Eight weeks of high-intensity interval training versus stretching do not change the psychoneuroendocrine response to a social stress test in emotionally impulsive humans.

PURPOSE: Research supports physical activity as a method to heighten stress resistance and resilience through positive metabolic alterations mostly affecting the neuroendocrine system. High-intensity interval training (HIIT) has been proposed as a highly effective time-saving method to induce those changes. However, existing literature relies heavily on cross-sectional analyses, with few randomised controlled trials highlighting the necessity for more exercise interventions. Thus, this study aims to investigate the effects of HIIT versus an active control group on the stress response to an acute psychosocial stressor in emotionally impulsive humans (suggested as being strong stress responders). METHODS: The study protocol was registered online (DRKS00016589) before data collection. Sedentary, emotionally impulsive adults (30.69 ± 8.20 y) were recruited for a supervised intervention of 8 weeks and randomly allocated to either a HIIT (n = 25) or a stretching group (n = 19, acting as active controls). Participants were submitted to a test battery, including saliva samples, questionnaires (self-efficacy- and perceived stress-related), visual analogue scales (physical exercise- and stress-related), and resting electroencephalography and electrocardiography assessing their reaction to an acute psychological stressor (Trier Social Stress Test) before and after the exercise intervention. RESULTS: HIIT increased aerobic fitness in all participants, whereas stretching did not. Participants from the HIIT group reported perceiving exercising more intensively than those from the active control group (ƞp2 = 0.108, p = 0.038). No further group differences were detected. Both interventions largely increased levels of joy post-TSST (ƞp2 = 0.209, p = 0.003) whilst decreasing tension (ƞp2 = 0.262, p < 0.001) and worries (ƞp2 = 0.113, p = 0.037). Finally, both interventions largely increased perceived levels of general self-efficacy (ƞp2 = 0.120, p = 0.029). CONCLUSION: This study suggests that 8 weeks of HIIT does not change the psychoneuroendocrine response to an acute psychological stress test compared to an active control group in emotionally impulsive humans. Further replications of supervised exercise studies highly powered with active and passive controls are warranted.

The impact of COVID-19 on the well-being of Victorian children born with cleft lip and/or palate.

BACKGROUND: A longitudinal cohort study was established to investigate the well-being of children born with cleft lip and/or palate (CL/P) during the COVID-19 pandemic, in Victoria, Australia. MATERIALS AND METHODS: The Royal Children's Hospital cleft service database was used to identify children aged between 4 and 17 years old born with an isolated CL/P. Families of eligible children who consented to participate were asked to complete the Strengths and Difficulties Questionnaire (SDQ) between October and December 2020 and again 6-month later. SDQ results from typically developing Australian children during the COVID-19 pandemic were utilized from a previously published study. RESULTS: 63 parents completed the baseline questionnaire, with 44 completing the 6-month follow-up. For participants at baseline, the mean age was 8.9 years, with 55% male. All outcome domains of the SDQ improved between baseline and timepoint 2, with the difference in total difficulties scores being statistically significant, indicating a reduction in total difficulties at timepoint 2, associated with the easing of COVID-19 restrictions. When compared with the Australian population during the COVID-19 pandemic, Victorian children born with CL/P had lower SDQ scores for all difficulties outcome domains, with statistically significant results for conduct problems, hyperactivity, peer problems and total difficulties, indicating fewer difficulties for children born with CL/P. CONCLUSIONS: Children born with CL/P experienced fewer difficulties when compared with the typically developing Australian population during the COVID-19 pandemic. The level of restrictions imposed because of the pandemic also had little influence on the well-being of these children.

Modernising physician resource planning: a national interactive web platform for Canadian medical trainees.

