A pilot study of an integrated mental health, social and medical model for diabetes care in an inner-city setting: Three Dimensions for Diabetes (3DFD).

AIMS: We examined the effectiveness of a service innovation, Three Dimensions for Diabetes (3DFD), that consisted of a referral to an integrated mental health, social care and diabetes treatment model, compared with usual care in improving biomedical and health economic outcomes. METHODS: Using a non-randomized control design, the 3DFD model was offered in two inner-city boroughs in London, UK, where diabetes health professionals could refer adult residents with diabetes, suboptimal glycaemic control [HbA1c ≥ 75 mmol/mol (≥ 9.0%)] and mental health and/or social problems. In the usual care group, there was no referral pathway and anonymized data on individuals with HbA1c ≥ 75 mmol/mol (≥ 9.0%) were collected from primary care records. Change in HbA1c from baseline to 12 months was the primary outcome, and change in healthcare costs and biomedical variables were secondary outcomes. RESULTS: 3DFD participants had worse glycaemic control and higher healthcare costs than control participants at baseline. 3DFD participants had greater improvement in glycaemic control compared with control participants [-14 mmol/mol (-1.3%) vs. -6 mmol/mol (-0.6%) respectively, P < 0.001], adjusted for confounding. Total follow-up healthcare costs remained higher in the 3DFD group compared with the control group (mean difference £1715, 95% confidence intervals 591 to 2811), adjusted for confounding. The incremental cost-effectiveness ratio was £398 per mmol/mol unit decrease in HbA1c , indicating the 3DFD intervention was more effective and costed more than usual care. CONCLUSIONS: A biomedical, psychological and social criteria-based referral system for identifying and managing high-cost and high-risk individuals with poor glycaemic control can lead to improved health in all three dimensions.

Epigenetic reprogramming during spermatogenesis and male factor infertility.

Infertility is an often devastating diagnosis encountered by around one in six couples who are trying to conceive. Moving away from the long-held belief that infertility is primarily a female issue, it is now recognised that half, if not more, of these cases may be due to male factors. Recent evidence has suggested that epigenetic abnormalities in chromatin dynamics, DNA methylation or sperm-borne RNAs may contribute to male infertility. In light of advances in deep sequencing technologies, researchers have been able to increase the coverage and depth of sequencing results, which in turn has allowed more comprehensive analyses of spermatozoa chromatin dynamics and methylomes and enabled the discovery of new subsets of sperm RNAs. This review examines the most current literature related to epigenetic processes in the male germline and the associations of aberrant modifications with fertility and development.

Imprinted and DNA methyltransferase gene expression in the endometrium during the pre- and peri-implantation period in cattle.

The endometrium plays a key role in providing an optimal environment for attachment of the preimplantation embryo during the early stages of pregnancy. Investigations over the past 2 decades have demonstrated that vital epigenetic processes occur in the embryo during the preimplantation stages of development. However, few studies have investigated the potential role of imprinted genes and their associated modulators, the DNA methyltransferases (DNMTs), in the bovine endometrium during the pre- and peri-implantation period. Therefore, in the present study we examined the expression profiles of the DNMT genes (3A, 3A2 and 3B) and a panel of the most comprehensively studied imprinted genes in the endometrium of cyclic and pregnant animals. Intercaruncular (Days 5, 7, 13, 16 and 20) and caruncular (Days 16 and 20) regions were analysed for gene expression changes, with protein analysis also performed for DNMT3A, DNMT3A2 and DNMT3B on Days 16 and 20. An overall effect of day was observed for expression of several of the imprinted genes. Tissue-dependent gene expression was detected for all genes at Day 20. Differences in DNMT protein abundance were mostly observed in the intercaruncular regions of pregnant heifers at Day 16 when DNMT3A, DNMT3A2 and DNMT3B were all lower when compared with cyclic controls. At Day 20, DNMT3A2 expression was lower in the pregnant caruncular samples compared with cyclic animals. This study provides evidence that epigenetic mechanisms in the endometrium may be involved with implantation of the embryo during the early stages of pregnancy in cattle.

