Functional gastrointestinal disorders are increased in joint hypermobility-related disorders with concomitant postural orthostatic tachycardia syndrome.

Background Individuals with hypermobility spectrum disorders/hypermobile Ehlers‐Danlos syndrome (HSD/hEDS) frequently fulfill criteria for Rome IV functional gastrointestinal disorders (FGIDs). Postural orthostatic tachycardia syndrome (POTS) is also commonly reported in HSD/hEDS and may impact on co‐morbidity with and severity of FGIDs, although this remains to be studied. We determined the impact of concomitant POTS and HSD/hEDS on their association with Rome IV FGIDs. Methods With the help of the charity organization Ehlers‐Danlos Support UK, an online cross‐sectional health survey was completed by individuals with HSD/hEDS. The survey enquired for (a) self‐reported doctor diagnosis of POTS, chronic fatigue syndrome, and fibromyalgia, (b) the presence and symptom frequency of Rome IV FGIDs, and (c) anxiety and depression scores. Key Results Of 616 subjects with HSD/hEDS, 37.5% reported a doctor diagnosis of POTS. POTS‐positive individuals were significantly younger than POTS‐negative subjects (37 vs 40 years, P = 0.002), more likely to report chronic fatigue syndrome (44% vs 31%, P < 0.0001), and showed a trend toward increased prevalence of fibromyalgia (44% vs 37%, P = 0.06) and higher depression score (P = 0.07). POTS‐positive subjects were also more likely to fulfill criteria for Rome IV FGIDs across various organ domains and experienced both upper and lower gastrointestinal symptoms significantly more frequently. The increased associations for FGIDs and GI symptom frequency remained unchanged in HSD/hEDS subjects with POTS following adjustments for age, chronic fatigue syndrome, fibromyalgia, and depression scores. Conclusions and Inferences The high FGID burden in HSD/hEDS is further amplified in the presence of POTS. Future studies should elucidate the mechanism by which POTS arises in HSD/hEDS and is associated with increased GI symptoms

Rethinking elective cataract surgery diagnostics, assessments, and tools after the COVID-19 pandemic experience and beyond: Insights from the EUROCOVCAT group

The progressive deterioration of the visual function in patients on waiting lists for cataract surgery has a negative impact on their quality of life, especially in the elderly population. Patient waiting times for cataract surgeries in many healthcare settings have increased recently due to the prolonged stop or slowdown of elective cataract surgery as a result of coronavirus disease 19 (COVID-19). The aim of this review is to highlight the impact of such a “de-prioritization” of cataract surgery and to summarize some critical issues and useful hints on how to reorganize cataract pathways, with a special focus on perioperative diagnostic tools during the recovery phase and beyond. The experiences of a group of surgeons originating from nine different countries, named the European COVID-19 Cataract Group (EUROCOVCAT), have been combined with the literature and recommendations from scientific ophthalmic societies and healthcare institutions. Key considerations for elective cataract surgery should include the reduction of the number of unnecessary visits and examinations, adoption of precautionary measures, and implementation of telemedicine instruments. New strategies should be adopted to provide an adequate level of assistance and to guarantee safety conditions. Flexibility will be the watchword and regular updates would be necessary following scientific insights and the development of the pandemic

Early impact of COVID-19 outbreak on eye care: Insights from EUROCOVCAT group

The recent outbreak of coronavirus disease 2019 (COVID-19) has been declared a public health emergency worldwide. The scientific community has put in much effort and published studies that described COVID-19’s biology, transmission, clinical diagnosis, candidate therapeutics, and vaccines. However, to date, only a few data are available on the impact of COVID-19 pandemic on ophthalmological care in different health care systems, its future consequences in terms of disability, and access to sight-saving cures for many patients. To reduce human-to-human transmission of the virus and also ensure supply of infrastructures, human resources, and disposable medical devices to many regions, it is crucial to assess risks and postpone non-essential outpatient visits and elective surgical procedures, especially in older patients and those with comorbidities. This delay or suspension in essential eye procedures may cause significant and rapid vision impairment to irreversible blindness. Determining the risk-benefit profile of treating these ocular pathologies is a public health issue of supreme priority, even though many patients benefiting from therapeutic treatments are elderly, who are more vulnerable to COVID-19. If not reversible, this process could lead to a dramatic increase in disability and unsustainable social costs for many Governments

