Phenotypic shift of small intestinal intra-epithelial type 1 innate lymphoid cells in celiac disease is associated with enhanced cytotoxic potential.

The small intestinal (SI) epithelium harbors a heterogeneous population of lymphocytes that mediate mucosal damage and repair in celiac disease (CD). The composition and roles of human proximal SI intra-epithelial innate lymphoid cells (ILCs), and their alterations in CD, are not well understood. We report that duodenal intra-epithelial ILCs predominantly consist of natural killer (NK)p44+ CD127- cytotoxic ILC1s and NKp44- CD127+ helper ILC1s, while ILC3s only represent a minor population. In patients with newly diagnosed or active CD (ACD) and refractory CD type 1 (RCD I), the frequency of SI NKp44+ ILCs is decreased, with restoration of NKp44+ ILC frequency observed in patients adhering to a gluten-free diet who show evidence of mucosal healing. Moreover, the frequency of SI NKp44- ILCs is increased in ACD and RCD I patients and correlates with the severity of villous atrophy and epithelial damage, as assessed by serum levels of fatty acid binding protein 2 (FABP2). We show that the ILC alterations in CD represent a phenotypic shift of cytotoxic ILC1s rather than an increase in helper ILC1s or transdifferentiation of ILC1s to ILC3s, and activation-induced loss of NKp44 by cytotoxic ILC1s is associated with increased interferon (IFN)-γ expression and release of lytic granules. These findings suggest that intra-epithelial NKp44- CD127- cytotoxic ILC1s may contribute to mucosal damage in CD.

Using Annual Data to Estimate the Public Health Impact of Extreme Temperatures.

Short-term associations between both hot and cold ambient temperatures and higher mortality have been found worldwide. Few studies have examined these associations on longer time scales. Age-standardized mortality rates (ASMRs) were calculated for 1976-2012 for Hong Kong SAR, People's Republic of China, defining "annual" time periods in 2 ways: from May through April of the following year and from November through October. Annual frequency and severity of extreme temperatures were summarized by using a degree-days approach with extreme heat expressed as annual degree-days >29.3°C and cold as annual degree-days <27.5°C. For example, a day with a mean temperature of 25.0°C contributes 2.5 cold degree-days to the annual total. Generalized additive models were used to estimate the association between annual hot and cold degree-days and the ASMR, with adjustment for long-term trends. Increases of 10 hot or 200 cold degree-days in an annual period, the approximate interquartile ranges for these variables, were significantly (all P's ≤ 0.011) associated with 1.9% or 3.1% increases, respectively, in the annual ASMR for the May-April analyses and with 2.2% or 2.8% increases, respectively, in the November-October analyses. Associations were stronger for noncancer and elderly mortality. Mortality increases associated with extreme temperature are not simply due to short-term forward displacement of deaths that would have occurred anyway within a few weeks.

Fucosyltransferase gene expression in goat endometrium during the estrous cycle and early pregnancy.

Regulation of the expression of the alpha(1,2)fucosyltransferase (FUT) genes and their enzymatic products, including the H-type 1 antigen (HT1), on the luminal surface of the uterus is believed to be critical for establishment of pregnancy in mammals. The FUT1 gene is a marker for conception rates in dairy cows and HT1 is a marker for uterine receptivity in rodents. To determine the spatiotemporal expression patterns of FUT1 and FUT2 genes in goats, endometrial tissues were obtained on six days spanning the estrous cycle (Days 5, 11, 13, 15, 17 and 19) and seven days spanning early pregnancy (Days 5, 11, 13, 15, 17, 19 and 25). In all data, we found no effect of status (cyclic or pregnant; P > 0.1) and pooled data where appropriate. We cloned FUT1 cDNA from goat endometrium and made probes from it for Northern and slot blot analyses. The analyses indicated that FUT1 gene expression was high until Day 13, and then declined. In situ hybridization revealed a change in the cell-specificity of FUT1 gene expression over the estrous cycle and early pregnancy. In situ hybridization signal intensity scores indicated that FUT1 expression by uterine epithelium was high on Day 5, moderate on Day 11, and minimal on subsequent days. In situ hybridization signals in uterine glandular epithelial cells remained high from Day 5 to Day 13, with weaker signals thereafter. Quantitative reverse transcription-PCR (RT-qPCR) assays were used for quantitation of FUT1 and FUT2 mRNAs. Quantitative RT-qPCR data were generated from endometrium collected from cyclic and pregnant animals on Days 5, 11 and 17. Relative levels of FUT1 mRNA were high on Days 5 and 11, but then fell 5-fold by Day 17 (P < 0.01). FUT2 mRNA concentrations were below the accurate detectable limit of the assay. High levels of HT1 were observed on the apical surface of uterine luminal epithelia on Days 5, 15, 17 and 19, with much lower levels on Days 11 and 13. Thus, data suggests that FUT1 is the primary enzyme responsible for the high levels of HT1 antigen present on the uterine luminal epithelium between Days 5 and 11 of the estrous cycle and early pregnancy. But changes in the expression of the FUT1 gene does not directly correlate to HT1 staining, which increased from Day 13-15. Future studies are required to understand the regulation of the HT1 antigen on the luminal surface of endometrium.

