Miracle-dz/UniFAR-FTUs huggingface dataset:
Fish intake may limit the increase in risk of coronary heart disease morbidity and mortality among heavy smokers. The Honolulu Heart Program.

BACKGROUND Research has shown that fish consumption limits damage to the lungs caused by cigarette smoking, possibly by the effects of fish on arachidonic acid metabolism. We explored this fish-smoking interaction using coronary heart disease (CHD) incidence and mortality as the outcome. METHODS AND RESULTS The Honolulu Heart Program began in 1965 to follow a cohort of 8006 Japanese-American men aged 45 to 65 years who lived on Oahu, Hawaii, in 1965. Fish intake was measured at baseline by use of a questionnaire. For current smokers at baseline (n = 3310) who reported low fish intake (< 2 times/wk), age-adjusted 23-year CHD mortality rates increased with the number of cigarettes smoked per day (2.3, 3.1, and 6.9 per 1000 person-years for men who smoked < 20, 20 to 30, and > 30 cigarettes/d, respectively; trend test P < .0001). Among current smokers whose fish intake was high (> or = 2 times/wk), CHD mortality rates showed no relation with cigarettes/d (3.7, 3.2, and 3.7 per 1000 person-years for the corresponding levels of smoking). A Cox proportional hazards model based on current smokers, adjusted for age, years in Japan, calories/d, alcohol intake, physical activity index, years smoked, hypertension, and serum cholesterol, blood glucose, and uric acid levels, was examined. In the high-smoking group, the risk factor-adjusted relative risk (RR) for CHD mortality among those with high fish intake was half that of those with low fish consumption (RR = 0.5, 95% confidence interval = 0.28 to 0.91). A Cox model that adjusted for similar risk factors confirmed a significant interaction of cigarettes/d and fish intake (P < .01) on CHD mortality. Analyses for CHD incidence showed similar results. CONCLUSIONS Despite the findings of this investigation, the public health message for smokers continues to be to stop smoking. However, an interaction between fish intake and cigarette smoking is biologically plausible and deserves further investigation. The study of this phenomenon may shed light on the biological mechanisms by which cigarette smoking leads to CHD.
A comprehensive examination of Smad4, Smad6 and Smad7 mRNA expression in pancreatic ductal adenocarcinoma.

BACKGROUND Smad4, Smad6 and Smad7 are important molecules in TGF-beta pathway, which plays an important role in pancreatic ductal adenocarcinoma (PDAC) biology. Aims : This study examined the expression profiles of Smad4, Smad6 and Smad7 mRNA in patient samples of PDAC and their relationship to Smad protein expression, SMAD4 gene mutations, clinicopathological parameters and patient survival. SETTINGS AND DESIGN Surgically resected, paired normal and tumor tissues of 25 patients of PDAC were studied. MATERIALS AND METHODS Protein and mRNA levels were assessed by immunohistochemistry and RT-PCR, respectively. STATISTICAL METHODS Statistical analysis was done using Student's t-test, Pearson's chi-square test, Spearman's Rank Correlation, Pearson's Correlation test and Kaplan-Meier Logrank test. RESULTS While there was a highly significant difference in the protein levels of all three Smads in tumor as compared to normal samples, mRNA levels were significantly different only for Smad4. Protein levels did not correlate significantly with mRNA levels for any of the three Smads. The mRNA levels of Smad4 and Smad6, Smad4 and Smad7, and Smad6 and Smad7 in tumor samples showed a significant positive correlation. The relationship of Smad4 mRNA expression to SMAD4 gene status and Smad4 protein expression was discordant and there was no significant correlation between mRNA expression and clinicopathological parameters and patient survival. CONCLUSION The absence of concordance between SMAD4 gene status, mRNA expression and Smad4 protein expression suggests the presence of other regulatory mechanisms in Smad4 transcription and translation in PDAC.
The Andalusian trial on heroin-assisted treatment: a 2 year follow-up.

