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Background: Recent studies suggest that 5α-reductase inhibitors (5ARIs) for benign prostate hyperplasia (BPH) result in abnormal retinal anatomical alteration., Objective: To compare age-related macular degeneration (AMD) incidence in BPH patients receiving 5ARIs or tamsulosin., Design: Retrospective, population-based cohort study using new-user and active-comparator design., Setting: General population., Subjects: Males with BPH, newly receiving 5ARIs or tamsulosin from 2010 to 2018., Methods: Data were extracted from Taiwan's National Health Insurance Research Database. We used Cox proportional hazards model with 1:4 propensity score (PS) matching, based on intention-to-treat analysis to determine the risk of incident AMD. Sensitivity analyses included an as-treated approach and weighting-based PS methods. We also separately reported the risks of incident AMD in patients receiving finasteride and dutasteride to determine risk differences among different 5ARIs., Results: We included 13 586 5ARIs users (mean age: 69 years) and 54 344 tamsulosin users (mean age: 68.37 years). After a mean follow-up of 3.7 years, no differences were observed in the risk of incident AMD between 5ARIs and tamsulosin users [hazard ratio (HR): 1.06; 95% confidence intervals (95% CI): 0.98-1.15], with similar results from sensitivity analyses. However, increased risk of incident age-related macular degeneration was observed in patients receiving dutasteride [HR: 1.13; 95% CI: 1.02-1.25], but not in those receiving finasteride [HR: 0.99; 95% CI: 0.87-1.12], in the subgroup analyses., Conclusions: We found no difference between 5ARIs and tamsulosin regarding the incidence of AMD in BPH patients. However, the risk profiles for AMD differed slightly between dutasteride and finasteride, suggesting that the potency of androgen inhibition is a factor related to AMD incidence., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Tissue infiltration by circulating leukocytes via directed migration (also referred to as chemotaxis) is a common pathogenic mechanism of inflammatory diseases. G protein-coupled receptors (GPCRs) are essential for sensing chemokine gradients and directing the movement of leukocytes during immune responses. The tumor necrosis factor α-induced protein 8-like (TIPE or TNFAIP8L) family of proteins are newly described pilot proteins that control directed migration of murine leukocytes. However, how leukocytes integrate site-specific directional cues, such as chemokine gradients, and utilize GPCR and TIPE proteins to make directional decisions are not well understood. Using both gene knockdown and biochemical methods, we demonstrated here that 2 human TIPE family members, TNFAIP8 and TIPE2, were essential for directed migration of human CD4+ T cells. T cells deficient in both of these proteins completely lost their directionality. TNFAIP8 interacted with the Gαi subunit of heterotrimeric (α, β, γ) G proteins, whereas TIPE2 bound to PIP2 and PIP3 to spatiotemporally control immune cell migration. Using deletion and site-directed mutagenesis, we established that Gαi interacted with TNFAIP8 through its C-terminal amino acids, and that TIPE2 protein interacted with PIP2 and PIP3 through its positively charged amino acids on the α0 helix and at the grip-like entrance. We also discovered that TIPE protein membrane translocation (i.e. crucial for sensing chemokine gradients) was dependent on PIP2. Collectively, our work describes a new mechanistic paradigm for how human T cells integrate GPCR and phospholipid signaling pathways to control directed migration. These findings have implications for therapeutically targeting TIPE proteins in human inflammatory and autoimmune diseases., Competing Interests: Conflict of interest. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of Society for Leukocyte Biology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Maternal tenofovir disoproxil fumarate (TDF) therapy during late pregnancy can reduce mother-to-infant transmission of hepatitis B virus (HBV). We investigated HBV mutations associated with maternal TDF therapy and their role in infant immunonophylaxis failure (IPF)., Methods: Serum samples from untreated (n = 89) and TDF-treated (n = 68), highly viremic, chronically infected mothers and their infants were analyzed for HBV DNA by nested polymerase chain reaction (PCR) and direct sequencing., Results: At delivery, compared with untreated mothers, TDF-treated mothers had a lower HBV DNA titer and a higher frequency of basal core promoter (BCP) gene mutations, but they had similar frequencies in pre-S/S and pre-core/core mutations. The 14 mothers harboring surface "a" determinant mutants did not transmit the mutants to their immunized infants. Such mutants were found in 3 of 13 IPF infants; the 13 mothers had wild-type hepatitis B surface antigen (HBsAg). In univariable analysis, maternal HBV DNA titer (odds ratio [OR]: 1.54; 95% confidence intervals [CI]: 1.02-2.33; P = .039), genotype C (OR: 4.18; 95% CI: 1.28-13.62; P = .018) and pre-S1 wild-type sequence (OR: 6.33; 95% CI: 1.85-21.68; P = .003) at delivery were associated with infant IPF. Multivariable analyses showed that maternal genotype C (OR: 3.71; 95% CI: 1.11-12.36; P = .033) and pre-S1 wild-type (OR: 6.34; 95% CI: 1.79-22.44; P = .004) were associated with infant IPF independently of maternal viremia., Conclusions: Along with high maternal HBV DNA titer at delivery, maternal genotype C and pre-S1 wild-type sequence were potential risk factors for infant IPF, although BCP mutations were not. The offspring of pregnant women harboring "a" determinant mutants as major strains seemed to be protected by immunoprophylaxis., Clinical Trials Registration: NCT01312012., Competing Interests: Potential conflicts of interest. The authors have no reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Proper knowledge and understanding of climatic variability across different seasons are important in farm management. To learn more about the potential effects of climate change on dairying in Hawaii, we conducted a study on site-specific climate characterization using several variables including rainfall, wind speed ( WS ), solar radiation, and temperature, at two dairy farms located on Hawai`i Island, Hawai`i, in Ookala named "OK DAIRY" and in Upolu Point named "UP DAIRY." Temperature-humidity index ( THI ) and WS variations in the hottest four months (June to September) were analyzed to determine when critical thresholds that affect animal health are exceeded. Rainfall data were used to estimate the capacity of forage production in 6-mo wet (November to April) and dry (May to October) seasons. Future projections of temperature and rainfall were assessed using mid- and end-century gridded data products for low (RCP 4.5) and high emissions (RCP 8.5) scenarios. Our results showed that the "OK DAIRY" site received higher rainfall than the "UP DAIRY" site, favoring grass growth and forage availability. In addition, the "UP DAIRY" site was more stressful for animals during the summer (THI 69 to 73) than the "OK DAIRY" site (THI 67 to 70) as the THI exceeded the critical threshold of 68, which is conducive for high-lactating cattle. On the "UP DAIRY" site, the THI did not drop below 68 during the summer nights, which created fewer opportunities for cattle to recover from heat stress. Future projections indicated that air temperature would increase 1.3 to 1.8 °C by mid-century and 1.6 to 3.2 °C by the end-century at both farms, and rainfall will increase at the "OK DAIRY" site and decrease at the "UP DAIRY" site by the end-century. The agriculture and livestock industries, particularly the dairy and beef subsectors in Hawai`i, are vulnerable to climate changes as higher temperatures and less rainfall will have adverse effects on cattle. The findings in this study demonstrated how both observed and projected changes in climate support the development of long-term strategies for breeding and holistic livestock management practices to adapt to changing climate conditions., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society of Animal Science.)

