Quantifying Older Black Americans' Exposure to Structural Racial Discrimination: How Can We Measure the Water In Which We Swim?

The USA was built on legalized racism that started with enslavement and continues in the form of structural racial discrimination. This discrimination is difficult to measure because its many manifestations are hard to observe and dynamic. A useful tool would measure across settings, institutions, time periods in a person's life and the country's history. The purpose of this study was to design a measure of structural racial discrimination that meets those criteria and can be used in large national datasets. To do this, we started with an exploratory mixed-methods instrument design, including qualitative interviews with 15 older Black adults and focus groups with 38 discrimination researchers and other key stakeholders. We then identified 27 indicators of structural racial discrimination across nine theorized discrimination contexts. We matched these with historical administrative data sets to develop an instrument that could quantify older Black Americans' exposure to structural racial discrimination across contexts, the life course, and geographies. These can be mapped to the life course of structural discrimination based on the home addresses of those surveyed. Linking these to available indicators is a promising approach. It is a low burden for participants and enables increasingly multifaceted and focused measurement as more national datasets become available. A flexible, feasible comprehensive measure of structural discrimination could allow not only more thorough documentation of inequities but also allow informed decision making about policies and programs intended to promote racial equity. SIGNIFICANCE STATEMENT: To our knowledge, this is the first study that presents a framework for assessing structural racial discrimination across contexts, life course, and geography that is grounded in theory and in the lived experience of intended participants. Leading researchers and policy makers have called for improved measures of structural racism and discrimination and specifically for a lifecourse approach to measurement. This study is a step in that direction. CLASSIFICATION: Social Sciences.

"I've Lived that Thing that We do with Families": Understanding the Experiences of Practitioners' Undertaking a Three-Year Open Dialogue UK Training Programme.

Open dialogue is a systemically-based approach to mental healthcare, originating from Finland. Growing numbers of practitioners are being trained internationally, but little is known about the impact of such trainings within a UK setting. This study used interpretative phenomenological analysis of focus group data to explore the experiences of thirteen individuals undertaking a three-year UK open dialogue training. Four themes emerged: (1) a powerful experiential process; (2) personal therapeutic change; (3) deeper and more open relationships and (4) altered relationships to power in working practice. The findings suggest that open dialogue trainees experience greater depth in relationships with both clients and colleagues as a result of training, even participants who already had therapeutic training backgrounds. The findings also contribute to Transformational Learning literature regarding how experiential, non-hierarchical, dialogical teaching methods may enhance learning on therapeutic programmes and, therefore, lead to positive changes within clinical practice.

The latest FAD - Faecal antibody detection in cattle. Protocol and results from three UK beef farms naturally infected with gastrointestinal nematodes.

Antibodies at gastrointestinal mucosal membranes play a vital role in immunological protection against a range of pathogens, including helminths. Gastrointestinal health is central to efficient livestock production, and such infections cause significant losses. Fecal samples were taken from 114 cattle, across three beef farms, with matched blood samples taken from 22 of those animals. To achieve fecal antibody detection, a novel fecal supernatant was extracted. Fecal supernatant and serum samples were then analysed, using adapted enzyme-linked immunosorbent assay protocols, for levels of total immunoglobulin (Ig)A, IgG, IgM, and Teladorsagia circumcincta-specific IgA, IgG, IgM and IgE (in the absence of reagents for cattle-specific nematode species). Fecal nematode egg counts were conducted on all fecal samples. Assays performed successfully and showed that IgA was the predominant antibody in fecal samples, whereas IgG was predominant in serum. Total IgA in feces and serum correlated within individuals (0.581, P = 0.005), but other Ig types did not. Results support the hypothesis that the tested protocols are an effective method for the non-invasive assessment of cattle immunology. The method could be used as part of animal health assessments, although further work is required to interpret the relationship between results and levels of infection and immunity.

Development of stratum corneum chymotrypsin-like protease activity and natural moisturizing factors from birth to 4 weeks of age compared with adults.

