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Sensing of nutrients by chemosensory cells in the gastrointestinal tract plays a key role in transmitting food-related signals, linking information about the composition of ingested foods to digestive processes. In recent years, a number of G protein-coupled receptors (GPCR) responsive to a range of nutrients have been identified. Many are localised to intestinal enteroendocrine (chemosensory) cells, promoting hormonal and neuronal signalling locally, centrally and to the periphery. The field of gut sensory systems is relatively new and still evolving. Despite huge interest in these nutrient-sensing GPCR, both as sensors for nutritional status and targets for preventing the development of metabolic diseases, major challenges remain to be resolved. However, the gut expressed sweet taste receptor, resident in L-enteroendocrine cells and responsive to dietary sweetener additives, has already been successfully explored and utilised as a therapeutic target, treating weaning-related disorders in young animals. In addition to sensing nutrients, many GPCR are targets for drugs used in clinical practice. As such these receptors, in particular those expressed in L-cells, are currently being assessed as potential new pathways for treating diabetes and obesity. Furthermore, growing recognition of gut chemosensing of microbial-produced SCFA acids has led further attention to the association between nutrition and development of chronic disorders focusing on the relationship between nutrients, gut microbiota and health. The central importance of gut nutrient sensing in the control of gastrointestinal physiology, health promotion and gut–brain communication offers promise that further therapeutic successes and nutritional recommendations will arise from research in this area.
There is a requirement in some beef markets to slaughter bulls at under 16 months of age. This requires high levels of concentrate feeding. Increasing the slaughter age of bulls to 19 months facilitates the inclusion of a grazing period, thereby decreasing the cost of production. Recent data indicate few quality differences in longissimus thoracis (LT) muscle from conventionally reared 16-month bulls and 19-month-old bulls that had a grazing period prior to finishing on concentrates. The aim of the present study was to expand this observation to additional commercially important muscles/cuts. The production systems selected were concentrates offered ad libitum and slaughter at under 16 months of age (16-C) or at 19 months of age (19-CC) to examine the effect of age per se, and the cheaper alternative for 19-month bulls described above (19-GC). The results indicate that muscles from 19-CC were more red, had more intramuscular fat and higher cook loss than those from 16-C. No differences in muscle objective texture or sensory texture and acceptability were found between treatments. The expected differences in composition and quality between the muscles were generally consistent across the production systems examined. Therefore, for the type of animal and range of ages investigated, the effect of the production system on LT quality was generally representative of the effect on the other muscles analysed. In addition, the data do not support the under 16- month age restriction, based on meat acceptability, in commercial suckler bull production.
Although genetic and environmental factors operating before or around the time of birth have been demonstrated to be relevant to the aetiology of the major psychoses, a seasonal variation in the rates of admission of such patients has long been recognised. Few studies have compared first and readmissions. This study examined for seasonal variation of admission in the major psychoses, and compared diagnostic categories by admission status. Patients admitted to Irish psychiatric inpatient facilities between 1989 and 1994 with an ICD-9/10 diagnosis of schizophrenia or affective disorder were identified from the National Psychiatric Inpatient Reporting System (NPIRS). The data were analysed using a hierarchical log linear model, the chi-square test, a Kolmogorov-Smirnov (KS) type statistic, and the method of Walter and Elwood. The hierarchical log linear model demonstrated significant interactions between the month of admission and admission order (change in scaled deviance 28.77, df = 11, P < 0.003). Both first admissions with mania, and readmissions with bipolar affective disorder exhibited significant seasonality. In contrast, only first admissions with schizophrenia showed significant seasonal effects. Although first admissions with mania and readmissions with bipolar disorder both show seasonality, seasonal influences appear to be more relevant to onset of schizophrenia than subsequent relapse.
This experiment aimed to assess the effect of different indoor winter growth rates (WGR) followed by different concentrate supplementation levels at pasture on meat quality of 90 bulls. During the first winter, bulls were offered grass silage ad libitum and either 3 kg (WGR3) or 6 kg (WGR6) of concentrates. After turn-out to pasture, bulls were offered: grass without supplementation (PO), grass plus 0.2 predicted dry matter intake (DMI) as concentrates (PL) or grass plus 0.4 predicted DMI as concentrates (PH). After finishing, colour, chemical composition (unaged), instrumental texture and sensory characteristics (14 days of ageing) of longissimus thoracis were measured. WGR6 bulls had heavier carcasses than WGR3 bulls. There was an interaction between WGR and supplementation for instrumental texture and redness (a). Within WGR3, PO beef was the most tender, whereas within WRG6, PL was the most tender. However, these differences were not detected by the sensory panel. Within WGR3, redness was the lowest for PL, whereas within WRG6, PO was the least red. No differences were found for chemical composition. The multivariate analysis highlighted WGR as the main variable affecting meat quality characteristics. In conclusion, variations in growth path exerted minor effects on appearance and instrumental texture which did not affect the perception of bull beef by a trained sensory panel.