Context: Maternal lipids during pregnancy and placental growth factors are associated with excess fetal growth. However, how these factors interact to increase the risk of delivering large-for-gestational-age (LGA) neonates remains unclear. In this study, we investigated the relationship between maternal plasma triglycerides (TGs) and free fatty acids (FFAs) during pregnancy, cord blood insulin-like growth factors (IGF), and LGA., Objective: In a cell model, we studied the effect of different FAs on placental IGF-1 secretion., Methods: This cohort study included pregnant women with term pregnancy and without diabetes or hypertensive disorders in pregnancy. Maternal fasting plasma TGs and FFAs were measured in the second trimester. Cord blood IGF-1, IGF-2, and IGF binding protein-1 and protein-3 were measured at the time of delivery. A human trophoblast cell line, 3A-sub-E, was used to evaluate the effect of different FFAs on placental IGF-1 secretion., Results: We recruited 598 pregnant women-neonate pairs. Maternal plasma TG (180 mg/dL [152.5-185.5 mg/dL] vs 166 mg/dL [133-206 mg/dL], P = .04) and cord blood IGF-1 concentrations (72.7 ± 23.0 vs 54.1 ± 22.8 ng/mL, P < .001) were higher in the LGA group and were significantly associated with birth weight z score. Maternal plasma free palmitic acid (PA) and stearic acid (SA), but not oleic acid (OA) or linoleic acid (LA), were significantly associated with cord blood IGF-1 concentrations. In 3A-sub-E cells, treatment with PA, SA, and LA, but not OA, induced IGF-1 expression and secretion., Conclusion: Certain FFAs can induce placental IGF-1 secretion, which suggests a potential pathophysiology linking maternal plasma lipids and LGA., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: What do patients want when looking for an aesthetic surgeon? When faced with attributes like reputation, years in practice, testimonials, photos, and pricing, which is more valuable? Moreover, are attributes procedure-specific? Currently, inadequate evidence exists on which attributes are most important to patients, and to our knowledge, none on procedure-specific preferences., Objectives: First, to determine the most important attributes to breast augmentation, combined breast/abdominal surgery, and facelift patients using conjoint analysis. Second, to test the conjoint using an internet crowdsourcing service (Amazon Mechanical Turk [MTurk])., Methods: Anonymous university members were asked, via mass electronic survey, to pick a surgeon for facelift surgery based on five attributes. Attribute importance and preference was calculated. Once pre-tested, the facelift, breast augmentation and combined breast/abdominal surgery surveys were administered worldwide to MTurk., Results: The university facelift cohort valued testimonials (33.9%) as the most important, followed by photos (31.6%), reputation (18.2%), pricing (14.4%), and practice years (1.9%). MTurk breast augmentation participants valued photos (35.3%), then testimonials (33.9%), reputation (15.7%), pricing (12.2%), and practice years (3%). MTurk combined breast/abdominal surgery and facelift participants valued testimonials (38.3% and 38.1%, respectively), then photos (27.9%, 29.4%), reputation (17.5%, 15.8%), pricing (13.9%, 13.9%), practice years (2.4%, 2.8%)., Conclusions: Breast augmentation patients placed higher importance on photos; combined breast/abdominal surgery and facelift patients valued testimonials. Conjoint analysis has had limited application in plastic surgery. To our knowledge, internet crowdsourcing is a novel participant recruitment method in plastic surgery. Its unique benefits include broad, diverse and anonymous participant pools, low-cost, rapid data collection, and high completion rate., (© 2016 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com.)

