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551.
Alison G. Paquette James MacDonald Samantha Lapehn Theo Bammler Laken Kruger Drew B. Day Nathan D. Price Christine Loftus Kurunthachalam Kannan Carmen Marsit W. Alex Mason Nicole R. Bush Kaja Z. LeWinn Daniel A. Enquobahrie Bhagwat Prasad Catherine J. Karr Sheela Sathyanarayana 《Environmental health perspectives》2021,129(9)
552.
Tartaglia N Davis S Hench A Nimishakavi S Beauregard R Reynolds A Fenton L Albrecht L Ross J Visootsak J Hansen R Hagerman R 《American journal of medical genetics. Part A》2008,(12):1509-1522
XXYY syndrome occurs in approximately 1:18,000-1:40,000 males. Although the physical phenotype is similar to 47,XXY (tall stature, hypergonadotropic hypogonadism, and infertility), XXYY is associated with additional medical problems and more significant neurodevelopmental and psychological features. We report on the results of a cross-sectional, multi-center study of 95 males age 1-55 with XXYY syndrome (mean age 14.9 years), describing diagnosis, physical features, medical problems, medications, and psychological features stratified by age groups. The mean age of diagnosis was 7.7 years. Developmental delays and behavioral problems were the most common primary indication for genetic testing (68.4%). Physical and facial features varied with age, although hypertelorism, clinodactyly, pes planus, and dental problems were common across all age groups. Tall stature was present in adolescents and adults, with a mean adult stature of 192.4 cm (SD 7.5; n = 22). Common medical problems included allergies and asthma (>50%), congenital heart defects (19.4%), radioulnar synostosis (17.2%), inguinal hernia and/or cryptorchidism (16.1%), and seizures (15%). Medical features in adulthood included hypogonadism (100%), DVT (18.2%), intention tremor (71%) and type II diabetes (18.2%). Brain MRI (n = 35) showed white matter abnormalities in 45.7% of patients and enlarged ventricles in 22.8%. Neurodevelopmental and psychological difficulties were a significant component of the behavioral phenotype, with developmental delays and learning disabilities universal but variable in severity. Twenty-six percent had full-scale IQs in the range of intellectual disability (MR), and adaptive functioning was significantly impacted with 68% with adaptive composite scores <70. Rates of neurodevelopmental disorders, including ADHD (72.2%), autism spectrum disorders (28.3%), mood disorders (46.8%), and tic disorders (18.9%), were elevated with 55.9% on psychopharmacologic medication overall. Recommendations for evaluation and treatment are summarized. 相似文献
553.
Rob S. Sellar Adam S. Sperling Mikoaj Sabicki Jessica A. Gasser Marie E. McConkey Katherine A. Donovan Nada Mageed Dylan N. Adams Charles Zou Peter G. Miller Ravi K. Dutta Steffen Boettcher Amy E. Lin Brittany Sandoval Vanessa A. Quevedo Barrios Veronica Kovalcik Jonas Koeppel Elizabeth K. Henderson Emma C. Fink Lu Yang Anthony Chan Sheela Pangeni Pokharel Erik J. Bergstrom Rajan Burt Namrata D. Udeshi Steven A. Carr Eric S. Fischer Chun-Wei Chen Benjamin L. Ebert 《The Journal of clinical investigation》2022,132(16)
Targeted protein degradation is a rapidly advancing and expanding therapeutic approach. Drugs that degrade GSPT1 via the CRL4CRBN ubiquitin ligase are a new class of cancer therapy in active clinical development with evidence of activity against acute myeloid leukemia in early-phase trials. However, other than activation of the integrated stress response, the downstream effects of GSPT1 degradation leading to cell death are largely undefined, and no murine models are available to study these agents. We identified the domains of GSPT1 essential for cell survival and show that GSPT1 degradation leads to impaired translation termination, activation of the integrated stress response pathway, and TP53-independent cell death. CRISPR/Cas9 screens implicated decreased translation initiation as protective following GSPT1 degradation, suggesting that cells with higher levels of translation are more susceptible to the effects of GSPT1 degradation. We defined 2 Crbn amino acids that prevent Gspt1 degradation in mice, generated a knockin mouse with alteration of these residues, and demonstrated the efficacy of GSPT1-degrading drugs in vivo with relative sparing of numbers and function of long-term hematopoietic stem cells. Our results provide a mechanistic basis for the use of GSPT1 degraders for the treatment of cancer, including TP53-mutant acute myeloid leukemia. 相似文献
554.