TIPS versus paracentesis for cirrhotic patients with refractory ascites.

BACKGROUND: Refractory ascites (ie, ascites that cannot be mobilized despite sodium restriction and diuretic treatment) occurs in 10 per cent of patients with cirrhosis. It is associated with substantial morbidity and mortality with a one-year survival rate of less than 50 per cent. Few therapeutic options currently exist for the management of refractory ascites. OBJECTIVES: To compare transjugular intrahepatic portosystemic stent-shunts (TIPS) versus paracentesis for the treatment of refractory ascites in patients with cirrhosis. SEARCH STRATEGY: We searched The Cochrane Hepato-Biliary Group Controlled Trials Register (January 2006), the Cochrane Central Register of Controlled Trials in The Cochrane Library (Issue 4, 2005), MEDLINE (1950 to January 2006), EMBASE (1980 to January 2006), CINAHL (1982 to August 2004), and Science Citation Index Expanded (1945 to January 2006). SELECTION CRITERIA: We included randomised clinical trials comparing TIPS and paracentesis with or without volume expanders for cirrhotic patients with refractory ascites. DATA COLLECTION AND ANALYSIS: We evaluated the methodological quality of the randomised clinical trials by the generation of the allocation section, allocation concealment, and follow-up. Two authors independently extracted data from each trial. We contacted trial authors for additional information. Dichotomous outcomes were reported as odds ratio (OR) with 95% confidence interval (CI). MAIN RESULTS: Five randomised clinical trials, including 330 patients, met the inclusion criteria. The majority of trials had adequate allocation concealment, but only one employed blinded outcome assessment. Mortality at 30-days (OR 1.00, 95% CI 0.10 to 10.06, P = 1.0) and 24-months (OR 1.29, 95% CI 0.65 to 2.56, P = 0.5) did not differ significantly between TIPS and paracentesis. Transjugular intrahepatic portosystemic stent-shunts significantly reduced the re-accumulation of ascites at 3-months (OR 0.07, 95% CI 0.03 to 0.18, P < 0.01) and 12-months (OR 0.14, 95% CI 0.06 to 0.28, P < 0.01). Hepatic encephalopathy occurred significantly more often in the TIPS group (OR 2.24, 95% CI 1.39 to 3.6, P < 0.01), but gastrointestinal bleeding, infection, and acute renal failure did not differ significantly between the two groups. AUTHORS' CONCLUSIONS: The meta-analysis supports that TIPS was more effective at removing ascites as compared with paracentesis without a significant difference in mortality, gastrointestinal bleeding, infection, and acute renal failure. However, TIPS patients develop hepatic encephalopathy significantly more often.

An unusual complication of dental radiography: case report.

We present the case of a 46-year-old man who was undergoing a routine dental examination when a radiograph film plate became lodged in his upper aero-digestive tract. The foreign body was successfully removed in the ENT department of the local hospital without significant harm being done. The case highlights the potential risks of even the simplest procedures, and makes a good argument for using radiograph film holders, when possible.

Informed consent: is it a myth?