Background: To compare the clinical and laboratory features of non-typhoid Salmonella (NTS) and Campylobacter jejuni enterocolitis in children and formulate a risk scoring system (with receiver-operating characteristic curve) to facilitate early decision making and avoid antibiotic overuse in C. jejuni enterocolitis., Methods: Between January 2008 and December 2011, children (age <18 years) diagnosed as having C. jejuni enterocolitis and NTS enterocolitis in Kaohsiung Chang Gung Memorial Hospital were retrospectively enrolled. Clinical features and laboratory data were collected for analysis and a risk calculation score is created for the identification of Campylobacter infections., Results: A total of 309 cases of C. jejuni enterocolitis and 496 cases of NTS enterocolitis were enrolled. Compared with Salmonella group clinically, the Campylobacter group had older age (81.06 ± 50.65 vs. 32.70 ± 34.88 months, p <; 0.001), more abdominal pain (69.26% vs. 37.5%, p <; 0.001) and more watery diarrhea (79.94% vs. 20.77%, p <; 0.001). In laboratory data, the Campylobacter group had higher level of white blood cell count (11 208 ± 4380 vs. 9095 ± 3598 cell/mm3, p <; 0.001)., Conclusion: Four criteria including age (≥5 years), leukocytosis (≥10 000 cell/mm3), abdominal pain and watery diarrhea were identified as good predictors of Campylobacter enterocolitis. When three criteria were fulfilled, Campylobacter enterocolitis was highly suspected and antibiotic could be withheld even when C-reactive protein is high and before stool culture results are known. When four criteria were fulfilled, antibiotic usage was absolutely unnecessary., (© The Author [2014]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Eukaryotic genomes contain numerous DNA transposons that move by a cut-and-paste mechanism. The majority of these elements are self-insufficient and dependent on their autonomous relatives to transpose. Miniature inverted repeat transposable elements (MITEs) are often the most numerous nonautonomous DNA elements in a higher eukaryotic genome. Little is known about the origin of these MITE families as few of them are accompanied by their direct ancestral elements in a genome. Analyses of MITEs in the yellow fever mosquito identified its youngest MITE family, designated as Gnome, that contains at least 116 identical copies. Genome-wide search for direct ancestral autonomous elements of Gnome revealed an elusive single copy Tc1/Mariner-like element, named as Ozma, that encodes a transposase with a DD37E triad motif. Strikingly, Ozma also gave rise to two additional MITE families, designated as Elf and Goblin. These three MITE families were derived at different times during evolution and bear internal sequences originated from different regions of Ozma. Upon close inspection of the sequence junctions, the internal deletions during the formation of these three MITE families always occurred between two microhomologous sites (6-8 bp). These results suggest that multiple MITE families may originate from a single ancestral autonomous element, and formation of MITEs can be mediated by sequence microhomology. Ozma and its related MITEs are exceptional candidates for the long sought-after endogenous active transposon tool in genetic control of mosquitoes.