The Submillimeter Array (SMA) has been used to image the emission from radio recombination lines of hydrogen at subarcsecond angular resolution from the young high-mass star MWC349A in the H26α, H30α, and H31α transitions at 353, 232, and 211 GHz, respectively. Emission was seen over a range of 80 km s−1 in velocity and 50 mas (corresponding to 60 AU for a distance of 1200 pc). The emission at each frequency has two distinct components, one from gas in a nearly edge-on annular disk structure in Keplerian motion, and another from gas lifted off the disk at distances of up to about 25 AU from the star. The slopes of the position-velocity (PV) curves for the disk emission show a monotonic progression of the emission radius with frequency with relative radii of 0.85 ± 0.04, 1, and 1.02 ± 0.01 for the H26α, H30α, and H31α transitions, respectively. This trend is consistent with theoretical excitation models of maser emission from a region where the density decreases with radius and the lower transitions are preferentially excited at higher densities. The mass is difficult to estimate from the PV diagrams because the wind components dominate the emission at the disk edges. The mass estimate is constrained to be only in the range of 10–30 solar masses. The distribution of the wind emission among the transitions is surprisingly different, which reflects its sensitivity to excitation conditions. The wind probably extracts significant angular momentum from the system.
OBJECTIVES/SPECIFIC AIMS: Allergic asthma is a chronic lung disease driven by inappropriate inflammatory responses against inhaled allergens. Neuropilin-2 (NRP2) is a pleiotropic transmembrane receptor expressed in the lung, but its role in allergic airway inflammation is unknown. Here, we characterized NRP2 expression in lung immune cells and investigated the effects of NRP2 deficiency on airway inflammation. METHODS/STUDY POPULATION: NRP2 expression by lung immune cells from NRP2 reporter mice was determined by flow cytometry. NRP2 expression by human alveolar macrophages (AM) from healthy individuals was determined by mRNA analysis and flow cytometry. Airway inflammation in NRP2-deficient mice was assessed by bronchoalveolar lavage (BAL) cytology and inflammatory gene expression in lung tissue. RESULTS/ANTICIPATED RESULTS: NRP2 expression in lung immune cells was negligible under steady-state conditions. In contrast, inhalational exposure to lipopolysaccharide (LPS) adjuvant dramatically induced NRP2 expression in AM, as 63.3% of AM from LPS-treated mice were NRP2+ compared with 1.5% of AM from control mice. Ex vivo treatment of human AM with LPS resulted in a 1.5-fold and 2.6-fold increase in NRP2 mRNA and surface protein expression, respectively. Compared to littermate controls, NRP2-deficient mice had greater numbers of BAL leukocytes and increased lung expression of the T helper type 2 cytokines IL-4 and IL-5. Furthermore, NRP2 deficiency resulted in stochastic development of allergic airway inflammation, as spontaneous airway eosinophilia was detected in 25% (2/8) of NRP2-deficient mice compared with 0% (0/8) of littermate controls. DISCUSSION/SIGNIFICANCE OF IMPACT: NRP2 is expressed by activated human and murine AM and suppresses the spontaneous development of allergic airway inflammation. These findings suggest that NRP2 may play a key role in allergic asthma pathogenesis, and could prove to be an important therapeutic target in patients with asthma and other allergic diseases.
The impact of underlying parental psychological vulnerability on the future mental health of offspring is not fully understood. Using a prospective cohort design, we investigated the association between dysfunctional parental personality traits and risks of offspring self-harm, depression and anxiety.
The association between dysfunctional parental personality traits (monotony avoidance, impulsivity, anger, suspicion, and detachment), measured in both mothers and fathers when offspring were age 9 years, and risk of offspring depression, anxiety and self-harm at age 18 years, was investigated in a population-based cohort (ALSPAC) from over 8000 parents and children.
Higher levels of dysfunctional maternal, but not paternal, personality traits were associated with an increased risk of self-harm, depression, and anxiety in offspring. Maternal associations were best explained by the accumulation of dysfunctional traits. Associations were strongest for offspring depression: Offspring of mothers with three or more dysfunctional personality traits were 2.27 (1.45–3.54, p < 0.001) times as likely to be depressed, compared with offspring of mothers with no dysfunctional personality traits, independently of maternal depression and other variables.