Exposure of bovine oocytes and embryos to elevated non-esterified fatty acid concentrations: integration of epigenetic and transcriptomic signatures in resultant blastocysts.

BACKGROUND: Metabolic stress associated with negative energy balance in high producing dairy cattle and obesity in women is a risk factor for decreased fertility. Non-esterified fatty acids (NEFA) are involved in this pathogenesis as they jeopardize oocyte and embryo development. Growing evidence indicates that maternal metabolic disorders can disturb epigenetic programming, such as DNA methylation, in the offspring. Oocyte maturation and early embryo development coincide with methylation changes and both are sensitive to adverse environments. Therefore, we investigated whether elevated NEFA concentrations affect establishment and maintenance of DNA methylation in oocytes and embryos, subsequently altering transcriptomic profiles and developmental competence of resultant blastocysts. RESULTS: Bovine oocytes and embryos were exposed to different NEFA concentrations in separate experiments. In the first experiment, oocytes were matured in vitro for 24 h in medium containing: 1) physiological ("BASAL") concentrations of oleic (OA), palmitic (PA) and stearic (SA) acid or 2) pathophysiological ("HIGH COMBI") concentrations of OA, PA and SA. In the second experiment, zygotes were cultivated in vitro for 6.5 days under BASAL or HIGH COMBI conditions. Developmental competence was evaluated by assessing cleavage and blastocyst rate. Overall gene expression and DNA methylation of resultant blastocysts were analyzed using microarray. DNA methylation data were re-evaluated by pyrosequencing. HIGH COMBI-exposed oocytes and embryos displayed a lower competence to develop into blastocysts compared to BASAL-exposed counterparts (19.3% compared to 23.2% and 18.2% compared to 25.3%, respectively) (P < 0.05). HIGH COMBI-exposed oocytes and embryos resulted in blastocysts with altered DNA methylation and transcriptomic fingerprints, compared to BASAL-exposed counterparts. Differences in gene expression and methylation were more pronounced after exposure during culture compared to maturation suggesting that zygotes are more susceptible to adverse environments. Main gene networks affected were related to lipid and carbohydrate metabolism, cell death, immune response and metabolic disorders. CONCLUSIONS: Overall, high variation in methylation between blastocysts made it difficult to draw conclusions concerning methylation of individual genes, although a clear overview of affected pathways was obtained. This may offer clues regarding the high rate of embryonic loss and metabolic diseases during later life observed in offspring from mothers displaying lipolytic disorders.

Substance use and self-harm emergency department presentations during COVID19: evidence from a National Clinical Programme for Self-Harm.

INTRODUCTION: Given the evidence that drinking patterns and self-harm hospital presentations have changed during COVID-19, this study aimed to examine any change in self-harm and suicide-related ideation presentations, together with any possible contribution made by alcohol or substance misuse, to Irish Emergency Departments in 2020, compared with 2018 and 2019. METHODS: A population-based cohort with self-harm and suicide-related ideation presenting to Irish hospitals derived from the National Clinical Programme for Self-Harm was analysed. Descriptive analyses were conducted based on sociodemographic variables and types of presentation for the period January to August 2020 and compared with the same period in 2018 and 2019. Binomial regression analyses were performed to investigate the independent effect of demographic characteristics and pre/during COVID-19 periods on the use of substances as contributory factors in the self-harm and suicide-related ideation presentations. RESULTS: 12,075 presentations due to self-harm and suicide-related ideation were recorded for the periods January-August 2018-2020 across nine emergency departments. The COVID-19 year was significantly associated with substances contributing to self-harm and suicide-related ideation ED presentations (OR = 1.183; 95% CI, 1.075-1.301, p < 0.001). No changes in the demographic characteristics were found for those with self-harm or suicide-related ideation across the years. Suicide-related ideation seemed to be increased after May 2020 compared with previous years. In terms of self-harm episodes with comorbid drug and alcohol overdose and poisoning, these were significantly increased in January-August 2020, compared with previous timepoints (χ2 = 42.424, df = 6, p < 0.001). CONCLUSION: An increase in suicide-related ideation and substance-related self-harm presentations may indicate longer term effects of the pandemic and its relevant restrictions. Future studies might explore whether those presenting with ideation will develop a risk of suicide in post-pandemic periods.