Corticotropin-releasing hormone, its binding protein and receptors in human cervical tissue at preterm and term labor in comparison to non-pregnant state

BACKGROUND: Preterm birth is still the leading cause of neonatal morbidity and mortality. The level of corticotropin-releasing hormone (CRH) is known to be significantly elevated in the maternal plasma at preterm birth. Although, CRH, CRH-binding protein (CRH-BP), CRH-receptor 1 (CRH-R1) and CRH-R2 have been identified both at mRNA and protein level in human placenta, deciduas, fetal membranes, endometrium and myometrium, no corresponding information is yet available on cervix. Thus, the aim of this study was to compare the levels of the mRNA species coding for CRH, CRH-BP, CRH-R1 and CRH-R2 in human cervical tissue and myometrium at preterm and term labor and not in labor as well as in the non-pregnant state, and to localize the corresponding proteins employing immunohistochemical analysis. METHODS: Cervical, isthmic and fundal (from non-pregnant subjects only) biopsies were taken from 67 women. Subjects were divided in 5 groups: preterm labor (14), preterm not in labor (7), term labor (18), term not in labor (21) and non-pregnant (7). Real-time RT-PCR was employed for quantification of mRNA levels and the corresponding proteins were localized by immunohistochemical analysis. RESULTS: The levels of CRH-BP, CRH-R1 and CRH-R2 mRNA in the pregnant tissues were lower than those in non-pregnant subjects. No significant differences were observed between preterm and term groups. CRH-BP and CRH-R2 mRNA and the corresponding proteins were present at lower levels in the laboring cervix than in the non-laboring cervix, irrespective of gestational age. In most of the samples, with the exception of four myometrial biopsies the level of CRH mRNA was below the limit of detection. All of these proteins could be detected and localized in the cervix and the myometrium by immunohistochemical analysis. CONCLUSION: Expression of CRH-BP, CRH-R1 and CRH-R2 in uterine tissues is down-regulated during pregnancy. The most pronounced down-regulation of CRH-BP and CRH-R2 occurred in laboring cervix, irrespective the length of gestation. The detection of substantial expression of the CRH and its receptor proteins, as well as receptor mRNA in the cervix suggests that the cervix may be a target for CRH action. Further studies are required to elucidate the role of CRH in cervical ripening

Exploring the genetics of irritable bowel syndrome: A GWA study in the general population and replication in multinational case-control cohorts

OBJECTIVE: IBS shows genetic predisposition, but adequately powered gene-hunting efforts have been scarce so far. We sought to identify true IBS genetic risk factors by means of genome-wide association (GWA) and independent replication studies. DESIGN: We conducted a GWA study (GWAS) of IBS in a general population sample of 11\u2005326 Swedish twins. IBS cases (N=534) and asymptomatic controls (N=4932) were identified based on questionnaire data. Suggestive association signals were followed-up in 3511 individuals from six case-control cohorts. We sought genotype-gene expression correlations through single nucleotide polymorphism (SNP)-expression quantitative trait loci interactions testing, and performed in silico prediction of gene function. We compared candidate gene expression by real-time qPCR in rectal mucosal biopsies of patients with IBS and controls. RESULTS: One locus at 7p22.1, which includes the genes KDELR2 (KDEL endoplasmic reticulum protein retention receptor 2) and GRID2IP (glutamate receptor, ionotropic, delta 2 (Grid2) interacting protein), showed consistent IBS risk effects in the index GWAS and all replication cohorts and reached p=9.31 710(-6) in a meta-analysis of all datasets. Several SNPs in this region are associated with cis effects on KDELR2 expression, and a trend for increased mucosal KDLER2 mRNA expression was observed in IBS cases compared with controls. CONCLUSIONS: Our results demonstrate that general population-based studies combined with analyses of patient cohorts provide good opportunities for gene discovery in IBS. The 7p22.1 and other risk signals detected in this study constitute a good starting platform for hypothesis testing in future functional investigations. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions

Excess cases of prostate cancer and estimated overdiagnosis associated with PSA testing in East Anglia

This study aimed to estimate the extent of 'overdiagnosis' of prostate cancer attributable to prostate-specific antigen (PSA) testing in the Cambridge area between 1996 and 2002. Overdiagnosis was defined conceptually as detection of prostate cancer through PSA testing that otherwise would not have been diagnosed within the patient's lifetime. Records of PSA tests in Addenbrookes Hospital were linked to prostate cancer registrations by NHS number. Differences in prostate cancer registration rates between those receiving and not receiving prediagnosis PSA tests were calculated. The proportion of men aged 40 years or over with a prediagnosis PSA test increased from 1.4 to 5.2% from 1996 to 2002. The rate of diagnosis of prostate cancer was 45% higher (rate ratios (RR) = 1.45, 95% confidence intervals (CI) 1.02-2.07) in men with a history of prediagnosis PSA testing. Assuming average lead times of 5 to 10 years, 40-64% of the PSA-detected cases were estimated to be overdiagnosed. In East Anglia, from 1996 to 2000, a 1.6% excess of cases was associated with PSA testing (around a quarter of the 5.3% excess incidence cases observed in East Anglia from 1996 to 2000). Further quantification of the overdiagnosis will result from continued surveillance and from linkage of incidence to testing in other hospitals

Chlamydia trachomatis antigens in enteroendocrine cells and macrophages of the small bowel in patients with severe irritable bowel syndrome

<p>Abstract</p> <p>Background</p> <p>Inflammation and immune activation have repeatedly been suggested as pathogentic factors in irritable bowel syndrome (IBS). The driving force for immune activation in IBS remains unknown. The aim of our study was to find out if the obligate intracellular pathogen <it>Chlamydia </it>could be involved in the pathogenesis of IBS.</p> <p>Methods</p> <p>We studied 65 patients (61 females) with IBS and 42 (29 females) healthy controls in which IBS had been excluded. Full thickness biopsies from the jejunum and mucosa biopsies from the duodenum and the jejunum were stained with a monoclonal antibody to <it>Chlamydia </it>lipopolysaccharide (LPS) and species-specific monoclonal antibodies to <it>C. trachomatis </it>and <it>C. pneumoniae</it>. We used polyclonal antibodies to chromogranin A, CD68, CD11c, and CD117 to identify enteroendocrine cells, macrophages, dendritic, and mast cells, respectively.</p> <p>Results</p> <p><it>Chlamydia </it>LPS was present in 89% of patients with IBS, but in only 14% of healthy controls (p < 0.001) and 79% of LPS-positive biopsies were also positive for <it>C. trachomatis </it>major outer membrane protein (MOMP). Staining for <it>C. pneumoniae </it>was negative in both patients and controls. <it>Chlamydia </it>LPS was detected in enteroendocrine cells of the mucosa in 90% of positive biopsies and in subepithelial macrophages in 69% of biopsies. Biopsies taken at different time points in 19 patients revealed persistence of <it>Chlamydia </it>LPS up to 11 years. The odds ratio for the association of <it>Chlamydia </it>LPS with presence of IBS (43.1; 95% CI: 13.2-140.7) is much higher than any previously described pathogenetic marker in IBS.</p> <p>Conclusions</p> <p>We found <it>C. trachomatis </it>antigens in enteroendocrine cells and macrophages in the small bowel mucosa of patients with IBS. Further studies are required to clarify if the presence of such antigens has a role in the pathogenesis of IBS.</p

