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The latter two amino acids preferentially interact with both the backbone amide and the side-chain hydroxyl (bidentate interaction) to promote binding by short sequences. We conclude that the first αβα sandwich domains emerged from shorter and simpler polypeptides that bound phospho-ligands via N-helix sites.Proteins' interactions with ancient ligands may reveal how molecular recognition emerged and evolved. We explore how proteins recognize adenine a planar rigid fragment found in the most common and ancient ligands. We have developed a computational pipeline that extracts protein-adenine complexes from the Protein Data Bank, structurally superimposes their adenine fragments, and detects the hydrogen bonds mediating the interaction. Our analysis extends the known motifs of protein-adenine interactions in the Watson-Crick edge of adenine and shows that all of adenine's edges may contribute to molecular recognition. We further show that, on the proteins' side, binding is often mediated by specific amino acid segments ("themes") that recur across different proteins, such that different proteins use the same themes when binding the same adenine-containing ligands. We identify numerous proteins that feature these themes and are thus likely to bind adenine-containing ligands. Our analysis suggests that adenine binding has emerged multiple times in evolution. Copyright © 2020 the Author(s). Published by PNAS.This is the case of a previously healthy 15-month-old girl who initially presented to her primary pediatrician with a 2-week history of intermittent periorbital edema. The edema had improved by the time of the visit, and a urine specimen was unable to be obtained in the clinic. A routine fingerstick demonstrated anemia to 8.8 mg/dL, so the patient was started on ferrous sulfate. She then returned to the emergency department 1 month later with severe periorbital edema and pallor but no other significant symptoms. On physical examination, she was tachycardic with striking periorbital edema and an otherwise normal physical examination. She was noted to have a severe microcytic anemia (hemoglobin of 3.9 mg/dL and mean corpuscular volume of 53.1 fL) and hypoalbuminemia (albumin of 1.9 g/dL and total protein of 3.3 g/dL). The remainder of her electrolytes and liver function test results were within normal limits. A urinalysis was sent, which was negative for protein. Our panel of experts reviews her case to determine a unifying diagnosis for both her severe anemia and her hypoalbuminemia. Copyright © 2020 by the American Academy of Pediatrics.BACKGROUND AND OBJECTIVES National guidelines recommend against routine use of chest radiography (CXR) for community-acquired pneumonia (CAP) diagnosis in the pediatric emergency department (ED). Given that CXR is often used to exclude the diagnosis of CAP, a reduction in CXR use may result in overdiagnosis of CAP. We sought to evaluate trends in CXR use and assess the association between CXR performance and CAP diagnosis among children discharged from pediatric EDs. METHODS Children 3 months to 18 years of age discharged from 30 US EDs with (1) CAP or (2) fever or respiratory illness between 2008 and 2018 were included. Temporal trends in CXR use and rates of CAP diagnoses among patients with fever or respiratory illness were assessed. Correlation between hospital-level CXR use and CAP diagnosis rates were evaluated by using Spearman's correlation weighted by hospital volume. RESULTS CXR usage decreased from 86.6% to 80.4% (P less then .001) for patients with CAP and from 30.4% to 18.6% (P less then .001) for children with fever or respiratory illness over the 10-year study period. CAP diagnosis rates also declined from 7.8% to 5.9% (P less then .001). Hospital-level CXR use was correlated with pneumonia diagnosis rates (correlation coefficient 0.58; P less then .001). CONCLUSIONS Over the past decade, there has been a decline in CXR use in the ED among children with pneumonia and respiratory illnesses, with a decrease in pneumonia diagnoses over the same time period. Future studies are needed to assess the role of CXR in the evaluation of children with possible pneumonia in the ED setting. Copyright © 2020 by the American Academy of Pediatrics.OBJECTIVES To explore the association of sickness absence ascribed to pain at specific anatomical sites with wider propensity to musculoskeletal pain. METHODS As part of the CUPID (Cultural and Psychosocial Influences on Disability) study, potential risk factors for sickness absence from musculoskeletal pain were determined for 11 922 participants from 45 occupational groups in 18 countries. After approximately 14 months, 9119 (78%) provided follow-up information about sickness in the past month because of musculoskeletal pain, including 8610 who were still in the same job. Associations with absence for pain at specific anatomical sites were assessed by logistic regression and summarised by ORs with 95% CIs. RESULTS 861 participants (10%) reported absence from work because of musculoskeletal pain during the month before follow-up. After allowance for potential confounders, risk of absence ascribed entirely to low back pain (n=235) increased with the number of anatomical sites other than low back that had been reported as painful in the year before baseline (ORs 1.6 to 1.7 for ≥4 vs 0 painful sites). Similarly, associations with wider propensity to pain were observed for absence attributed entirely to pain in the neck (ORs up to 2.0) and shoulders (ORs up to 3.4). CONCLUSIONS Sickness absence for pain at specific anatomical sites is importantly associated with wider propensity to pain, the determinants of which extend beyond established risk factors such as somatising tendency and low mood. Better understanding of why some individuals are generally more prone to musculoskeletal pain might point to useful opportunities for prevention. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.OBJECTIVE The objective of the study was to examine the effects of occupational exposure to diisononyl phthalate (DINP) on serum testosterone levels in male workers. METHODS From 2015 to 2018, 97 male workers were recruited from six French factories in the plastics industry. In a short longitudinal study, changes over 3 days in the level of total or free serum testosterone and DINP exposure were measured. DINP exposure was measured by urinary biomonitoring mono-4-methyl-7-oxo-octyl phthalate (OXO-MINP), mono-4-methyl-7-hydroxy-octyl phthalate (OH-MINP) and mono-4-methyl-7-carboxyheptylphthalate (CX-MINP). We further analysed changes in follicle-stimulating hormone, luteinising hormone, total testosterone to oestradiol ratio and two bone turnover markers (procollagen-type-I-N propeptide, C terminal cross-linking telopeptide of type I collagen), and erectile dysfunction via standardised questionnaires (International Index of Erectile Function, Androgen Deficiency in Aging Males). Linear mixed models were used with the variables 'age' and 'abdominal diameter' included as confounder. RESULTS Increased urinary OXO-MINP was associated with a significant decrease in total serum testosterone concentrations, but only for workers who exhibited the smallest variations and lowest exposures (p=0.002). The same pattern was observed for CX-MINP but was not significant; no association with OH-MINP was detectable. selleck inhibitor More self-reported erectile problems were found in workers exposed directly to DINP at the workstation (p=0.01). No changes were observed for the other biological parameters. CONCLUSIONS Short-term exposure to DINP is associated with a decrease in total serum testosterone levels in male workers. Our results suggest that DINP could present weak antiandrogenic properties in humans, but these need to be confirmed by other studies. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.OBJECTIVES To establish normative reference values for work ability in healthy Australian adults using the Work Ability Score and investigate the association of physical performance factors. METHODS The Work Ability Score was collected from 720 participants aged 18-101 years from the 1000 Norms Project. Physical performance was evaluated by assessing isometric strength of 13 muscle groups; flexibility of six joints; and 11 functional measures categorised as gross motor, fine motor and balance tasks. Correlations and multiple regression analyses were performed to identify physical performance factors independently associated with work ability. RESULTS Age-stratified reference values were generated for work ability. Work ability increased during young adulthood (18-44 years) and declined from middle adulthood (45-64 years) into older adulthood (≥65 years), with no sex differences. Greater gross motor function and balance correlated with work ability (r=-0.498 to -0.285; p less then 0.001). Multiple regression identified younger age, being employed and a faster timed up and down stairs test as significant independent factors associated with work ability (r2=0.333, p less then 0.001). CONCLUSIONS Reference data can be used to identify individuals with low work ability. This study has identified physical factors associated with work ability that can potentially be targeted to maintain longevity in work. Physical tests such as the timed up and down stairs test may assist in the development of objective job-specific screening tools to assess work ability, supplementing subjective evaluation. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.OBJECTIVE With the expansion of the use of minimally invasive surgical techniques within the field of gynecological oncology, a robot assisted procedure seems to be an attractive technique for para-aortic lymph node sampling. The aim of this study was to compare robotic versus conventional laparoscopic para-aortic lymphadenectomy in patients with locally advanced cervical cancer. METHODS In this monocentric retrospective study, we included patients with locally-advanced cervical cancer (International Federation of Gynecology and Obstetrics (FIGO) 2009 stage IB2-IVA or IB1 with suspicious pelvic lymph nodes), who underwent a para-aortic lymphadenectomy up to the inferior mesenteric artery between December 1994 and December 2016 (robotic technique starting from December 2012). link2 RESULTS A total of 217 patients were included in the study (robotic, n=55 vs laparoscopic, n=162). When comparing conventional laparoscopic versus robotic para-aortic lymphadenectomy, the median age was 48 versus 49 years and the median bh groups 66%) (p=0.472). Also, 2 year overall survival was similar between the groups (77% vs 81% for robotic vs conventional laparoscopy group, respectively) (p=0.749). CONCLUSION Robotic para-aortic lymphadenectomy in patients with locally-advanced cervical cancer resulted in better perioperative outcomes and similar survival outcomes when compared with a conventional laparoscopic approach. © IGCS and ESGO 2020. No commercial re-use. See rights and permissions. Published by BMJ.OBJECTIVE To evaluate the combination of positron emission tomography/computed tomography (PET/CT) and sentinel lymph node (SLN) biopsy in women with apparent early-stage endometrial carcinoma. link3 The correlation between radiomics features extracted from PET images of the primary tumor and the presence of nodal metastases was also analyzed. METHODS From November 2006 to March 2019, 167 patients with endometrial cancer were included. All women underwent PET/CT and surgical staging 60/167 underwent systematic lymphadenectomy (Group 1) while, more recently, 107/167 underwent SLN biopsy (Group 2) with technetium-99m +blue dye or indocyanine green. Histology was used as standard reference. PET endometrial lesions were segmented (n=98); 167 radiomics features were computed inside tumor contours using standard Image Biomarker Standardization Initiative (IBSI) methods. Radiomics features associated with lymph node metastases were identified (Mann-Whitney test) in the training group (A); receiver operating characteristic (ROC) curves, area under the curve (AUC) values were computed and optimal cut-off (Youden index) were assessed in the test group (B).
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