Metachrony drives effective mucociliary transport via a calcium-dependent mechanism.

The mucociliary transport apparatus is critical for maintaining lung health via the coordinated movement of cilia to clear mucus and particulates. A metachronal wave propagates across the epithelium when cilia on adjacent multiciliated cells beat slightly out of phase along the proximal-distal axis of the airways in alignment with anatomically directed mucociliary clearance. We hypothesized that metachrony optimizes mucociliary transport (MCT) and that disruptions of calcium signaling would abolish metachrony and decrease MCT. We imaged bronchi from human explants and ferret tracheae using micro-Optical Coherence Tomography (µOCT) to evaluate airway surface liquid depth (ASL), periciliary liquid depth (PCL), cilia beat frequency (CBF), MCT, and metachrony in situ. We developed statistical models that included covariates of MCT. Ferret tracheae were treated with BAPTA-AM (chelator of intracellular Ca2+), lanthanum chloride (nonpermeable Ca2+channel competitive antagonist), and repaglinide (inhibitor of calaxin) to test calcium-dependence of metachrony. We demonstrated metachrony contributes to mucociliary transport of human and ferret airways. MCT was augmented in regions of metachrony compared to non-metachronous regions by 48.1%, P=0.0009 or 47.5%, P<0.0020 in humans and ferrets, respectively. PCL and metachrony were independent contributors to MCT rate in humans; ASL, CBF, and metachrony contribute to ferret MCT rates. Metachrony can be disrupted by interference with calcium signaling including intracellular, mechanosensitive channels, and calaxin. Our results support that the presence of metachrony augments MCT in a calcium-dependent mechanism.

Racial/Ethnic differences in inflammation levels among older adults 56+: an examination of sociodemographic differences across inflammation measure.

OBJECTIVE: Chronic inflammation is a key biological risk factor for many widespread adult health conditions. This study examines racial/ethnic differences in inflammation across several inflammatory markers, including selected cytokines that are identified as important for aging and age-related health outcomes. METHODS: Data came from the 2016 Venous Blood Collection Subsample of the Health and Retirement Study. Using logistic regression models, we compared high-risk categories of C-reactive protein and cytokine markers (IL-6, IL-10, IL-1RA, TNFR1, and TGF-Beta), across race/ethnicity and whether these differences persisted among men and women. RESULTS: The findings provided evidence of significant race/ethnic differences in inflammatory measures, but the patterns differed across marker types. CONCLUSIONS: These findings emphasize that race/ethnic differences are not consistently captured across markers of inflammation and that researchers should proceed with caution when using individual markers of inflammation in an effort to not overlook potential racial/ethnic differences in biological risk.

The effect of psychiatric decision unit services on inpatient admissions and mental health presentations in emergency departments: an interrupted time series analysis from two cities and one rural area in England.

