A case series of premenstrual disorders presenting to the UK's National Female Hormone Clinic.

AIMS AND METHOD: We aimed to describe the clinical characteristics of female patients presenting with premenstrual disorders to a tertiary service in the UK. We conducted a retrospective case-note review of referrals to the National Female Hormone Clinic from April 2014 to August 2020. Based on clinical assessment, we determined whether the patient met criteria for premenstrual dysphoric disorder or premenstrual exacerbation of an underlying psychiatric disorder. RESULTS: Of 146 patients seen in clinic for premenstrual disorders, an ICD-10 psychiatric diagnosis was made in 130 (89.0%); a minority 16 (11.0%) did not have a psychiatric diagnosis. Following assessment, 94 patients (64.4%) met criteria for premenstrual dysphoric disorder and 67 (45.6%) had exacerbation of a psychiatric disorder. CLINICAL IMPLICATIONS: Patients presenting to this specialist service had complex psychiatric comorbidity; almost half presented with exacerbation of a psychiatric disorder.

Gluten Induces Subtle Histological Changes in Duodenal Mucosa of Patients with Non-Coeliac Gluten Sensitivity: A Multicentre Study.

Background: Histological changes induced by gluten in the duodenal mucosa of patients with non-coeliac gluten sensitivity (NCGS) are poorly defined. Objectives: To evaluate the structural and inflammatory features of NCGS compared to controls and coeliac disease (CeD) with milder enteropathy (Marsh I-II). Methods: Well-oriented biopsies of 262 control cases with normal gastroscopy and histologic findings, 261 CeD, and 175 NCGS biopsies from 9 contributing countries were examined. Villus height (VH, in µm), crypt depth (CrD, in µm), villus-to-crypt ratios (VCR), IELs (intraepithelial lymphocytes/100 enterocytes), and other relevant histological, serologic, and demographic parameters were quantified. Results: The median VH in NCGS was significantly shorter (600, IQR: 400−705) than controls (900, IQR: 667−1112) (p < 0.001). NCGS patients with Marsh I-II had similar VH and VCR to CeD [465 µm (IQR: 390−620) vs. 427 µm (IQR: 348−569, p = 0·176)]. The VCR in NCGS with Marsh 0 was lower than controls (p < 0.001). The median IEL in NCGS with Marsh 0 was higher than controls (23.0 vs. 13.7, p < 0.001). To distinguish Marsh 0 NCGS from controls, an IEL cut-off of 14 showed 79% sensitivity and 55% specificity. IEL densities in Marsh I-II NCGS and CeD groups were similar. Conclusion: NCGS duodenal mucosa exhibits distinctive changes consistent with an intestinal response to luminal antigens, even at the Marsh 0 stage of villus architecture.

Quality criteria for randomized controlled studies: obstetrical journal guidelines.

BACKGROUND: Most retractions of obstetrics and gynecology manuscripts are because of scientific misconduct. It would be preferable to prevent randomized controlled trials with scientific misconduct from ever appearing in the peer-reviewed scientific literature, rather than to have to retract them later. OBJECTIVE: This study aimed to evaluate the policies of obstetrics and gynecology and top medical journals in their author guidelines and electronic submission systems regarding prospective randomized controlled trial registration, ethics committee approval, research protocols, Consolidated Standards of Reporting Trial guidelines, and data sharing and to detect the most common quality criteria requested for randomized controlled trials in these journals. STUDY DESIGN: Author guidelines were identified via online Google searches from the websites of selected peer-reviewed medical journals. Journals in obstetrics and gynecology were selected from the list of journals with impact factors based on the Journal Citation Report released by Clarivate Analytics on June 29, 2020, focusing on those publishing original clinical research in obstetrics, in particular randomized controlled trials. In addition, 4 of the top impact factor peer-reviewed general medical journals publishing randomized controlled trials were included. The requirements for selected quality criteria for randomized controlled trials analyzed in the author guidelines for each journal were details of 5 general issues: prospective randomized controlled trial registration (4 subcategories), ethics committee approval (4 subcategories), research protocol (3 subcategories), Consolidated Standards of Reporting Trials guidelines (3 subcategories), and data sharing (3 subcategories). To evaluate the requirements within the electronic submission system, a mock submission of a randomized controlled trial was also done for each journal, and the same criteria were assessed on the online software for submission. The primary outcome was the overall percentage for each of the quality criteria that were listed as required within the author guidelines or required in the submission system among all journals. Planned subgroup analyses were top general medicine vs obstetrics and gynecology journals and top 4 obstetrics and gynecology vs other obstetrics and gynecology journals. RESULTS: Most studied peer-reviewed journals listed in their author guidelines 7 specific criteria for submission of randomized controlled trials: prospective registration and registration number, statement of ethical approval with name of approving committee and statement of informed consent, statement of adherence to Consolidated Standards of Reporting Trials guidelines, and data sharing statement. For most journals, the submission software did not require these or any other criteria for submission. There were minimal differences in criteria listed for top medical journals vs other obstetrics and gynecology journals and among top vs other obstetrics and gynecology journals. CONCLUSION: Prospective registration and registration number, statement of ethical approval with name of approving committee and statement of informed consent, statement of adherence to Consolidated Standards of Reporting Trials guidelines, and data sharing statement are the randomized controlled trial quality criteria requested by leading medical and obstetrics and gynecology journals. These obstetrics and gynecology journals agree to make, as much as possible, these criteria uniform and mandatory in author guidelines and also through improved submission software.