BACKGROUND: Healthcare systems rely heavily upon human resources to ensure high-quality access to care for the general population. With significant health worker shortages predicted worldwide in the coming decades, maximizing the current workforce by means of a physician resource planning (PRP) strategy that ensures the right number, mix, and distribution of physicians to meet population needs is warranted. In Canada, there is an insufficient number of primary care providers, and disproportionately low numbers of specialist physicians in rural compared to urban regions. Currently, Canadian medical students are not effectively included in PRP strategy and lack the required information for career orientation to help rebalance the population's workforce needs. This paper present the Health Human Resource (HHR) Platform, a comprehensive web tool that includes relevant workforce data to empower medical students in choosing a discipline based on both personal interests and social accountability. RESULTS: Physician workforce data, comments from Canadian residency program directors, and career planning resources were collected by the Canadian Federation of Medical Student's (CFMS) HHR Task Force. This information was consolidated to create a national interactive platform that uses a map, comparison table, and trend graphs to illustrate over 500,000 unique data points from 37 datasets, including specific information and resources spanning 62 medical specialties from 2015 onwards. There was a 24.6% response rate for program director comments. During the first 4 months of the HHR Platform launch, there were 2434 different users, of which 985 were returning, with an average of 20.0 users per day spending on average 3 min on the platform. CONCLUSIONS: The HHR Platform constitutes a national approach to PRP informing medical students on the mix and distribution of physicians needed to meet the future healthcare demands of the Canadian population.

A unified framework for land cover monitoring based on a discrete global sampling grid (GSG).

Environmental monitoring and assessment of the extent and change of land uses and their renewable natural resources over time is a key element in many international processes and one crucial basis for sustainable management. Remote sensing plays an increasingly important role in these monitoring systems, especially if the interest is in large areas. Integration of remote sensing requires comprehensive and careful preprocessing and a high level of expertise which is not always at hand in all applications. However, easy-to-implement sampling techniques based on visual interpretation are an alternative approach for utilizing remote sensing imagery, including the evolving archives of georeferenced and preprocessed data provided by virtual globes like Google Earth, Bing, and others. The goal of this paper is to propose a simple unified framework that may be used in the context of sampling studies and environmental monitoring from local to global scale. Besides the definition of a sampling design, the observation or plot design, i.e., defining how observations are to be made and recorded, has a strong influence on the precision of estimates as well as the overall efficiency of a sampling exercise. As an example, we present a simulation study focusing on the estimation of forest cover in artificial landscapes with different coverage and degree of fragmentation. The sampling units we compare are point clusters with different configuration and spatial extent.

Early barriers to neonatal porcine islet engraftment in a dual transplant model.

Porcine islet xenografts have the potential to provide an inexhaustible source of islets for ß cell replacement. Proof-of-concept has been established in nonhuman primates. However, significant barriers to xenoislet transplantation remain, including the poorly understood instant blood-mediated inflammatory reaction and a thorough understanding of early xeno-specific immune responses. A paucity of data exist comparing xeno-specific immune responses with alloislet (AI) responses in primates. We recently developed a dual islet transplant model, which enables direct histologic comparison of early engraftment immunobiology. In this study, we investigate early immune responses to neonatal porcine islet (NPI) xenografts compared with rhesus islet allografts at 1 hour, 24 hours, and 7 days. Within the first 24 hours after intraportal infusion, we identified greater apoptosis (caspase 3 activity and TUNEL [terminal deoxynucleotidyl transferase dUTP nick end labeling])-positive cells) of NPIs compared with AIs. Macrophage infiltration was significantly greater at 24 hours compared with 1 hour in both NPI (wild-type) and AIs. At 7 days, IgM and macrophages were highly specific for NPIs (α1,3-galactosyltransferase knockout) compared with AIs. These findings demonstrate an augmented macrophage and antibody response toward xenografts compared with allografts. These data may inform future immune or genetic manipulations required to improve xenoislet engraftment.

Fatal SV40-associated pneumonia and nephropathy following renal allotransplantation in rhesus macaque.