AIMS: High-quality evidence is lacking for the impact on healthcare utilisation of short-stay alternatives to psychiatric inpatient services for people experiencing acute and/or complex mental health crises (known in England as psychiatric decision units [PDUs]). We assessed the extent to which changes in psychiatric hospital and emergency department (ED) activity were explained by implementation of PDUs in England using a quasi-experimental approach. METHODS: We conducted an interrupted time series (ITS) analysis of weekly aggregated data pre- and post-PDU implementation in one rural and two urban sites using segmented regression, adjusting for temporal and seasonal trends. Primary outcomes were changes in the number of voluntary inpatient admissions to (acute) adult psychiatric wards and number of ED adult mental health-related attendances in the 24 months post-PDU implementation compared to that in the 24 months pre-PDU implementation. RESULTS: The two PDUs (one urban and one rural) with longer (average) stays and high staff-to-patient ratios observed post-PDU decreases in the pattern of weekly voluntary psychiatric admissions relative to pre-PDU trend (Rural: -0.45%/week, 95% confidence interval [CI] = -0.78%, -0.12%; Urban: -0.49%/week, 95% CI = -0.73%, -0.25%); PDU implementation in each was associated with an estimated 35-38% reduction in total voluntary admissions in the post-PDU period. The (urban) PDU with the highest throughput, lowest staff-to-patient ratio and shortest average stay observed a 20% (-20.4%, CI = -29.7%, -10.0%) level reduction in mental health-related ED attendances post-PDU, although there was little impact on long-term trend. Pooled analyses across sites indicated a significant reduction in the number of voluntary admissions following PDU implementation (-16.6%, 95% CI = -23.9%, -8.5%) but no significant (long-term) trend change (-0.20%/week, 95% CI = -0.74%, 0.34%) and no short- (-2.8%, 95% CI = -19.3%, 17.0%) or long-term (0.08%/week, 95% CI = -0.13, 0.28%) effects on mental health-related ED attendances. Findings were largely unchanged in secondary (ITS) analyses that considered the introduction of other service initiatives in the study period. CONCLUSIONS: The introduction of PDUs was associated with an immediate reduction of voluntary psychiatric inpatient admissions. The extent to which PDUs change long-term trends of voluntary psychiatric admissions or impact on psychiatric presentations at ED may be linked to their configuration. PDUs with a large capacity, short length of stay and low staff-to-patient ratio can positively impact ED mental health presentations, while PDUs with longer length of stay and higher staff-to-patient ratios have potential to reduce voluntary psychiatric admissions over an extended period. Taken as a whole, our analyses suggest that when establishing a PDU, consideration of the primary crisis-care need that underlies the creation of the unit is key.

Stimulus control of habits: Evidence for both stimulus specificity and devaluation insensitivity in a dual-response task.

Goal-directed and habitual actions are clearly defined by their associative relations. Whereas goal-directed control can be confirmed via tests of outcome devaluation and contingency-degradation sensitivity, a comparable criterion for positively detecting habits has not been established. To confirm habitual responding, a test of control by the stimulus-response association is required while also ruling out goal-directed control. Here we describe an approach to developing such a test in rats using two discriminative stimuli that set the occasion for two different responses that then earn the same outcome. Performance was insensitive to outcome devaluation and showed stimulus-response specificity, indicative of stimulus-controlled behavior. The reliance of stimulus-response associations was further supported by a lack of sensitivity during the single extinction test session used here. These results demonstrate that two concurrently trained responses can come under habitual control when they share a common outcome. By reducing the ability of one stimulus to signal its corresponding response-outcome association, we found evidence for goal-directed control that can be dissociated from habits. Overall, these experiments provide evidence that tests assessing specific stimulus-response associations can be used to investigate habits.

"It's about time they taught us": a qualitative study evaluating the barriers to finding and screening child contacts under five at risk for TB in Gauteng Province, South Africa from the provider and caregiver perspectives.

BACKGROUND: Inadequate numbers of children under five years of age who are exposed to tuberculosis (TB) in the home (child contact) are initiated on TB preventive treatment (TPT) in South Africa. We assessed barriers of initiating isoniazid preventive therapy (IPT) in this age group. METHODS: We conducted a qualitative study at two primary health clinics in the Ekurhuleni district in Gauteng Province. Between April and July 2019, we enrolled facility managers, TB staff and parents or legal guardians of child contacts (caregivers) attending for care, at the two facilities. Semi-structured questionnaires, facility observations and in-depth interviews using a semi-structured interview guide were used to collect data. Findings from the semi-structured questionnaires with facility staff and facility observations were summarized. Thematic analysis with a deductive approach was used to analyse the data from the in-depth interviews with caregivers. RESULTS: Two facility managers took part in the study and were assisted to complete the semi-structured questionnaires by TB staff. Fifteen caregivers aged between 18 and 43 years were interviewed of which 13 (87%) were female. Facility managers and TB staff (facility staff) felt that even though caregivers knew of family members who were on TB treatment, they delayed bringing their children for TB screening and TPT. Facility staff perceived caregivers as not understanding the purpose and benefits of TB prevention strategies such as TPT. Caregivers expressed the desire for their children to be screened for TB. However, caregivers lacked knowledge on TB transmission and the value of TB prevention in children at high risk of infection. CONCLUSION: While facility staff perceived caregivers to lack responsibility, caregivers expressed limited knowledge on the value of screening their children for TB as reasons for not accessing TB preventive services. Health education on TB transmission, screening, and TB prevention strategies at a community level, clinics, creches, schools and via media are important to achieve the global end TB goal of early detection and prevention of TB.

