Preliminary validation of a self-efficacy scale for pediatric chronic illness.

BACKGROUND: Tracking self-efficacy may be useful for identifying children at risk for medical noncompliance. We created the Pediatric Rating of Chronic Illness Self-Efficacy (PRCISE) to measure self-efficacy in youth dealing with a chronic illness. METHOD: Data were collected from 217 families where one child aged 7-20 (Mage  = 13.62, SDage  = 2.92; 62.7% Latino, 58.1% female) had a chronic illness. Parent participants provided demographic information. Youth completed a depression measure, the Patient Health Questionnaire for Adolescents and the PRCISE. To determine the underlying latent structure of the scale, an exploratory factor analysis was conducted using parallel analysis. We also carried out two multiple linear regressions to explore the data and establish preliminary predictive validity. RESULTS: The measure was reduced to 15 items, demonstrating a one-factor solution with strong reliability. Predictors of lower self-efficacy included having parents who had not attended college, being African American, and having higher Patient Health Questionnaire for Adolescents scores, R2  = .23, F(11, 174) = 5.62, p < .001. Main effects were qualified by a two-way interaction, such that the decrease in PRCISE scores associated with depressive symptoms was attenuated in children with less educated parents. In terms of predictive validity, higher PRCISE scores unexpectedly predicted more number of emergency room visits, R2  = .12, F(9, 113) = 2.73, p < .01. CONCLUSIONS: The PRCISE appears to be a reliable measure of a single self-efficacy construct. Secondary analyses revealed important health disparities in pediatric chronic illness self-efficacy. Next steps may include validation of the PRCISE using confirmatory factor analysis.

Diagnosis and outcome of childhood perineurioma.

INTRODUCTION: Intraneural perineurioma is a rare peripheral nerve tumor of childhood and early adulthood. Patients demonstrate progressive muscle weakness and atrophy largely without sensory complaints. CASE: We report two children with perineurioma affecting the radial and femoral nerves. Electromyography (EMG), ultrasound, and 3-T MR imaging were important tools for localizing perineurioma and permitting its differentiation from other nerve lesions. The first patient underwent surgical excision of the perineurioma and a traditional nerve graft. At 10 months post-operative follow-up, she demonstrated no meaningful recovery of muscle strength compared to her pre-operative assessment. EMG did confirm axonal continuity indicating that reinnervation had occurred via the nerve graft. The second patient underwent a two-staged surgical procedure that included an end-to-side nerve transfer. At 18 months post-operative follow-up, she demonstrated mild improvement in muscle strength and EMG evidence of ongoing reinnervation. CONCLUSION: The surgical management of perineurioma remains controversial, and reports of clinical recovery after nerve grafts and nerve transfers vary. Nerve transfers have been reported to provide superior results to traditional nerve grafting in adults with post-traumatic plexus injuries. The modest gain in strength of our patient who underwent a nerve transfer raises the question if this may also apply to patients with perineurioma. Additional studies will be required, which must also take into consideration that features of long-standing neuropathy (i.e., limb length discrepancy) have the potential to reduce the likelihood of reinnervation and clinical recovery.

The effects of glucuronic acid and N-acetyl-D-glucosamine on in vitro fertilisation of porcine oocytes.

High incidences of polyspermic penetration continue to challenge researchers during porcine in vitro fertilisation (IVF). The aim of this study was to reduce the incidence of polyspermy by increasing the perivitelline space thickness with glucuronic acid and N-acetyl-D-glucosamine (GlcNAc) supplementation during oocyte maturation. After maturation, zona pellucida and perivitelline space thicknesses, intracellular glutathione concentrations and fertilisation kinetics were measured, in addition to embryonic cleavage and blastocyst formation at 48h and 144h after IVF, respectively. There were no significant differences between the treatments for zona pellucida thickness, penetration rates, male pronuclear formation or cortical granule exocytosis. Glucuronic acid supplementation significantly increased (PPPP<0.05) of cleavage and blastocyst formation by 48 and 144h after IVF compared with all other groups. These results indicate that supplementing with 0.005mM glucuronic acid and 0.005mM GlcNAc during oocyte maturation decreases the incidence of polyspermic penetration by increasing perivitelline space thickness and improving embryo development in pigs.