The issue of informed consent at it relates to neurosurgical professional malpractice liability and litigation has been of concern for 20 years or more. The problem persists, and the subject has been addressed by providing patient education with full disclosure regarding neurosurgical procedures. In the process of imparting informed consent, the authors studied the effectiveness of specific neurosurgical health care teaching. One hundred six persons undergoing anterior cervical fusion or lumbar laminectomy were instructed by a neurosurgeon and clinical nurse specialist with a master's degree in neurosurgery. Written testing was performed in each case immediately after a formal teaching session before surgery. Questions were simple and covered only four general topics: 1) diagnosis and surgical techniques; 2) operative risks; 3) postoperative care; and 4) goals and benefits relating to surgery. The mean score on testing immediate retention of information revealed a 43.5% overall performance rate. When patients were tested approximately 6 weeks later, the score dropped to 38.4%. This was statistically significant (chi 2, P less than 0.05). The authors encourage the concept of patient education. The data in the current study, however, suggest that the reasonable and prudent neurosurgeon making a concerted effort at patient education, with the assistance of a professional educator, cannot necessarily expect accurate patient or family recall or comprehension. Fulfillment of the doctrine of informed consent by neurosurgeons may very well be mythical.

Effects of estrogen and nonylphenol on the post-transcriptional regulation of vitellogenin gene expression.

Estrogenic chemicals have drawn considerable attention over the past several years because they are known to be responsible for increased breast and prostate cancer. Vitellogenin expression driven by estrogen has been becoming a model for studying estrogenic effects in aquatic species. For the first time, we showed evidence that, without stimulation, vitellogenin mRNA precursor is expressed in both male and female immature fish. After 4 h, in fish treated with estradiol, the vitellogenin mRNA was synthesized and the precursor mRNA began to disappear. The environmental chemical, nonylphenol, showed the same effect on the vitellogenin gene expression as estrogen. It is suggested that estrogen and nonylphenol may be involved in a post-transcriptional regulation process -- possibly in the initiation of pre-mRNA splicing.

Locus of control of children with learning disabilities and perceived locus of control by significant others.

The perceptions of parents and teachers of 24 children with learning disabilities regarding their children's or students' locus of control (LC) orientation were compared to the LC orientation held by the children themselves. While no significant differences were found between parents and children, teachers were found to perceive in their students with learning disabilities significantly more internally oriented success experiences than the students perceived in themselves. Significant differences in LC orientation were also found between the children with learning disabilities and a comparable group of nondisabled subjects. Implications for both preservice and inservice teacher education are presented.

Uptake, disposition, and persistence of nonylphenol from water in rainbow trout (Oncorhynchus mykiss).

1. Nonylphenol is an environmental estrogenic compound. Little is known about its interaction with aquatic species since most of the work on oestrogenic alkylphenols has been done in vitro using cells in culture. 2. Rainbow trout (Oncorhynchus mykiss) were exposed to 14C-nonylphenol at 18 and 36 ppb in water to study its distribution, persistence, and bioaccumulation. 3. Nonylphenol, or its metabolites, were distributed through the body of rainbow trout including the edible tissues of dorsal muscle and fat. 4. Nonylphenol was rapidly taken up into most tissues and had an apparent half-life of 19-20 +/- 4 SE hours in the muscle and fat. 5. The apparent bioaccumulation factor in viscera and carcass ranged from 40 in carcass to 100 in viscera. 6. Three glucuronide metabolites were separated by thin-layer chromatography following treatment of bile with beta-glucuronidase.

Educational assortative mating across marriage markets: non-Hispanic whites in the United States.

Whether local marriage market conditions shape marriage behavior is a central social demographic question. Most work on this subject, however, focuses on one type of market condition--sex ratios--and on a single outcome--marital timing or sorting. We examine the impact of local marriage markets' educational composition on educational assortative mating and on how sorting varies with age. We estimate a discrete-time competing-risks model of educational sorting outcomes, using individual data from the NLSY and community descriptors aggregated from census microdata. Results show that residents of educationally less favorable marriage markets are more likely to marry down on education, and that (for women) their chance of doing so increases with age more than for residents of more favorable markets.

In vivo estrogenic activity of nonylphenol in rainbow trout.

