Tributyltin (TBT) and triphenyltin (TPT) in different marine environmental compartments such as seawater, sediments, and inshore fishes were investigated in 21 Taiwanese harbors between 2001 and 2004 ...in order to determine the major factors influencing their distribution. The existence of major input sources and the limited water exchange rate inside the harbors were indicated by higher TBT concentrations in seawater from inner harbor than from outer harbor areas. The levels of TBT in sediments were found to be mainly affected by their geographic distribution, water exchange rates and shipping activity. No significant correlations in TBT concentrations between water, sediment and fish suggested TBT accumulation by fish might not result from water and sediment, but from their food. TPT were detected in most fish samples, but found in few sediment samples and none in seawater, indicating fish could be as a target element for monitoring contaminated levels of TPT in the aquatic environment. Mean concentrations of TBT in fish muscle higher than tolerable average residue levels (TARLs), and mean hazard indices of TBT and TPT higher than 1 suggested consumption of fishes from Taiwanese harbor areas might have potential high risk to human health.
Abstract Purpose Studies have shown that arecoline, the major alkaloid component of betel nuts, alters the activity of enzymes in the cytochrome P450 (CYP-450) family. Tacrolimus, an ...immunosuppressant that protects against organ rejection in transplant recipients, not only is mainly metabolized by CYP3A enzymes but also has a narrow therapeutic range. We aimed to investigate whether dose-adjusted blood trough levels of tacrolimus differed over time between betel nut-chewing and non–betel nut-chewing liver transplant recipients. Methods In this retrospective case-control study, 14 active betel nut-using liver recipients were matched at a 1:2 ratio to 28 non-betel nut-using liver recipients by sex, age, graft source, duration of follow-up after liver transplantation, and estimated glomerular filtration rate. Differences in liver function index, renal function index, and dose-adjusted blood trough levels of tacrolimus over an 18-month period were compared between the 2 groups by using the Generalized Estimating Equation approach. Results Dose-adjusted blood trough levels of tacrolimus tended to be significantly ( P = .04) lower in betel nut chewers (mean = 0.81, medium = 0.7, 95% confidence interval CI = 0.73 to 0.90) than in nonchewers (mean = 1.12, medium = 0.88, 95% CI = 1.03 to 1.22) during the 18-month study period. However, there was no significant difference in renal and liver function index between the 2 groups. Conclusion Liver transplant recipients receiving tacrolimus tend to have lower blood trough levels of the drug over time if they chew betel nuts.
Background. The study aimed to evaluate the risk of hepatitis C virus (HCV) infection on hepatic and extrahepatic deaths. Methods. A cohort of 23 820 adults aged 30—65 years old were enrolled during ...1991—1992. The seromarkers hepatitis B surface antigen (HBsAg), anti-HCV, and serum HCV RNA levels at study entry were tested. The vital status was ascertained through computerized linkage with national death certification profiles from 1991 to 2008. Results. There were 19 636 HBsAg-seronegatives, including 18 541 anti-HCV seronegatives and 1095 anti-HCV seropositives. Among anti-HCV seropositives, 69.4% had detectable serum HCV RNA levels. There were 2394 deaths that occurred during an average follow-up period of 16.2 years. Compared with anti-HCV seronegatives, anti-HCV seropositives had higher mortality from both hepatic and extrahepatic diseases, showing multivariate-adjusted hazard ratio (95% confidence interval) of 1.89 (1.66—2.15) for all causes of death; 12.48 (9.34—16.66) for hepatic diseases; 1.35 (1.15—1.57) for extrahepatic diseases; 1.50 (1.10—2.03) for circulatory diseases; 2.77 (1.49—5.15) for nephritis, nephrotic syndrome, and nephrosis; 4.08 (1.38—12.08) for esophageal cancer; 4.19 (1.18—14.94) for prostate cancer; and 8.22 (1.36—49.66) for thyroid cancer. Anti-HCV seropositives with detectable HCV RNA levels had significantly higher mortality from hepatic and extrahepatic diseases than anti-HCV seropositives with undetectable HCV RNA. Conclusions. Monitoring HCV RNA in anti-HCV seropositives is essential for the prediction of mortality associated with hepatitis C.
A promising Mg-Zn-Y alloy with the long-period stacking ordered (LPSO) second phase has been developed for about twenty years. Because the LPSO phase has the unique 18R crystal structure, ...particularly for its packing sequence along 0001, as well as it plays an important role in strengthening mechanisms, it is interesting to clarify in terms of mechanical properties and deformation mechanisms. In this study, uniaxial micro-pillar compression tests are conducted on LPSO along the 0001 direction. At the same time, nanoindentation system equipped with the Berkovich tip is used to extract the basic mechanical properties of (0001) plane. The basal dislocations are found to be activated first, causing the bending of the sample. The bending would lead to the shear stress field downward and thus would cause the nucleation and movement of prism dislocations with 0001 Burgers vector. Prism dislocations can form the fatal 45° slip trace inside the micro-pillar and finally go through the whole sample causing fracture. The basal dislocations are found at the Zn6Y8-Mg interface which might be originated from the local strain field between them.