A Low-Voltage, High-Force Capacity Electroadhesive Clutch Based on Ionoelastomer Heterojunctions.

Electroadhesive devices with dielectric films can electrically program changes in stiffness and adhesion, but require hundreds of volts and are subject to failure by dielectric breakdown. Recent work on ionoelastomer heterojunctions has enabled reversible electroadhesion with low voltages, but these materials exhibit limited force capacities and high detachment forces. It is a grand challenge to engineer electroadhesives with large force capacities and programmable detachment at low voltages (<10 V). In this work, tough ionoelastomer/metal mesh composites with low surface energies are synthesized and surface roughness is controlled to realize sub-ten-volt clutches that are small, strong, and easily detachable. Models based on fracture and contact mechanics explain how clutch compliance and surface texture affect force capacity and contact area, which is validated over different geometries and voltages. These ionoelastomer clutches outperform the best existing electroadhesive clutches by fivefold in force capacity per unit area (102 N cm-2 ), with a 40-fold reduction in operating voltage (± 7.5 V). Finally, the ability of the ionoelastomer clutches to resist bending moments in a finger wearable and as a reversible adhesive in an adjustable phone mount is demonstrated.

Highly purified cannabidiol in the treatment of drug-resistant epilepsies: A real-life impact on seizure frequency, quality of life, behavior, and sleep patterns from a single Italian center.

Seizure frequency in treatment-resistant epilepsies seems to be decreased by cannabidiol (CBD), but contrasting data are available on its effect on sleep, behavior, and quality of life (QoL), and no data is reported on its effect on parental stress in patients with epilepsy (PWE). Thus, we conducted a retrospective study on a cohort of children and adults with drug-resistant epilepsy (DRE) who had been treated with highly purified, pharmaceutical-grade CBD to evaluate its effects on seizure frequency, QoL, behavior, parental stress, and sleep. Eighteen patients (12 adults and 6 children) were included in the cohort and followed for a median of 9 months. At the last follow-up (Tn), nine patients (50%) were considered CBD responders with at least a 50% decrease in seizure frequency. No serious adverse effects were found. No statistically significant differences were found concerning sleep, including daytime sleepiness, and no statistically significant effect was found on parental stress at Tn. An improvement was found for social interaction in quality of life (p < 0.05) for all patients. Our results demonstrate that CBD is a safe and effective antiseizure medication (ASM). CBD doesn't seem to affect sleep measures in adults and children or worsen daytime sleepiness. However, CBD improves specific QoL measures, which could indicate a possible use of CBD for other childhood disabilities. No impact of CBD was seen on parental stress, which could possibly be due to the limited follow-up or could mean that parental stress is not dependent on seizure frequency.

Effective data sampling strategies and boundary condition constraints of physics-informed neural networks for identifying material properties in solid mechanics.

Material identification is critical for understanding the relationship between mechanical properties and the associated mechanical functions. However, material identification is a challenging task, especially when the characteristic of the material is highly nonlinear in nature, as is common in biological tissue. In this work, we identify unknown material properties in continuum solid mechanics via physics-informed neural networks (PINNs). To improve the accuracy and efficiency of PINNs, we develop efficient strategies to nonuniformly sample observational data. We also investigate different approaches to enforce Dirichlet-type boundary conditions (BCs) as soft or hard constraints. Finally, we apply the proposed methods to a diverse set of time-dependent and time-independent solid mechanic examples that span linear elastic and hyperelastic material space. The estimated material parameters achieve relative errors of less than 1%. As such, this work is relevant to diverse applications, including optimizing structural integrity and developing novel materials.

Authoritarianism, psychopathy, and resistance to wearing masks during the COVID-19 pandemic: A partial replication and extension of key findings.