INTRODUCTION AND AIMS In 2003, a randomised controlled trial comparing injected diacetylmorphine and oral methadone was carried out in Andalusia, Spain. The subsequent follow-up study evaluated the health and drug use status of participants, 2 years after the completion of the trial. DESIGN AND METHODS This follow-up cohort study was carried out between March and August 2006. Data collected included information on socio-demographics, drug use, health and health-related quality of life. We compared data collected before randomisation and at 2 years for the following three groups: those currently on heroin-assisted treatment (C-HAT), those who have discontinued HAT (D-HAT), and those who have never received HAT (N-HAT). RESULTS From the total 62 randomised participants in 2003, 54 (87%) were interviewed for this study. Participants were distributed as follow: C-HAT 44.4% (24), N-HAT 22.2% (12) and D-HAT 33.3% (18). Illicit heroin use had a statistically significant decrease in the three groups from baseline to 2 years post trial. Mean days of heroin use were 2.42 (SD = 3.02); 6.56 (SD = 9.48) and 13.92 (SD = 12.59) for the C-HAT, D-HAT and N-HAT groups, respectively. Those currently on HAT were the only group that sustained at 2 years, their marked improvement in health after 9 months of treatment during the trial period. DISCUSSION AND CONCLUSIONS Patients who received HAT showed better outcomes compared with those not on HAT. The results of this study strengthen the evidence showing that HAT can improve and stabilise the health of long-term heroin users with severe comorbidities and high mortality.
Gene Expression Analyses Identify Narp Contribution in the Development of l-DOPA-Induced Dyskinesia

In Parkinson's disease, long-term dopamine replacement therapy is complicated by the appearance of l-DOPA-induced dyskinesia (LID). One major hypothesis is that LID results from an aberrant transcriptional program in striatal neurons induced by l-DOPA and triggered by the activation of ERK. To identify these genes, we performed transcriptome analyses in the striatum in 6-hydroxydopamine-lesioned mice. A time course analysis (0–6 h after treatment with l-DOPA) identified an acute signature of 709 genes, among which genes involved in protein phosphatase activity were overrepresented, suggesting a negative feedback on ERK activation by l-DOPA. l-DOPA-dependent deregulation of 28 genes was blocked by pretreatment with SL327, an inhibitor of ERK activation, and 26 genes were found differentially expressed between highly and weakly dyskinetic animals after treatment with l-DOPA. The intersection list identified five genes: FosB, Th, Nptx2, Nedd4l, and Ccrn4l. Nptx2 encodes neuronal pentraxin II (or neuronal activity-regulated pentraxin, Narp), which is involved in the clustering of glutamate receptors. We confirmed increased Nptx2 expression after l-DOPA and its blockade by SL327 using quantitative RT-PCR in independent experiments. Using an escalating l-DOPA dose protocol, LID severity was decreased in Narp knock-out mice compared with their wild-type littermates or after overexpression of a dominant-negative form of Narp in the striatum. In conclusion, we have identified a molecular signature induced by l-DOPA in the dopamine-denervated striatum that is dependent on ERK and associated with LID. Here, we demonstrate the implication of one of these genes, Nptx2, in the development of LID.
A Review of Indian Research on Co-occurring Psychiatric Disorders and Alcohol use Disorders

Excessive use of alcohol has been identified as a major contributor to the global burden of disease. Excessive use of alcohol is a component cause of more than 200 disease and injury conditions. Alcohol use has been associated with increased morbidity and mortality across all regions of the world including South-East Asia. Epidemiological as well as clinic-based studies from Western countries have reported a high prevalence of co-occurrence of alcohol use disorder and psychiatric disorders. The research has established the clinical relevance of this comorbidity as it is often associated with poor treatment outcome, severe illness course, and high service utilization. Understandably, dual disorders in from of alcohol use disorders and psychiatric disorders present diagnostic and management challenge. The current article is aimed to review systematically the published Indian literature on comorbid alcohol use disorders and psychiatric disorders.
Survey of porcine circovirus 2 and postweaning multisystemic wasting syndrome in New South Wales piggeries.