Recrudescence of latent and dormant viruses may lead to overwhelming viremia in immunosuppressed hosts. In immunocompromised hosts, Simian virus 40 (SV40) reactivation is known to cause nephritis and demyelinating central nervous system disease. Here, we report SV40 viremia leading to fatal interstitial pneumonia in an immunosuppressed host following renal allotransplantation.

Selective Targeting of High-Affinity LFA-1 Does Not Augment Costimulation Blockade in a Nonhuman Primate Renal Transplantation Model.

Costimulation blockade (CoB) via belatacept is a lower-morbidity alternative to calcineurin inhibitor (CNI)-based immunosuppression. However, it has higher rates of early acute rejection. These early rejections are mediated in part by memory T cells, which have reduced dependence on the pathway targeted by belatacept and increased adhesion molecule expression. One such molecule is leukocyte function antigen (LFA)-1. LFA-1 exists in two forms: a commonly expressed, low-affinity form and a transient, high-affinity form, expressed only during activation. We have shown that antibodies reactive with LFA-1 regardless of its configuration are effective in eliminating memory T cells but at the cost of impaired protective immunity. Here we test two novel agents, leukotoxin A and AL-579, each of which targets the high-affinity form of LFA-1, to determine whether this more precise targeting prevents belatacept-resistant rejection. Despite evidence of ex vivo and in vivo ligand-specific activity, neither agent when combined with belatacept proved superior to belatacept monotherapy. Leukotoxin A approached a ceiling of toxicity before efficacy, while AL-579 failed to significantly alter the peripheral immune response. These data, and prior studies, suggest that LFA-1 blockade may not be a suitable adjuvant agent for CoB-resistant rejection.

Dynamic control over catalytic function using responsive bisthiourea catalysts.

Two novel bisthiourea molecular motor-based catalysts were designed and their dynamic control of activity and stereoselectivity in the Henry reaction using heat and light as external stimuli was investigated. Enantioselective organocatalysis studies established that a basic functional group is not required within the catalyst core to effect efficient dual stereocontrol, illustrating novel stimuli responsive organocatalysts.

Current practice of continence advisors in managing faecal incontinence in the United Kingdom: results of an online survey.

AIM: To investigate the current practice of continence advisors in the United Kingdom. METHOD: Continence advisors were contacted by email or letter to participate in a survey. The survey contained 27 questions which addressed the practice of each continence advisor, their knowledge of continence management and the adequacy of their training. RESULTS: Two hundred and twenty-six out of a total of 448 continence advisors (50.4%), responded. One hundred and seventy (76.9%) advisors treated both faecal and urinary incontinence, 51 (23.1%) treated urinary incontinence. Thirty-six advisors (16.1%) were lone workers and 130 (58.6%) had more than 10 years' experience. The majority of the advisors (75.6%) performed a digital rectal examination as part of their assessment. Regarding the management of faecal incontinence, 148 prescribed suppositories, 127 offered enemas and 147 advised on rectal irrigation. Most of the advisors taught pelvic floor exercises (n = 207) and urge resistance techniques (n = 188). One hundred and fifty-nine (87.4%) prescribed the Peristeen Coloplast® anal plug and 78 (47.6%) prescribed the Renew® anal insert. Eighty-nine advisors (42.6%) felt they had not been adequately trained to provide a bowel continence service. CONCLUSION: The majority of continence advisors in the UK manage faecal incontinence. They are able to initiate a broad range of conservative treatment options; however, almost half of the advisors who answered the survey felt inadequately trained and may be better supported by further training.

Promoting health and reducing costs: a role for reform of self-monitoring of blood glucose provision within the National Health Service.

