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Osteoporosis is primarily associated with bone loss, but changes in bone tissue matrix composition and osteocyte mechanotransduction have also been identified. However, the molecular mechanisms underlying these changes and their relation to bone loss are not fully understood. The objectives of this study were to (1) conduct comprehensive temporal gene expression analyses on cortical bone tissue from ovariectomized rats, with a specific focus on genes known to govern matrix degradation, matrix production, and mechanotransduction, and (2) correlate these findings with bone mass, trabecular and cortical microarchitecture, and mineral and matrix composition. Microarray data revealed 35 differentially expressed genes in the cortical bone tissue of the ovariectomized cohort. We report that catabolic gene expression abates after the initial accelerated bone loss period, which occurs within the first 4 wk of estrogen deficiency. However, in long-term estrogen deficiency, we report increased expression of genes associated with extracellular matrix deposition (Spp1, COL1A1, COL1A2, OCN) and mechanotransduction (Cx43) compared with age-matched controls and short-term estrogen deficiency. These changes coincided with increased heterogeneity of mineral-to-matrix ratio and collagen maturity, to which extracellular matrix markers COL1A1 and COL1A2 were positively correlated. Interestingly, mineral heterogeneity and collagen maturity, exhibited a negative correlation with PHEX and IFT88, associated with mechanosensory cilia formation and Hedgehog (Hh) signaling. This study provides the first insight into the underlying mechanisms governing secondary mineralization and heterogeneity of matrix composition of bone tissue in long-term estrogen deficiency. We propose that altered mechanobiological responses in long-term estrogen deficiency may play a role in these changes.
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Globally, the region of South Asia reports the highest number of women (87 million) with unmet needs of contraception. Amongst the lower-middle-income countries of South Asia, Pakistan has performed poorly in enhancing contraceptive prevalence, as evident by the Contraceptive Prevalence Rate (CPR) of 34%. Factors including restricted access to contraception, a restricted selection of techniques, cultural/religious resistance, gender-based hurdles, and societal factors, such as the couple's education level, are among the most important causes for this gap in desire and usage. Thus, this study aimed to evaluate the association between couple's education level and their influence on their choice of contraception. In addition, the study also assessed the role of socioeconomic status in modifying the association between couple's education and contraception choice. Using PDHS 2017-18 data, couple's education status, preferences of contraceptive use and wealth quintiles were analyzed through multinomial logistic regression after adjusting for other confounding factors. The findings of our study revealed that out of the total sample of 14,368 women, 67.52% (n = 9701) were categorized as non-users, 23.55% (n = 3383) employed modern contraceptive methods, and 8.94% (n = 1284) utilized traditional contraceptive methods. Multivariable analysis showed that educated couples belonging to higher socioeconomic status (SES) had the highest adjusted odds ratio [7.66 (CI: 4.89-11.96)] of using modern contraceptives as opposed to uneducated couples of low socioeconomic statuses. Our analysis also revealed that the odds of using modern contraceptives were higher amongst mothers with five or more children [8.55 (CI:7.09-10.31)] as compared to mothers with less children when adjusted for other covariates. Thus, this study concludes the dynamic interplay between couple's level of education, contraceptive preference, and socioeconomic status This study contributes valuable insights for the policy makers and stakeholders to understand the intricate relationship between these factors.
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Indoor air pollution arising from burning of biomass fuels poses a significant threat to child health in rural areas of Pakistan. This cross-sectional study aimed to assess health implications associated with indoor air pollution resulting from biomass burning among children under 12 years of age in rural Punjab. A questionnaire-based survey was conducted in six randomly selected rural districts of Punjab, characterized by their primary reliance on biomass fuels. The findings revealed that several characteristics, such as monthly household income, number of living rooms, secondary use of solid fuels, kitchen type, type of cooking stove, and presence of child in the kitchen with their mother, exhibited significant associations (p < 0.05) with negative health impacts among children. Reported health effects among the children included coughing (18.7%), watery eyes (17.7%), eye irritation (12.3%), runny nose (11.8%), breathing difficulties (8.5%), phlegm (38%), headache (25%), nausea (20.1%), dizziness (6.7%), asthma (6.4%), tuberculosis (1.8%), and pneumonia (1.5%).
