versus vitrification), and data on ICSI were only available in the fresh embryo ART group. In the OI/IUI group, it was not possible to differentiate type of non-ART treatment utilized, and in both the ART and OI/IUI groups, data were unavailable on duration of infertility. Since OI/IUI is underreported on the birth certificate, some OI/IUI children were likely included among the naturally conceived children, which will decrease the difference between all the groups and the naturally conceived children. WIDER IMPLICATIONS OF THE FINDINGS: The use of ART is associated with increased risks of major nonchromosomal birth defects. The presence of birth defects is associated with greater risks for cancer, which adds to the baseline risk in the ART group. Although this study does not show causality, these findings indicate that children conceived with ART, non-ART siblings, and all children with birth defects should be monitored more closely for the subsequent development of cancer. STUDY FUNDING/COMPETING INTEREST(S): This project was supported by grant R01 HD084377 from the National Institute of Child Health and Human Development. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Child Health and Human Development, or the National Institutes of Health, nor any of the State Departments of Health which contributed data. M.L.E. reports consultancy for Ro, Hannah, Dadi, Sandstone and Underdog; presidency of SSMR; and SMRU board member. The remaining authors report no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.


Assuntos
Infertilidade , Leucemia , Neoplasias , Gravidez , Lactente , Masculino , Criança , Humanos , Feminino , Estudos de Coortes , Neoplasias/etiologia , Técnicas de Reprodução Assistida/efeitos adversos , Infertilidade/etiologia
5.
Indian Pediatr ; 59(7): 553-562, 2022 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-35481486

RESUMO

JUSTIFICATION: Suicide is an important cause of adolescent mortality and morbidity in India. As pediatricians are often the first point of contact for adolescents and their families in the healthcare system, they need guidelines to screen, assess, manage and prevent adolescent suicidal behavior to ensure survival, health and mental well-being of this vulnerable population. OBJECTIVES: To formulate guidelines to aid pediatricians for prevention and management of adolescent suicidal behavior. PROCESS: Indian Academy of Pediatrics, in association with Adolescent Health Academy, formed a multidisciplinary committee of subject experts in June, 2019 to formulate guidelines for adolescent suicide prevention and management. After a review of current scientific literature and preparation of draft guidelines, a national consultative meeting was organized on 16 August, 2019 for detailed discussions and deliberations. This was followed by refining of draft guidelines, and discussions over e-mail where suggestions were incorporated and the final document was approved. GUIDELINES: Pediatricians should screen for mental distress, mental disorders and suicidal and para-suicidal (non-suicidal self-injury) behavior during adolescent health visits. Those with suicidal behavior should be referred to a psychiatrist after providing emergency healthcare, risk assessment, immediate counselling and formulation of a safety plan. Pediatricians should partner with the community and policymakers for primary and secondary prevention of adolescent suicide.


Assuntos
Aconselhamento , Encaminhamento e Consulta , Adolescente , Povo Asiático , Criança , Consenso , Humanos , Medição de Risco
6.
Indian Pediatr ; 59(6): 477-484, 2022 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-35481487

RESUMO

JUSTIFICATION: Adolescent health is critical to the current and future well- being of the world. Pediatricians need country specific guidelines in accordance with international and national standards to establish comprehensive adolescent friendly health services in clinical practice. PROCESS: Indian Academy of Pediatrics (IAP) in association with Adolescent Health Academy formed a committee of subject experts in June, 2019 to formulate guidelines for adolescent friendly health services. After a review of current scientific literature and drafting guidelines on each topic, a national consultative meeting was organized on 16 August, 2019 for detailed discussions and deliberations. This was followed by discussions over e-mail and refining of draft recommendations. The final guidelines were approved by the IAP Executive Board in December, 2021. OBJECTIVE: To formulate guidelines to enable pediatricians to establish adolescent friendly health services. Recommendations: Pediatricians should coordinate healthcare for adolescents and plan for transition of care to an adult physician by 18 years of age. Pediatricians should establish respectful, confidential and quality adolescent friendly health services for both out-patient and in-patient care. The healthcare facility should provide preventive, therapeutic, and health promoting services. Pediatricians should partner with the multidisciplinary speciality services, community, and adolescents to expand the scope and reach of adolescent friendly health services.