Attempted suicide: does lethality matter?

OBJECTIVES: To investigate whether high-lethality suicide attempters align to the demographic and clinical features observed in completed suicide in the national and international literature, and whether low-lethality attempters more closely align with the clinical profile of non-attempter ideators. METHODS: A retrospective chart review of adult suicide ideators and attempters presenting to an urban tertiary care hospital was performed. Suicide ideators (n = 50) and attempters (n = 50) were coded for variables including demographics and clinical characteristics (e.g. psychiatric diagnosis and previous suicide attempt). Method and lethality of suicide attempt were coded using the medical Lethality Rating Scale. RESULTS: High-lethality attempters were more likely to be younger in age than low-lethality attempters (p = 0.026) and ideators (p = 0.041). The lethality scores of suicide attempts were significantly inversely correlated with age (p = 0.017). CONCLUSIONS: Our study adds to the small but increasing body of literature investigating the characteristics of high-lethality suicide attempters and suggests younger adult age is a risk factor for a high-lethality attempt. Further understanding of this unique group would be aided by widespread agreement on the definition of a high-lethality suicide attempt and longitudinal studies of this cohort.

There is more to this fever than meets the eye: A case of neuroleptic malignant-like syndrome (NMLS) secondary to withdrawal of procyclidine and L-dopa on a background of long-standing flupenthixol depot use.

This case report highlights the risk of development of Neuroleptic Malignant-Like Syndrome secondary to withdrawal of procyclidine with brief withdrawal of L-dopa and long-term typical antipsychotic depot. The patient responded to reintroduction of procyclidine, sedation and supportive treatment. The mechanism and management of NMS and NMLS is also reviewed. This case emphasises that any changes in antipsychotic and antiparkinsonian medications should be undertaken with extreme caution and patient should be closely monitored for development of NMLS after alteration in these medications.

Lockdown logistics in consultation-liaison psychiatry.

We describe the adaptation of services to allow flexible and practical responses to the coronavirus-19 (COVID-19) public health crisis by four Consultation-Liaison Psychiatry (CLP) services; Galway University Hospital (GUH), Beaumont Hospital, University Hospital Waterford and St Vincent's University Hospital (SVUH) CLP services. This article also illustrates close collaboration with community adult mental health services and Emergency Department (ED) colleagues to implement effective community diversion pathways and develop safe, effective patient assessment pathways within the EDs. It highlights the high levels of activity within each of the CLP services, while also signposting that many of the rapidly implemented changes to our practice may herald improvements to mental health patient care delivery in the post-COVID-19 world, if our psychiatry services receive appropriate resources.

Consultant psychiatrists' experience of the impact of the COVID-19 pandemic on mental health services.