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Introduction.Fannyhessea vaginae (formerly Atopobium vaginae) is an anaerobic organism commonly associated with female genital flora, with rare cases of invasive disease reported in females. Case report. We discuss the case of an 81-year-old male who presented with an acute history of back pain and signs of urinary tract infection in the context of intermittent self-urinary catheterisation. Multiple blood cultures grew Fannyhessea vaginae with a later finding of lumbar vertebral osteomyelitis as the cause of back pain. Treatment was commenced with ampicillin, later switched to ceftriaxone, with improvement of acute signs of infection. Conclusion. Gram-positive anaerobic organisms including Fannyhessea vaginae are possibly under-recognised causes of urinary tract particularly in older males. These bacteria may prove challenging to grow in standard protocols for urine culture; anaerobic or extended incubation could be considered particularly in complicated cases of urinary tract infection without an identifiable pathogen.
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Natural disasters and human demolition create vast amounts of construction and demolition waste (CDW), with a substantial portion being concrete waste. Managing this concrete waste is a daunting challenge for developing countries with limited resources, aiming to mitigate its harmful environmental effects. Therefore, the proposed approach involves using recycled fine aggregates (RFA) instead of fresh fine aggregates (FFA) in concrete, which aligns closely with achieving sustainable environmental objectives. Extensive laboratory tests were conducted to assess the effects of adding RFA to concrete. The influence of 0 to 100% RFA replacement and different curing times was investigated on compressive strength, tensile strength, resistance against chloride ion penetration and chemicals exposure, and quality of aggregates. So, around 30%, 35%, 20%, and 79% reductions in compression strength, tensile strength, modulus of elasticity, and workability were estimated when 100% RFA was used in recycled aggregate concrete (RAC). However, according to results analyses, the performance of RAC is reliable up to 50% of RFA in proposed conditions and mix design. In addition, major environmental impacts such as global warming potential, aquatic eutrophication, and aquatic acidification were reduced by 47%, 40%, and 18%, respectively, for concrete having 50% RFA than concrete having 100% FFA.
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Materiales de Construcción , Reciclaje , Ambiente , Resistencia a la TracciónRESUMEN
Bone is highly susceptible to cancer metastasis, and both tumor and bone cells enable tumor invasion through a "vicious cycle" of biochemical signaling. Tumor metastasis into bone also alters biophysical cues to both tumor and bone cells, which are highly sensitive to their mechanical environment. However, the mechanobiological feedback between these cells that perpetuate this cycle has not been studied. Here, we develop highly advanced in vitro and computational models to provide an advanced understanding of how tumor growth is regulated by the synergistic influence of tumor-bone cell signaling and mechanobiological cues. In particular, we develop a multicellular healthy and metastatic bone model that can account for physiological mechanical signals within a custom bioreactor. These models successfully recapitulated mineralization, mechanobiological responses, osteolysis, and metastatic activity. Ultimately, we demonstrate that mechanical stimulus provided protective effects against tumor-induced osteolysis, confirming the importance of mechanobiological factors in bone metastasis development.