Assuntos
Serviços de Saúde do Adolescente , Pediatria , Adolescente , Criança , Consenso , Humanos , Encaminhamento e Consulta
7.
Methods Mol Biol ; 2454: 1-15, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-33837517

RESUMO

Human induced pluripotent stem cells (iPSCs) have emerged as an invaluable resource for basic research, disease modeling, and drug discovery over recent years. Given the numerous advantages of iPSCs over alternative models-including their human origin, their ability to be differentiated into almost any cell type, and the therapeutic potential of patient-specific iPSCs in personalized medicine-many labs are now considering iPSC models for their studies. As the quality of the starting population of iPSCs is a key determinant in the success of any one of these applications, it is crucial to adhere to best practices in iPSC culture. In the following protocol, we offer a comprehensive guide to the culture, cryopreservation, and quality control methods required for the establishment and maintenance of high-quality iPSC cultures.


Assuntos
Células-Tronco Pluripotentes Induzidas , Diferenciação Celular , Criopreservação , Humanos , Medicina de Precisão
8.
Ann Glob Health ; 87(1): 12, 2021 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-33598410

RESUMO

This viewpoint examines the impact of COVID-19 travel bans and remote education on the global health education of students from high-income countries (HIC) and low- and middle-income countries (LMIC) and explores potential opportunities for strengthening global health education based upon more dispersed and equitable practices. Global health is unique in the opportunities it can offer to students during the pandemic if programs can manage and learn from the pandemic's many challenges. Global health educators can: shift to sustainable remote engagement and mobilize resources globally to facilitate this; collaborate with partners to support the efforts to deal with the current pandemic and to prepare for its next phases; partner in new ways with health care professional students and faculty from other countries; collaborate in research with partners in studies of pandemic related health disparities in any country; and document and examine the impact of the pandemic on health care workers and students in different global contexts. These strategies can help work around pandemic travel restrictions, overcome the limitations of existing inequitable models of engagement, and better position global health education and face future challenges while providing the needed support to LMIC partners to participate more equally.


Assuntos
COVID-19 , Controle de Doenças Transmissíveis , Educação Médica/tendências , Educação em Enfermagem/tendências , Educação Profissional em Saúde Pública/tendências , Educação , Saúde Global/educação , COVID-19/epidemiologia , COVID-19/prevenção & controle , Controle de Doenças Transmissíveis/métodos , Controle de Doenças Transmissíveis/organização & administração , Educação/métodos , Educação/organização & administração , Educação a Distância/métodos , Educação a Distância/organização & administração , Humanos , Cooperação Internacional , Modelos Educacionais , Quarentena , SARS-CoV-2
10.
JAMA Netw Open ; 3(10): e2022927, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-33119107