Controversial recent research suggests Americans with more authoritarian tendencies showed less concern about COVID-19 and self-report less mask wearing. The present study set out to replicate this result with a larger sample. The study also sought to extend the original research by investigating how the Dark Triad traits of narcissism, psychopathy, and Machiavellianism are related 1 COVID-19 attitudes and behaviors. Nine-hundred ninety-six United States high school graduates were asked 8 questions about their level of concern about the effects of the virus on health and finances, how frequently they wore masks, which authority figures they trusted, and whether China was responsible for the virus. Correlational and regression analyzes showed that authoritarianism, Machiavellianism, narcissism, and psychopathy were all negatively related to self-reported mask wearing. An explanation is offered for an apparent contradiction between the presented results and studies that showed authoritarian support for lockdowns early during the outbreak.

Establishing an SEIR-based framework for local modelling of COVID-19 infections, hospitalisations and deaths.

Without timely assessments of the number of COVID-19 cases requiring hospitalisation, healthcare providers will struggle to ensure an appropriate number of beds are made available. Too few could cause excess deaths while too many could result in additional waits for elective treatment. As well as supporting capacity considerations, reliably projecting future "waves" is important to inform the nature, timing and magnitude of any localised restrictions to reduce transmission. In making the case for locally owned and locally configurable models, this paper details the approach taken by one major healthcare system in founding a multi-disciplinary "Scenario Review Working Group", comprising commissioners, public health officials and academic epidemiologists. The role of this group, which met weekly during the pandemic, was to define and maintain an evolving library of plausible scenarios to underpin projections obtained through an SEIR-based compartmental model. Outputs have informed decision-making at the system's major incident Bronze, Silver and Gold Commands. This paper presents illustrated examples of use and offers practical considerations for other healthcare systems that may benefit from such a framework.

Clinical characteristics of two-hundred thirty-two dogs (2006-2018) treated for suspected anaphylaxis in Perth, Western Australia.

OBJECTIVE: To describe the clinical features of dogs treated for suspected anaphylaxis in Perth, Western Australia. DESIGN: Single-centre observational case series with retrospective and prospective phases. METHODS: This was a two-phase study of dogs with clinical suspicion of anaphylaxis presenting to the emergency service of a university teaching hospital. Dogs required evidence of, and appropriate treatment of, a type 1 hypersensitivity reaction as well as two or more organs affected (or cardiovascular signs alone) to be included. Phase 1 includes retrospective case series of 186 dogs (March 2006-December 2018). Phase 2 includes prospective descriptive case series of 46 dogs (October 2017-July 2018) focused on clinical signs. RESULTS: In phase 1, 88 (47%) dogs had evidence of insect exposure prior to the acute event. One hundred forty (75%) dogs had dermatological signs, 141 (76%) had gastrointestinal signs and 129 (69%) had cardiovascular signs. Ninety-two (49%) dogs had vasoconstrictive shock (5 with bradycardia), 24 (13%) had vasodilatory shock, 8 (4%) had mixed vasodilatory and vasoconstrictive shock and 5 (3%) had unclassifiable shock. On focused abdominal ultrasound, 42 of 71 (59%) dogs had gallbladder wall oedema and 3 of 71 (4%) dogs had peritoneal free fluid. In phase 2, the distributions of insect exposure, organ dysfunction and sonographic abnormalities were similar to phase 1. CONCLUSION: Dogs presenting with suspected anaphylaxis showed a broad range of presentations. Dermatological signs were absent in a proportion of dogs, vasoconstrictive shock was more frequent than vasodilatory and unique features of shock were identified. This study highlights the challenges of diagnosis based on presenting features alone.

Concordance of 3 alternative teratogenicity assays with results from corresponding in vivo embryo-fetal development studies: Final report from the International Consortium for Innovation and Quality in Pharmaceutical Development (IQ) DruSafe working group 2.