Diagnostic SOX10 gene signatures in salivary adenoid cystic and breast basal-like carcinomas.

BACKGROUND: Salivary adenoid cystic carcinoma (ACC) is an insidious slow-growing cancer with the propensity to recur and metastasise to distant sites. Basal-like breast carcinoma (BBC) is a molecular subtype that constitutes 15-20% of breast cancers, shares histological similarities and basal cell markers with ACC, lacks expression of ER (oestrogen receptor), PR (progesterone receptor), and HER2 (human epidermal growth factor receptor 2), and, similar to ACC, metastasises predominantly to the lung and brain. Both cancers lack targeted therapies owing to poor understanding of their molecular drivers. METHODS: Gene expression profiling, immunohistochemical staining, western blot, RT-PCR, and in silico analysis of massive cancer data sets were used to identify novel markers and potential therapeutic targets for ACC and BBC. For the detection and comparison of gene signatures, we performed co-expression analysis using a recently developed web-based multi-experiment matrix tool for visualisation and rank aggregation. RESULTS: In ACC and BBC we identified characteristic and overlapping SOX10 gene signatures that contained a large set of novel potential molecular markers. SOX10 was validated as a sensitive diagnostic marker for both cancers and its expression was linked to normal and malignant myoepithelial/basal cells. In ACC, BBC, and melanoma (MEL), SOX10 expression strongly co-segregated with the expression of ROPN1B, GPM6B, COL9A3, and MIA. In ACC and breast cancers, SOX10 expression negatively correlated with FOXA1, a cell identity marker and major regulator of the luminal breast subtype. Diagnostic significance of several conserved elements of the SOX10 signature (MIA, TRIM2, ROPN1, and ROPN1B) was validated on BBC cell lines. CONCLUSION: SOX10 expression in ACC and BBC appears to be a part of a highly coordinated transcriptional programme characteristic for cancers with basal/myoepithelial features. Comparison between ACC/BBC and other cancers, such as neuroblastomaand MEL, reveals potential molecular markers specific for these cancers that are likely linked to their cell identity. SOX10 as a novel diagnostic marker for ACC and BBC provides important molecular insight into their molecular aetiology and cell origin. Given that SOX10 was recently described as a principal driver of MEL, identification of conserved elements of the SOX10 signatures may help in better understanding of SOX10-related signalling and development of novel diagnostic and therapeutic tools.

Socio-ecological factors shape the distribution of a cultural keystone species in Malaysian Borneo.

Biophysical and socio-cultural factors have jointly shaped the distribution of global biodiversity, yet relatively few studies have quantitatively assessed the influence of social and ecological landscapes on wildlife distributions. We sought to determine whether social and ecological covariates shape the distribution of a cultural keystone species, the bearded pig (Sus barbatus). Drawing on a dataset of 295 total camera trap locations and 25,755 trap days across 18 field sites and three years in Sabah and Sarawak, Malaysian Borneo, we fitted occupancy models that incorporated socio-cultural covariates and ecological covariates hypothesized to influence bearded pig occupancy. We found that all competitive occupancy models included both socio-cultural and ecological covariates. Moreover, we found quantitative evidence supporting Indigenous pig hunting rights: predicted pig occupancy was positively associated with predicted high levels of Indigenous pig-hunting groups in low-accessibility areas, and predicted pig occupancy was positively associated with predicted medium and low levels of Indigenous pig-hunting groups in high-accessibility areas. These results suggest that bearded pig populations in Malaysian Borneo should be managed with context-specific strategies, promoting Indigenous pig hunting rights. We also provide important baseline information on bearded pig occupancy levels prior to the 2020-2021 outbreak of African Swine Fever (ASF), which caused social and ecological concerns after mass dieoffs of bearded pigs in Borneo. The abstract provided in Malay is in the Supplementary file.

Cancer Trial Impact: Understanding Implementation of the Short Course Oncology Treatment (SCOT) Trial Findings in colorectal cancer at a National Level.