OBJECTIVES: The novel coronavirus 2019 (COVID-19) has spread worldwide threatening human health. To reduce transmission, a 'lockdown' was introduced in Ireland between March and May 2020. The aim of this study is to capture the experiences of consultant psychiatrists during lockdown and their perception of it's impact on mental health services. METHODS: A questionnaire designed by the Royal College of Psychiatrists was adapted and circulated to consultant members of the College of Psychiatrists of Ireland following the easing of restrictions. The questionnaire assessed the perceived impact on referral rates, mental health act provision, availability of information technology (IT), consultant well-being and availability of personal protective equipment (PPE). Thematic analysis was employed to analyse free-text sections. RESULTS: Response rate was 32% (n = 197/623). Consultants reported an initial decrease/significant decrease in referrals in the first month of lockdown (68%, n = 95/140) followed by an increase/significant increase in the second month for both new (83%, n = 100/137) and previously attending patients (65%, n = 88/136). Social isolation and reduced face-to-face mental health supports were among the main reasons identified. The needs of children and older adults were highlighted. Most consultants (76%, n = 98/129) felt their working day was affected and their well-being reduced (52%, n = 61/119). The majority felt IT equipment availability was inadequate (67%, n = 88/132). Main themes identified from free-text sections were service management, relationship between patients and healthcare service and effects on consultants' lives. CONCLUSIONS: The COVID-19 pandemic has placed increased pressure on service provision and consultant wellness. This further supports the longstanding need to increase mental health service investment.

Endometrial expression of progesterone-induced blocking factor and galectins-1, -3, -9, and -3 binding protein in the luteal phase and early pregnancy in cattle.

Progesterone-induced blocking factor (PIBF) and galectins modulate the maternal immune response during pregnancy. We hypothesized that the relative transcript abundance of the above genes would be different during the luteal phase/early pregnancy and would be affected by progesterone supplementation. To further test this, hypothesis protein expression analyses were carried out to evaluate the abundance and localization of LGALS9 and PIBF. Following estrus synchronization, heifers were inseminated (n = 140) or not (n = 70). Half the heifers in each status (cyclic or potentially pregnant) were randomly assigned to receive a progesterone-releasing intravaginal device (PRID) on day 3 after estrus, which elevated progesterone concentrations from day 3.5 to 8 (P < 0.05), resulting in four treatment groups: cyclic and pregnant heifers, each with normal and high progesterone. After confirmation of pregnancy status in inseminated animals, uterine tissue was collected on days 5, 7, 13, or 16 of the luteal phase of the cycle/pregnancy. Gene and protein expression was determined using Q-RT-PCR and IHC, respectively, on 5 heifers per treatment per time point (i.e., 80 in total). Progesterone concentrations did not affect expression of any of the genes (P > 0.05). LGALS9 and LGALS3BP were expressed at low levels in both cyclic and pregnant endometria until day 13. On day 16, expression increased only in the pregnant heifers (P < 0.0001). LGALS1 and LGALS3 decreased on day 7 (P < 0.0001) and remained low until day 16. Pregnancy had no effect on the expression of LGALS1, LGALS3, and PIBF. Additionally, LGALS9 and PIBF proteins were expressed in distinct uterine cell types. These results indicate that the galectins may be involved in uterine receptivity and/or implantation in heifers.

COVID-19 and its effect on emergency presentations to a tertiary hospital with self-harm in Ireland.

OBJECTIVES: This study aimed to assess the impact of COVID-19 on presentations to an acute hospital with self-harm. METHODS: All presentations to University Hospital Galway with self-harm were assessed during the peak period of the coronavirus crisis in Ireland, over the 3 months from 1 March to 31 May 2020. These data were compared with presentations in the same months in the 3 years preceding (2017-2019). Data were obtained from the anonymised service database. RESULTS: This study found that in 2020, the rate of presentation with self-harm dropped by 35% from March to April and rose by 104% from April to May, peaking from mid-May. When trends over a 4-year period were examined, there was a significantly higher lethality of attempt (p < 0.001), and significant differences in diagnosis (p = 0.031) in 2020 in comparison with the three previous years. The increased lethality of presentations remained significant after age and gender were controlled for (p = 0.036). There were also significant differences in the underlying psychiatric diagnoses (p = 0.018), notably with a significant increase in substance misuse disorders presenting during the 2020 study period. CONCLUSIONS: COVID-19 showed a reduction in self-harm presentations initially, followed by a sharp increase in May 2020. If a period of economic instability follows as predicted, it is likely that this will further impact the mental health of the population, along with rates of self-harm and suicidal behaviours. There is a need for research into the longer-term effect of COVID-19 and lockdown restrictions, especially with respect to self-harm.