BACKGROUND: From birth, the functional properties of the neonatal epidermal barrier mature whereby the stratum corneum (SC) hydrates and the skin surface acidifies. The identification of a thinner infant SC compared with adults suggests underdeveloped mechanisms underlying differentiation and desquamation. OBJECTIVES: To assess the functional properties of the neonatal SC from birth, in conjunction with the quantification of superficial chymotrypsin-like protease activity [kallikrein-7 (KLK-7)] and filaggrin-derived natural moisturizing factors (NMF). METHODS: A total of 115 neonates recruited to the Oil in Baby SkincaRE (OBSeRvE) randomized controlled trial underwent a full evaluation of the SC at birth (< 72 h old) and at 4 weeks of age (n = 39, no oil control group) using minimally invasive instrumentation and methodology. A cohort of 20 unrelated adults was recruited for comparison. RESULTS: At birth NMF levels correlated with SC hydration (r = 0·50) and skin-surface pH (r = -0·54). From birth to 4 weeks, transepidermal water loss (TEWL), superficial KLK-7 activity and filaggrin-derived NMF significantly elevated. Impaired epidermal barrier function at birth (> 75th percentile TEWL) was accompanied by significantly elevated chymotrypsin-like protease activity and reduced levels of NMF. CONCLUSIONS: The biophysical, biological and functional properties of the developing neonatal SC are transitional from birth to 4 weeks of age and differ significantly from adults. The presence of impaired barrier function with elevated protease activity and reduced NMF at birth suggests why certain infants are predisposed to epidermal barrier breakdown and the development of atopic dermatitis.

Marvellous to mediocre: findings of national survey of UK practice and provision of care in pregnancies after stillbirth or neonatal death.

BACKGROUND: Pregnancy after stillbirth or neonatal death is an emotionally challenging life-event for women and adequate emotional support during pregnancy should be considered an essential component of quality maternity care. There is a lack of evidence surrounding the role of UK maternity services in meeting womens' emotional and psychological needs in subsequent pregnancies. This study aimed to gain an overview of current UK practice and womens' experiences of care in pregnancy after the death of a baby. METHODS: Online cross-sectional surveys, including open and closed questions, were completed on behalf of 138 United Kingdom (UK) Maternity Units and by 547 women who had experience of UK maternity care in pregnancy after the death of a baby. Quantitative data were analysed descriptively using SPSS software. Open textual responses were managed manually and analysed using the framework method. RESULTS: Variable provision of care and support in subsequent pregnancies was identified from maternity unit responses. A minority had specific written guidance to support care delivery, with a focus on antenatal surveillance and monitoring for complications through increased consultant involvement and technological surveillance (ultrasound/cardiotocography). Availability of specialist services and professionals with specific skills to provide emotional and psychological support was patchy. There was a lack of evaluation/dissemination of developments and innovative practice. Responses across all UK regions demonstrated that women engaged early with maternity care and placed high value on professionals as a source of emotional support. Many women were positive about their care, but a significant minority reported negative experiences. Four common themes summarised womens' perceptions of the most important influences on quality and areas for development: sensitive communication and conduct of staff, appropriate organisation and delivery of services, increased monitoring and surveillance and perception of standard vs. special care. CONCLUSIONS: These findings expose likely inequity in provision of care for UK parents in pregnancy after stillbirth or neonatal death. Many parents do not receive adequate emotional and psychological support increasing the risk of poor health outcomes. There is an urgent need to improve the evidence base and develop specific interventions to enhance appropriate and sensitive care pathways for parents.

Parents' experiences and expectations of care in pregnancy after stillbirth or neonatal death: a metasynthesis.

BACKGROUND: Pregnancy after perinatal death is characterised by elevated stress and anxiety, increasing the risk of adverse short-term and long-term outcomes. OBJECTIVES: This metasynthesis aimed to improve understanding of parents' experiences of maternity care in pregnancy after stillbirth or neonatal death. SEARCH STRATEGY: Six electronic databases were searched using predefined search terms. SELECTION CRITERIA: English language studies using qualitative methods to explore the experiences of parents in pregnancy after perinatal loss, were included subject to quality appraisal framework. DATA COLLECTION AND ANALYSIS: Searches were initiated in December 2011 and finalised in March 2013. Studies were synthesised using an interpretive approach derived from meta-ethnography. MAIN RESULTS: Fourteen studies were included in the synthesis, graded A (no or few flaws, high trustworthiness; n = 5), B (some flaws, unlikely to affect trustworthiness; n = 5) and C (some flaws, possible impact on trustworthiness; n = 4). Three main themes were identified; co-existence of emotions, helpful and unhelpful coping activities and seeking reasssurance through interactions. CONCLUSION: Parents' experiences of pregnancy are profoundly altered by previous perinatal death; conflicted emotions, extreme anxiety, isolation and a lack of trust in a good outcome are commonly reported. Emotional and psychological support improves parents' experiences of subsequent pregnancy, but the absence of an evidence base may limit consistent delivery of optimal care within current services.