The accumulation of dysfunctional maternal personality traits is associated with the risk of self-harm, depression, anxiety in offspring independently of maternal depression and other confounding variables. The absence of associations for equivalent paternal traits makes a genetic explanation for the findings unlikely. Further research is required to elucidate the underlying mechanism. Mothers with high levels of dysfunctional personality traits may benefit from additional support to reduce the risk of adverse psychological outcomes occurring in their offspring.
Haiti has the highest human rabies burden in the Western Hemisphere. There is no published literature describing the public's perceptions of rabies in Haiti, information that is critical to developing effective interventions and government policies. We conducted a knowledge, attitudes and practices survey of 550 community members and 116 health professionals in Pétionville, Haiti in 2013 to understand the perception of rabies in these populations. The majority of respondents (85%) knew that dogs were the primary reservoir for rabies, yet only 1% were aware that bats and mongooses could transmit rabies. Animal bites were recognized as a mechanism of rabies transmission by 77% of the population and 76% were aware that the disease could be prevented by vaccination. Of 172 persons reporting a bite, only 37% sought medical treatment. The annual bite incidence rate in respondents was 0·9%. Only 31% of bite victims reported that they started the rabies vaccination series. Only 38% of respondents reported that their dog had been vaccinated against rabies. The majority of medical professionals recognized that dogs were the main reservoir for rabies (98%), but only 28% reported bats and 14% reported mongooses as posing a risk for rabies infection. Bites were reported as a mechanism of rabies transmission by 73% of respondents; exposure to saliva was reported by 20%. Thirty-four percent of medical professionals reported they would wash a bite wound with soap and water and 2·8% specifically mentioned rabies vaccination as a component of post-bite treatment. The majority of healthcare professionals recommended some form of rabies assessment for biting animals; 68·9% recommended a 14-day observation period, 60·4% recommended a veterinary consultation, and 13·2% recommended checking the vaccination status of the animal. Fewer than 15% of healthcare professionals had ever received training on rabies prevention and 77% did not know where to go to procure rabies vaccine for bite victims. Both study populations had a high level of knowledge about the primary reservoir for rabies and the mode of transmission. However, there is a need to improve the level of knowledge regarding the importance of seeking medical care for dog bites and additional training on rabies prevention for healthcare professionals. Distribution channels for rabies vaccines should be evaluated, as the majority of healthcare providers did not know where rabies vaccines could be obtained. Canine rabies vaccination is the primary intervention for rabies control programmes, yet most owned dogs in this population were not vaccinated.
Little is known about the relative extent of crime against people with
severe mental illness (SMI).
To assess the prevalence and impact of crime among people with SMI
compared with the general population.
A total of 361 psychiatric patients were interviewed using the national
crime survey questionnaire, and findings compared with those from 3138
general population controls participating in the contemporaneous national
Past-year crime was experienced by 40% of patients v.
14% of controls (adjusted odds ratio (OR) = 2.8, 95% CI 2.0–3.8); and
violent assaults by 19% of patients v. 3% of controls
(adjusted OR = 5.3, 95% CI 3.1–8.8). Women with SMI had four-, ten- and
four-fold increases in the odds of experiencing domestic, community and
sexual violence, respectively. Victims with SMI were more likely to
report psychosocial morbidity following violence than victims from the
People with SMI are at greatly increased risk of crime and associated
morbidity. Violence prevention policies should be particularly focused on
people with SMI.
Domestic and sexual violence are significant public health problems but little is known about the extent to which men and women with severe mental illness (SMI) are at risk compared with the general population. We aimed to compare the prevalence and impact of violence against SMI patients and the general population.
Three hundred and three randomly recruited psychiatric patients, in contact with community services for ⩾1 year, were interviewed using the British Crime Survey domestic/sexual violence questionnaire. Prevalence and correlates of violence in this sample were compared with those from 22 606 general population controls participating in the contemporaneous 2011/12 national crime survey.
Past-year domestic violence was reported by 27% v. 9% of SMI and control women, respectively [odds ratio (OR) adjusted for socio-demographics, aOR 2.7, 95% confidence interval (CI) 1.7–4.0], and by 13% v. 5% of SMI and control men, respectively (aOR 1.6, 95% CI 1.0–2.8). Past-year sexual violence was reported by 10% v. 2.0% of SMI and control women respectively (aOR 2.9, 95% CI 1.4–5.8). Family (non-partner) violence comprised a greater proportion of overall domestic violence among SMI than control victims (63% v. 35%, p < 0.01). Adulthood serious sexual assault led to attempted suicide more often among SMI than control female victims (53% v. 3.4%, p < 0.001).
