Prostate cancer risk-associated variants have been reported in populations of European descent, African-Americans and Japanese using genome-wide association studies (GWAS). To systematically ...investigate prostate cancer risk-associated variants in Chinese men, we performed the first GWAS in Han Chinese. In addition to confirming several associations reported in other ancestry groups, this study identified two new risk-associated loci for prostate cancer on chromosomes 9q31.2 (rs817826, P = 5.45 × 10(-14)) and 19q13.4 (rs103294, P = 5.34 × 10(-16)) in 4,484 prostate cancer cases and 8,934 controls. The rs103294 marker at 19q13.4 is in strong linkage equilibrium with a 6.7-kb germline deletion that removes the first six of seven exons in LILRA3, a gene regulating inflammatory response, and was significantly associated with the mRNA expression of LILRA3 in T cells (P < 1 × 10(-4)). These findings may advance the understanding of genetic susceptibility to prostate cancer.
Low bone mineral density (BMD) is a risk factor for fracture. Although the current “gold standard” test is DXA of the hip and spine, this method is not universally available. No large studies have ...evaluated the ability of new, less expensive peripheral technologies to predict fracture. We studied the association between BMD measurements at peripheral sites and subsequent fracture risk at the hip, wrist/forearm, spine, and rib in 149,524 postmenopausal white women, without prior diagnosis of osteoporosis. At enrollment, each participant completed a risk assessment questionnaire and had BMD testing at the heel, forearm, or finger. Main outcomes were new fractures of the hip, wrist/forearm, spine, or rib within the first 12 months after testing. After 1 year, 2259 women reported 2340 new fractures. Based on manufacturers' normative data and multivariable adjusted analyses, women who had T scores ≤ −2.5 SD were 2.15 (finger) to 3.94 (heel ultrasound US) times more likely to fracture than women with normal BMD. All measurement sites/devices predicted fracture equally well, and risk prediction was similar whether calculated from the manufacturers' young normal values (T scores) or using SDs from the mean age of the National Osteoporosis Risk Assessment (NORA) population. The areas under receiver operating characteristic (ROC) curves for hip fracture were comparable with those published using measurements at hip sites. We conclude that low BMD found by peripheral technologies, regardless of the site measured, is associated with at least a twofold increased risk of fracture within 1 year, even at skeletal sites other than the one measured.
Background: Calreticulin (CRT), an endoplasmic reticulum protein, has been reported to be essential for the differentiation of neuroblastoma (NB) cells, suggesting that CRT may affect the tumor ...behavior of neuroblastoma. The aim of this study was to evaluate the association of clinicopathologic factors and patient survival with the expression of CRT in patients with NB. Patients and methods: Sixty-eight NBs were investigated by immunohistochemical staining against CRT, and were divided into positive and negative immunostaining groups. Correlations between calreticulin expression, various clinicopathologic and biologic factors, and patient survival were studied. In seven tumor samples, CRT mRNAs and proteins were evaluated with real-time PCR and western blot, respectively, and correlated with immunohistochemical findings. Results: Among 68 NBs, 32 (47.1%) showed positive CRT expression. Positive CRT immunostaining strongly correlated with differentiated histologies, as well as known favorable prognostic factors such as detected from mass screening, younger age (≤1 year) at diagnosis and early clinical stages, but inversely correlated with MYCN amplification. Kaplan–Meier analysis revealed that NB patients with CRT expression did have better survival. Multivariate analysis demonstrated CRT expression to be an independent prognostic factor. Moreover, CRT expression also predicted better survival in patients with advanced-stage NBs, and its absence predicted poorer survival in patients whose tumor had no MYCN amplification. The amount of CRT mRNAs and proteins in NB tumor samples tested correlated well with the immunohistochemical expressions. Conclusions: CRT expression correlates with the differentiation of NB and predicts favorable survival, thereby suggesting CRT to be a useful indicator for planning treatment of NB.
We aim to determine the utility of CT scan as a method to accurately confirm pediatric airway foreign bodies (AFBs), the current gold standard of which is chest X-ray as the primary imaging modality ...in the investigation screening of AFBs with progression to microlaryngobronchoscopy.
A retrospective cohort study of children diagnosed with suspected AFBs between July 2019 and June 2020 was conducted. The primary outcome of missed AFBs from radiologic investigations was recorded.
A total of 226 children with an average age of 1.94 years were included in this study. One hundred and two children were eventually admitted to the hospital for microlaryngobronchoscopy. A total of 89 cases were initially examined by chest X-ray with the diagnosis confirmed in 26 cases. The initial examination was chest CT scan in 105 cases, of which the diagnosis was confirmed in 46 cases. The initial examination was chest CT scan with airway reconstruction in 32 cases, and the diagnosis was confirmed in 17 cases. Patients with negative chest CT scan with airway reconstruction were observed to have resolution of symptoms with no further need for bronchoscopy.
Chest CT scan with airway reconstruction had the highest rate of confirmed diagnosis of pediatric AFBs on initial scanning, followed by chest CT scan, and finally chest X-ray with fluoroscopy; there was no missed diagnosis in chest CT scan with airway reconstruction. Chest CT scan with airway reconstruction can accurately and quickly detect AFBs and reduce unnecessary bronchoscopy.
The hydrothermal reaction of 1,3‐di(4‐pyridyl)propane with Cu(OH)2 in the presence of 1,4‐cyclohexanedicarboxylic acid and dilute HCl generates an unprecedented tetratopic ligand (chtpy) and a family ...of interesting coordination networks in situ (see scheme). The topological diversification of the CuI–chtpy nets can be controlled simply by changing the molar ratio of the starting materials.