Comparison of the welfare of beef cattle in housed and grazing systems: hormones, health, and behaviour.

Animal welfare encompasses all aspects of an animal's life and the interactions between animals. Consequently, welfare must be measured across a variety of factors that consider aspects such as health, behaviour, and mental state. Decisions regarding housing and grazing are central to farm management. In this study, two beef cattle systems and their herds were compared from weaning to slaughter across numerous indicators. One herd ("HH") were continuously housed, the other ("HG") were housed only during winter. Inspections of animals were conducted to assess body condition, cleanliness, diarrhoea, hairlessness, nasal discharge, and ocular discharge. Hair and nasal mucus samples were taken for quantification of cortisol and serotonin. Qualitative behaviour assessments (QBA) were also conducted and performance monitored. Physical health indicators were similar between herds with the exception of nasal discharge which was more prevalent in HH (P < 0.001). During winter, QBA yielded differences between herds over PC1 (arousal) (P = 0.032), but not PC2 (mood) (P = 0.139). Through summer, there was a strong difference across both PC1 (P < 0.001) and PC2 (P = 0.002), with HG exhibiting more positive behaviour. A difference was found in hair cortisol levels, with the greatest concentrations observed in HG (P = 0.011), however such a pattern was not seen for nasal mucus cortisol, or for serotonin. Overall, providing summer grazing (HG) appeared to afford welfare benefits to the cattle as shown with more positive QBA assessments, but also slightly better health indicators, notwithstanding the higher levels of cortisol in that group.

V-QBA vs. QBA-How Do Video and Live Analysis Compare for Qualitative Behaviour Assessment?

Animal welfare is an inextricable part of livestock production and sustainability. Assessing welfare, beyond physical indicators of health, is challenging and often relies on qualitative techniques. Behaviour is a key component of welfare to consider and Qualitative Behaviour Assessment (QBA) aims to achieve this by systematically scoring behaviour across specific terms. In recent years, numerous studies have conducted QBA by using video footage, however, the method was not originally developed using video and video QBA (V-QBA) requires validation. Forty live QBAs were conducted, by two assessors, on housed beef cattle to help fill this validation gap. Video was recorded over the assessment period and a second video assessment was conducted. Live and video scores for each term were compared for both correlation and significant difference. Principle component analysis (PCA) was then conducted and correlations and differences between QBA and V-QBA for the first two components were calculated. Of the 20 terms, three were removed due to an overwhelming majority of scores of zero. Of the remaining 17 terms, 12 correlated significantly, and a significant pairwise difference was found for one ("Bored"). QBA and V-QBA results correlated across both PC1 (defined as "arousal") and PC2 (defined as "mood"). Whilst there was no significant difference between the techniques for PC1, there was for PC2, with V-QBA generally yielding lower scores than QBA. Furthermore, based on PC1 and PC2, corresponding QBA and V-QBA scores were significantly closer than would be expected at random. Results found broad agreement between QBA and V-QBA at both univariate and multivariate levels. However, the lack of absolute agreement and muted V-QBA results for PC2 mean that caution should be taken when implementing V-QBA and that it should ideally be treated independently from live QBA until further evidence is published. Future research should focus on a greater variety of animals, environments, and assessors to address further validation of the method.

SARS-CoV-2 Infection and Antibody Seroprevalence among UK Healthcare Professionals Working with Cancer Patients during the First Wave of the COVID-19 Pandemic.

AIMS: The proportion of UK oncology healthcare professionals (HCPs) infected with SARS-CoV-2 during the COVID-19 pandemic's first wave is unknown. The primary aim of this study was to determine the SARS-CoV-2 infection and seroprevalence rates among HCPs. MATERIALS AND METHODS: Patient-facing oncology HCPs working at three large UK hospitals during the COVID-19 pandemic's first wave underwent polymerase chain reaction (PCR) and antibody testing [Luminex and point-of-care (POC) tests] on two occasions 28 days apart (June-July 2020). RESULTS: In total, 434 HCPs were recruited: nurses (58.3%), doctors (21.2%), radiographers (10.4%), administrators (10.1%); 26.3% reported prior symptoms suggestive of SARS-CoV-2. All participants were PCR negative during the study, but 18.4% were Luminex seropositive on day 1, of whom 42.5% were POC seropositive. Nurses had the highest seropositive prevalence trend (21.3%, P = 0.2). Thirty-eight per cent of seropositive HCPs reported previous SARS-CoV-2 symptoms: 1.9 times higher odds than seronegative HCPs (P = 0.01). Of 400 participants retested on day 28, 13.3% were Luminex seropositive (92.5% previously, 7.5% newly). Thirty-two per cent of initially seropositive HCPs were seronegative on day 28. CONCLUSION: In this large cohort of PCR-negative patient-facing oncology HCPs, almost one in five were SARS-CoV-2 antibody positive at the start of the pandemic's first wave. Our findings that one in three seropositive HCPs retested 28 days later became seronegative support regular SARS-CoV-2 PCR and antibody testing until widespread immunity is achieved by effective vaccination.