AIM: To determine the cost-effectiveness of all options for the self-monitoring of blood glucose funded by the National Health Service, providing guidance for disinvestment and testing the hypothesis that advanced meter features may justify higher prices. METHODS: Using data from the Health and Social Care Information Centre concerning all 8 340 700 self-monitoring of blood glucose-related prescriptions during 2013/2014, we conducted a cost-minimization analysis, considering both strip and lancet costs, including all clinically equivalent technologies for self-monitoring of blood glucose, as determined by the ability to meet ISO-15197:2013 guidelines for meter accuracy. RESULTS: A total of 56 glucose monitor, test strip and lancet combinations were identified, of which 38 met the required accuracy standards. Of these, the mean (range) net ingredient costs for test strips and lancets were £0.27 (£0.14-£0.32) and £0.04 (£0.02-£0.05), respectively, resulting in a weighted average of £0.28 (£0.18-£0.37) per test. Systems providing four or more advanced features were priced equal to those providing just one feature. A total of £12 m was invested in providing 42 million self-monitoring of blood glucose tests with systems that fail to meet acceptable accuracy standards, and efficiency savings of £23.2 m per annum are achievable if the National Health Service were to disinvest from technologies providing lesser functionality than available alternatives, but at a much higher price. CONCLUSION: The study uncovered considerable variation in the price paid by the National Health Service for self-monitoring of blood glucose, which could not be explained by the availability of advanced meter features. A standardized approach to self-monitoring of blood glucose prescribing could achieve significant efficiency savings for the National Health Service, whilst increasing overall utilisation and improving safety for those currently using systems that fail to meet acceptable standards for measurement accuracy.

Bilateral transcutaneous tibial nerve stimulation for chronic constipation.

AIM: Chronic constipation is difficult to treat when symptoms are intractable. Colonic propulsion may be altered by distal neuromodulation but this is conventionally delivered percutaneously. Transcutaneous tibial nerve stimulation is noninvasive and cheap: this study aimed to assess its efficacy in chronic constipation. METHOD: Eighteen patients (median age 46 years, 12 female) with chronic constipation were recruited consecutively. Conservative and behavioural therapy had failed to improve symptoms in all 18. Thirty minutes of daily bilateral transcutaneous tibial nerve stimulation was administered by each patient at home for 6 weeks. The primary outcome measure was a change in the Patient Assessment of Constipation Quality of Life (PAC-QoL) score. Change in Patient Assessment of Constipation Symptoms (PAC-SYM), weekly bowel frequency and visual analogue scale (VAS) score were also measured. RESULTS: Fifteen patients (12 female) completed the trial. The PAC-QoL score improved significantly with treatment [pretreatment, median 2.95, interquartile range (IQR) 1.18; posttreatment, median 2.50, IQR 0.70; P = 0.047]. There was no change in PAC-SYM score (pretreatment, median 2.36, IQR 1.59; posttreatment, median 2.08, IQR 0.92; P = 0.53). Weekly stool frequency improved as did VAS score, but these did not reach statistical significance (P = 0.229 and 0.161). The PAC-QoL and PAC-SYM scores both improved in four (26%) patients. Two patients reported complete cure. There were no adverse events reported. CONCLUSION: Bilateral transcutaneous tibial nerve stimulation appears to be effective in a quarter of patients with chronic constipation. Carefully selected patients with less severe disease may benefit more. This requires further study.

Dual islet transplantation modeling of the instant blood-mediated inflammatory reaction.

Islet xenotransplantation is a potential treatment for diabetes without the limitations of tissue availability. Although successful experimentally, early islet loss remains substantial and attributed to an instant blood-mediated inflammatory reaction (IBMIR). This syndrome of islet destruction has been incompletely defined and characterization in pig-to-primate models has been hampered by logistical and statistical limitations of large animal studies. To further investigate IBMIR, we developed a novel in vivo dual islet transplant model to precisely characterize IBMIR as proof-of-concept that this model can serve to properly control experiments comparing modified xenoislet preparations. WT and α1,3-galactosyltransferase knockout (GTKO) neonatal porcine islets were studied in nonimmunosuppressed rhesus macaques. Inert polyethylene microspheres served as a control for the effects of portal embolization. Digital analysis of immunohistochemistry targeting IBMIR mediators was performed at 1 and 24 h after intraportal islet infusion. Early findings observed in transplanted islets include complement and antibody deposition, and infiltration by neutrophils, macrophages and platelets. Insulin, complement, antibody, neutrophils, macrophages and platelets were similar between GTKO and WT islets, with increasing macrophage infiltration at 24 h in both phenotypes. This model provides an objective and internally controlled study of distinct islet preparations and documents the temporal histology of IBMIR.