OBJECTIVE To determine if postweaning multisystemic wasting syndrome (PMWS) is occurring in the New South Wales pig population and to determine the current and past seroprevalence of porcine circovirus 2 (PCV2). DESIGN Pig veterinarians were contacted seeking submission of tissues from animals with clinical signs suggestive of PMWS. Samples were also accepted from suspected cases of porcine dermatitis and nephropathy syndrome (PDNS). Serological studies were also undertaken on archival sera and sera submitted during the study. PROCEDURE Histopathological examination was undertaken on all tissues submitted. The presence of PCV2 was determined by immunohistochemistry. Sera were tested for PCV2 using a commercial enzyme linked immunosorbent assay kit modified for testing of serum samples. RESULTS No cases of PMWS were identified during the study. Four cases of PDNS were identified. PCV2 antibody was detected in 80% of archival sera from 1995 and 75.8% from 2001. Seroprevalence in samples tested during 2002-2003 was 87.8%. PCV2 was isolated from tissues of a case of PDNS. CONCLUSION PCV2 is widespread in the New South Wales pig population and has been since at least 1995. This study describes the first isolation of an Australian PCV2. No cases of PMWS were identified in New South Wales.
Mature hippocampal astrocytes exhibit functional metabotropic and ionotropic glutamate receptors in situ

Astrocytes closely contact neurons where they respond to neuronally released glutamate in immature brain slices. In previous studies, neither metabotropic nor ionotropic glutamate receptor–mediated responses were detected by imaging Ca2+ in astrocytes from mature (P21–P42) animals, suggesting astrocyte glutamate receptors only contribute to hippocampus physiology during development. In contrast to Ca2+ imaging, published electrophysiological experiments suggest P30–P35 astrocytes have α‐amino‐hydroxy‐5‐methyl‐4–isoxazolepropionic acid (AMPA) receptors. For this study, we imaged astrocytes in P31–P38 hippocampal slices to determine if metabotropic and ionotropic glutamate receptor activation elevates intracellular calcium in mature astrocytes. Drugs were perfused while [Ca2+]i was monitored (confocal imaging) in cells loaded with Calcium Green 1‐AM. Imaged cells were subsequently identified as astrocytes by GFAP/S‐100 immunostaining. Astrocytic Ca2+ increased after glutamate application in the presence of a glutamate uptake inhibitor. An agonist at group I/II metabotropic glutamate receptors, (±)‐1‐aminocyclopentane‐trans‐1,3‐dicarboxylic acid (t‐ACPD), elicited Ca2+ increases as did group I agonist 3,5‐dihydroxyphenylglycine (DHPG), suggesting that mature astrocytes respond to glutamate via metabotropic glutamate receptors. AMPA also elicited Ca2+ elevations that were inhibited by 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione (CNQX) and occurred after treatment with ω‐conotoxin MVIIC to block neurotransmitter release. These results demonstrate that astrocytes in mature hippocampus have functional ionotropic and metabotropic glutamate receptors that regulate astrocytic calcium levels. Glutamatergic regulation of astrocytic [Ca2+]i may be involved in synapse modeling, long‐term potentiation, excitotoxicity and other events dependent on glutamatergic transmission in adult hippocampus. GLIA 26:1‐11, 1999. © 1999 Wiley‐Liss, Inc.
Progression of alachlor‐induced olfactory mucosal tumours

Alachlor is an herbicide used primarily in the production of corn (maize), peanuts, and soybeans and is associated with cancer of the nasal cavity, thyroid, and stomach in rats. Previous work from our laboratory demonstrated that the nasal cavity tumours originate from the olfactory mucosa, and that neoplasms were present following 6 months of exposure (126 mg/kg/day in the diet). The studies presented herein were conducted to determine more precisely the earliest time point at which alachlor‐induced tumours were present, and to describe the histological changes that occur en route to tumour formation. We determined that dramatic histological changes, including respiratory metaplasia of the olfactory mucosa, were present following 3 months of exposure, and the earliest alachlor‐induced olfactory mucosal tumours were detected following 5 months of treatment. Because alachlor is positive in short‐term mutagenicity assays with olfactory mucosal activation, and because of the relatively short time‐to‐tumour formation observed with alachlor, we also conducted a ‘stop’ study in which rats were treated with alachlor for 1 month and then held without further treatment for an additional 5 months. This study demonstrated that abbreviated alachlor exposure did not result in subsequent tumour formation within the 6‐month observation period.
The personal and professional impact of undertaking an educational module on human caring.