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•Basal dislocations activate first and then bend, leading to downward shear stress.•Prism dislocations form 45-degree slip band inside micro-pillar would cause fracture.•The local strain field at the Zn6Y8-Mg interface induces the basal dislocations.
Receptors for Wingless and other signalling molecules of the Wnt gene family have yet to be identified. We show here that cultured Drosophila cells transfected with a novel member of the frizzled ...gene family in Drosophila, Dfz2, respond to added Wingless protein by elevating the level of the Armadillo protein. Moreover, Wingless binds to Drosophila or human cells expressing Dfz2. These data demonstrate that Dfz2 functions as a Wingless receptor, and they imply, in general, that Frizzled proteins are receptors for the Wnt signalling molecules.
We present a patient with positive donor-specific antibodies (DSA) and crossmatch of ABO-incompatible (ABOi) combined liver and kidney transplantation (CLKT). Antibody-mediated rejection did not ...occur and the graft had survived for over one year at the time of writing without infectious complications. A 56-year-old man with positive DSA and positive crossmatch underwent living donor CLKT. The preoperative protocol for ABOi consisted of a single dose of rituximab and total plasma exchange (TPE). The result of anti-B antibody titer for IgG was 1:32. The evaluations of complement-dependent cytotoxicity and flow cytometry cross-match revealed a change from T+/B+ to T-/B+. The patient required adult living donor CLKT. Acute rejection episodes were treated using antithymocyte globulin, and the kidney required 7 days' treatment to recover. No further rejection and infectious episodes have been observed in past 13 months since the transplant. DSA and crossmatches are important for antibody detection and analysis. In the rituximab era, TPE can be used to achieve a successful decrease in antibody titer. In countries with a severe shortage of cadaveric organ donors, it may be possible to select ABOi candidate donors with positive DSA and crossmatch.
•Positive DSA and crossmatch in ABOi combined liver-kidney transplantation has not been previously reported.•A patient with ABO and crossmatch incompatibilities underwent a successful combined liver-kidney transplantation following preoperative intervention.•We demonstrate that DSA/crossmatch positive and ABO-incompatible individuals could still be organ donor candidates.
Purpose: Following major trauma, genes involved in adaptive immunity are downregulated, which accompanies the upregulation of genes involved in systemic inflammatory responses. This study ...investigated microRNA (miRNA)-mRNA interactome dysregulation in circulating T cells of patients with major trauma. Patients and Methods: This study included adult trauma patients who had an injury severity score greater than or equal to16 and required ventilator support for more than 48 h in the intensive care unit. Next-generation sequencing was used to profile the miRNAs and mRNAs expressed in CD3.sup.+ T cells isolated from patient blood samples collected during the injury and recovery stages. Results: In the 26 studied patients, 9 miRNAs (hsa-miR-16-2-3p, hsa-miR-16-5p, hsa-miR-185-5p, hsa-miR-192-5p, hsa-miR-197-3p, hsa-miR-23a-3p, hsa-miR-26b-5p, hsa-miR-223-3p, and hsa-miR-485-5p) were significantly upregulated, while 58 mRNAs were significantly downregulated in T cells following major trauma. A network consisting of 8 miRNAs and 22 mRNAs interactions was revealed by miRWalk, with three miRNAs (hsa-miR-185-5p, hsa-miR-197-3p, and hsa-miR-485-5p) acting as hub genes that regulate the network. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis suggested that "chemokine signaling pathway" was the predominant pathway. Conclusion: The study revealed a miRNA-mRNA interactome consisting of 8 miRNAs and 22 mRNAs that are predominantly involved in chemokine signaling in circulating T cells of patients following major trauma. Keywords: miRNA, next-generation sequencing, T cells, adaptive immunity, major trauma, critical illness
In this study, we develop an innovative method that assists computer-aided diagnosis in the determination process of the exact location of the femoral neck junction in plain radiographs. Our ...algorithm consists of two phases, i.e., coarse prediction and fine matching, which are implemented by supervised deep learning method and unsupervised clustering, respectively. In coarse prediction, standard masks are first produced by a specialist and trained in our proposed feature propagation network (FPU-Net) with supervised learning on the femoral neck dataset. In fine matching, the standard masks are first classified into different categories using our proposed three parameters with unsupervised learning. The predicted mask from FPU-Net is matched with each category of standard masks by calculating the values of intersection of union (IOU), and finally the predicted mask is substituted by the standard mask with the largest IOU value. A total of 4320 femoral neck parts in anterior–posterior (AP) pelvis radiographs collected from China Medical University Hospital database were used to test our method. Simulation results show that, on the one hand, compared with other segmentation methods, the method proposed in this paper has a larger IOU value and better suppression of noise outside the region of interest; on the other hand, the introduction of unsupervised learning for fine matching can help in the accurate localization segmentation of femoral neck images. Accurate femoral neck segmentation can assist surgeons to diagnose and reduce the misdiagnosis rate and burden.
To characterize the referral patterns and characteristics of men presenting for infertility evaluation using data obtained from the Andrology Research Consortium.