Estrogenic compounds have shown to induce specific endocrine system responds in various species. The protein vitellogenin and its corresponding mRNA have been shown to be induced by estrogenic chemicals in aquatic species. In this investigation the estrogenic chemical nonylphenol was studied in rainbow trout for lethality, estrogenicity, and persistence of effects through the use of reverse transcription polymerase chain reaction of liver vitellogenin mRNA. These results show that nonylphenol produces estrogenic effects in rainbow trout at concentrations well below the LC50.

Lectin receptors for endometrial H-type 1 antigen on goat conceptuses.

PROBLEM: The goal of this study was to determine if caprine conceptuses express lectin-like receptors for endometrial H-type 1 (HT1) antigen. METHOD OF STUDY: Conceptus tissues were collected during the apposition, adhesion and attachment phases of placentation and evaluated using immunofluorescence microscopy. RESULTS: Conceptus staining for the trisaccharide lacto-N-fucopentaose-1 was strong and uniform during apposition of fetal and maternal tissues but changed by day 25 of pregnancy when large aggregates of intense staining were observed. Monoclonal antibodies to galectin-3 did not stain conceptus tissue during the apposition phase but intense punctate staining was observed after day 25. Strong uniform staining for Lewis Y antigen was detected only on day 17 of pregnancy. CONCLUSION: Conceptus tissue expresses potential receptors for endometrial HT1 antigen. Carbohydrate-lectin interactions may facilitate attachment of the apical surfaces of uterine epithelial cells and trophectoderm during the early stages of placentation.

Binding of acrylonitrile to parvalbumin.

A previous study has shown that acrylonitrile (ACN) has a long half-life in rainbow trout muscle and that [14C]ACN appears to be bound to a 10,000-Da protein in muscle. The labeled protein was purified from muscle of trout exposed to [14C]ACN, separated on 20% SDS-PAGE, and digested for amino acid analysis and sequence analysis. These studies indicated that the labeled protein was the Ca(2+)-binding protein parvalbumin. Parvalbumin is an important calcium-binding protein thought to be involved in the regulation of calcium levels in various parts of the body ranging from neurons to fast-twitch muscle contractions. To study the reaction between parvalbumin and [14C]ACN, frog parvalbumin was incubated with [14C]ACN in vitro under various conditions. These studies indicated that the maximum labeling occurred at 1 nmol/nmol parvalbumin and at pH 7. Amino acid analysis of the labeled protein indicated that the labeled amino acid was probably histidine, and endoproteinase Glu-C (V-8) digestion studies revealed that the 14C was in the 1-81 amino acid segment of the protein, an area that contains two histidines.

Ursodiol prophylaxis against hepatic complications of allogeneic bone marrow transplantation. A randomized, double-blind, placebo-controlled trial.

BACKGROUND: Hepatic complications are a major cause of illness and death after bone marrow transplantation. OBJECTIVE: To confirm the results of a pilot study that indicated that ursodiol prophylaxis could reduce the incidence of veno-occlusive disease of the liver. DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: Tertiary care teaching hospital. PATIENTS: 67 consecutive patients undergoing transplantation with allogeneic bone marrow (donated by a relative) in whom busulfan plus cyclophosphamide was used as the preparative regimen and cyclosporine plus methotrexate was used to prevent graft-versus-host disease. INTERVENTION: Before the preparative regimen was started, patients were randomly assigned to receive ursodiol, 300 mg twice daily (or 300 mg in the morning and 600 mg in the evening if body weight was > 90 kg), or placebo. MEASUREMENTS: Patients were prospectively evaluated for the clinical diagnosis of veno-occlusive disease, the occurrence of acute graft-versus-host disease, and survival. RESULTS: The incidence of veno-occlusive disease was 40% (13 of 32 patients) in placebo recipients and 15% (5 of 34 patients) in ursodiol recipients (P = 0.03). Assignment to placebo was the only pretransplantation characteristic that predicted the development of veno-occlusive disease. The most significant predictor of 100-day mortality was the diagnosis of veno-occlusive disease. The difference in actuarial risk for hematologic relapse in patients with chronic myelogenous leukemia and nonhepatic toxicities between the two groups was not statistically significant (13% in the ursodiol group and 20% in the placebo group; P > 0.2). CONCLUSION: Ursodiol prophylaxis seemed to decrease the incidence of hepatic complications after allogeneic bone marrow transplantation in patients who received a preparative regimen with busulfan plus cyclophosphamide.