RESUMO

Importance: Children with birth defects have a greater risk of developing cancer, but this association has not yet been evaluated in children conceived with in vitro fertilization (IVF). Objective: To assess whether the association between birth defects and cancer is greater in children conceived via IVF compared with children conceived naturally. Design, Setting, and Participants: This cohort study of live births, birth defects, and cancer from Massachusetts, New York, North Carolina, and Texas included 1 000 639 children born to fertile women and 52 776 children conceived via IVF (using autologous oocytes and fresh embryos) during 2004-2016 in Massachusetts and North Carolina, 2004-2015 in New York, and 2004-2013 in Texas. Children were followed up for an average of 5.7 years (6 008 985 total person-years of exposure). Data analysis was conducted from April 1 to August 31, 2020. Exposures: Conception by IVF for state residents who gave birth to liveborn singletons during the study period. Birth defect diagnoses recorded by statewide registries. Main Outcomes and Measures: Cancer diagnosis as recorded by state cancer registries. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% CIs for birth defect-cancer associations separately in fertile and IVF groups. Results: A total of 1 000 639 children (51.3% boys; 69.7% White; and 38.3% born between 2009-2012) were in the fertile group and 52 776 were in the IVF group (51.3% boys; 81.3% White; and 39.6% born between 2009-2012). Compared with children without birth defects, cancer risks were higher among children with a major birth defect in the fertile group (hazard ratio [HR], 3.15; 95% CI, 2.40-4.14) and IVF group (HR, 6.90; 95% CI, 3.73-12.74). The HR of cancer among children with a major nonchromosomal defect was 2.07 (95% CI, 1.47-2.91) among children in the fertile group and 4.04 (95% CI, 1.86-8.77) among children in the IVF group. The HR of cancer among children with a chromosomal defect was 15.45 (95% CI, 10.00-23.86) in the fertile group and 38.91 (95% CI, 15.56-97.33) in the IVF group. Conclusions and Relevance: This study found that among children with birth defects, those conceived via IVF were at greater risk of developing cancer compared with children conceived naturally.


Assuntos
Anormalidades Congênitas/diagnóstico , Fertilização in vitro/efeitos adversos , Neoplasias/diagnóstico , Medição de Risco/métodos , Adolescente , Adulto , Estudos de Coortes , Anormalidades Congênitas/epidemiologia , Feminino , Fertilização in vitro/métodos , Fertilização in vitro/estatística & dados numéricos , Humanos , Masculino , Massachusetts/epidemiologia , Neoplasias/epidemiologia , New York/epidemiologia , North Carolina/epidemiologia , Vigilância da População/métodos , Gravidez , Resultado da Gravidez/epidemiologia , Sistema de Registros/estatística & dados numéricos , Medição de Risco/estatística & dados numéricos , Texas/epidemiologia
11.
Development ; 147(12)2020 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-32487737

RESUMO

The intrinsic mechanisms that link extracellular signalling to the onset of neural differentiation are not well understood. In pluripotent mouse cells, BMP blocks entry into the neural lineage via transcriptional upregulation of inhibitor of differentiation (Id) factors. We have previously identified the major binding partner of Id proteins in pluripotent cells as the basic helix-loop-helix (bHLH) transcription factor (TF) E2A. Id1 can prevent E2A from forming heterodimers with bHLH TFs or from forming homodimers. Here, we show that overexpression of a forced E2A homodimer is sufficient to drive robust neural commitment in pluripotent cells, even under non-permissive conditions. Conversely, we find that E2A null cells display a defect in their neural differentiation capacity. E2A acts as an upstream activator of neural lineage genes, including Sox1 and Foxd4, and as a repressor of Nodal signalling. Our results suggest a crucial role for E2A in establishing neural lineage commitment in pluripotent cells.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Diferenciação Celular , Neurônios/metabolismo , Regiões 3' não Traduzidas , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/deficiência , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Sistemas CRISPR-Cas/genética , Linhagem da Célula , Autorrenovação Celular , Dimerização , Camundongos , Células-Tronco Embrionárias Murinas/citologia , Células-Tronco Embrionárias Murinas/metabolismo , Neurônios/citologia , Fator 3 de Transcrição de Octâmero/deficiência , Fator 3 de Transcrição de Octâmero/genética , Fator 3 de Transcrição de Octâmero/metabolismo , RNA Guia de Cinetoplastídeos/metabolismo , Fatores de Transcrição SOXB1/deficiência , Fatores de Transcrição SOXB1/genética , Fatores de Transcrição SOXB1/metabolismo , Transcriptoma , Regulação para Cima
12.
Cancer Epidemiol ; 64: 101652, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31811983