Environmental enrichment for captive stumptail macaques (Macaca arctoides).

BACKGROUND: The behavior of animals is modified by captivity. Environmental enrichment (EE) is a program designed to enhance the welfare of confined animals by providing them with a more stimulating background. This is carried out by the implementation of a series of activities that encourages them to present behaviors typical of their species, as well as keeps them active. The aim of this study was the evaluation of the influence of the EE in the behavioral variables in a colony of 24 stumptail macaques (Macaca arctoides). Our hypothesis is that the application of this program will reduce aggression, stereotypes and coprophilia behaviors and, at the same time, will increase exploration and solitary play. METHODS: The behavioral frequency previous to EE was compared with that during EE implementation. RESULTS: Our results showed that aggression, coprophilia stereotypic behaviors and social play were significantly reduced during EE, whereas exploration was significantly enhanced. The response of the individuals according to gender was similar for both sexes. CONCLUSIONS: Environmental enrichment programs are indispensable for captive animals' wellbeing as they reduce aggression and stress while providing animals both physical and cognitive entertainment.

Munchausen's syndrome--more common than we realize?

Munchausen's syndrome is a condition whereby a patient deliberately simulates symptoms of an illness in order to gain admission to hospital and gain the sick role. It is an uncommon condition and is possibly underdiagnosed. This case-series examines the cases of three patients with Munchausen's syndrome who presented to a Dublin hospital within a four-month period. Two of the presentations involved the feigning of psychiatric symptoms. It is important that clinicians not only in psychiatry, but in all medical specialities have an awareness of this disorder, so that unnecessary procedures and treatments may be avoided.

Sleep characterization of a one-month-old freely moving stumptail macaque (Macaca arctoides): a pilot study.

Electroencephalographic (EEG) activity during both human and adult primates' sleep has been proven to be similar and consequently, it could be assessed under similar parameters. However, there is no information regarding this EEG activity in the early stages of development in non-human primates. Therefore, the aim of this study was to describe EEG sleep patterns in a 1-month-old Macaca arctoides with a non-invasive and free-movement method. Sleep stages were initially scored using the criteria of quiet sleep and active sleep. This procedure allowed us to observe graphoelements to distinguish sleep phases as described in adult macaques. Afterwards, the final score was recorded following the Slow Wave Sleep and Rapid Eye Movement Sleep criteria. The present results suggest that sleep features of this monkey are similar to those of a 2-month-old human neonate.

Are brief alcohol interventions targeting alcohol use efficacious in military and veteran populations? A meta-analysis.

BACKGROUND: Rates of hazardous and harm-related drinking are higher in the military and veteran populations compared to the general population. Brief alcohol interventions (BAIs) targeting alcohol use appear to reduce harmful drinking in the general population. However, less is known about the efficacy of BAIs targeting alcohol in military and veteran populations. METHODS: A systematic review and meta-analysis was conducted to assess the type and efficacy of BAIs used to reduce alcohol use in military and veteran populations conducted from 2000 onwards. The meta-analysis was conducted using a standardised outcome measure of change in average weekly drinks (AWDs) from baseline to follow-up. RESULTS: The search revealed 10 papers that met the search criteria, and that reported data on 11 interventions included in the systematic review. 8 papers (reporting on 9 different interventions) were included in the meta-analysis after 2 papers were excluded for which the relevant outcome data were not available. There was no overall effect of BAIs; a non-significant weekly drink reduction of 0.95 drinks was found (95% CI, -0.17 to 2.07). This lack of efficacy persisted regardless of military group (conscripts, serving or veterans) and method of delivery (i.e., face-to-face, web-based or written information). Furthermore, sensitivity analyses revealed this small drink reduction was driven mainly by a single study. CONCLUSIONS: Based on these findings, existing BAIs do not seem to be efficacious in reducing alcohol use in military populations, despite some encouraging results from one electronic intervention which was of extensive duration.