Using the Center for International Blood and Marrow Transplant Research (CIBMTR) registry, we analyzed 1404 umbilical cord blood transplantation (UCBT) patients (single (<18 years)=810, double (⩾18 ...years)=594) with acute leukemia to define the incidence of acute GvHD (aGvHD) and chronic GvHD (cGvHD), analyze clinical risk factors and investigate outcomes. After single UCBT, 100-day incidence of grade II-IV aGvHD was 39% (95% confidence interval (CI), 36-43%), grade III-IV aGvHD was 18% (95% CI, 15-20%) and 1-year cGvHD was 27% (95% CI, 24-30%). After double UCBT, 100-day incidence of grade II-IV aGvHD was 45% (95% CI, 41-49%), grade III-IV aGvHD was 22% (95% CI, 19-26%) and 1-year cGvHD was 26% (95% CI, 22-29%). For single UCBT, multivariate analysis showed that absence of antithymocyte globulin (ATG) was associated with aGvHD, whereas prior aGvHD was associated with cGvHD. For double UCBT, absence of ATG and myeloablative conditioning were associated with aGvHD, whereas prior aGvHD predicted for cGvHD. Grade III-IV aGvHD led to worse survival, whereas cGvHD had no significant effect on disease-free or overall survival. GvHD is prevalent after UCBT with severe aGvHD leading to higher mortality. Future research in UCBT should prioritize prevention of GvHD.
Spermatozoa undergo a poorly understood activation process induced by bicarbonate and mediated by cyclic adenosine 3′,5′-monophosphate (cAMP). It has been assumed that bicarbonate mediates its ...effects through changes in intracellular pH or membrane potential; however, we demonstrate here that bicarbonate directly stimulates mammalian soluble adenylyl cyclase (sAC) activity in vivo and in vitro in a pH-independent manner. sAC is most similar to adenylyl cyclases from cyanobacteria, and bicarbonate regulation of cyclase activity is conserved in these early forms of life. sAC is also expressed in other bicarbonate-responsive tissues, which suggests that bicarbonate regulation of cAMP signaling plays a fundamental role in many biological systems.
Little is known about the metabolic outcomes of adolescent bariatric surgery. We report changes in weight, metabolic profile, and types of complications seen in a multicenter cohort.
One-year ...outcomes were included. For weight loss comparisons, a nonsurgical cohort (n = 12) was used. The primary outcome was weight change (n = 30) and secondary outcomes were metabolic variables (n = 24) and complications (n = 36). Data were analyzed using signed rank or paired
t tests.
Mean body mass index fell 37% (from 56.5 preoperatively to 35.8 kg/m
2;
P < .001) in surgical patients and 3% (from 47.2 to 46 kg/m
2;
P = NS) in nonsurgical patients. Surgical patients showed significant improvements in triglycerides (−65 mg/dL), total cholesterol (−28 mg/dL), fasting blood glucose (−12 mg/dL), and fasting insulin (−21
μM/mL). Improvement in high-density lipoprotein cholesterol (−3.9 mg/dL) and low-density lipoprotein cholesterol (−8.8 mg/dL) was not statistically significant. Sixty-one percent of surgical patients had no complications. Of 15 patients with complications, 9 had minor complications with no long-term sequelae, 4 had at least 1 moderate complication with sequelae for at least 1 month and 2 had at least 1 severe medical complication with long-term consequences (including beriberi and death). There were no perioperative deaths or other severe surgical complications in this series.
Postoperatively, adolescents lose significant weight and realize major metabolic improvements. The complication profile compares favorably to severely obese (body mass index >40 kg/m
2) adults; however, small sample size precludes calculation of complication rates. Although there are considerable risks of bariatric surgery, early experience suggests that risks are offset by health benefits.
Four copper complexes with hydroxylated bipyridyl‐like ligands, namely Cu2(ophen)2 (1), Cu4(ophen)4(tp) (2), Cu4(obpy)4(tp) (3), and Cu4(obpy)4(dpdc)⋅2H2O (4), (Hophen=2‐hydroxy‐1,10‐phenanthroline, ...Hobpy=6‐hydroxy‐2,2′‐bipyridine, tp=terephthalate, dpdc=diphenyl‐4,4′‐dicarboxylate) have been synthesized hydrothermally. X‐ray single‐crystal structural analyses of these complexes reveal that 1,10‐phenanthroline (phen) or 2,2′‐bipyridine (bpy) ligands are hydroxylated into ophen or obpy during the reaction, which provides structural evidence for the long‐time argued Gillard mechanism. The dinuclear copper(I) complex 1 has three supramolecular isomers in the solid state, in which short copper–copper distances (2.66–2.68 Å) indicate weak metal–metal bonding interactions. Each of the mixed‐valence copper(i,ii) complexes 2–4 consists of a pair of Cu2(ophen)2+ or Cu2(obpy)2+ fragments bridged by a dicarboxylate ligand into a neutral tetranuclear dumbbell structure. Dinuclear 1 is an intermediate in the formation of 2 and can be converted into 2 in the presence of additional copper(II) salt and tp ligands under hydrothermal conditions. In addition to the ophen‐centered π→π* excited‐state emission, 1 shows strong emissions at ambient temperature, which may be tentatively assigned as an admixture of copper‐centered d→s,p and MLCT excited states.
Structural evidence for the Gillard mechanism is provided by four polynuclear copper(I) and copper(i,ii) complexes with hydroxylated bipyridyl‐like ligands (see picture). During the hydrothermal synthesis of these copper complexes, 1,10‐phenanthroline or 2,2′‐bipyridine ligands are hydroxylated. The structures, physical properties, and the formation mechanism of these compounds are discussed.
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