AIM OF THE STUDY To evaluate the personal and professional impact of undertaking a 15-week degree level module on nursing as human caring. BACKGROUND Little is known about how to teach and enhance caring practices. An innovative module was implemented on a 4-year, postregistration nursing degree course in Wales to develop students' capacity to be caring practitioners. An understanding of its impact was sought to facilitate better future preparation of students. RESEARCH METHODS A full cohort of 25 part-time students, divided into four groups, participated in audio-taped focus groups before and after undertaking the module. FINDINGS From a personal perspective, the students experienced increased spiritual awareness characterized by: (1) enhanced connecting relationships with self and others, (2) finding purpose and meaning in life, and (3) clarification of values. Professionally, the module resulted in: (1) an increased knowledge and understanding of caring theory and related concepts, (2) a more holistic approach to care, and (3) enhanced caring practice. CONCLUSIONS Education may enhance students' capacity to be caring practitioners. Spirituality, in particular, was illuminated for the students as an important means of developing both themselves and their caring practices. They experienced transformative learning, and the focus groups, employed as the research method, served as a useful vehicle in this process. Reflective groups will be used as a teaching method on future modules.
THIS ARTICLE HAS BEEN RETRACTED: Spinal 2‐chloroprocaine: effective dose for ambulatory surgery

Background: There is an interest in finding a safe, short‐acting spinal anaesthetic, suitable for ambulatory surgery. In this prospective study, we evaluated the effective dose of plain 2‐chloroprocaine (2‐CP) for lower limb surgery, including knee arthroscopy and saphenectomy.
Board Monitoring in a Privately Held Firm: When Does CEO Duality Matter? The Moderating Effect of Ownership

Drawing from agency theory and the attention‐based view of the firm, this study extends the understanding of the conditions under which CEO duality is negatively associated with board monitoring in a privately held firm context. Measuring monitoring in terms of board members’ involvement in behavioral control, output control, and strategy control tasks (Huse [Huse, M., 2005]), results show that CEO duality is significantly and negatively related only to the behavioral control task. In addition, we show that this negative effect is contingent on whether ownership is concentrated in the hands of a controlling shareholder as well as the type of controlling shareholder.
Association between human opioid receptor genes polymorphisms and pressure pain sensitivity in females*

This study examined the association between pressure pain sensitivity and various single nucleotide polymorphisms (SNPs) of human μ‐, κ‐, and δ‐opioid receptor (i.e. OPRM1, OPRK1, and OPRD1) genes in 72 healthy adult Taiwanese women of Han Chinese race. Pressure pain threshold and tolerance were measured by an algometer and polymorphisms of the opioid receptor genes determined from blood samples. Our data revealed that pressure pain threshold, but not tolerance, in subjects with the minor allele (termed ‘GA’) genotype of the IVS2+31G>A polymorphism of the OPRM1 gene was significantly higher than those with major allele (termed ‘GG’) genotype. Neither pressure pain threshold nor tolerance between major and minor alleles of other SNPs of the OPRM1, OPRK1, and OPRD1 genes were significantly different. These data suggest an association between the IVS2+31G>A SNP of the OPRM1 gene and pressure pain sensitivity in healthy adult females.
Molecular Cloning of a Peptidylglycine α-Hydroxylating Monooxygenase from Sea Anemones

Abstract Cnidarians are the lowest animal group having a nervous system. The primitive nervous systems of cnidarians produce large amounts of a variety of neuropeptides, of which many or perhaps all are amidated at their C terminus. In vertebrates, peptide amidation is catalyzed by two enzymes acting sequentially, peptidyl-glycine α-hydroxylating monooxygenase (PHM) and peptidyl-α-hydroxyglycine α-amidating lyase (PAL). In mammals both enzymatic activities are contained within a bifunctional protein that is coded for by a single gene. Using PCR and degenerated oligonucleotides derived from conserved regions of PHM, we have now cloned a PHM from the sea anemone Calliactis parasitica showing 42% amino acid sequence identity with rat PHM. Among the conserved (identical) amino acid residues are five histidine and one methionine residue, which bind two Cu 2+ atoms that are essential for PHM activity. No cDNA coding for PAL could be identified, suggesting that sea anemone PAL is coded for by a gene that is different from the sea anemone PHM gene, a situation similar to the one found in insects. This is the first report on the molecular cloning of a cnidarian PHM.
The Effect of a Surgery-Specific Cardiac Output–Guided Haemodynamic Algorithm on Outcomes in Patients Undergoing Pancreaticoduodenectomy in a High-Volume Centre: A Retrospective Comparative Study