Lipopolysaccharide (LPS) disrupts particle transport, cilia function and sperm motility in an ex vivo oviduct model.

The oviduct functions in the transportation of gametes to the site of fertilization (the ampulla) and is the site of early embryonic development. Alterations of this early developmental environment, such as the presence of sexually transmitted pathogens, may affect oviduct function leading to reduced fertilization rates and contribute to compromised embryonic development. In this study, sperm interactions, particle transport speed (PTS) and cilia beat frequency (CBF) in the ampulla following exposure to lipopolysaccharide (LPS), a constituent of the sexually transmitted pathogens Chlamydia trachomatis and Chlamydia abortus, was investigated. Three complementary experiments were performed to analyse; (1) bound sperm motility and cilia function (2) transport velocity in the oviduct and (3) the expression of genes related to immune function and inflammatory response (CASP3, CD14, MYD88, TLR4 and TRAF6). The motility of bound sperm was significantly lower in ampullae that were exposed to LPS. CBF and PTS significantly increased after treatment with LPS for 2 hours. Finally, gene expression analysis revealed that CASP3 and CD14 were significantly upregulated and TLR4 trended towards increased expression following treatment with LPS. These findings provide an insight on the impact of LPS on the oviduct sperm interaction, and have implications for both male and female fertility.

Phosphodiesterase 4 inhibitors as novel anti-inflammatory agents.

Preclinical and clinical studies of phosphodiesterase 4 inhibitors have shown that these agents may find utility in a wide range of inflammatory disorders, including asthma, chronic obstructive pulmonary disease, atopic dermatitis, rheumatoid arthritis, multiple sclerosis and various neurological disorders. The future of this class of drugs will depend upon the ability to demonstrate a reasonable safety margin against emesis and other typical phosphodieserase (PDE4) side effects, as well as in identification of the inflammatory disorder(s) most relevant to PDE4 inhibition.

Endothelin receptor antagonist increases cerebral perfusion and reduces ischaemic damage in feline focal cerebral ischaemia.

These investigations characterised the cerebrovascular effects of an endothelin ETA-receptor antagonist PD156707 in normal and ischaemic cat brain. A dose of PD156707 that inhibited the effects of exogenous endothelin-1 was established in nonischaemic cerebral resistance arterioles. Perivascular microapplication of the endothelin-receptor antagonist PD156707 (0.03-3 microM) had a minimal effect on nonischaemic pial resistance arterioles. The perivascular co-application of PD156707 and ET-1 (10 nM) effected a dose-dependent attenuation of the ET-1 vasoconstrictive response (IC50 = 0.1 microM). Intravenous administration of PD156707 (3 mumol/kg bolus + 5 mumol/kg/h infusion) attenuated the vasoconstriction elicited by perivascular ET-1 (10 nM) in normal pial arterioles (ET-1 vasoconstriction: -37 +/- 13% from preinjection baseline; after intravenous PD156707: 6 +/- 10% from preinjection baseline). In the focal ischaemia studies, cerebral perfusion was measured in the suprasylvian and ectosylvian gyri (by laser Doppler flowmetry). Occlusion of the middle cerebral artery reduced cerebral perfusion in the suprasylvian and ectosylvian gyri by approximately 50%. Intravenous administration of PD156707 (3 mumol/kg bolus + 5 mumol/kg/h infusion), initiated 30 min after middle cerebral artery occlusion, effected a progressive increase in cerebral perfusion up to preocclusion baseline levels, whereas cerebral perfusion in vehicle-treated animals did not vary from its postocclusion level. In these animals, the intravenous administration of PD156707 reduced the hemispheric volume of ischaemic damage by 45% (vehicle: 2,376 +/- 1,107 mm3; PD156707: 1,307 +/- 548 mm3; p < 0.05). Our investigations indicate that endothelin receptor antagonism may be a new therapeutic strategy for the amelioration of focal ischaemic damage.