Rightward shift of optimal fascicle length with decreasing voluntary activity level in the soleus and lateral gastrocnemius muscles.

Much of our understanding of in vivo skeletal muscle properties is based on studies performed under maximal activation, which is problematic because muscles are rarely activated maximally during movements such as walking. Currently, force-length properties of the human triceps surae at submaximal voluntary muscle activity levels are not characterized. We therefore evaluated plantar flexor torque- and force-ankle angle, and torque- and force-fascicle length properties of the soleus and lateral gastrocnemius muscles during voluntary contractions at three activity levels: 100, 30 and 22% of maximal voluntary contraction. Soleus activity levels were controlled by participants via real-time electromyography feedback and contractions were performed at ankle angles ranging from 10 deg plantar flexion to 35 deg dorsiflexion. Using dynamometry and ultrasound imaging, torque-fascicle length curves of the soleus and lateral gastrocnemius muscles were constructed. The results indicate that small muscle activity reductions shift the torque- and force-angle, and torque- and force-fascicle length curves of these muscles to more dorsiflexed ankle angles and longer fascicle lengths (from 3 to 20% optimal fascicle length, depending on ankle angle). The shift in the torque- and force-fascicle length curves during submaximal voluntary contraction have potential implications for human locomotion (e.g. walking) as the operating range of fascicles shifts to the ascending limb, where muscle force capacity is reduced by at least 15%. These data demonstrate the need to match activity levels during construction of the torque- and force-fascicle length curves to activity levels achieved during movement to better characterize the lengths that muscles operate at relative to their optimum during a specific task.

From 2-dimensional to 3-dimensional: Overcoming dilemmas in intestinal mucosal interpretation.

The purpose of this review is to provide a definitive account of small intestinal mucosal structure and interpretation. The coeliac lesion has been well known, but not well described to date and this review aims to identify the interpretative difficulties which have arisen over time with the histological assessment of coeliac disease. In early coeliac interpretation, there were significant inaccuracies, particularly surrounding intraepithelial lymphocyte counts and the degree of villous flattening which occurred in the tissue. Many of these interpretive pitfalls are still encountered today, increasing the potential for diagnostic errors. These difficulties are mostly due to the fact that stained 2-dimensional sections can never truly represent the 3-dimensional framework of the intestinal tissue under investigation. Therefore, this review offers a critical account occasioned by these 2-dimensional interpretative errors and which, in our opinion, should in general be jettisoned. As a result, we leave a framework regarding the true 3-dimensional knowledge of mucosal structure accrued over the 70-year period of study, and one which is available for future reference.

Diagnosing celiac disease: A critical overview.

The diagnosis of celiac disease (CD) no longer rests on a malabsorptive state or severe mucosal lesions. For the present, diagnosis will always require the gold-standard of a biopsy, interpreted through its progressive phases (Marsh classification). Marsh classification articulated the immunopathological spectrum of gluten-induced mucosal changes in association with the recognition of innate (Marsh I infiltration) and T cell-based adaptive (Marsh II, and the surface re-organisation typifying Marsh III lesions) responses. Through the Marsh classification the diagnostic goalposts were considerably widened thus, over its time-course, permitting countless patients to begin a gluten-free diet but who, on previous criteria, would have been denied such vital treatment. The revisions of this classification failed to provide additional insight in the interpretation of mucosal pathology. Morever, the subclassification of Marsh 3 imposed an enormous amount of extra work on pathologists with no aid in diagnosis, treatment, or prognosis. Therefore, it should now be apparent that if gastroenterologists ignore these sub-classifications in clinical decision-making, then on that basis alone, there is no need whatsoever for pathologists to persist in reporting them. Since new treatments are under critical assessment, we might have to consider use of some other higher level histological techniques sensitive enough to detect the changes sought. A promising alternative would be to hear more voices from imaginative histopathologists or morphologists together with some more insightful approaches, involving molecular-based techniques and stem cell research may be to evaluate mucosal pathology in CD.

Exploring the villus.