Compared to the general population, patients with SMI are at substantially increased risk of domestic and sexual violence, with a relative excess of family violence and adverse health impact following victimization. Psychiatric services, and public health and criminal justice policies, need to address domestic and sexual violence in this at-risk group.
The neurocognitive deficits and other correlates of problem gambling are also observable in individuals with lower cognitive abilities, suggesting that a low IQ may be a determinant of problem gambling. There has been very little research into this possibility. This study aimed to investigate the characteristics associated with problem gambling in a large population-based study in England, with a particular focus on IQ.
The Adult Psychiatric Morbidity Survey (APMS) 2007 comprised detailed interviews with 7403 individuals living in private households in England. Problem gambling was ascertained using a questionnaire based on DSM-IV criteria. Verbal IQ was estimated using the National Adult Reading Test (NART). Confounders included socio-economic and demographic factors, common mental disorders, impulsivity, smoking, and hazardous drug and alcohol use.
More than two-thirds of the population reported engaging in some form of gambling in the previous year, but problem gambling was rare [prevalence 0.7%, 95% confidence interval (CI) 0.5–1.0]. The odds of problem gambling doubled with each standard deviation drop in estimated verbal IQ [adjusted odds ratio (OR) 2.1, 95% CI 1.3–3.4, p = 0.003], after adjusting for other characteristics associated with problem gambling including age, sex, socio-economic factors, drug and alcohol dependence, smoking, impulsivity and common mental disorders. There was no strong relationship observed between IQ and non-problem gambling.
People with lower IQs may be at a higher risk of problem gambling. Further work is required to replicate and study the mechanisms behind these findings, and may aid the understanding of problem gambling and inform preventative measures and interventions.
Maternal protein restriction (MPR) during pregnancy impaired the reproduction of male offspring. We investigated, during the first wave of spermatogenesis, whether MPR exerts deleterious effects on germ cell proliferation and differentiation, as well as androgen receptor (AR) protein expression, which was used as a marker for Sertoli cell (SC) maturation. At the beginning of pregnancy (day 0), dams were fed a control diet (C: 20% casein) or a restricted isocaloric diet (R: 10% casein). After birth, four groups were established: CC, RR, CR and RC (first letter diet during pregnancy and second during lactation). Male offspring were studied at postnatal days 14, 21 and 36. At birth, pup body weight was unchanged. Body weight and testis weight were reduced in RR and CR groups at all ages evaluated. MPR delayed the germinal epithelium development at all ages evaluated. On performing Western blot and immunohistochemistry, AR expression was found to be lower in the three restricted groups. The results suggest that MPR during pregnancy and/or lactation delays SC maturation and germ cell differentiation, and affects intratubular organization. These changes might be responsible for the lower fertility rate at older ages.
Common mental disorders (CMDs) are associated with occupational impairment and the receipt of disability benefits (DBs). Little is known about the relationship between personality disorders (PDs) and work disability, and whether the association between CMDs and work disability is affected by the presence of co-morbid PDs. The aim of this study was to examine the association between DB and individual categories of PDs, with special attention to the effect of co-morbid CMDs on this association.
The association between DB and PD was examined using data from the 2000 British National Survey of Psychiatric Morbidity. Probable PD caseness was identified using the Structured Clinical Interview for DSM-IV Personality Disorders (SCID-II) screening questionnaire. The impact of CMDs, assessed with the revised version of the Clinical Interview Schedule (CIS-R), was examined as a covariate and in a stratified analysis of co-morbidity. Other covariates included sociodemographic factors, long-standing illnesses and substance use.
Probable PD was associated with DB, with the strongest associations found for borderline, dependent and schizotypal PD. Antisocial PD was not associated with DB. The relationship between PD and DB was strongly modified by CMD, reducing the association from an odds ratio (OR) of 2.84 to 1.34 [95% confidence interval (CI) 1.00–1.79)]. In the stratified analysis, co-morbid PD and CMD showed a stronger association with DB than PD without CMD but, when fully adjusted, this effect was not significantly different from the association between CMD without PD.
Individuals screening positive for PD are more likely to experience severe occupational outcomes, especially in the presence of co-morbid CMD.
By using the citrate reduction procedure we have synthesized Ag nanoparticles, applying several conditions of preparation, being after characterized by UV-visible spectrophotometry. Following a logical sequence, the starting experiment was realized varying the reaction time, after that it was varied the concentration of the reductor agent, and finally it was varied the volume of the reductor agent. According to this methodology, TEM measurements show that firstly we have nanostructures with different shape and size, whereas in the last part of the experiment we have Ag nanoparticles with homogeneous shape and size.