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Neoplasias Óseas , Neoplasias de la Mama , Osteólisis , Neoplasias Óseas/secundario , Neoplasias Óseas/metabolismo , Neoplasias Óseas/patología , Osteólisis/patología , Osteólisis/metabolismo , Neoplasias de la Mama/patología , Neoplasias de la Mama/metabolismo , Humanos , Femenino , Línea Celular Tumoral , Animales , Modelos Biológicos , Ratones , Fenómenos Biomecánicos , Mecanotransducción CelularRESUMEN
Background: Respiratory syncytial virus (RSV) is the most common cause of viral lower respiratory tract infections (LRTIs) in young children around the world and an important cause of LRTI in the elderly. The available treatments and FDA-approved vaccines for RSV only lessen the severity of the infection and are recommended for infants and elderly people. Methods: We focused on developing a broad-spectrum vaccine that activates the immune system to directly combat RSV. The objective of this study is to identify CD4+ and CD8+ T-cell epitopes using an immunoinformatics approach to develop RSV vaccines. The efficacy of these peptides was validated through in-vitro and in-vivo studies involving healthy and diseased animal models. Results: For each major histocompatibility complex (MHC) class-I and II, we found three epitopes of RSV proteins including F, G, and SH with an antigenic score of >0.5 and a projected SVM score of <5. Experimental validation of these peptides on female BALB/c mice was conducted before and after infection with the RSV A2 line 19f. We found that the 3RVMHCI (CD8+) epitope of the F protein showed significant results of white blood cells (19.72 × 103 cells/µl), neutrophils (6.01 × 103 cells/µl), lymphocytes (12.98 × 103 cells/µl), IgG antibodies (36.9 µg/ml), IFN-γ (86.96 ng/L), and granzyme B (691.35 pg/ml) compared to control at the second booster dose of 10 µg. Similarly, 4RVMHCII (CD4+) of the F protein substantially induced white blood cells (27.08 × 103 cells/µl), neutrophils (6.58 × 103 cells/µl), lymphocytes (16.64 × 103 cells/µl), IgG antibodies (46.13 µg/ml), IFN-γ (96.45 ng/L), and granzyme B (675.09 pg/ml). In-vitro studies showed that 4RVMHCII produced a significant level of antibodies in sera on day 45 comparable to mice infected with the virus. 4RVMHCII also induced high IFN-γ and IL-2 secretions on the fourth day of the challenge compared to the preinfectional stage. Conclusion: In conclusion, epitopes of the F protein showed considerable immune response and are suitable for further validation.
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Epítopos de Linfocito T , Infecciones por Virus Sincitial Respiratorio , Virus Sincitial Respiratorio Humano , Anciano , Animales , Niño , Preescolar , Femenino , Humanos , Lactante , Ratones , Anticuerpos Antivirales , Linfocitos T CD4-Positivos , Linfocitos T CD8-positivos , Epítopos de Linfocito T/metabolismo , Granzimas , Inmunoglobulina G , Péptidos , Infecciones por Virus Sincitial Respiratorio/inmunología , Virus Sincitial Respiratorio Humano/metabolismoRESUMEN
Culinary herbs and spices are primarily known as flavor enhancers, research suggests that black pepper (Piper nigrum) and turmeric (Curcuma longa) have now been proven to prevent many non-communicable chronic diseases such as diabetes. Bioactive components of black pepper and turmeric ameliorate glucose metabolism and appetite regulation. The present research was designed to investigate the impact of turmeric and black pepper on blood glycemia, gastrointestinal well-being, appetite, and palatability. In a randomized crossover study, four iso-caloric experimental meals each having 50 g of available carbohydrates were subjected to healthy human participants (N = 20). Turmeric and black pepper were incorporated in the breakfast meal, 1 g black pepper (BP), 1 g turmeric (TR), and combination of the (BP + TR) was added in the breakfast. Standard questionnaires were used to evaluate palatability, subjective appetite, and gastrointestinal well-being. Blood glycemia, subjective gastrointestinal well-being, and appetite were measured at 0, 30, 60, 120, and 180 min. Experimental meals BP and BP + TR resulted in lower blood glycemia (p < .05) significantly compared to control meal. A decrease in perceived eating ability and hunger, and an increase in satiety after BP + TR and BP meal was observed. No significant changes were observed after consuming test meals on gastrointestinal well-being. Compared to control and BP + TR meals, BP and TR meals had considerably lower palatability. Results showed that compared to the control intake of starchy meals supplemented with black pepper and turmeric reduced postprandial glycemia, hunger, and perceived eating ability without affecting gastrointestinal well-being.