RESUMO

BACKGROUND: Population-based cancer registries collect information on first course of treatment that may be utilized in research on cancer care quality, yet few studies have investigated the validity of this information. We examined the accuracy and completeness of registry-based treatment information in a cohort of adolescent and young adult women. METHODS: Women diagnosed with breast cancer, lymphoma, thyroid cancer, cervical/uterine cancer or ovarian cancer at ages 15-39 during 2003-2014 were identified using data from the North Carolina Central Cancer Registry (CCR) (N = 2342). CCR data were linked to Medicaid and private insurance claims data, and claims were reviewed for the 12 months following diagnosis to identify cancer treatments received. Using claims data as the gold standard, we calculated the sensitivity and positive predictive value (PPV) of CCR data for receipt of chemotherapy, radiation and hormone therapy. We also compared dates of treatment initiation between the two data sources. RESULTS: For all cancer types combined, the sensitivity of the CCR data was high for chemotherapy (86%) and moderate for radiation (74%). PPVs were 82% and 83% for chemotherapy and radiation, respectively. Both the sensitivity (67%) and PPV (70%) were lower for hormone therapy for breast cancer. For all three treatment types, dates of initiation in the registry and the claims differed by ≤30 days for most women. CONCLUSIONS: In this cohort of young women, population-based cancer registry data on chemotherapy receipt was reasonably accurate and complete in comparison with insurance claims. Radiation and hormone therapy appeared to be less complete.


Assuntos
Neoplasias/epidemiologia , Neoplasias/terapia , Adolescente , Adulto , Estudos de Coortes , Feminino , Humanos , Sistema de Registros , Adulto Jovem
13.
Indian J Surg Oncol ; 10(2): 377-381, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31168266

RESUMO

Triple-negative breast cancer (TNBC) is an aggressive subgroup of breast cancer which lacks effective target therapy. Expression of biomarkers is one of the important deciding factors for treatment strategies. The aim of this study was to evaluate expression of E cadherin and Ki 67 in relation to clinicopathological features. This prospective observational study included 141 cases of TNBC. Immunohistochemical staining was employed to analyze two biomarkers: E cadherin and Ki 67 on formalin-fixed paraffin-embedded tumor samples obtained from patients defined as TNBC. The age of the patients ranged from 26 to 84 years. Positive lymph nodes were found in 82 (58.1%). The tumor was grade 3 in 105 (74.4%). The E cadherin receptor was positive in 83 (58.8%). The Ki Index was > 10% in 89 (63.12%). The Ki 67 expression was significantly associated with a high nuclear grade (p = 0.000). The significant association noted between loss of E cadherin expression and positive lymph node (p = 0.0296). According to the results, TNBCs are frequently associated with the younger age groups, and the majority is poorly differentiated. The majorities of these have high expression of the Ki 67 and significantly associated with the higher nuclear grade. Loss of E cadherin was significantly associated with positive lymph nodes. Hence, evaluating the expression of E cadherin and Ki 67 routinely would be helpful for evaluating prognostic implications.

14.
Cancer ; 125(6): 933-942, 2019 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-30624768

RESUMO

BACKGROUND: Transplant recipients have an elevated risk of cancer because of immunosuppressive medications used to prevent organ rejection, but to the authors' knowledge no study to date has comprehensively examined associations between transplantation status and mortality after a cancer diagnosis. METHODS: The authors assessed cases in the US general population (N=7,147,476) for 16 different cancer types as ascertained from 11 cancer registries. The presence of a solid organ transplant prior to diagnosis (N=11,416 cancer cases) was identified through linkage with the national transplantation registry (1987-2014). Cox models were used to examine the association between transplantation status and cancer-specific mortality, adjusting for demographic characteristics and cancer stage. RESULTS: For the majority of cancers, cancer-specific mortality was higher in transplant recipients compared with other patients with cancer. The increase was particularly pronounced for melanoma (adjusted hazard ratio [aHR], 2.59; 95% confidence interval [95% CI], 2.18-3.00) and cancers of the breast (aHR, 1.88; 95% CI, 1.61-2.19), bladder (aHR, 1.85; 95% CI, 1.58-2.17), and colorectum (aHR, 1.77; 95% CI, 1.60-1.96), but it also was increased for cancers of the oral cavity/pharynx, stomach, pancreas, kidney, and lung as well as diffuse large B-cell lymphoma (aHR range, 1.21-1.47). Associations remained significant after adjustment for first-course cancer treatment and generally were stronger among patients with local-stage cancers for whom potentially curative treatment was provided, including patients with melanoma (aHR, 3.82; 95% CI, 2.94-4.97) and cancers of the colorectum (aHR, 2.77; 95% CI, 2.07-3.70), breast (aHR, 2.08; 95% CI, 1.50-2.88), and prostate (aHR, 1.60; 95% CI, 1.12-2.29), despite the lack of an association for prostate cancer overall. CONCLUSIONS: For multiple cancer types, transplant recipients with cancer appear to have an elevated risk of dying of their cancer, even after adjustment for stage and treatment, which may be due to impaired immunity.