An IQ DruSafe working group evaluated the concordance of 3 alternative teratogenicity assays (rat whole embryo culture, rWEC; zebrafish embryo culture, ZEC; and murine embryonic stem cells, mESC) with findings from rat or rabbit embryo-fetal development (EFD) studies. Data for 90 individual compounds from 9 companies were entered into a database. In vivo findings were deemed positive if malformations or embryo-fetal lethality were reported in either species. Each company used their own criteria for deciding whether the alternative assay predicted the in vivo findings. Standard concordance parameters were calculated, positive and negative predictive values (PPV and NPV) were adjusted for the aggregate portfolio prevalence of positive compounds (established by a survey of participating companies), and positive and negative likelihood ratios (LR+ and iLR-) were calculated. Of the 3 assays, only rWEC data were robustly predictive, particularly for negative predictions (NPVadj = 92%). However, both LR+ (4.92) and iLR- (4.72) were statistically significant for the rWEC assay. When analyzed separately for rats, the NPVadj and iLR-values for the rWEC assay increased to 96% and 9.75, respectively. These data suggest that a negative rWEC outcome could defer or replace a rat EFD study in certain regulatory settings.

Seizure outcome after epilepsy surgery in tuberous sclerosis complex: Results and analysis of predictors from a multicenter study.

Epilepsy surgery is recommended in selected patients with Tuberous Sclerosis Complex (TSC). However, reports on predictive factors of seizure outcome are variable. Here we report on seizure and cognitive outcome of 35 TSC patients who received surgery for refractory epilepsy in 7 Italian centers over a period of 22 years (1997-2019). The rate of seizure-free individuals at last follow-up (mean 7.5 years, range 1-21 years) was 51%. Patients with longer follow-up (≥10 years) had a lower rate of Engel I outcome (11.1%) than those who received surgery in the last 10 years (65.4%, p = 0.003). Factors associated with Engel II, III, IV outcome in our cohort included: high number of cortical tubers (≥5); presence of subependymal nodules (SENs); seizure onset before age 1 year; and multifocal interictal epileptic discharges (IEDs) on electroencephalogram (EEG). A subset of patients evaluated with Vineland Adaptive Behaviour Scales (VABS) showed developmental gains, in line with their developmental trajectories, but no improvement in standard scores after surgery was noted. Our study demonstrates that the rates of successful seizure outcome of epilepsy surgery in TSC have improved in the last 10 years. More than half of the patients achieved seizure freedom, and a high proportion of affected individuals experienced a reduction in seizure burden and in antiseizure medications. A comprehensive assessment after surgery should be performed in TSC patients to evaluate the overall neurodevelopmental outcome, as measures that are based only on seizure control do not adequately identify the benefits of surgery on global functioning in these patients.

Increased risk of eosinophilic esophagitis with poor environmental quality as measured by the Environmental Quality Index.

Geographic differences in eosinophilic esophagitis (EoE) prevalence suggest the possibility that environmental exposures contribute to EoE pathogenesis. We aimed to examine the association between environmental quality and risk of EoE, using the Environmental Quality Index (EQI), which provides quantification of environmental quality in five domains: air, land, water, built, and sociodemographic for all counties in the United States. To do this, we performed a case-control study in a large pathology database. EoE cases were defined by ≥15 eosinophils per high-power field with other pathologic diagnoses excluded; controls did not have EoE. The pathology data were geocoded and linked with the EQI by county of residence. Logistic regression was used to estimate odds ratio (OR and 95% confidence interval [CI]) of EoE with overall EQI and for each domain, after adjusting for sex, age, and proportion minority race or ethnicity at the county level (higher EQI score indicates worse environmental quality). Of 29,802 EoE cases and 593,329 controls analyzed, odds of EoE were highest in the worst quintile of EQI (OR 1.25; 95% CI: 1.04-1.50), which was largely explained by poor scores in the water domain (OR: 1.33; 1.17-1.50). Conversely, odds of EoE were reduced with higher scores in the air domain (OR: 0.87, 0.74-1.03) and land domain (OR 0.87; 0.76-0.99). Poor EQI, mostly reflected by poor water quality, was associated with increased odds of EoE, while poor air and land quality were inversely associated with EoE. Additional work to identify specific water pollutants that may have an etiologic role in EoE may be warranted.