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OBJECTIVE: To compare the cost-utility of initial management of high-grade T1 non-muscle invasive bladder cancer (HGT1 NMIBC) with intravesical BCG vs immediate radical cystectomy. High-risk NMIBC patients may climb a costly ladder of treatments, culminating in radical cystectomy for oncologic or symptomatic benefit in up to one-third. This high healthcare resource utilization presents a challenging dilemma in balancing sufficiently aggressive management with cost, toxicity, and quality-of-life. METHODS: Cost-utility of initially managing HGT1 with intravesical BCG and early radical cystectomy with ileal conduit urinary diversion was compared using decision-analytic Markov models. Five-year oncologic outcomes, adverse event rates, and published utility values were extracted from literature. Costs were calculated from a US Medicare perspective in 2021 US dollars. Sensitivity analysis identified drivers of cost and break-even points for recurrence and progression. RESULTS: Mean costs were $26,093 for intravesical BCG and $39,720 for immediate radical cystectomy, though cystectomy generated a gain of 2.2 quality-adjusted life years (QALYs) compared to intravesical BCG. Immediate cystectomy was a more cost-effective management strategy for HGT1 NMIBC with an incremental CE ratios (ICER) of $7120/QALY. The costs associated with cystectomy, TURBT, and BCG toxicity had the greatest impact on ICER. One-way sensitivity analysis demonstrated that intravesical BCG became a cost-effective management strategy if the 5-year recurrence rate of HG T1 was less than 56% or the 5-year progression rate to MIBC was less than 4%. CONCLUSION: At current prices, treatment of high-grade T1 NMIBC with early radical cystectomy is more cost-effective management strategy than initial treatment with intravesical BCG.
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Adyuvantes Inmunológicos , Vacuna BCG , Análisis Costo-Beneficio , Cistectomía , Neoplasias de la Vejiga Urinaria , Neoplasias de la Vejiga Urinaria/cirugía , Neoplasias de la Vejiga Urinaria/economía , Humanos , Cistectomía/economía , Cistectomía/métodos , Vacuna BCG/economía , Vacuna BCG/administración & dosificación , Vacuna BCG/uso terapéutico , Administración Intravesical , Adyuvantes Inmunológicos/economía , Adyuvantes Inmunológicos/administración & dosificación , Adyuvantes Inmunológicos/uso terapéutico , Clasificación del Tumor , Estadificación de Neoplasias , Cadenas de Markov , Años de Vida Ajustados por Calidad de Vida , Estados UnidosRESUMEN
INTRODUCTION: Physical activity (PA) promotion among school-aged youth is a global health priority. Recommendations for such promotion include implementing whole-of-school approaches that maximize resources across the school environment. This study examined schools' participation in an annual, government-led, and emirate-wide initiative in Dubai, called the Dubai Fitness Challenge, in which the goal is to accrue 30 minutes of PA every day for 30 days (as such, the initiative is colloquially referred to as "Dubai 30x30"). METHODS: A mixed-methods design was employed for this study. Three schools were recruited using convenience sampling. Participants were 18 physical education teachers, 20 classroom teachers, 2 principals and 45 students. Data sources included surveys, focus groups, and interviews. Data were analyzed using descriptive statistics, multinomial logistic regression, and open and axial coding to develop themes. RESULTS: School staff reported that most Dubai 30x30 activities were provided in physical education, at break times during school, and before and after school. Students reported that they mainly participated in Dubai 30x30 activities during physical education and occasionally participated in activities after school and on weekends. During school, students were more likely to reach higher PA intensity levels when they were in contexts other than the regular classroom setting. Among school staff, physical education teachers were most involved and classroom teachers were least involved in promoting Dubai 30x30. Parent engagement was high. Staff perceived that Dubai 30x30 brought the community together, but physical education teachers also indicated there was a lack of implementation guidance and they felt burdened. Participants believed Dubai 30x30 increased PA participation and helped to promote their schools. DISCUSSION: This study provides an initial glimpse into schools' participation in Dubai 30x30 and suggests that a whole-of-school PA lens is useful in gleaning information that could help to increase and optimize PA opportunities for students.
