An exploration of gut hormone therapy to treat infertility caused by Type 2 Diabetes

Background Type II Diabetes Mellitus is a common disease associated with multiple debilitating symptoms, including reduced fertility in women of reproductive age. Gut hormone therapies have shown promise in improving fertility in these patients.     Objectives: To identify the relationship between the human gut microbiota and the successful functioning of the female reproductive system. To explore treatments to improve bacteria culture in the gut, and to examine if these improvements affect fertility in female patients with Type II Diabetes.   Method: A systematic search was undertaken; studies were collected from PubMed and The Diabetology and Metabolic Syndrome Journal. Searches were performed between January, 2023 and March, 2023. Studies focused on female patients suffering simultaneously from Type II Diabetes Mellitus and fertility complications. Ten papers that met criteria were appraised and included.   Results: There is evidence to suggest a causative relationship between the gut microbiome and reproductive functioning. Infertile patients had increased abundance of the phylum Verrucomicrobia and Phascolarctobacterium in the gastrointestinal tract, and decreased amounts of genera Stenotrophomonas, Streptococcus, and Roseburia. These abnormalities were associated with depleted circulating oestrogen concentrations, irregular menstrual cycling, and hyperandrogenism.   Evidence authenticates the use of probiotics and hormone therapy in treatment of Type II Diabetes and its associated symptoms. Supplements studied included metformin, GIP agonists, and GLP-1 receptors. Across studies, patients showed significant improvements in Type II Diabetes management following treatment.    Conclusion Alterations to the composition of the gut microbiome are associated with improvements in glycemic control as well as improvements in fertility in female patients with Type II Diabetes Mellitus

An exploration of the positive and negative relationships associated with the development of asthma and atopic disorders in primary school children in Cork

Childhood asthma, allergic rhinitis and eczema are complex heterogenic chronic inflammatory allergic disorders which constitute a major burden to children, their families. The prevalence of childhood allergic disorders is increasing worldwide and merely rudimentary understanding exists regarding causality, or the influence of the environment on disease expression. Phase Three of the International Study of Asthma and Allergy in Childhood (ISAAC) reported that Irish adolescents had the 4th highest eczema and rhinoconjunctivitis prevalence and 3rd highest asthma prevalence in the world. There are no ISAAC data pertaining to young Irish children. In 2002, Sturley reported a high prevalence of current asthma in Cork primary school children aged 6-9 years. This thesis comprises of three cross-sectional studies which examined the prevalence of and associations with childhood allergy and a quasi-retrospective cohort study which observed the natural history of allergy from 6-9 until 11-13 years. Although not part of ISAAC, data was attained by parentally completed ISAAC-based questionnaires, using the ISAAC protocol. The prevalence, natural history and risk factors of childhood allergy in Ireland, as described in this thesis, echo those in worldwide allergy research. The variations of prevalence in different populations worldwide and the recurring themes of associations between childhood allergy and microbial exposures, from farming environments and/or gastrointestinal infections, as shown in this thesis, strengthen the mounting evidence that microbial exposure on GALT may hold the key to the mechanisms of allergy development. In this regard, probiotics may be an area of particular interest in allergy modification. Although their effects in relation to allergy, have been investigated now for several years, our knowledge of their diversity, complex functions and interactions with gut microflora, remain rudimentary. Birth cohort studies which include genomic and microbiomic research are recommended in order to examine the underlying mechanisms and the natural course of allergic diseases

Aortic valve replacement via mini-sternotomy: Results of a single centre analysis

Background: The traditional method of Aortic Valve Replacement (AVR) is via full sternotomy. However, this incision may not heal properly and cause significant pain. Minimally-invasive approaches have been adopted, including mini-sternotomy. These have gained popularity due to smaller incision, reducing surgical trauma. The hypothesis is that AVR via mini-sternotomy is a safe alternative to full sternotomy. The objective was to analyse and describe results of patients who underwent the procedure, including post-operative outcomes. Methods: A retrospective database review was performed on patients who underwent AVR via mini-sternotomy between September 2016 and December 2022 in Cork University Hospital (CUH). Exclusion criteria included patients who had an aortic procedure concurrently, such as ascending aorta replacement, and those under 18 years. Results for variables, such as age, were expressed as a mean. Results: 93 patients were included; the average age was 68. Average bypass and cross-clamp times were 92 and 73 minutes respectively. Median post-operative length of stay was 8 days and median ICU length of stay was 3 days. There were no in-hospital mortalities. Conclusion: AVR via mini-sternotomy has cosmetic advantages and is particularly useful in frail patients who may suffer from a conventional sternotomy and associated morbidities. It is shown to be a safe alternative with comparable intra- and post-operative outcomes to those described internationally

Does cannabis use predict psychometric schizotypy via aberrant salience?