Triggering a second T cell receptor on diabetogenic T cells can prevent induction of diabetes.

In this paper, we test the hypothesis that triggering of a second T cell receptor (TCR) expressed on diabetogenic T cells might initiate the onset of diabetes. A cross between two TCR-transgenic strains, the BDC2.5 strain that carries diabetogenic TCRs and the A18 strain that carries receptors specific for C5, was set up to monitor development of diabetes after activation through the C5 TCR. F1 BDC2. 5 x A18 mice developed diabetes spontaneously beyond 3-4 mo of age. Although their T cells express both TCRs constitutively, the A18 receptor is expressed at extremely low levels. In vitro activation of dual TCR T cells followed by adoptive transfer into neonatal or adult F1 mice resulted in diabetes onset and death within 10 d after transfer. In contrast, in vivo immunization of F1 mice with different forms of C5 antigen not only failed to induce diabetes but protected mice from the spontaneous onset of diabetes. We propose that antigenic stimulation of cells with low levels of TCR produces signals inadequate for full activation, resulting instead in anergy.

A thyroxine-containing peptide can induce murine experimental autoimmune thyroiditis.

A synthetic peptide based on a sequence containing thyroxine at position 2553 in thyroglobulin (Tg), and already shown to be recognized by two clonotypically distinct murine Tg autoreactive T cell hybridomas, can trigger primed lymph node cells to transfer thyroiditis to naive recipients. Donor lymph node cells could be prepared from mice immunized either with intact mouse Tg or with this peptide itself. After a second exposure to the priming antigen in vitro, both these populations induced 100% thyroiditis in recipient animals. The importance of the T4 residue in the development of disease was demonstrated by the failure of Tg tryptic peptides depleted of T4 to stimulate pathogenic effectors in vitro, even when the lymph node cells had been taken from mice primed with whole Tg. We conclude that this T4-containing 12mer sequence is a major thyroiditogenic epitope in CBA/J mice although we cannot exclude the possibility that there are other pathogenic epitopes present in the whole Tg molecule.

Identification of a thyroxine-containing self-epitope of thyroglobulin which triggers thyroid autoreactive T cells.

Although thyroglobulin (Tg), the thyroid prohormone, is well known as a T cell dependent autoantigen in human and experimental autoimmune thyroid disease, very little is known about the molecular basis of Tg recognition by T cells. In this paper, we have characterized the epitopes recognized by two clonotypically distinct, murine Tg autoreactive T cell hybridomas, CH9 and ADA2. In vitro iodination of a Tg preparation which was deficient in in vivo organified iodine was first used to confirm our previous observation that these T cells recognize iodination-related epitopes in the Tg molecule. Affinity chromatography of tryptic peptides derived from normally iodinated human Tg revealed that these epitopes were exclusively located in thyroxine (T4) containing peptides. Through the use of synthetic T4-containing peptides, representing the four major hormonogenic sites in Tg, we demonstrated that both CH9 and ADA2 recognize an epitope containing the T4 at position 2553 in human Tg. Sets of overlapping 5mer to 12mer peptides around this T4 showed that the most potent peptide was a 9mer beginning at Asp 2551. The T4 was shown to be a critical residue, since its replacement with any of the 20 naturally occurring amino acids produced only nonstimulatory peptides. Since the T cell hybridomas could also be stimulated by major histocompatibility complex class II positive (interferon-gamma-treated) thyroid epithelial cells in vitro, and their parent T cell lines can induce thyroiditis on adoptive transfer, the T4-containing Tg sequence described here is implicated as a pathogenic epitope in murine thyroid autoimmunity.

Prevalence of genetic haemochromatosis and iron overload in patients attending rheumatology and joint replacement clinics.