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Ejercicio Físico , Instituciones Académicas , Adolescente , Humanos , Niño , Estudiantes , Motivación , Grupos de Población , Servicios de Salud Escolar , Promoción de la Salud/métodosRESUMEN
Epigenetic regulation plays a crucial role in the pathogenesis of autoimmune diseases such as inflammatory arthritis. DNA hypomethylating agents, such as decitabine (DAC), have been shown to dampen inflammation and restore immune homeostasis. In the present study, we demonstrate that DAC elicits potent anti-inflammatory effects and attenuates disease symptoms in several animal models of arthritis. Transcriptomic and epigenomic profiling show that DAC-mediated hypomethylation regulates a wide range of cell types in arthritis, altering the differentiation trajectories of anti-inflammatory macrophage populations, regulatory T cells, and tissue-protective synovial fibroblasts (SFs). Mechanistically, DAC-mediated demethylation of intragenic 5'-Cytosine phosphate Guanine-3' (CpG) islands of the transcription factor Irf8 (interferon regulatory factor 8) induced its re-expression and promoted its repressor activity. As a result, DAC restored joint homeostasis by resetting the transcriptomic signature of negative regulators of inflammation in synovial macrophages (MerTK, Trem2, and Cx3cr1), TREGs (Foxp3), and SFs (Pdpn and Fapα). In conclusion, we found that Irf8 is necessary for the inhibitory effect of DAC in murine arthritis and that direct expression of Irf8 is sufficient to significantly mitigate arthritis.
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Artritis , Azacitidina , Ratones , Animales , Decitabina/farmacología , Azacitidina/farmacología , Epigénesis Genética , Metilación de ADN , Factores Reguladores del Interferón/metabolismo , Inflamación/genética , Artritis/genética , Antiinflamatorios , Glicoproteínas de Membrana/metabolismo , Receptores Inmunológicos/genéticaRESUMEN
This review aims to assess the prevalence of malaria in pregnancy during antenatal visits and delivery, species-specific burden together with regional variation in the burden of disease. It also aims to estimate the proportions of adverse pregnancy outcomes in malaria-positive women. Based on the PRISMA guidelines, a thorough and systematic search was conducted in July 2023 across two electronic databases (including PubMed and CENTRAL). Forest plots were constructed for each outcome of interest highlighting the effect measure, confidence interval, sample size, and its associated weightage. All the statistical meta-analysis were conducted using R-Studio version 2022.07. Sensitivity analyses, publication bias assessment, and meta-regression analyses were also performed to ensure robustness of the review. According to the pooled estimates of 253 studies, the overall prevalence of malaria was 18.95% (95% CI: 16.95-21.11), during antenatal visits was 20.09% (95% CI: 17.43-23.06), and at delivery was 17.32% (95% CI: 14.47-20.61). The highest proportion of malarial infection was observed in Africa approximating 21.50% (95% CI: 18.52-24.81) during ANC and 20.41% (95% CI: 17.04-24.24) at the time of delivery. Our analysis also revealed that the odds of having anaemia were 2.40 times (95% CI: 1.87-3.06), having low birthweight were 1.99 times (95% CI: 1.60-2.48), having preterm birth were 1.65 times (95% CI: 1.29-2.10), and having stillbirths were 1.40 times (95% CI: 1.15-1.71) in pregnant women with malaria.