Preterm birth: inflammation, fetal injury and treatment strategies

Preterm birth (PTB) is the leading cause of childhood mortality in children under 5 and accounts for approximately 11% of births worldwide. Premature babies are at risk of a number of health complications, notably cerebral palsy, but also respiratory and gastrointestinal disorders. Preterm deliveries can be medically indicated/elective procedures or they can occur spontaneously. Spontaneous PTB is commonly associated with intrauterine infection/inflammation. The presence of inflammatory mediators in utero has been associated with fetal injury, particularly affecting the fetal lungs and brain. This review will outline (i) the role of inflammation in term and PTB, (ii) the effect infection/inflammation has on fetal development and (iii) recent strategies to target PTB. Further research is urgently required to develop effective methods for the prevention and treatment of PTB and above all, to reduce fetal injury

Impaired leukocyte influx in cervix of postterm women not responding to prostaglandin priming

<p>Abstract</p> <p>Background</p> <p>Prolonged pregnancies are associated with increased rate of maternal and fetal complications. Post term women could be divided into at least two subgroups, one where parturition is possible to induce by prostaglandins and one where it is not. Our aim was to study parameters in cervical biopsies in women with spontaneous delivery at term (controls) and compare to those that are successfully induced post term (responders), and those that are not induced (non-responders), by local prostaglandin treatment.</p> <p>Methods</p> <p>Stromal parameters examined in this study were the accumulation of leukocytes (CD45, CD68), mRNAs and/or proteins for the extracellular matrix degrading enzymes (matrix metalloproteinase (MMP)-2, MMP-8 and MMP-9), their inhibitors (tissue inhibitor of MMP (TIMP)-1 and TIMP-2), interleukin-8 (IL-8), the platelet activating factor-receptor (PAF-R), syndecan-1 and estrogen binding receptors (estrogen receptor (ER)α, ERβ and G-coupled protein receptor (GPR) 30) as well as the proliferation marker Ki-67.</p> <p>Results</p> <p>The influx of leukocytes as assessed by CD45 was strongest in the responders, thereafter in the controls and significantly lower in the non-responders. IL-8, PAF-R and MMP-9, all predominantly expressed in leukocytes, showed significantly reduced immunostaining in the group of non-responders, while ERα and GPR30 were more abundant in the non-responders, as compared to the controls.</p> <p>Conclusion</p> <p>The impaired leukocyte influx, as reflected by the reduced number of CD45 positive cells as well as decreased immunostaining of IL-8, PAF-R and MMP-9 in the non-responders, could be one explanation of the failed ripening of the cervix in post term women. If the decreased leukocyte influx is a primary explanation to absent ripening or secondary, as a result of other factors, is yet to be established.</p

Anti-inflammatory effects of nicotine in obesity and ulcerative colitis

Cigarette smoke is a major risk factor for a number of diseases including lung cancer and respiratory infections. Paradoxically, it also contains nicotine, an anti-inflammatory alkaloid. There is increasing evidence that smokers have a lower incidence of some inflammatory diseases, including ulcerative colitis, and the protective effect involves the activation of a cholinergic anti-inflammatory pathway that requires the α7 nicotinic acetylcholine receptor (α7nAChR) on immune cells. Obesity is characterized by chronic low-grade inflammation, which contributes to insulin resistance. Nicotine significantly improves glucose homeostasis and insulin sensitivity in genetically obese and diet-induced obese mice, which is associated with suppressed adipose tissue inflammation. Inflammation that results in disruption of the epithelial barrier is a hallmark of inflammatory bowel disease, and nicotine is protective in ulcerative colitis. This article summarizes current evidence for the anti-inflammatory effects of nicotine in obesity and ulcerative colitis. Selective agonists for the α7nAChR could represent a promising pharmacological strategy for the treatment of inflammation in obesity and ulcerative colitis. Nevertheless, we should keep in mind that the anti-inflammatory effects of nicotine could be mediated via the expression of several nAChRs on a particular target cell