In this retrospective observational study performed in a high-volume hepatobiliary–pancreatic unit, we evaluated the effect of a surgery-specific goal-directed therapy (GDT) physiologic algorithm on complications and length of hospital stay. We compared patients who underwent pancreaticoduodenectomy with either a standardised Enhanced Recovery After Surgery program (usual care group), or a standardised Enhanced Recovery After Surgery program in combination with a surgery-specific cardiac output–guided algorithm (GDT group). We included 145 consecutive patients: 47 in the GDT group and 98 in the usual care group. Multivariable associations between GDT and lengths of stay and complications were investigated using negative binomial regression. Postoperative complications were common and occurred at similar frequencies amongst the GDT and usual care groups: 64% versus 68% respectively, P=0.71; odds ratio 0.82; (95% confidence interval 0.39–1.70). There were fewer cardiorespiratory complications in the GDT group. Median (interquartile range) length of hospital stay was ten days (8.0–14.0) in the GDT group compared to 13 days (8.8–21.3) in the usual care group, P=0.01. Median (interquartile range) total intraoperative fluid was 3,000 ml (2,050–4,175) in the GDT group compared to 4,500 ml (3,275–5,325) in the usual care group, P <0.0001; but by day one, the median (interquartile range) fluid balance was similar (1,198 ml [700–1,729] in the GDT group versus 977 ml [419–2,044] in the usual care group, P=0.96). Use of vasoactive medications was higher in the GDT group. In our patients undergoing pancreaticoduodenectomy, GDT was associated with restrictive intraoperative fluid intervention, fewer cardiorespiratory complications and a shorter hospital length of stay compared to usual care. However, we could not exclude an influence of surgical caseload, which we have previously found to be an important variable. We also could not relate the increased hospital length of stay to cardiorespiratory complications in individual patients. Therefore, these observational retrospective findings would require confirmation in a prospective randomised study.
Molecular Testing in Melanoma

AbstractMelanoma is the deadliest form of skin cancer and is increasing in incidence. Recent treatment advances have been made, but there remains a need for continued development of effective therapy options, as treatment rarely leads to cure. Many melanomas contain somatic mutations involved in tumor pathogenesis. Accurate identification of these mutations is necessary to stratify patients for the purpose of treatment and potential for clinical trials, given the absence or presence of a specific mutation. There are a number of techniques available that will identify genetic mutations and genomic aberrations present within melanoma tumor samples which are reviewed here. The type of mutation and sample number will drive selection of a given mutation detection strategy. The strengths and weaknesses, along with limitations, of the various methods will also be discussed. The discovery of somatic mutations integral in melanoma will increase our understanding of tumor pathogenesis and should facilitate identification of mutations relevant to clinical treatment decisions, advancing progress toward personalized medicine.
Maternal and fetal adropin levels in gestational diabetes mellitus

Abstract Aim: To evaluate maternal and cord blood serum adropin concentrations in pregnant women with gestational diabetes mellitus (GDM). Study design: Twenty pregnant women with GDM and 20 gestational age-matched healthy pregnant women participated in the study. Maternal serum and cord blood adropin levels were assessed using an enzyme immunosorbent assay, at the time of birth. The relation of maternal serum and cord blood adropin levels with metabolic parameters were also assessed. Results: The mean maternal and cord serum adropin in the GDM group were significantly lower than those of the control women (P=0.01 and P<0.001, respectively). Maternal serum adropin levels did not correlate with either fetal serum adropin levels or maternal metabolic values. Conclusion: The data suggest that low adropin levels may contribute to the underlying pathogenesis of GDM.