Assuntos
Neoplasias/diagnóstico , Neoplasias/mortalidade , Transplantados/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transplante de Órgãos/mortalidade , Modelos de Riscos Proporcionais , Sistema de Registros , Análise de Sobrevida , Estados Unidos/epidemiologia
15.
Indian J Psychiatry ; 59(2): 202-207, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28827868

RESUMO

INTRODUCTION: In 2007, Ministry of Women and Child Welfare, supported by United Nations Children's Fund, save the children and Prayas conducted a study to understand the magnitude of child abuse in India, they found that 53.22% children faced one or more forms of sexual abuse; among them, the number of boys abused was 52.94%. AIM: The aim of this study was to explore the barriers for seeking psychiatric help by qualitative analysis of stake holders of male victims of child abuse. MATERIALS AND METHODS: All the statements made by the stakeholders regarding psychiatric assessment and treatment were recorded in each referral made to the psychiatrist. Semistructured interviews and in-depth interviews were conducted to explore the topic of understanding the need for psychiatric treatment to the victims. RESULTS: Collaborative child response unit, a multidisciplinary team, to tackle child sexual abuse in a general hospital received three referrals of male child abuse among the 27 referrals in 20 months. The main theme of the barrier that was generated by interviewing the stakeholders of male child victims of abuse was the misconception of superiority of a male victim due to gender (patriarchy) an expectation that he will outgrow the experience. In-depth interviews of three cases of homosexual abuse explored the theme. CONCLUSION: Patriarchy is oppressing male children and acts as a barrier to seek psychiatric help in collaborative child response unit.

16.
Indian J Psychol Med ; 39(1): 12-20, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28250553

RESUMO

Child abuse is a serious criminal act against children in our country and punishable according to protection of children from sexual offenses act 2012. No one agency has the ability to respond completely to the abuse. Hence a multidisciplinary team approach was developed in India. Aim is to narrate the collaborative effort among the multiple disciplines in a general hospital to deliver child protection services and explore the barriers to integrate psychiatric services. METHODOLOGY: Members of the team were recruited from different disciplines and trained by experts. A mission statement, protocol to assess the victims and provide treatment was formulated as an algorithm. The barriers to psychiatric treatment among the stakeholders were analyzed using framework method of qualitative analysis. Results (After 20 months) the unit received 27 referrals in 20 months, 24 females, and 3 males. Age of the victims was between 8 months and 17 years. Two cases found to be physically abused. Penetrative sexual abuse was found in 23 cases, pregnant victims were 4. Most referrals were by police, trafficking found in 6 cases. DISCUSSION: It was possible to provide multidisciplinary care to the victims and families. Recurrent themes of barriers to psychiatric treatment were stigma, victim blaming; focus on termination of pregnancy, minimization of abuse in males by stakeholders. Conclusion is collaboration needs more effort to integrate psychiatric services but can minimize the reduplication of services.