Objectives: Extracellular matrix (ECM) remodelling of the vessel wall is hypothesized to be an important step in atherosclerosis. Changes of the ECM are associated with the gradual progression of an atherosclerotic lesion from a lipid streak to complicated unstable plaque, leading to a complete vessel occlusion and eventually myocardial infarction (MI). Understanding of this process is critical in the treatment and prevention of ischaemic heart disease (IHD)., Methods: We investigated the histopathological characteristics of aortic wall ECM in IHD patients. Collagen I, collagen III and elastin were assessed immunohistochemically in patients with acute MI and those with stable angina, using aortic punch tissues obtained from coronary artery bypass graft surgery. Fluorescence tissue images were analysed using the tissue microarray technique., Results: The results showed that collagen III expression was found to be significantly lower in the acute MI group (P < 0.001). As a result of this change, the patients with MI also revealed a significant reduction in the collagen III/collagen I ratio. The elastin/collagen III ratio was significantly higher in the MI group (P < 0.001)., Conclusions: Our study provided evidence of a decrease in collagen III content in patients with MI, which could possibly explain the mechanism of plaque vulnerability and weakening of the plaque cap. A reduction in collagen III content, particularly away from the atherosclerotic lesions, might be explained by the systemic vascular changes in patients with MI, and inflammation and immune responses could be potential causes of these systemic transformations. The biochemical mechanisms and factors regulating collagen III production might be potential markers to predict possible cardiovascular events.

Context: Preeclampsia is a pregnancy-specific disorder that features insufficient extravillous trophoblast (EVT) invasion. We have previously shown that MUC1 expression in human placenta increases with gestational age and inhibits choriocarcinoma cell invasion., Objective: Here, we studied whether MUC1 expression in preeclamptic placentas is dysregulated and the mechanism of EVT invasion regulated by MUC1., Design: MUC1 expression in severe preeclamptic placentas and gestational age-matched control placentas was analyzed by real-time RT-PCR, Western blot analysis, and immunohistochemistry. The effects of MUC1 expression on cell-matrix adhesion, invasion, and cell signaling were studied in HTR8/SVneo EVT cells., Results: We found that MUC1 mRNA and MUC1 protein were significantly up-regulated in severe preeclamptic placentas when compared with the gestational age-matched control placentas. Immunohistochemical analyses showed increased expression of MUC1 in the syncytiotrophoblast and EVT of severe preeclamptic placentas. In addition, MUC1 overexpression suppressed cell-matrix adhesion and invasion of EVT cells. Importantly, our data showed that MUC1 overexpression inhibited β1-integrin activity and phosphorylation of focal adhesion kinase, whereas the surface expression of β1-integrin was not significantly changed., Conclusions: Our findings suggest that MUC1 is overexpressed in severe preeclamptic placentas and that MUC1 overexpression suppresses EVT invasion mainly via modulating β1-integrin signaling.

Objective: To provide health-care providers, patients, and the general public with a responsible assessment of currently available data on the diagnosis and management of ductal carcinoma in situ (DCIS)., Participants: A non-Department of Health and Human Services, nonadvocate, 14-member panel representing the fields of oncology, radiology, surgery (general and reconstructive), pathology, radiation oncology, internal medicine, epidemiology, biostatistics, nursing, obstetrics and gynecology, preventative medicine and population health, and social work. In addition, 22 experts from pertinent fields presented data to the panel and conference audience., Evidence: Presentations by experts and a systematic review of the literature prepared by the Minnesota Evidence-based Practice Center, through the Agency for Healthcare Research and Quality. Scientific evidence was given precedence over anecdotal experience., Conference Process: The panel drafted its statement based on scientific evidence presented in open forum and on published scientific literature. The draft statement was presented on the final day of the conference and circulated to the audience for comment. The panel released a revised statement later that day at http://consensus.nih.gov. This statement is an independent report of the panel and is not a policy statement of the National Institutes of Health or the Federal Government., Conclusions: Clearly, the diagnosis and management of DCIS is highly complex with many unanswered questions, including the fundamental natural history of untreated disease. Because of the noninvasive nature of DCIS, coupled with its favorable prognosis, strong consideration should be given to elimination of the use of the anxiety-producing term "carcinoma" from the description of DCIS. The outcomes in women treated with available therapies are excellent. Thus, the primary question for future research must focus on the accurate identification of patient subsets diagnosed with DCIS, including those persons who may be managed with less therapeutic intervention without sacrificing the excellent outcomes presently achieved. Essential in this quest will be the development and validation of accurate risk stratification methods based on a comprehensive understanding of the clinical, pathological, and biological factors associated with DCIS.

Intercellular exchange of protein and RNA-containing microparticles is an increasingly important mode of cell-cell communication. Here we investigate if mesenchymal stem cells (MSCs) known for secreting therapeutic paracrine factors also secrete RNA-containing microparticles. We observed that human embryonic stem cell (hESC)-derived MSC conditioned medium contained small RNAs (less than 300 nt) encapsulated in cholesterol-rich phospholipid vesicles as evidenced by their RNase sensitivity only in the presence of a sodium dodecyl sulfate-based cell lysis buffer, phospholipase A2 and a chelator of cholesterol, cyclodextrin and the restoration of their lower than expected density by detergent or phospholipase A2 treatment. MicroRNAs (miRNAs) such as hsa-let-7b and hsa-let-7g were present in a high precursor (pre)- to mature miRNA ratio by microarray analysis and quantitative reverse transcription-polymerase chain reaction. The pre-miRNAs were cleaved to mature miRNA by RNase III in vitro. High performance liquid chromatography-purified RNA-containing vesicles have a hydrodynamic radius of 55-65 nm and were readily taken up by H9C2 cardiomyocytes. This study suggests that MSCs could facilitate miRNA-mediated intercellular communication by secreting microparticles enriched for pre-miRNA.