Standardized male infertility ...questionnaire.
Male infertility centers.
Men presenting for fertility evaluation.
Not applicable.
Demographic, infertility history, and referral data.
The questionnaires were completed by 4,287 men, with a mean male age of 40 years ± 7.4 years and female partners age of 37 years ± 4.9 years. Most were Caucasian (54%) with other races being less commonly represented (Asian 18.6%, and African American 5.5%). The majority (59.7%) were referred by a reproductive gynecologist, 19.4% were referred by their primary care physician, 4.2% were self-referred, and 621 (14.5%) were referred by “other.” Before the male infertility investigation, 12.1% of couples had undergone intrauterine insemination, and 4.9% of couples had undergone in vitro fertilization (up to six cycles). Among the male participants, 0.9% reported using finasteride (5α-reductase inhibitor) at a dose used for androgenic alopecia, and 1.6% reported exogenous testosterone use.
This broad North American patient survey shows that reproductive gynecologists are the de facto gateway for most male infertility referrals, with most men being assessed in the male infertility service being referred by reproductive endocrinologists. Some of the couples with apparent male factor infertility are treated with assisted reproductive technologies before a male factor investigation. The survey also identified potentially reversible causes for the male infertility including lifestyle factors such as testosterone and 5α-reductase inhibitor use.
Los endocrinólogos reproductivos son los guardianes del cuidado de la infertilidad masculina en América del Norte: resultados de una encuesta norteamericana sobre los patrones de referencia y características de hombres que se presentan al especialista en infertilidad masculina para investigaciones de infertilidad
Caracterizar los patrones de referencia y las características de los hombres que se presentan para evaluación de la infertilidad utilizando datos obtenidos de El Consorcio de Investigación Andrológica.
Cuestionario estandarizado de infertilidad masculina.
Centros de infertilidad masculina.
Hombres que se presentan para evaluación de fertilidad.
No aplicable.
Datos demográficos, antecedentes de infertilidad y datos de referencia.
Los cuestionarios fueron completados por 4,287 hombres, con una edad media masculina de 40 años ± 7,4 años y edad de parejas femeninas de 37 años ± 4.9 años. La mayoría eran caucásicos (54%) junto con otras razas menos representadas (Asiáticos 18.6% y Afroamericanos 5,5%). La mayoría (59.7%) fueron referidos por un ginecólogo reproductivo, el 19.4% fueron referidos por su médico de atención primaria, 4.2% fueron referidos por sí mismos, y 621 (14.5%) fueron referidos por "otro". Antes de la investigación de infertilidad masculina, el 12.1% de las parejas se habían sometido a inseminación intrauterina, y el 4.9% de las parejas se habían sometido a fertilización in vitro (hasta seis ciclos). Entre los hombres participantes, el 0.9% informó haber usado finasterida (inhibidor de la 5a-reductasa) a una dosis utilizada para la alopecia androgénica, y el 1.6% informó el uso de testosterona exógena.
Esta amplia encuesta de pacientes en América del Norte muestra que los ginecólogos reproductivos son la puerta de entrada de facto para la mayoría de las referencias de infertilidad masculina, donde la mayoría de hombres que están siendo evaluados en el servicio de infertilidad masculina han sido referidos por endocrinólogos reproductivos. Algunas de las parejas con aparente infertilidad por factor masculino son tratadas con tecnologías de reproducción asistida antes de realizar una investigación del factor masculino. La encuesta también identificó causas potencialmente reversibles para la infertilidad masculina, incluidos factores de estilo de vida como el uso de testosterona y del inhibidor de la 5a-reductasa.
We have previously identified mouse DDA3 as a p53-inducible gene. To explore the functional role of DDA3, we screened a mouse brain cDNA library by the yeast two-hybrid assay, and identified the ...microtubule plus-end binding protein EB3 as a DDA3-interacting protein. Binding of DDA3 to EB3 was verified by glutathione S-transferase (GST) pull-down assay and subcellular colocalization; co-immunoprecipitation further indicated that interaction of these two proteins within cells required intact microtubules. Domains of DDA3-EB3 interaction were mapped by GST pull-down assay to amino acids 118-241 and 242-329 of DDA3 and the N- and C-termini of EB3. Immunofluorescence analysis revealed colocalization of DDA3 with microtubules in various cell phases, and regions encompassing aa 118-241 and 242-329 contained microtubule-interacting and bundling activities. In vitro microtubule-binding assay showed that DDA3 and EB3 associated directly with microtubules, and cooperated with each other for microtubule binding. In addition, DDA3 bound to the EB3 interacting partner adenomatous polyposis coli 2 (APC2), a homolog of the tumor suppressor APC, which is a component of the beta-catenin destruction complex. Ectopic expression of DDA3 and EB3 enhanced beta-catenin-dependent transactivation and cyclin D1 production, whereas knockdown of endogenous DDA3 or EB3 inhibited beta-catenin-mediated transactivation and the ability of cells to form colonies. Together, our results identify DDA3 as a novel microtubule-associated protein that binds to EB3, and implicate DDA3 and EB3 in the beta-catenin-mediated growth signaling.
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