The incidence and implications of cerebral palsy following potentially avoidable obstetric complications: a preliminary burden of disease study.

OBJECTIVE: To determine the extent of cerebral palsy attributable to adverse obstetric events, and estimate the lifetime mortality and morbidity expectations of these individuals relative to age-matched members of the UK general population. DESIGN: Simulation model. SETTING UK POPULATION: All projected live births during 2014. METHODS: Using published data regarding the incidence and aetiology of cerebral palsy, we simulated the outcomes of a hypothetical cohort of UK live births. Survival and quality of life (QoL) for those with cerebral palsy were compared with age-matched individuals representative of the UK general population, in order to estimate the number of quality-adjusted life years (QALYs) lost following asphyxia-related cerebral palsy. MAIN OUTCOME MEASURES: Incidence of asphyxia-related cerebral palsy, QALYS, QoL, and survival. RESULTS: A total of 207 (95% CI 169-245) cases of asphyxia-related cerebral palsy were projected amongst UK children born during the year 2014, with approximately 15.2 QALYs lost per case. If these results held true in a real birth cohort, 3142 (95% CI 2321-3963) QALYs would be lost as a consequence of asphyxia-related cerebral palsy, a loss valued by the UK National Health Service at £62.9 m (95% CI £46.4-79.3 m). CONCLUSIONS: Cerebral palsy following intrapartum asphyxiation leads to significant reductions in QoL and survival; however, this may often be prevented. For those with GMFCS 1 and GMFCS 2 cerebral palsy (Gross Motor Function Classification System), lifetime QALYs accrued largely resemble those experienced by the UK general population, whereas for GMFCS 3 and GMFCS 4 QALYs are reduced considerably, and are negative in the case of GMFCS 5.

Liver transplantation in an adolescent with acute liver failure from acute lymphoblastic leukemia.

The most common identifiable causes of acute liver failure in pediatric patients are infection, drug toxicity, metabolic disease, and autoimmune processes. In many cases, the etiology of acute liver failure cannot be determined. Acute leukemia is an extremely rare cause of acute liver failure, and liver transplantation has traditionally been contraindicated in this setting. We report a case of acute liver failure in a previously healthy 15-yr-old male from pre-B-cell acute lymphoblastic leukemia. He underwent liver transplantation before the diagnosis was established, and has subsequently received chemotherapy for pre-B-cell acute lymphoblastic leukemia. He is currently alive 31 months post-transplantation. The published literature describing acute lymphoblastic leukemia as a cause of acute liver failure is reviewed.

Posterior reversible encephalopathy syndrome independently associated with tacrolimus and sirolimus after multivisceral transplantation.

Posterior reversible encephalopathy syndrome (PRES) is a small vessel microangiopathy of the cerebral vasculature that occurs in 0.5-5% of solid organ transplant recipients, most commonly associated with tacrolimus (Tac). Clinical manifestations include hypertension and neurologic symptoms. We report an adult multivisceral transplant recipient who experienced recurrent PRES initially associated with Tac and subsequently with sirolimus. A 49-year-old woman with short bowel syndrome underwent multivisceral transplantation due to total parenteral nutrition-related liver disease. She was initially maintained on Tac, mycophenalate mofetil (MMF) and prednisone. Three months after transplantation, she developed renal dysfunction, leading to a reduction in Tac and the addition of sirolimus. Eight months after transplantation, she developed PRES. Tac was discontinued and PRES resolved. Sirolimus was increased to maintain trough levels of 12-15 ng/mL. Fourteen months after transplant, she experienced recurrent PRES which resolved after discontinuing sirolimus. Currently 3 years posttransplant, she is maintained on cyclosporine, MMF and prednisone with no PRES recurrence. In addition to calcineurin inhibitors, sirolimus may also be associated with PRES after solid organ transplantation. Ours is the first report of sirolimus-associated PRES in the setting of multivisceral transplantation. Identifying a safe alternative immunosuppression regimen was challenging but ultimately successful.