BACKGROUND & AIMS: Genetic Haemochromatosis (GH) is common in North European and Celtic populations and is associated with arthropathy. We aimed to measure the frequency of the common GH mutations (C282Y and H63D), the carrier frequency of C282Y and markers of iron overload in patients who were referred to our rheumatology and joint replacement clinics. METHODS: Unselected patients attending these clinics were anonymously tested for the described mutations. Transferrin saturation and serum ferritin were also measured and if elevated, the patients had predictive counselling then named GH mutation testing. The carrier and mutation frequencies were also determined in 340 local controls. RESULTS: One hundred and sixty-one unselected patients attending these clinics were studied. The C282Y mutation carrier frequency was 1 in 5.2 in patients compared with 1 in 8.1 in controls (p < 0.005). The overall mutation frequencies were similar in patients and controls. One patient was found to be a homozygous for the C282Y mutation and eight were compound heterozygotes. Seven other patients had a raised ferritin, one of whom was a C282Y heterozygote. CONCLUSION: The C282Y carrier frequency is significantly higher in patients attending rheumatology and joint replacement clinics than in controls. Screening of these patients for GH should be considered.

Does dissemination of guidelines alone increase the use of palliative single-fraction radiotherapy? Initial report of a longitudinal change management campaign at a provincial cancer program.

Background: Despite level 1 evidence demonstrating the equivalence of single-fraction radiotherapy (sfrt) and multiple-fraction radiotherapy (mfrt) for the palliation of painful bone metastases, sfrt remains underused. In 2015, to encourage the sustainable use of palliative radiation oncology resources, CancerCare Manitoba disseminated, to each radiation oncologist in Manitoba, guidelines from Choosing Wisely Canada (cwc) that recommend sfrt. We assessed whether dissemination of the guidelines influenced sfrt use in Manitoba in 2016, and we identified factors associated with mfrt. Methods: All patients treated with palliative radiotherapy for bone metastasis in Manitoba from 1 January 2016 to 31 December 2016 were identified from the provincial radiotherapy database. Patient, treatment, and disease characteristics were extracted from the electronic medical record and tabulated by fractionation schedule. Univariable and multivariable logistic regression analyses were performed to identify risk factors associated with mfrt. Results: In 2016, 807 patients (mean age: 70 years; range: 35-96 years) received palliative radiotherapy for bone metastasis, with 69% of the patients having uncomplicated bone metastasis. The most common primary malignancies were prostate (27.1%), lung (20.6%), and breast cancer (15.9%). In 62% of cases, mfrt was used-a proportion that was unchanged from 2015. On multivariable analysis, a gastrointestinal [odds ratio (or): 5.3] or lung primary (or: 3.3), complicated bone metastasis (or: 4.3), and treatment at a subsidiary site (or: 4.4) increased the odds of mfrt use. Conclusions: Dissemination of cwc recommendations alone did not increase sfrt use by radiation oncologists in 2016. A more comprehensive knowledge translation effort is therefore warranted and is now underway to encourage increased uptake of sfrt in Manitoba.

Open reduction and internal fixation for concomitant talar neck, talar body, and medial malleolar fractures: a case report.

Fractures of the talus are rare and generally associated with severe trauma. The mechanism of injury is usually forced dorsiflexion or a fall from a height. Severe talar fractures pose a challenge for surgeons as they are often associated with complications such as avascular necrosis, collapse, malunion, secondary osteoarthritis and pain. This has led some institutions to advocate primary arthrodesis for these injuries. We report an unusual complex fracture of the talus that was successfully managed with open reduction and internal fixation. By restoring a near-normal range of motion and function to a fit, young male, the severely limiting effects of arthrodesis were avoided or at least delayed. We use this case to highlight that primary arthrodesis should only be reserved for cases that fail to respond to open reduction and internal fixation or deteriorate to the point where it is the only reasonable and justifiable alternative.

Stigma: a linguistic analysis of the UK red-top tabloids press' representation of schizophrenia.