Population Data Centre Profile: The Manitoba Centre for Health Policy.

OBJECTIVE: To profile the Manitoba Centre for Health Policy (MCHP), a population health data centre located at the University of Manitoba in Winnipeg, Canada. APPROACH: We describe how MCHP was established and funded, and how it continues to operate based on a foundation of trust and respect between researchers at the University of Manitoba and stakeholders in the Manitoba Government's Department of Health. MCHP's research priorities are jointly determined by its scientists' own research interests and by questions put forward from Manitoba government ministries. Data governance, data privacy, data linkage processes and data access are discussed in detail. We also provide three illustrative examples of the MCHP Data Repository in action, demonstrating how studies using a variety of Repository datasets have had an impact on health and social policies and programs in Manitoba. DISCUSSION: MCHP has experienced tremendous growth over the last three decades. We discuss emerging research directions as the capacity for innovation at MCHP continues to expand, including a focus on natural language processing and other applications of artificial intelligence techniques, a leadership role in the new SPOR Canadian Data Platform, and a foray into social policy evaluation and analysis. With these and other exciting opportunities on the horizon, the future at MCHP looks exceptionally bright.

Intramyocardial haematoma causing right ventricular outflow obstruction after brown snake (Pseudonaja species) envenomation in a dog.

A 15-month-old, male neutered Staffordshire Bull Terrier cross was presented to its referring veterinarian collapsed and agonal. He was immediately intubated, manually ventilated, and treatment commenced for presumptive snake envenomation with two vials of Tiger/Multi-Brown Snake Antivenom (minimum 7000 units/vial). The dog was transferred to a referral hospital intubated. Additional diagnostics performed following arrival at the referral hospital included a urine snake venom detection kit test, which was positive for brown snake immunotype. Three additional vials of Tiger/Multi-Brown Snake Antivenom (minimum 7000 units/vial) were administered until the dog was extubated and able to stand. Venom-induced consumptive coagulopathy (VICC) was diagnosed based on prolonged clotting times and scleral haemorrhage. Paroxysms of right ventricular outflow tract (RVOT) origin ventricular arrhythmias were treated with lignocaine and sotalol. Four days after presentation, a new-grade IV/VI systolic heart murmur was auscultated, prompting an echocardiogram. An anechoic and compartmentalised mass measuring 43 mm × 19 mm was visualized within the right ventricular wall at the RVOT, immediately adjacent to the pulmonic valve. The mass was causing a RVOT obstruction. Its appearance was suggestive of an intramyocardial haematoma, most likely secondary to VICC. The dog remained cardiovascularly stable, and treatment consisted of supportive care. Recheck echocardiograms at 2 and 7 weeks after discharge revealed progressive improvement of the intramyocardial mass and resolution of the associated heart murmur. Although intramyocardial haematomas are rare, it should be considered as a differential in dogs that develop a newly diagnosed heart murmur and/or cardiac arrhythmia following brown snake envenomation.

What is the impact of psychiatric decision units on mental health crisis care pathways? Protocol for an interrupted time series analysis with a synthetic control study.