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Malaria , Complicaciones Parasitarias del Embarazo , Humanos , Embarazo , Femenino , Prevalencia , Malaria/epidemiología , Complicaciones Parasitarias del Embarazo/epidemiología , Resultado del Embarazo/epidemiologíaRESUMEN
BACKGROUND: Individuals with a Prior Cancer History (PCH) are often excluded from clinical trials. However, a growing body of evidence suggests that prior cancer history does not present adverse outcomes on cancer patients. The evidence on the survival of brain cancer patients in this regard remains widely unknown. METHODS: We conducted a retrospective cohort study to estimate the prevalence and impact of prior cancer on survival of patients diagnosed with brain cancer. Data of patients who were diagnosed with brain cancer as their first or second primary malignancy between 2000 and 2019 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Propensity Score Matching (PSM) was used to ensure comparable baseline characteristics among the patients. Survival analysis was conducted using the Kaplan-Meier method, as well as multivariate Cox proportional hazard and multivariate competing risk models. RESULTS: Out of 42 726 patients, 1189 (2.78%) had PCH. Genitourinary (40.4%), Breast (13.6%), Hematologic and Lymphatic (11.4%), and Gastrointestinal malignancies (11.3%) were the most common types of prior cancer. PCH served as a significant risk factor for Overall Survival (OS) (Adjusted Hazard Ratio [AHR] 1.26; 95% CI [1.15-1.39]; p < .001) but did not have a statistically significant impact on Brain Cancer-Specific Survival (BCSS) (AHR 0.97; 95% CI [0.88-1.07]; p = .54). Glioblastoma exhibited the most substantial and statistically significant impact on survival as compared to other histological types. Of all the organs systems, only prior Gastrointestinal and Hematologic and Lymphatic malignancies had a statistically significant impact on OS of patients. CONCLUSION: Our findings indicate that PCH does not exert a substantial impact on the survival of brain cancer patients, except in cases involving gastrointestinal or hematologic and lymphatic PCH, or when the brain cancer is glioblastoma.
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Neoplasias Encefálicas , Glioblastoma , Neoplasias Primarias Secundarias , Humanos , Estudios Retrospectivos , Puntaje de Propensión , Programa de VERF , Estimación de Kaplan-Meier , Neoplasias Encefálicas/epidemiología , Neoplasias Primarias Secundarias/epidemiología , Neoplasias Primarias Secundarias/patologíaRESUMEN
Recurrent Graves' disease due to regrowth of thyroid tissue is a rare complication of near-total thyroidectomy, which can be challenging to recognize and manage. Here, we present the case of a 30-year-old woman with Graves' disease and thyroid eye disease who underwent near-total thyroidectomy with resultant hypothyroidism. Her levothyroxine dose requirement gradually decreased and thyroglobulin level increased, which led to the diagnosis of recurrent Graves' disease. A neck ultrasound showed regrowth of thyroid tissue. The treatment options in such cases are repeat thyroid surgery and radioactive iodine ablation. The patient had moderate-severe active thyroid eye disease, so radioactive iodine ablation was contraindicated. Repeat surgery was deemed high risk due to the location of the residual thyroid tissue near the recurrent laryngeal nerve. Watchful waiting with serial thyrotropin (TSH) receptor antibody monitoring was chosen, and her levothyroxine dose was adjusted based on her thyroid function tests. There was a normalization of her TSH receptor antibody level over the next two and half years and stabilization of levothyroxine dose requirement. Recurrent Graves' disease must be considered when there is an ongoing decrease in the levothyroxine dose requirement associated with a rise in the serum thyroglobulin level following near-total thyroidectomy. Conservative management with medical therapy can induce remission in the case of recurrent Graves' disease following near-total thyroidectomy, without the need for radioactive iodine ablation or repeat thyroid surgery.
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INTRODUCTION: Currently 11 infectious agents are classified as carcinogenic but the role of infectious agents on outcomes of epithelial ovarian cancer is largely unknown. OBJECTIVE: To explore the association between infectious agents and ovarian cancer, we investigated the prevalence of viral DNA in primary ovarian cancer tumors and its association with clinical outcomes. METHODS: Archived tumors from 98 patients diagnosed with high-grade serous epithelial ovarian cancer were collected between 1/1/1994 and 12/31/2010. After DNA extraction, Luminex technology was utilized to identify polymerase chain reaction-amplified viral DNA for 113 specific viruses. Demographic data and disease characteristics were summarized using descriptive statistics. We used logistic regression and Cox proportional hazards model to assess associations between tumor viral status and disease outcome and between tumor viral presence and overall survival (OS), respectively. RESULTS: Forty-six cases (45.9%) contained at least one virus. Six highly prevalent viruses were associated with clinical outcomes and considered viruses of interest (VOI; Epstein-Barr virus 1, Merkel cell polyomavirus, human herpes virus 6b, and human papillomaviruses 4, 16, and 23). Factors independently associated with OS were presence of VOI (HR 4.11, P = 0.0001) and platinum sensitivity (HR 0.21, P<0.0001). Median OS was significantly decreased when tumors showed VOI versus not having these viruses (22 vs 44 months, P<0.0001). Women <70 year old with VOI in tumors had significantly lower median OS versus age-matched women without VOI (20 vs 57 months, P = 0.0006); however, among women ≥70 years old, there was no difference in OS by tumor virus status. CONCLUSIONS: The presence of a VOI was significantly associated with a lower OS. These findings may have implications for clinical management of ovarian cancer but require additional studies.