AIMS: Media representations of mental health problems may influence readers' understanding of, and attitude towards, people who have received psychiatric diagnoses. Negative beliefs and attitudes may then lead to discriminatory behaviour, which is understood as stigma. This study explored the language used in popular national newspapers when writing about schizophrenia and considered how this may have contributed to the processes of stigmatisation towards people with this diagnosis. METHODS: Using corpus linguistic methods, a sample of newspaper articles over a 24-month period that mentioned the word 'schizophrenia' was compared with a similar sample of articles about diabetes. This enabled a theory-driven exploration of linguistic characteristics to explore stigmatising messages, while supported by statistical tests (log-likelihood) to compare the data sets and identify words with a high relative frequency. RESULTS: Analysis of the 'schizophrenia' data set identified that overtly stigmatising language (e.g. 'schizo') was relatively infrequent, but that there was frequent use of linguistic signatures of violence. Articles frequently used graphic language referring to acts of violence, descriptions of violent acts, implements used in violence, identity labels and exemplars of well-known individuals who had committed violent acts. The word 'schizophrenic' was used with a high frequency ( n = 108) and most commonly to name individuals who had committed acts of violence. DISCUSSION: The study suggests that while the press has largely avoided the use of words that press guidance has steered them away from (e.g. 'schizo' and 'psycho'), they still use a range of graphic language to present people with a diagnosis of schizophrenia as frighteningly 'other' and as prone to violence. This repetition of negative stereotypical messages may well contribute to the processes of stigmatisation many people who experience psychosis have to contend with.

Design, structure activity relationships and X-Ray co-crystallography of non-steroidal LXR agonists.

The Liver X Receptor (LXR) alpha and beta isoforms are members of the type II nuclear receptor family which function as a heterodimer with the Retinoid X Receptor (RXR). Upon agonist binding, the formation of the LXR/RXR heterodimer takes place and ultimately the regulation of a number of genes begins. The LXR isoforms share 77% sequence homology, with LXRalpha having highest expression in liver, intestine, adipose tissue, and macrophages and LXRbeta being ubiquitously expressed. The aim of this article is to review the reported medicinal chemistry strategies towards the optimisation of novel non-steroidal chemotypes as LXR agonists. An analysis of the structural features important for LXR ligand binding will be given, utilising both structural activity relationship data obtained from LXR assays as well as X-ray co-crystallographic data obtained with LXR ligands and the LXR ligand binding domain (LBD). The X-ray co-crystallographic data analysis will detail the key structural interactions required for LXR binding/agonist activity and reveal the differences observed between chemotype classes. It has been postulated that a LXRbeta selective compound may have a beneficial outcome on the lipid profile for a ligand by dissociating the favourable and unfavourable effects of LXR agonists. Whilst there have been a few examples of compounds showing a modest level of LXRalpha selectivity, obtaining a potent LXRbeta selective compound has been more challenging. Analysis of the SAR and X-ray co-crystallographic data suggests that the rational design of a LXRbeta selective compound will not be trivial.

Induction and protection of autoimmune rheumatic diseases. The role of infections.

It is thought that in genetically predisposed individuals, autoimmune diseases can be promoted and/or exacerbated by viruses, bacteria, or parasitic infectious agents. Pathogens can activate innate immune response interacting with Toll-like receptors that recognize pathogen-associated molecules. As a consequence of infections, a prolonged inflammatory response may occur leading to chronic inflammation with activation of adaptive immune response. In addition, the defective clearance of apoptotic infected cells, which progress- es to secondary necrosis, can foster the autoimmune reactions. Although numerous data from humans and/or animal models support the hypothesis of a direct contribution of pathogens to the induction of the disease, some infectious agents are able to prevent autoimmune disorders. In this review, data on the innate and adaptive immune response induced by pathogens are summarized, focusing on the possible protective or non-protective role of infections in the development of autoimmune diseases.

Autoimmune disease. Gadding around the beta cell.

Recent studies shed new light on the process by which T-cell tolerance to pancreatic beta-cell antigens breaks down, leading to the autoimmune disease insulin-dependent diabetes mellitus.

An inhibitory innervation at the gastroduodenal junction.

Transverse muscle strips, 2-mm wide, were cut serially from the gastroduodenal junction in opossums, cats, dogs, and man. Electrical field stimulation with trains of rectangular current pulses of 0.5 ms in all opossums, all cats, some dogs, and the one human specimen induced relaxation in strips from the thickened circular muscle proximal to the mucosal junction. In some opossums weak relaxations also occurred in the first few strips below the mucosal junction. All other strips contracted or showed no response. This relaxation in opossums was abolished by tetrodotoxin but was not affected by antagonists to adrenergic and cholinergic transmission, nor by tripelennamine, methysergide, pentagastrin, secretin, cerulein, or cholecystokinin. Optimal frequency for stimulus-relaxation was 12 Hz. Chronaxie was 0.85 ms. The junctional strips also showed greater resistances to stretch than those remote from the junction. With apparent species variations, the junctional muscle possesses a nonadrenergic inhibitory innervation which is either absent or unexpressed in adjacent muscle of stomach and duodenum. This suggests the existence of a distinctive inhibitory neural control mechanism for pyloric muscle.