David K Lau Maria Aresu Timothy Planche Amina Tran Retchel Lazaro-Alcausi Julie Duncan Shannon Kidd Susan Cromarty Ruwaida Begum Isma Rana Su Li Ali Abdulnabi Suwaidan Irene Monahan David J Clark Nicholas Eckersley Henry M Staines Elisabetta Groppelli Sanjeev Krishna Martin Mayora-Neto Nigel Temperton Charlotte Fribbens David Watkins Naureen Starling Ian Chau David Cunningham Sheela Rao 《The oncologist》2023,28(1):e1
IntroductionPatients with gastrointestinal (GI) cancers have an increased risk of serious complications and death from SARS-CoV-2 infection. The immunogenicity of vaccines in patients with GI cancers receiving anti-cancer therapies is unclear. We conducted a prospective study to evaluate the prevalence of neutralizing antibodies in a cohort of GI cancer patients receiving chemotherapy following SARS-CoV-2 vaccination.Materials and MethodsBetween September 2020 and April 2021, patients with cancer undergoing chemotherapy were enrolled. At baseline (day 0), days 28, 56, and 84, we assessed serum antibodies to SARS-CoV-2 spike (anti-S) and anti-nucleocapsid (anti-NP) and concomitantly assessed virus neutralization using a pseudovirus neutralization assay. Patients received either the Pfizer/BioNTech BNT162b2, or the Oxford/AstraZeneca ChAdOx1 vaccine.ResultsAll 152 patients enrolled had a prior diagnosis of cancer; colorectal (n = 80, 52.6%), oesophagogastric (n = 38, 25.0%), and hepato pancreatic biliary (n = 22, 12.5%). Nearly all were receiving systemic anti-cancer therapy (99.3%). Of the 51 patients who did not receive a vaccination prior to, or during the study, 5 patients had detectable anti-NP antibodies. Ninety-nine patients received at least one dose of vaccine prior to, or during the study. Within 19 days following the first dose of vaccine, 30.0% had anti-S detected in serum which increased to 70.2% at days 20-39. In the 19 days following a second dose, anti-S positivity was 84.2% (32/38). However, pseudovirus neutralization titers (pVNT80) decreased from days 20 to 39.ConclusionDespite the immunosuppressive effects of chemotherapy, 2 doses of SARS-CoV-2 vaccines are able to elicit a protective immune response in patients’ ongoing treatment for gastrointestinal cancers. Decreases in pseudoviral neutralization were observed after 20-39 days, re-affirming the current recommendation for vaccine booster doses.Clinical Trial Registration Number. NCT04427280相似文献
555.
BackgroundEarly diagnosis and treatment of tuberculosis is of vital importance both to cure patients and to reduce transmission for effective control of tuberculosis, It is important to know whether tuberculosis is diagnosed in time and also what causes delay if any.ObjectivesThe study was conducted with the objective of knowing the time taken to diagnose tuberculosis from the onset of symptoms and to identify the causes for delay if any.MethodsA study was conducted in the District of Malapppuram Kerala, South India among newly diagnosed smear positive tuberculosis patients. 489 patients were interviewed soon after diagnosis and their socio-demographic characteristics and details from onset of symptoms to diagnosis were collected using a structured format.ResultsThe mean time taken by the patient for consultation after onset was 36 days and the mean time for diagnosis was 42 days and total time until diagnosis was 78 days. 72.8% patients consult within 6 weeks of onset and 74.7% are diagnosed within 6 weeks of consultation. The delay for diagnosis was more with private institutions. Diagnosis took less time when government facilities are consulted and when cough was a prominent symptom. Socio demographic factors are seen not affecting the time.ConclusionsThere is delay in diagnosing tuberculosis especially with private health providers and more efforts are required to reduce the same. 相似文献
556.