The small intestinal villus and its associated epithelium includes enterocytes as the main cell type and differentiated goblet and argentaffin cells, while the invaginated crypt epithelium is the site of cell division and hence the origin of all epithelial components. Enterocytes form a cohesive monolayer which acts both as a permeability barrier between lumen and the interior, and an important gateway for nutrient digestion, absorption and transport. Differentiation and polarisation of enterocytes depends on cytoskeletal proteins that control cell shape and maintain functionally specialised membrane domains; extracellular matrix (ECM) receptors; channels and transporters regulating ion/solute transfer across the cell. The mesenchymally-derived basement membrane dynamically controls morphogenesis, cell differentiation and polarity, while also providing the structural basis for villi, crypts and the microvasculature of the lamina propria so that tissue morphology, crucially, is preserved in the absence of epithelium. Mucosal re-organisation requires immense cooperation between all elements within the lamina, including marked revisions of the microvasculature and extensive alterations to all basement membranes providing support for endodermal and mesenchymal components. In this context, subepithelial myofibroblasts fulfil important regulatory activities in terms of tissue morphogenesis; remodelling; control of epithelial cell development, polarity and functional attributes; and an intimate involvement in repair, inflammation and fibrosis. This paper reviews the main structural and functional aspects of the villus, including the epithelium and its outer glycocalyx and microvillous border; and subjacent to the epithelium, the basement membrane with its attached web of myo-fibroblasts together with the lamina propria core of the villi, and its microvasculature and lacteals. Finally, some comments on the rapidity with which the overall structure of the villi changes in their response to both external, and internal, influences.

Perspectives of rural health and human service practitioners following suicide prevention training programme in Australia: A thematic analysis.

There are well-established training programmes available to support health and human services professionals working with people vulnerable to suicide. However, little is known about involving people with lived experience in the delivery of suicide prevention training with communities with increased rates of suicide. The aim of this paper was to report on a formative dialogical evaluation that explored the views of health and human services workers with regard to a suicide prevention training programme in regional (including rural and remote areas) South Australia which included meaningful involvement of a person with lived experience in the development and delivery of the training. In 2015, eight suicide prevention training workshops were conducted with health and human services workers. All 248 participants lived and worked in South Australian regional communities. We interviewed a subsample of 24 participants across eight sites. A thematic analysis of the interviews identified five themes: Coproduction is key, It is okay to ask the question, Caring for my community, I can make a difference and Learning for future training. The overall meta-theme was "Involvement of a person with lived experience in suicide prevention training supports regional communities to look out for people at risk of suicide." This paper highlights the need for suicide prevention training and other workforce development programmes to include lived experience participation as a core component in development and delivery.

ROC-king onwards: intraepithelial lymphocyte counts, distribution & role in coeliac disease mucosal interpretation.

OBJECTIVES: Counting intraepithelial lymphocytes (IEL) is central to the histological diagnosis of coeliac disease (CD), but no definitive 'normal' IEL range has ever been published. In this multicentre study, receiver operating characteristic (ROC) curve analysis was used to determine the optimal cut-off between normal and CD (Marsh III lesion) duodenal mucosa, based on IEL counts on >400 mucosal biopsy specimens. DESIGN: The study was designed at the International Meeting on Digestive Pathology, Bucharest 2015. Investigators from 19 centres, eight countries of three continents, recruited 198 patients with Marsh III histology and 203 controls and used one agreed protocol to count IEL/100 enterocytes in well-oriented duodenal biopsies. Demographic and serological data were also collected. RESULTS: The mean ages of CD and control groups were 45.5 (neonate to 82) and 38.3 (2-88) years. Mean IEL count was 54±18/100 enterocytes in CD and 13±8 in normal controls (p=0.0001). ROC analysis indicated an optimal cut-off point of 25 IEL/100 enterocytes, with 99% sensitivity, 92% specificity and 99.5% area under the curve. Other cut-offs between 20 and 40 IEL were less discriminatory. Additionally, there was a sufficiently high number of biopsies to explore IEL counts across the subclassification of the Marsh III lesion. CONCLUSION: Our ROC curve analyses demonstrate that for Marsh III lesions, a cut-off of 25 IEL/100 enterocytes optimises discrimination between normal control and CD biopsies. No differences in IEL counts were found between Marsh III a, b and c lesions. There was an indication of a continuously graded dose-response by IEL to environmental (gluten) antigenic influence.

Instrumentation for electrochemical performance characterization of neural electrodes.

In an effort to determine the chronic stability, sensitivity, and thus the potential viability of various neurochemical recording electrode designs and compositions, we have developed a custom device called the Voltammetry Instrument for Neurochemical Applications (VINA). Here, we describe the design of the VINA and initial testing of its functionality for prototype neurochemical sensing electrodes. The VINA consists of multiple electrode fixtures, a flowing electrolyte bath, associated reservoirs, peristaltic pump, voltage waveform generator, data acquisition hardware, and system software written in National Instrument's LabVIEW. The operation of VINA was demonstrated on a set of boron-doped diamond neurochemical recording electrodes, which were subjected to an applied waveform for a period of eighteen days. Each electrode's cyclic voltammograms (CVs) were recorded, and sensitivity calibration to dopamine (DA) was performed. Results showed an initial decline with subsequent stabilization in the CV current measured during the voltammetric sweep, corresponding closely with changes in electrode sensitivity to DA. The VINA has demonstrated itself as a useful tool for the characterization of electrode stability and chronic electrochemical performance.