AIMS: The Short Course Oncology Treatment (SCOT) trial indicated that 3 months of adjuvant doublet chemotherapy was non-inferior to 6 months of treatment for patients with colorectal cancer, with considerably less toxicity. The SCOT trial results were disseminated in June 2017. The aim of this study was to understand if SCOT trial findings were implemented in Scotland. MATERIALS AND METHODS: A retrospective analysis was carried out on a dataset derived from a source population of 5.4 million people. Eligible patients were those with stage II or III colorectal cancer who received adjuvant chemotherapy. Logistic regression was applied to understand the extent of practice change to a 3-month adjuvant chemotherapy duration after the SCOT trial results were disseminated. Interrupted time series analysis was used to visualise differences in prescribing trends before and after June 2017 for the overall cohort, and by SCOT trial eligibility. RESULTS: In total, 2310 patients were included in the study; 1957 and 353 treated pre- and post-June 2017, respectively. The median treatment duration decreased from 21 weeks (interquartile range 14-24) prior to June 2017 to 12 weeks (interquartile range 12-21 weeks) after June 2017 (P < 0.001). The proportion of patients receiving over 3 months of adjuvant treatment decreased from 75% to 42% (P < 0.001). This change was most noticeable for patients who met the SCOT trial eligibility criteria, and specifically for those with low-risk stage III disease and those treated with capecitabine and oxaliplatin (CAPOX). Although practice change occurred in all locations, there were differences between regions that could be explained by pre-SCOT trial prescribing trends. DISCUSSION: A significant change in chemotherapy prescribing occurred after dissemination of the SCOT trial results. National, real-world data can be used to capture the extent of implementation of clinical trial results. In this case, implementation was aligned with clinical trial subgroup findings. This type of analysis could be conducted to evaluate the impact of other clinical trials.

Implementation of a Maternal Child Knowledgebase.

To advance the application of clinical data to address maternal health we developed and implemented a Maternal Child Knowledgebase (MCK). The MCK integrates data from every pregnancy that received care at the University of Iowa Hospitals & Clinics (UIHC) and links information from the pregnancy episode to the delivery episode and between the mother and child. This knowledgebase contains integrated information regarding diagnoses, medications, mother and child vitals, hospital admissions, depression screenings, laboratory value results, and procedure information. It also collates information from the electronic health record (EPIC), the Social Security Death Index, and the Medication Administration Record into one knowledgebase. To enhance usability, we designed a custom viewer with several pre-designed queries and reports that eliminates the need for users to be proficient in SQL coding. The recent implementation of the MCK has supported multiple projects and reduced the number of Obstetrics-related data queries to the Biomedical Informatics group.

Myofunctional therapy. Part 1: Culture, industrialisation and the shrinking human face.

Culture, industrialisation and the shrinking human face: Why is it important? Over the past 300,000 years, not only has the way we consume food from birth through our lifetime changed, there have also been changes related to the methods of food preparation, availability, processing, and storage. These diet-related factors, along with other epigenetic factors, have led to a widespread increase in orofacial myofunctional disorders (OMDs) and resultant human malocclusion phenotypes (HMPs) worldwide. Currently there is an increasing need for resolution of HMPs in early childhood and associated OMDs. This review will include reports of cases and describe the nature of the problem and strategies for effective solutions.

Maldevelopment of the cranio-facial-respiratory complex: A Darwinian perspective.

AIM: The mammalian Cranio-Facial-Respiratory Complex (CFRC) comprises several different biological tissues that collectively function under coordination from the central nervous and cardiorespiratory systems, primarily to breathe, eat and drink as well as integrating the sensory and motor systems for speech, communication and protective mechanisms. Anthropologists have long recognised that lifelong exposure to modern feeding regimens of readily available and highly processed foods, changes in breastfeeding and weaning, can impact expression of various phenotypic traits affecting the CFRC quite differently than does lifelong exposure to more traditional ancestral feeding regimens, typical of hunter-gather/foraging in non-Western-exposed cultures. The aim of this study is to highlight the role of the paediatric dentist in a multidisciplinary approach in which professionals working in and around the CFRC can actively prevent tooth decay and skeletal-dental malocclusion in the light of evolutionary oral medicine. RESULTS: As a result of changes in the environment, in the food quality, in eating and feeding practices starting from day one, two oral diseases of civilisation, tooth decay and skeletal-dental malocclusion, have both relatively recently reached worldwide epidemic proportions and afflict people of all ages. CONCLUSION: A multidisciplinary approach in which professionals working in and around the CFRC can actively promote prevention or reversal of dento-skeletal and myofunctional disorders, diagnose them when present and coordinate the appropriate therapy and life long maintenance programme.