Red-brown tattoos are usually treated with a frequency-doubled Q-switched (QS) neodymium:yttrium-aluminum-garnet Nd:YAG laser (532 nm), because red and pink pigments show maximum absorption between 500 and 570 nm. Using a QS laser for red-brown tattoo removal has sometimes led to paradoxical darkening of the tattoo pigments, and this darkened grey-black colour may be difficult to remove. A woman with red-brown cosmetic tattoos on her eyebrows was treated using a QS Nd:YAG laser (1064 nm) initially with low fluence and subsequently with increasing fluences at 6-weekly intervals. After the first treatment, a slight darkening of the tattoo pigments was seen, but this faded and complete clearance was achieved after five treatments. There was no downtime during every treatment and there were no scars, pigmentary alterations or textural changes.

Aims: To investigate the performance of an iodine-releasing filter medium for use as a protective device against airborne pathogens., Methods and Results: The filter's physical and viable removal efficiencies (VRE) were investigated with challenges of MS2 bacteriophage aerosols, and the infectivity of MS2 collected on the filter was analysed. To test a proposed inactivation mechanism, media containing thiosulfate or bovine serum albumin (BSA) were put in impingers to quench and consume I(2) released from the filter. In direct plating experiments, treated filters presented significantly higher VREs than did untreated filters; however, collection in excess BSA decreased VRE by half and in thiosulfate the apparent VRE decreased drastically. No significant difference in infectivity of retained viruses on treated and untreated filters was observed at the same environmental condition., Conclusions: Evidence presented herein for competition by dissolved I(2) in infectivity assays supports a mechanism of induced displacement and capture of I(2.) It also requires that dissociation of iodine from the filter and capture of iodine by MS2 aerosols as they pass through the filter be factored in the design of the assessment methodology. The filter's strong retention capability minimizes reaerosolization but also makes it difficult to discriminate the antimicrobial effect at the surface., Significance and Impact of the Study: This study shows the direct plating assay method to be sensitive to interference by iodine-releasing materials. This requires reevaluation of earlier reports of VRE measurements.

Background: Summary Left main disease (LMD) and associated cardiac risk factors are often perceived as a limiting factor for the outcome of off-pump coronary artery bypass (OPCAB) grafting. In this study, we assess whether the outcome of OPCAB surgery is affected in such patients., Methods: We retrospectively compared perioperative parameters in 66 OPCAB patients (group A) with LMD and 216 OPCAB patients without (group B) LMD. The patients were operated in the time frame between 2002 and 2007. LMD was defined as a stenosis >50%., Results: Patients in group A had a higher EuroSCORE (logistic: 3.7+/-0.1 vs 6.3+/-0.3, p=0.027), increased coronary artery disease (CAD) family history (p=0.015) and cerebrovascular accidents (p=0.027), increased history of congestive heart failure (p=0.013), more urgent surgery (p=0.008), previous percutaneous transluminal coronary angioplasties (PTCAs) (p=0.05) and previous stent implantation (p=0.023). An intra-aortic balloon pump (IABP) was inserted more frequently in the LMD group preoperatively (p=0.004). There were two conversions to on-pump during OPCAB surgery. There were no differences in the postoperative outcomes in the LMD group A versus group B, such as cardiac-related events, neurological deficits, cardiac enzyme course, arrhythmias, blood loss, infections and renal failure., Conclusions: The presence of LMD and higher EuroSCORE does not yield adverse outcomes in OPCAB patients.

We investigated the relationship between hypertriglyceridemia and the single-nucleotide polymorphisms (SNPs) on APOA5 in human immunodeficiency virus (HIV)-infected patients receiving highly active antiretroviral therapy (HAART) in Taiwan. Receipt of protease inhibitor-based HAART, high baseline triglyceride levels, and carriage of APOA5 SNP3 or c.553G>T variants or APOA5 SNP1T/SNP2G/SNP3C/c.553T haplotype were statistically significantly associated with development of extreme hypertriglyceridemia (triglyceride level, >500 mg/dL).