557.
558.
559.
Jacquelyn Manfredo George Capone Lisa Yanek Robert McCarter Babette Zemel Andrea Kelly Sheela N. Magge 《American journal of medical genetics. Part A》2023,191(7):1758-1768
Studies regarding cardiometabolic risk (CMR) for individuals with Down syndrome (DS) conflict. Our previous research in youth with DS, aged 10–20 years, found increased prevalence of dyslipidemia and prediabetes compared to matched peers without DS. Herein, we compare CMR in young adults with DS, aged 18–35 years, to a similar population-based sample from the 2001–2018 National Health and Nutrition Examination Survey (NHANES). The group with DS had higher NonHDL-C (mean DS 131.9 mg/dL; NHANES 126.1 p < 0.001), lower HDL-C (DS 47.5 mg/dL; NHANES 52.2 p < 0.001), higher LDL-C (DS 109.3 mg/dL; NHANES 105.4 p < 0.001), higher triglycerides (DS 102.9 mg/dL; NHANES 86.9 p < 0.001), but lower fasting glucose (DS 85.8 mg/dL; NHANES 95.2 p < 0.0001), lower HOMA-IR (DS 2.17; NHANES 2.24 p = 0.0006), lower systolic (DS 109.7 mmHg; NHANES 114.6 p < 0.0001) and lower diastolic (DS 60.9 mmHg; NHANES 67.8 p < 0.0001) blood pressures. There was relationship of higher HDL-C, triglycerides, glucose, systolic, and diastolic blood pressure with increasing BMI in the NHANES cohort which was dampened in the group with DS. These results indicate that more information is needed to guide clinicians in screening for CMR in individuals with DS. 相似文献
560.
Kenneth G. Saag Sheela Kolluri Rachelle K. Koehnke Thomas A. Georgou John W. Rachow Gary W. Hunninghake David A. Schwartz 《Arthritis \u0026amp; Rheumatology》1996,39(10):1711-1719
Objective. To determine the prevalence and important clinical predictors of radiographic and physiologic abnormalities indicative of rheumatoid arthritis interstitial lung disease (RA-ILD). Methods. An unselected cohort of patients with a confirmed diagnosis of RA and known lung disease were identified (n = 336) and evaluated for RA disease activity and severity. Outcomes included abnormalities determined by the pulmonary function tests of forced vital capacity (FVC) and diffusion capacity for carbon monoxide (DLco), and/or chest radiographic findings of interstitial infiltrates. We used multivariable statistical modeling to determine the independent significance of cigarette smoking and other RA-specific factors on the pulmonary abnormalities of interest. Results. At least 1 of the 3 abnormal findings was identified by pulmonary tests in 32.4% of all patients. These abnormal findings included an FVC <80% of predicted in 42 patients, a DLco <80% of predicted in 64 patients, and evidence of radiographic interstitial infiltrates in 40 patients. After statistical adjustment for confounding factors, pack-years of cigarette smoking remained a significant predictor of low DLco (β = −0.07, 95% confidence interval [95% CI] −0.09, −0.04), low FVC (β = −0.003, 95% CI −0.006, −0.0004), and interstitial abnormalities on chest radiograph (odds ratio for ⩾25 pack-years = 3.76, 95% CI 1.59, 8.88). The Health Assessment Questionnaire (HAQ) Disability Index (DI) was also an important risk factor for the decline in both the DLco (β = −1.15, 95% CI −2.00, −0.30) and FVC (β = −0.23, 95% CI −0.32, −0.13). Conclusion. Although RA disease activity/severity (particularly as defined by the HAQ DI) was important, smoking was the most consistent independent predictor of radiographic and physiologic abnormalities suggestive of ILD in RA. 相似文献