Neurovascular coupling and oxygenation are decreased in hippocampus compared to neocortex because of microvascular differences.

The hippocampus is essential for spatial and episodic memory but is damaged early in Alzheimer's disease and is very sensitive to hypoxia. Understanding how it regulates its oxygen supply is therefore key for designing interventions to preserve its function. However, studies of neurovascular function in the hippocampus in vivo have been limited by its relative inaccessibility. Here we compared hippocampal and visual cortical neurovascular function in awake mice, using two photon imaging of individual neurons and vessels and measures of regional blood flow and haemoglobin oxygenation. We show that blood flow, blood oxygenation and neurovascular coupling were decreased in the hippocampus compared to neocortex, because of differences in both the vascular network and pericyte and endothelial cell function. Modelling oxygen diffusion indicates that these features of the hippocampal vasculature may restrict oxygen availability and could explain its sensitivity to damage during neurological conditions, including Alzheimer's disease, where the brain's energy supply is decreased.

Chatbots to Support Mental Wellbeing of People Living in Rural Areas: Can User Groups Contribute to Co-design?

Digital technologies such as chatbots can be used in the field of mental health. In particular, chatbots can be used to support citizens living in sparsely populated areas who face problems such as poor access to mental health services, lack of 24/7 support, barriers to engagement, lack of age appropriate support and reductions in health budgets. The aim of this study was to establish if user groups can design content for a chatbot to support the mental wellbeing of individuals in rural areas. University students and staff, mental health professionals and mental health service users (N = 78 total) were recruited to workshops across Northern Ireland, Ireland, Scotland, Finland and Sweden. The findings revealed that participants wanted a positive chatbot that was able to listen, support, inform and build a rapport with users. Gamification could be used within the chatbot to increase user engagement and retention. Content within the chatbot could include validated mental health scales and appropriate response triggers, such as signposting to external resources should the user disclose potentially harmful information or suicidal intent. Overall, the workshop participants identified user needs which can be transformed into chatbot requirements. Responsible design of mental healthcare chatbots should consider what users want or need, but also what chatbot features artificial intelligence can competently facilitate and which features mental health professionals would endorse.

Medical ethics and law for doctors of tomorrow: the 1998 Consensus Statement updated.

Knowledge of the ethical and legal basis of medicine is as essential to clinical practice as an understanding of basic medical sciences. In the UK, the General Medical Council (GMC) requires that medical graduates behave according to ethical and legal principles and must know about and comply with the GMC's ethical guidance and standards. We suggest that these standards can only be achieved when the teaching and learning of medical ethics, law and professionalism are fundamental to, and thoroughly integrated both vertically and horizontally throughout, the curricula of all medical schools as a shared obligation of all teachers. The GMC also requires that each medical school provides adequate teaching time and resources to achieve the above. We reiterate that the adequate provision and coordination of teaching and learning of ethics and law requires at least one full-time senior academic in ethics and law with relevant professional and academic expertise. In this paper we set out an updated indicative core content of learning for medical ethics and law in UK medical schools and describe its origins and the consultative process by which it was achieved.

A single episode of haematospermia can be safely managed in the community.