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Cistadenocarcinoma Seroso , Infecciones por Virus de Epstein-Barr , Neoplasias Ováricas , Humanos , Femenino , Lactante , Anciano , Carcinoma Epitelial de Ovario/epidemiología , Carcinoma Epitelial de Ovario/genética , ADN Viral/genética , Prevalencia , Herpesvirus Humano 4/genética , Neoplasias Ováricas/epidemiología , Neoplasias Ováricas/genética , Cistadenocarcinoma Seroso/patologíaRESUMEN
Intellectual disability (ID) involves compromised intellectual, learning and cognitive skills, and behavioral capabilities with reduced psychomotor skills. One of the preventable causes of ID is congenital hypothyroidism (CH), which may be due to biallelic mutations in thyroid peroxidase (TPO). In low- and middle-income countries with no newborn screening programs, CH poses a great risk of ID and long-term morbidity. We report two large Pakistani families with a total of 16 patients afflicted with CH. Detailed clinical and behavioral assessments, SNP-based homozygosity mapping, linkage analysis, and exome sequencing were performed. Initially, affected individuals were referred as suffering ID (in 11 of 16 patients) and developmental delay (in 14). Secondary/associated features were verbal apraxia (in 13), goiter (in 12), short stature (in 11), limb hypotonia (in 14), no pubertal onset (five of 10 of age ≥14 years), high myopia (in eight), muscle cramps (in six), and in some, variable microcephaly and enuresis/encopresis, fits, chronic fatigue, and other behavioral symptoms, which are not characteristics of CH. Molecular genetic analyses led to the discovery of homozygous variants in TPO: novel missense variant c.719A>G (p.Asp240Gly) in family 1 and rare c.2315A>G (p.Tyr772Cys) in family 2. In low-resource countries where neonatal screening programs do not include a CH test, the burden of neurodevelopmental disorders is likely to be increased due to untreated CH. Secondly, in the background of the high prevalence of recessive disorders due to high parental consanguinity, the severe manifestation of TPO-deficiency mimics a wide range of neurological and other presentations posing a diagnostic dilemma.
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Hipotiroidismo Congénito , Discapacidad Intelectual , Adolescente , Niño , Humanos , Hipotiroidismo Congénito/complicaciones , Hipotiroidismo Congénito/diagnóstico , Hipotiroidismo Congénito/genética , Discapacidades del Desarrollo/diagnóstico , Discapacidades del Desarrollo/genética , Audición , Discapacidad Intelectual/diagnóstico , Discapacidad Intelectual/genética , Yoduro Peroxidasa/genética , Mutación/genéticaRESUMEN
A conformal tri-band antenna tailored for flexible devices and body-centric wireless communications operating at the key frequency bands is proposed. The antenna is printed on a thin Rogers RT 5880 substrate, merely 0.254 mm thick, with an overall geometrical dimension of 15 × 20 × 0.254 mm3. This inventive design features a truncated corner monopole accompanied by branched stubs fed by a coplanar waveguide. The stubs, varying in length, serve as quarter-wavelength monopoles, facilitating multi-band functionality at 2.45, 3.5, and 5.8 GHz. Given the antenna's intended applications in flexible devices and body-centric networks, the conformability of the proposed design is investigated. Furthermore, an in-depth analysis of the Specific Absorption Rate (SAR) is conducted using a four-layered human tissue model. Notably, the SAR values for the proposed geometry at 2.45, 3.5, and 5.8 GHz stand at 1.48, 1.26, and 1.1 W/kg for 1 g of tissue, and 1.52, 1.41, and 0.62 W/kg for 10 g of tissue, respectively. Remarkably, these values comfortably adhere to both FCC and European Union standards, as they remain substantially beneath the threshold values of 1.6 W/kg and 2 W/kg for 1 g and 10 g tissues, respectively. The radiation characteristics and performance of the antenna in flat and different bending configurations validate the suitability of the antenna for flexible devices and body-centric wireless communications.