Cannabis can induce acute psychotic symptoms in healthy individuals and exacerbate pre-existing psychotic symptoms in patients with schizophrenia. Inappropriate salience allocation is hypothesised to be central to the association between dopamine dysregulation and psychotic symptoms. This study examined whether cannabis use is associated with self-reported salience dysfunction and schizotypal symptoms in a non-clinical population. 910 University students completed the following questionnaire battery: the cannabis experience questionnaire modified version (CEQmv); schizotypal personality questionnaire (SPQ); community assessment of psychic experience (CAPE); aberrant salience inventory (ASI). Mediation analysis was used to test whether aberrant salience mediated the relationship between cannabis use and schizotypal traits. Both frequent cannabis consumption during the previous year and ASI score predicted variation across selected positive and disorganised SPQ subscales. However, for the SPQ subscales ‘ideas of reference’ and ‘odd beliefs’, mediation analysis revealed that with the addition of ASI score as a mediating variable, current cannabis use no longer predicted scores on these subscales. Similarly, cannabis use frequency predicted higher total SPQ as well as specific Positive and Disorganised subscale scores, but ASI score as a mediating variable removed the significant predictive relationship between frequent cannabis use and ‘odd beliefs’, ‘ideas of reference’, ‘unusual perceptual experiences’, ‘odd speech’, and total SPQ scores. In summary, cannabis use was associated with increased psychometric schizotypy and aberrant salience. Using self-report measures in a non-clinical population, the cannabis-related increase in selected positive and disorganised SPQ subscale scores was shown to be, at least in part, mediated by disturbance in salience processing mechanisms

Deoxycholate induces COX-2 expression via Erk1/2-, p38-MAPK and AP-1-dependent mechanisms in esophageal cancer cells

<p>Abstract</p> <p>Background</p> <p>The progression from Barrett's metaplasia to adenocarcinoma is associated with the acquirement of an apoptosis-resistant phenotype. The bile acid deoxycholate (DCA) has been proposed to play an important role in the development of esophageal adenocarcinoma, but the precise molecular mechanisms remain undefined. The aim of this study was to investigate DCA-stimulated COX-2 signaling pathways and their possible contribution to deregulated cell survival and apoptosis in esophageal adenocarcinoma cells.</p> <p>Methods</p> <p>Following exposure of SKGT-4 cells to DCA, protein levels of COX-2, MAPK and PARP were examined by immunoblotting. AP-1 activity was assessed by mobility shift assay. DCA-induced toxicity was assessed by DNA fragmentation and MTT assay.</p> <p>Results</p> <p>DCA induced persistent activation of the AP-1 transcription factor with Fra-1 and JunB identified as the predominant components of the DCA-induced AP-1 complex. DCA activated Fra-1 via the Erk1/2- and p38 MAPK while Erk1/2 is upstream of JunB. Moreover, DCA stimulation mediated inhibition of proliferation with concomitant low levels of caspase-3-dependent PARP cleavage and DNA fragmentation. Induction of the anti-apoptotic protein COX-2 by DCA, via MAPK/AP-1 pathway appeared to balance the DCA mediated activation of pro-apoptotic markers such as PARP cleavage and DNA fragmentation. Both of these markers were increased upon COX-2 suppression by aspirin pretreatment prior to DCA exposure.</p> <p>Conclusion</p> <p>DCA regulates both apoptosis and COX-2-regulated cell survival in esophageal cells suggesting that the balance between these two opposing signals may determine the transformation potential of DCA as a component of the refluxate.</p

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Second report of the Suicide Support and Information System.

This is the second report of the Suicide Support and Information System (SSIS). The first report of the SSIS was published in July 2012 (Arensman et al, 2012). In 2008, The National Office for Suicide Prevention(NOSP) commissioned the National Suicide Research Foundation to establish a National Suicide Support and Information System in line with Action 25.2 of the Reach Out National Strategy for Action on Suicide Prevention 2005-2014 (HSE, 2005). The first SSIS report provided outcomes of the implementation of the SSIS during the pilot phase in the Cork region, descriptive characteristics of people who died by suicide and who were recorded by the SSIS, and details of a large cluster of suicide among young men identified by the SSIS. In total, 307 cases were recorded by the SSIS between September 2008 and June 2012 (275 suicides and 32 open verdicts fulfilling the case finding criteria). Coroner checklists were completed for all 307 cases

Letters to the Editors

We want to respond to two of the issues raised in Dr Blackman's letter. The first is that the early introduction of solid foods would have prevented the occurrence of dietary chloride deficiency in the infants ingesting chloride-deficient Neo-Mull-Soy. The Table shows the age at which solid foods were introduced into the diet of 11 of the 12 infants described in our paper.1 Solid foods were introduced into the diets of seven of 11 of the infants prior to 5 months of age.</jats:p