During emergency repair of acute Stanford type A aortic dissections, surgical compromises in the form of incomplete arch replacement are made due to the unstable condition of the patient and safety issues of the performing team. We report a case of delayed reoperation after previous incomplete surgery for acute type A aortic dissection in a young patient with Marfan's syndrome. He presented again with repetitive chest pain five years after initial surgical treatment. Extensive aneurysmal dilatation of the aorta and remaining dissection led to the decision to replace the ascending aorta and the aortic arch. After a good progress during the first days after surgery, the patient died due to a ruptured thoraco-abdominal aneurysm on the fifth postoperative day. Extensive surgical reconstruction including aortic arch replacement should be considered in patients with Marfan's syndrome who present with aortic dissections type A to avoid unnecessary reoperations and their complications.

Mucin (MUC)1 is a multifunctional mucin expressed by a variety of reproductive tract epithelia. Trophoblast invasion is essential for normal placental development. However, MUC1 expression in the human placenta throughout pregnancy and the role of MUC1 in trophoblast-like cell invasion are still unclear. In the present study, results from quantitative RT-PCR and Western blot demonstrated that MUC1 mRNA and MUC1 protein expression, respectively, increased with gestational age of the human placenta. Immunohistochemistry revealed that MUC1 in placental villi was mainly expressed by syncytiotrophoblasts throughout pregnancy and increased with gestational age. Interestingly, we found two populations of extravillous trophoblasts, MUC1-positive and MUC1-negative cells, in decidua. The numbers of MUC1-positive extravillous trophoblasts were increased during placental development. Furthermore, MUC1 overexpression significantly (P < 0.01) suppressed matrigel invasion of trophoblast-like JAR cells by 34.6% +/- 4.5% compared with control, which was associated with a decrease in MMP9 activity assessed by gelatin zymography. Our results suggest that MUC1 expression in the human placenta is increased during placental development, and its overexpression suppresses trophoblast-like cell invasion in vitro.

Objectives: To determine the prevalence and trends of antiretroviral drug resistance among HIV-1-infected Taiwanese patients who have been provided with free-of-charge antiretroviral therapy (ART) since 1990., Methods: Blood samples collected from 786 HIV-1-infected patients from 1999 to 2006 were subjected to genotypic resistance assay. Antiretroviral resistance mutations were identified in accordance with the antiretroviral resistance mutation list of the International AIDS Society-USA Consensus Guidelines. Trends of resistance were studied in patients enrolled in two periods: before (period 1, January 1999 to December 2003) and after (period 2, January 2004 to December 2006) the CRF07&#95;BC outbreak among injection drug users (IDUs)., Results: The frequency of HIV-1 isolates harbouring one or more primary mutations associated with antiretroviral resistance to reverse transcriptase inhibitors or protease inhibitors increased significantly from 6.6% in period 1 to 12.7% in period 2 (P = 0.003). A significant increase in prevalence of antiretroviral drug resistance was observed among men who have sex with men and patients infected with HIV subtype B. In multivariate analysis, hepatitis C virus (HCV) exposure, which exhibited collinearity with injection drug use and infection with CRF07&#95;BC, represented a lower risk for infection with resistant viruses., Conclusions: Our findings suggest that the prevalence of antiretroviral resistance has increased in Taiwan over the past 8 years after the introduction of combination ART. IDUs who were HCV-seropositive and infected with CRF07&#95;BC were at lower risk for infection with antiretroviral-resistant viruses.

Background: Trophoblast invasion is crucial for the development of normal placentas. Mucins are suggested to be involved in cancer invasion. However, the function of mucins in trophoblast invasion has never been reported. This study was to investigate the expression of mucin (MUC) 15 in human placenta and its role in trophoblast invasion., Methods: MUC15 mRNA in human tissues was analyzed by Northern blot. MUC15 mRNA and protein in human placenta were detected by real-time RT-PCR and Western blot, respectively. The distribution of MUC15 was revealed by immunohistochemistry. The effects of MUC15 on trophoblast invasion in vitro were analyzed by matrigel invasion assay in human choriocarcinoma JAR and JEG-3 cells., Results: MUC15 was expressed most highly in human placenta. MUC15 mRNA and protein increased with gestational age (P < 0.05, first versus third trimester). Immunohistochemistry showed that MUC15 protein was expressed by both cytotrophoblasts and syncytiotrophoblasts, especially at the apical membrane of syncytiotrophoblasts. In addition, MUC15 was found to be present in the glandular epithelium of the decidua. Overexpression of MUC15 substantially decreased matrigel invasion of JAR and JEG-3 cells by 87.5 +/- 1.1 and 83.8 +/- 5.7%, respectively, versus control, which was closely associated with an increase in mRNA expression of tissue inhibitors of metalloproteinases (TIMP)-1 and TIMP-2. Knockdown of MUC15 with small interfering RNA significantly reversed these effects (P < 0.05)., Conclusions: Differential expression of MUC15 in human placentas may play a critical role in the regulation of trophoblast invasion.