18.
Development ; 143(20): 3686-3699, 2016 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-27578791

RESUMO

Insufficient alveolar gas exchange capacity is a major contributor to lung disease. During lung development, a population of distal epithelial progenitors first produce bronchiolar-fated and subsequently alveolar-fated progeny. The mechanisms controlling this bronchiolar-to-alveolar developmental transition remain largely unknown. We developed a novel grafting assay to test if lung epithelial progenitors are intrinsically programmed or if alveolar cell identity is determined by environmental factors. These experiments revealed that embryonic lung epithelial identity is extrinsically determined. We show that both glucocorticoid and STAT3 signalling can control the timing of alveolar initiation, but that neither pathway is absolutely required for alveolar fate specification; rather, glucocorticoid receptor and STAT3 work in parallel to promote alveolar differentiation. Thus, developmental acquisition of lung alveolar fate is a robust process controlled by at least two independent extrinsic signalling inputs. Further elucidation of these pathways might provide therapeutic opportunities for restoring alveolar capacity.


Assuntos
Células Epiteliais/citologia , Células Epiteliais/metabolismo , Glucocorticoides/metabolismo , Pulmão/citologia , Pulmão/metabolismo , Células-Tronco/citologia , Células-Tronco/metabolismo , Adenoviridae/genética , Células Epiteliais Alveolares/citologia , Células Epiteliais Alveolares/metabolismo , Animais , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/genética , Células Cultivadas , Glucocorticoides/antagonistas & inibidores , Humanos , Camundongos , Mifepristona/farmacologia , Alvéolos Pulmonares/citologia , Alvéolos Pulmonares/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética
19.
J Clin Diagn Res ; 10(2): BF01-5, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27042448

RESUMO

INTRODUCTION: Diallyl disulphide is an organo-sulphur compound which is present in garlic and responsible for the characteristic odor of garlic. It is known for its anticancer and invitro membrane stabilizing properties. AIM: The main aim was to evaluate the haematopoietic, antioxidant and membrane stabilizing property of diallyl disulfide in irradiated mice. MATERIALS AND METHODS: Mice were grouped into 6 groups as control, drug control, radiation control and drug pre-treatment groups (i.e. drug administration + radiation group) The mice were fed orally for 15 consecutive days and on the 15(th) day, one hour after drug administration, the mice were irradiated with 6Gy electron beam radiation. The changes in blood cell count, total antioxidant levels, malondialdehyde and reduced glutathione levels were determined. The immunomodulatory response of DADS to the radiological effects was determined by the estimation of IL-6 levels. RESULTS: A significant improvement in pre-drug treatment group when compared to control groups in the haemoglobin, red blood cell count, white blood cell count, haematocrit and platelet counts was observed. There is an increased level of interleukin-6 in the drug treated groups compared to the radiation control. An increase in the malondialdehyde levels and decrease in the glutathione levels in the irradiated group indicate increased lipid peroxidation and oxidative stress, whereas, there is a significant reduction in the malondialdehyde levels and increased glutathione levels in the drug pre-treatment groups showing membrane stabilization. CONCLUSION: Thus DADS proves to be an effective haematopoietic and antioxidative agent to counter radiation induced haematopoietic suppression and oxidative stress.

20.
J Cancer Res Ther ; 11(3): 647, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26458608

RESUMO

Cervical region teratoma is a rare disease, accounting for 3-5% of all teratomas in the children. Teratomas of the head and neck due to their obscure origin, unpredictable behavior, and often manifest as a clinical surprise. Airway obstruction is the most serious postnatal complication of cervical teratoma. Prenatal diagnosis is crucial for early recognition of the neck masses that could obstruct the airway. We present a case of 4-month-old female child at age of 4 th month with right submandibular region swelling. Computed tomography neck showed ill-defined, multiloculated cystic lesion with enhancing thick septations in the right side of the neck. Excision biopsy revealed Grade I--immature teratoma--cervical region. On 1-year of close follow-up, no evidence of local recurrence or metastasis was seen. Unlike adults, teratomas in children are often congenital and very rarely turn malignant. The treating consultant should be aware of their natural history, clinical features, pathology, and principles of management.


Assuntos
Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Teratoma/diagnóstico por imagem , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Lactente , Radiografia , Teratoma/patologia
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