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BACKGROUND AND OBJECTIVES: Primary cutaneous leiomyosarcoma (cLMS), a rare, typically intradermal tumor, has previously been reported to exhibit an indolent course of disease with zero-to-low risk of local recurrence or distant metastasis. This study seeks to evaluate recurrence and survival of cLMS patients through study of its clinicopathologic and treatment characteristics. METHODS: All patients included underwent resection of primary cLMS at this institution between 2006 and 2019. A retrospective cohort study analysis of clinicopathologic characteristics, treatment, recurrence, and overall survival was performed. Data was assessed through descriptive statistics and outcome measures assessed by Cox proportional models and log-rank tests. RESULTS: Eighty-eight patients with cLMS were evaluated. The majority were men (n = 68, 77%) and Caucasian (n = 85, 97%), with median age at diagnosis of 66 years (range 20-96). 65% of tumors were located on the extremities, with a median size of 1.3 cm (range .3-15). Assessment revealed low (n = 41, 47%), intermediate (n = 29, 33%), and high (n = 18, 20%) grade tumors, demonstrating extension into subcutaneous tissue in 38/60 (60%), with 3 patients exhibiting extension into muscle (3%). All underwent resection as primary treatment with median 1 cm margins (range .5-2). With median follow-up of 27.5 months (IQR 8-51; range 1-131), no low-grade cases had recurrence or death while there was a recurrence rate of 19.1% (9/47) and death rate of 8.5% (4/47) in intermediate- to high-grade cases. CONCLUSIONS: Primary tumor resection of cLMS provides excellent local control for low-grade tumors as no low-grade cases experienced recurrence. For patients with intermediate- to high-grade tumors, there is potential for local recurrence, distant metastasis, and death, and therefore surveillance following treatment is encouraged.
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Leiomiosarcoma , Neoplasias Cutáneas , Masculino , Humanos , Femenino , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Leiomiosarcoma/cirugía , Leiomiosarcoma/patología , Estudios Retrospectivos , Neoplasias Cutáneas/cirugía , Neoplasias Cutáneas/patología , Modelos de Riesgos Proporcionales , Recurrencia Local de Neoplasia/epidemiología , Recurrencia Local de Neoplasia/patología , PronósticoRESUMEN
Objective: Specialty choices in health profession has long been influenced by gender. The field of General Surgery remains the least preferred specialty by females, especially in Pakistan. The objective of this study was to identify the factors leading to success and retention of females in General Surgery in Pakistan. Methods: Qualitative case study was conducted from February to May 2020 at Khyber Medical University, Peshawar. Ten semi-structured interviews were conducted with purposive sample of female surgeons at various academic position in different tertiary care hospitals of Pakistan. Data were thematically analyzed. Results: Participants were driven by their passion for surgery, which led them to choose this specialty in the beginning. Their survival in male dominant workplace was made possible by their own personality traits and conducive environment provided by the supervisors and peers. However, a structured mentorship program for females was found lacking. Conclusion: The necessary ingredients for success are passion and personality traits in any field but attention to nurturing and supportive environment for females in the General Surgery is paramount in determining success. Due consideration to the factors identified in the current study will enhance the retention and success of females in General Surgery.