INTRODUCTION: This study is a ten-year single institution retrospective study of patients presenting with haematospermia, to establish standard tests for investigation, and what tests have low yield and can be omitted. MATERIALS AND METHODS: Investigations that were used were analysed to establish their diagnostic yield. The parameters examined were: digital rectal examination (DRE) findings, prostate specific antigen (PSA), abdominal and scrotal ultrasound, TRUS biopsy result (wherever applicable), flexible cystoscopy findings and final diagnosis. RESULTS: The central findings were that abdominal ultrasound never yielded an abnormality and that flexible cystoscopy never showed bladder tumours. TRUS prostate biopsies were performed in 17% of patients, and prostate cancer was confirmed in 5% of patients. Testicular malignancy was found in 2%. In 90% of patients, no specific diagnosis was made, and 85% of patients were discharged at review. CONCLUSIONS: A single episode of haematospermia is usually benign. Flexible cystoscopy and abdominal ultrasound appear valueless. Assessment should consist of clinical examination (including testicular), DRE and PSA testing. It can safely be managed in the community and only referred in the presence of, abnormal examination, elevated PSA or recurrent symptoms.

The 2008 ACVP role delineation survey and initial data analysis: from the Role Delineation Task Force.

The American College of Veterinary Pathologists commissioned a role delineation survey to define the specialized tasks, knowledge, and tools that define the current practice of veterinary clinical pathology and veterinary anatomic pathology. The survey also identified when competence was acquired for each task (i.e., before certification or after certification). The response rate by diplomates was high, with approximately 50% of practicing pathologists within each specialty responding to each survey. Using the survey results, all tasks for each specialty were classified as either appropriate or unsuitable for testing in the certifying examinations. The role delineation survey data will facilitate the creation of test plans that objectively define the content in each certifying examination, the evaluation and enhancement of training curricula, and the optimization of continuing education opportunities for practicing veterinary pathologists.

Clarithromycin with low dose dexamethasone and thalidomide is effective therapy in relapsed/refractory myeloma.

A combination of clarithromycin, low dose of thalidomide and low dose dexamethasone was used in a phase II study to treat patients with relapsed and refractory myeloma. Thirty patients received clarithromycin 250 mg twice daily and thalidomide 50 mg at night on an ongoing basis with 4-d pulses of 10 mg dexamethasone given monthly. Eight patients had permitted escalation of thalidomide dosage up to 200 mg daily. The combination was well tolerated and could be given to elderly, infirm and severely cytopenic patients. Response rates were high, with 89% achieving at least 50% reduction in paraprotein and a 96% overall response rate. Although clarithromycin has only minimal anti-myeloma properties when used as a single agent, its combination with thalidomide and dexamethasone appears very effective, allowing these to be used in lower and more tolerable doses with good clinical effects.

De-stabilization of the positive vago-vagal reflex in bulimia nervosa.

Bulimia nervosa is characterized by consuming large amounts of food over a defined period with a loss of control over the eating. This is followed by a compensatory behavior directed at eliminating the consumed calories, usually vomiting. Current treatments include antidepressants and/or behavioral therapies. Consensus exists that these treatments are not very effective and are associated with high relapse rates. We review evidence from literature and present original data to evaluate the hypothesis that bulimia involves alterations in vago-vagal function. Evidence in support of this include (1) laboratory studies consistently illustrate deficits in meal size, meal termination, and satiety in bulimia; (2) basic science studies indicate that meal size and satiation are under vagal influences; (3) anatomical, behavioral and physiological data suggest that achieving satiety and the initiation of emesis involve common neural substrates; (4) abnormal vagal and vago-vagal reflexive functions extend to non-eating activational stimuli; and (5) studies from our laboratory modulating vagal activation have shown significant effects on binge/vomit frequencies and suggest a return of normal satiation. We propose a model for the pathophysiology of bulimia based upon de-stabilization of a bi-stable positive vago-vagal feedback loop. This model is not meant to be complete, but rather to stimulate anatomical, psychobiological, and translational neuroscience experiments aimed at elucidating the pathophysiology of bulimia and developing novel treatment strategies.

Researching experiences of terminal cancer: a systematic review of methodological issues and approaches.