Background: Deletions and duplications involving large DNA segments result in underexpression or overexpression, depending on the changes in allele dose, and are known to cause many common disorders. Detection of allele dose variations in the human genome is increasingly important in medical genetic diagnosis., Methods: We used multiplex quantitative PCR coupled with capillary electrophoresis for accurate allele dose determination. In cases of Prader-Willi syndrome (PWS), a total of 24 patients with PWS, as well as 205 control individuals from the general population, were analyzed by use of multiplex quantitative PCR to amplify the FGFR2 gene, the KRIT1 gene, and the SNRPN gene simultaneously. In cases of Duchenne muscular dystrophy (DMD), we optimized the multiplex quantitative PCR to amplify 38 exons to analyze the DMD gene for rapid diagnosis of 12 DMD-affected males, 12 obligate carriers from families, and 50 unaffected female controls., Results: We were able to unambiguously diagnose the deletion genotype in PWS patients and identify all deletion or duplication genotypes and carrier status in DMD-affected cases with 100% sensitivity and specificity., Conclusions: This report describes a novel single assay that can rapidly quantify allele dose to provide accurate clinical genetic diagnosis. This technique offers a valuable alternative for the rapid detection of genomic deletions or duplications and decreases costs because it does not require expensive fluorescent reagents.

The endothelium of patients with coronary artery disease shows increased expression of cyclooxygenase-2 (COX-2) during coronary artery bypass graft surgery (CABG) using cardiopulmonary bypass. This, together with serotonin, may lead to coronary microvessel spasm, which potentially, can contribute to myocardial ischemia and injury after surgery. We performed a randomized, double-blind, placebo-controlled trial in patients undergoing isolated CABG to determine whether short-term treatment with a selective COX-2 inhibitor, Rofecoxib (25 mg), given preoperatively and for 5 days after operation, can offer better myocardial protection in patients undergoing CABG by measuring serial cardiac troponin T (cTnT) levels. The study was powered to recruit 150 consecutive patients undergoing isolated CABG but the study was terminated prematurely by the worldwide withdrawal of rofecoxib. There were highly statistically significant (P<0.001) increases in cTnT in both groups at each time point (1, 6, 24 and 48 h after onset of cardiopulmonary bypass) compared to preoperative levels. cTnT levels were similar at all post-operative time points between the 2 groups. There is no evidence that short-term treatment with rofecoxib has a myocardial protective effect in patients undergoing CABG. There is also no evidence that its effect is deleterious to the myocardium in patients undergoing CABG.

A 64-year-old woman presented with a 2-week history of an asymptomatic mass involving the lower lip. Histopathological examination showed a well-circumscribed tumour composed of many lobules separated by thin, fibrous connective tissue. Individual lobules were composed of round or polyhedral tumour cells, which had a characteristic finely granular and vacuolated cytoplasm and eccentric hyperchromatic nuclei. Positive staining was observed with Periodic acid-Shiff, and immunohistochemistry for cytokeratin, alpha-1 antitrypsin, and S-100 protein resulting in a final diagnosis of acinic cell carcinoma. Acinic cell carcinoma represents a well-established, although uncommon, entity in the classification of neoplasms of salivary gland origin. The parotid salivary gland is the most frequent site of acinic cell carcinoma, whereas the lip is a particularly unusual site. The unusual presentation of this tumour may lead to confusion with a mucocele. Given these findings, we suggest that acinic cell carcinoma should be considered in the differential diagnosis of any mucocele-like mass on the lower lip.

Cardiac herniation following pericardial resection is a rare and potentially fatal complication. We present a case of a cardiac herniation after excision of pericardial thymic cyst. The patient had cardiac arrest one hour after surgery. Re-thoracotomy in the high dependency care unit, and reduction of cardiac herniation were done. There was no case report in the literature of cardiac herniation after excision of pericardial tumor.

Purpose: The compatibility, pH, and osmolality of N-acetylcysteine (NAC) nebulizing solution in the presence of ipratropium bromide or fenoterol hydrobromide were studied., Methods: Portions (400 microL) of each mixture were sampled immediately upon mixing and one, two, three, four, five, six, and seven hours after mixing and assayed by high-performance liquid chromatography. Osmolality was measured by sampling 100 microL from the filling cup at a five-minute interval during nebulization and by the freezing-point-depression method., Results: Adding NAC solution to fenoterol solution raised the pH from 3.20 to 7.90 and the osmolality to a mean +/- S.D. of 1400.67 +/- 4.51 mOsm/kg. Fenoterol concentrations decreased to 93.71% and NAC concentrations to 92.54% of initial concentrations after seven hours. Mixing ipratropium with NAC solution raised the pH from 3.74 to 7.95 and the osmolality to a mean +/- S.D. of 1413 +/- 11.79 mOsm/kg. The initial ipratropium concentration declined 7.39% and 10.91% one and two hours after mixing with NAC solution, respectively., Conclusion: NAC and ipratropium were stable in nebulizing solution within one hour of mixing. NAC and fenoterol were compatible for at least seven hours.