BACKGROUND: The UK mental health system is stretched to breaking point. Individuals presenting with mental health problems wait longer at the ED than those presenting with physical concerns and finding a bed when needed is difficult - 91% of psychiatric wards are operating at above the recommended occupancy rate. To address the pressure, a new type of facility - psychiatric decision units (also known as mental health decision units) - have been introduced in some areas. These are short-stay facilities, available upon referral, targeted to help individuals who may be able to avoid an inpatient admission or lengthy ED visit. To advance knowledge about the effectiveness of this service for this purpose, we will examine the effect of the service on the mental health crisis care pathway over a 4-year time period; the 2 years proceeding and following the introduction of the service. We use aggregate service level data of key indicators of the performance of this pathway. METHODS: Data from four mental health Trusts in England will be analysed using an interrupted time series (ITS) design with the primary outcomes of the rate of (i) ED psychiatric presentations and (ii) voluntary admissions to mental health wards. This will be supplemented with a synthetic control study with the same primary outcomes, in which a comparable control group is generated for each outcome using a donor pool of suitable National Health Service Trusts in England. The methods are well suited to an evaluation of an intervention at a service delivery level targeting population-level health outcome and the randomisation or 'trialability' of the intervention is limited. The synthetic control study controls for national trends over time, increasing our confidence in the results. The study has been designed and will be carried out with the involvement of service users and carers. DISCUSSION: This will be the first formal evaluation of psychiatric decision units in England. The analysis will provide estimates of the effect of the decision units on a number of important service use indicators, providing much-needed information for those designing service pathways. TRIAL REGISTRATION: primary registry: isrctn.com Identifying number: ISRCTN77588384 Link: Date of registration in primary registry: 27/02/2020. PRIMARY SPONSOR: St George's, University of London, Cramner Road, Tooting, SW17 ORE. Primary contact: Joe Montebello.

Endometrial development during the transition to menopause: preliminary associations with follicular dynamics.

Objective: This study aimed to test the hypothesis that the development of functional luteal phase dominant follicles (LPDFs) is associated with increased endometrial growth as women transition to menopause.Methods: Endometrial thickness (ET), follicle development, and hormone production were characterized in ovulatory women of mid-reproductive age (MRA; 18-35 years, n = 10) and advanced reproductive age (ARA; 45-55 years, n = 16). Transvaginal ultrasonography was conducted every 1-3 days during one interovulatory interval to quantify ET and the diameters of follicles ≥2 mm. Blood was drawn at each visit to measure progesterone, estradiol, inhibin A, follicle stimulating hormone, and luteinizing hormone.Results: In the MRA group, ET was lower (8.87 vs. 10.1 mm) in women with typical versus no LPDFs, in association with greater luteal phase estradiol (91.1 vs. 48.8 ng/l). In the ARA group, luteal phase endometrial growth was greater (12.0 vs. 10.4 mm) in women with typical versus no LPDFs, in association with lower progesterone (10.7 vs. 13.8 µg/l; LPDF effect p < 0.1) and inhibin A (35.6 vs. 51.17 ng/l; p < 0.10).Conclusions: Preliminary findings suggest that ET may be increased in women who develop LPDFs, in association with reduced luteal phase progesterone and inhibin A, during the transition to menopause. Continued research is required to confirm these findings.

Associations between gastric histopathology and the occurrence of colonic polyps.

AIM: Compromise of the gastric acid barrier may facilitate bacterial invasion of the lower intestinal tract and promote the development of colonic neoplasia. Our study aimed to test the associations between histopathological abnormalities of the upper and lower gastrointestinal tract in patients undergoing bidirectional endoscopy. METHOD: The Inform Diagnostics database is a national electronic repository of histopathological records of patients distributed throughout the USA. A case-control study of 302 061 patients, 163 168 of whom had colonic polyps, evaluated whether the occurrence of colonic polyps was influenced by the presence of the following gastro-oesophageal diagnoses: gastric Helicobacter pylori infection, gastric intestinal metaplasia, fundic gland polyps and gastric hyperplastic polyps. The influence of individual diagnoses on the occurrence of colonic polyps was expressed as odds ratios with their 95% confidence intervals. RESULTS: The odds ratio for tubular adenomas being associated with gastric H. pylori was 1.53 (1.49-1.58), with intestinal metaplasia 1.65 (1.59-1.71), with fundic gland polyps 1.49 (1.45-1.54) and with gastric hyperplastic polyps 1.85 (1.75-1.96). The odds ratio for sessile serrated polyps being associated with gastric H. pylori was 1.03 (0.96-1.10), with intestinal metaplasia 1.21 (1.13-1.30), with fundic gland polyps 1.79 (1.69-1.89) and with gastric hyperplastic polyps 1.52 (1.35-1.71. CONCLUSION: A diminished gastric acid barrier function, which occurs in various upper gastrointestinal diseases associated with lowered gastric acid output, may promote the development of colonic neoplasia.