The objectives of this review were to assess the methods and approaches applied to end-of-life cancer research based on papers focusing on approaches or methodological issues related to seeking the views of people affected by terminal cancer. A comprehensive search of 10 databases (January 1980-February 2004) was undertaken. References were screened, quality assessed and data extracted by two reviewers. Analysis followed a meta-narrative approach. Fifteen papers were included. They discussed 'traditional' approaches, such as focus groups, interviews, surveys, as well as innovative approaches allied to the arts. They reveal that mixed methods are gaining popularity. The emotional demands placed on researchers and the ethical issues involved in this research area were also discussed. We concluded that researchers should embrace innovative approaches from other areas of social science, such as the use of arts-based techniques. This may facilitate recruitment of the hard-to-reach groups and engage with experiences that may be otherwise difficult to verbalize. Although researching the needs of the dying carries challenges, these are not the exclusive domain of the cancer field. This study reveals that diverse methods, from research-based drama to postal questionnaires, can enhance end-of-life research. However, this review reveals the need for more methodological work to be undertaken and disseminated.

The key challenges of discussing end-of-life stroke care with patients and families: a mixed-methods electronic survey of hospital and community healthcare professionals.

BACKGROUND: Communication between professionals, patients and families about palliative and end-of-life care after stroke is complex and there is a need for educational resources in this area. METHODS: To explore the key learning needs of healthcare professionals, a multidisciplinary, expert group developed a short electronic survey with open and closed questions, and then distributed it to six UK multiprofessional networks and two groups of local clinicians. RESULTS: A total of 599 healthcare professionals responded. Educational topics that were either definitely or probably needed were: ensuring consistent messages to families and patients (88%); resolving conflicts among family members (83%); handling unrealistic expectations (88%); involving families in discussions without them feeling responsible for decisions (82%); discussion of prognostic uncertainties (79%); likely mode of death (72%); and oral feeding for 'comfort' in patients at risk of aspiration (71%). The free-text responses (n = 489) and 82 'memorable' cases identified similar themes. CONCLUSION: Key topics of unmet need for education in end-of-life care in stroke have been identified and these have influenced the content of an open access, web-based educational resource.

Myc versus USF: discrimination at the cad gene is determined by core promoter elements.

Carbamoyl-phosphate synthase/aspartate carbamoyltransferase/dihydroorotase, which is encoded by the cad gene, is required for the first three rate-limiting steps of de novo pyrimidine biosynthesis. It has been previously demonstrated that cad transcription increases at the G1/S-phase boundary, as quiescent cells reenter the proliferative cell cycle. The growth-responsive element has been mapped to an E box at +65 in the hamster cad promoter. Using an in vivo UV cross-linking and immunoprecipitation assay, we show that Myc, Max, and upstream stimulatory factor (USF) bind to the chromosomal cad promoter. To determine whether binding of Myc-Max or USF is critical for cad growth regulation, we analyzed promoter constructs which contain mutations in the nucleotides flanking the E box. We demonstrate that altering nucleotides which flank the cad E box to sequences which decrease Myc-Max binding in vitro correlates with a loss of cad G1/S-phase transcriptional activation. This result supports the conclusion that binding of Myc-Max, but not USF, is essential for cad regulation. Our investigations demonstrate that the endogenous cad E box can be bound by more than one transcription factor, but growth-induced cad expression is achieved only by Myc.

Coexamination of site-specific transcription factor binding and promoter activity in living cells.

Previously, we have used a chromatin cross-linking and immunoprecipitation protocol for the analysis of Myc and USF binding to the cad promoter. The adaptation of this technique for the study of mammalian transcription factors was a big step forward in the analysis of transcription factor family member specificity, allowing for the first time a definitive knowledge of which factor binds to a promoter region under normal physiological conditions. However, due to limitations of the assay, our previous studies could not definitively prove that both Myc and USF bound to the exact same site on the cad promoter, nor could we directly correlate loss of in vivo binding of a particular factor with loss of transcriptional activity. Therefore, we have further modified the chromatin immunoprecipitation protocol to alleviate these problems. We have now shown that it is possible to coexamine growth-regulated transcriptional activity and promoter occupancy by using stably integrated promoter constructs. We show that both Myc and USF bind to the exact same E box on the cad promoter, suggesting that competition between these two factors for a single site occurs in living cells. We also find that cad promoter constructs that retain USF binding but lose Myc binding in vivo no longer display an increase in transcriptional activity in mid- to late G(1) phase of the cell cycle. Finally, we propose that cell cycle-regulated transcriptional activation of the cad promoter may be a stochastic, rather than a predetermined, process.