The case of a young patient who presented with severe hemolysis after mitral valve repair is presented. Valve repair included chordal shortening, transposition of chordae tendinae, and annular remodelling using a Duran flexible ring. Reoperation and valve replacement were required to control hemolytic anemia. The possible mechanisms leading to such an uncommon complication after plastic repair of the mitral valve are commented on. The scanty literature concerned is reviewed.

Hepatoblastoma is an uncommon liver neoplasm in children but its intraatrial extension through the inferior vena cava is extremely rare. The case described is a 3-year-old boy in whom profound hypothermia and circulatory arrest were used to resect a hepatoblastoma and its extension to the right atrium. This technique allows maximal resection and relief of venous obstruction from atrial extension of hepatoblastoma.

Concentrations of progesterone in uterine and arterial tissue and in uterine and jugular venous plasma were determined. Blood was collected on Days 4 and 9 postestrus from the jugular vein and the first and last venous branches draining each uterine cornu; uterine tissue and arteries were subsequently collected. Progesterone was greater (p less than 0.05) in the cranial third than in the middle or caudal thirds of the uterine horn adjacent to the corpus luteum (CL)-bearing ovary or in any third of the contralateral horn. Progesterone in uterine arterial segments adjacent to the CL-bearing ovary was higher (p less than 0.05) than in contralateral segments. Progesterone was higher (p less than 0.05) in blood from the first venous branch of the cranial third of the uterine cornu adjacent to the ovary with the CL, than in the last branch of the caudal third, or contralateral horn, or in jugular blood. When oviductal veins were resected on Day 9 postestrus, progesterone in the first vein draining the cranial third of the uterine cornu adjacent to the CL-containing ovary was not different (p greater than 0.05) 48 h after resection than in the same vessel in the opposite horn or in jugular blood. We concluded that progesterone and other ovarian products may be delivered to the uterus locally.

At least six nuclear loci are responsible for the genetic control of malate dehydrogenase (L-malate: NAD oxidoreductase; EC 1.1.1.37; MDH) in coleoptiles of maize. Three independently segregating loci (Mdh1, Mdh2, Mdh3) govern the production of MDH isozymes resistant to inactivation by ascorbic acid and found largely or solely in the mitochondria. A rare recessive allele found at a fourth nuclear locus (mmm) causes increased electrophoretic mobility of the MDH isozymes governed by the Mdh1, Mdh2 and Mdh3 loci.-Two loci (Mdh4, Mdh5) govern MDH isozymes that are selectively inactivated by homogenization in an ascorbic acid solution and that appear to be nonmitochondrial (soluble). Mdh4 and Mdh5 segregate independently of each other and independently of Mdh1, Mdh2 and Mdh3. However, there is close linkage between the migration modifier and Mdh4.--Multiple alleles have been found for all of the Mdh loci except the migration modifier, and electrophoretically "null" or near "null" alleles (as expressed in standardized sections of maize coleoptile) have been found for all loci except Mdh4. Duplicate inheritance commonly occurs for Mdh1 and Mdh2 and also for Mdh4 and Mdh5.--Inter- and intragenic heterodimers are formed between sub-units specified by the three loci governing the mitochondrial MDH isozymes. The same is true of the alleles and nonalleles at the two loci governing the soluble variants. No such heterodimers are formed by interactions between mitochondrial and soluble MDH isozymes.

We describe an ultrafiltration technique for rapidly and directly determining free triiodothyronine or free thyroxine, or both. After equilibrating serum at 37 degrees C with purified tracer of high specific activity, we placed 0.15 mL of serum in 2.8 mL of phosphate buffer (0.1 mol/L, pH 7.4) in the ultrafiltration cell and obtained successive 0.2- and 0.6-mL fractions of protein-free ultrafiltrate. Under our conditions free ligand concentration was independent of flow rate. After purifying the second fraction with protein-coated charcoal, we could determine the proportion of free triiodothyronine or free thyroxine. Samples from normal adult men and women, including women who were taking oral contraceptives or were pregnant, and from hypo- and hyperthyroid patients gave results that agreed with those obtained by equilibrium dialysis. Speed is the main advantage of the method: one technologist can complete the procedure in 2 h and, using a multi-micro-ultrafiltration system, can process many samples in one day. For laboratories where index-type reactions are performed routinely and direct free triiodothyronine or free thyroxine is determined only on selected specimens, this method is superior to dialysis. It is also very convenient for rapidly purifying tracers, to at least 97% radiochemical purity, with 94% recovery and no dilution.