Polarized X-ray scattering reveals non-crystalline orientational ordering in organic films.

Molecular orientation critically influences the mechanical, chemical, optical and electronic properties of organic materials. So far, molecular-scale ordering in soft matter could be characterized with X-ray or electron microscopy techniques only if the sample exhibited sufficient crystallinity. Here, we show that the resonant scattering of polarized soft X-rays (P-SoXS) by molecular orbitals is not limited by crystallinity and that it can be used to probe molecular orientation down to size scales of 10 nm. We first apply the technique on highly crystalline small-molecule thin films and subsequently use its high sensitivity to probe the impact of liquid-crystalline ordering on charge mobility in polymeric transistors. P-SoXS also reveals scattering anisotropy in amorphous domains of all-polymer organic solar cells where interfacial interactions pattern orientational alignment in the matrix phase, which probably plays an important role in the photophysics. The energy and q-dependence of the scattering anisotropy allows the identification of the composition and the degree of orientational order in the domains.

PACK syndrome: A case series and review.

A rare overlap syndrome between CREST (calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia) syndrome and primary biliary cholangitis (PBC) is described as PACK syndrome, an acronym for primary biliary cholangitis, anticentromere antibodies, CREST syndrome, and keratoconjunctivitis sicca. In this retrospective cohort analysis and review, we present fourteen patients who meet diagnostic criteria for PACK syndrome in one of the largest case series of this group. All patients were female, 86% of whom were White with an average age of 66.7 years (range 39-78 years). The prevalence was 5.08% in our PBC cohort (n=256) similar to previous findings. CREST syndrome was diagnosed prior to PBC in 58% of our patients and limited pulmonary and renal involvement were observed. This syndrome is rare, but given its insidious development, clinicians should be aware of this potential overlap in CREST-only and PBC-only patients.

Use of vascularized posterior rectus sheath allograft in pediatric multivisceral transplantation--report of two cases.

Restoring abdominal wall cover and contour in children undergoing bowel and multivisceral transplantation is often challenging due to discrepancy in size between donor and recipient, poor musculature related to birth defects and loss of abdominal wall integrity from multiple surgeries. A recent innovation is the use of vascularized posterior rectus sheath to enable closure of abdomen. We describe the application of this technique in two pediatric multivisceral transplant recipients--one to buttress a lax abdominal wall in a 22-month-old child with megacystis microcolon intestinal hypoperistalsis syndrome and another to accommodate transplanted viscera in a 10-month child with short bowel secondary to gastoschisis and loss of domain. This is the first successful report of this procedure with long-term survival. The procedure has potential application to facilitate difficult abdominal closure in both adults and pediatric liver and multivisceral transplantation.

Percutaneous tibial nerve stimulation for slow transit constipation: a pilot study.

AIM: Chronic constipation is a problem with debilitating effects on patients' quality of life. This study aimed to evaluate the effectiveness of percutaneous tibial nerve stimulation in patients with slow transit constipation. METHOD: Eighteen patients (17 women, median age 47 years, range 21-74) with slow transit constipation previously failing maximal biofeedback therapy participated in the study. Patients had 12 sessions of 30 minutes of percutaneous tibial nerve stimulation. Wexner constipation score (0-30, 30 being the worst) was the primary outcome, colonic transit time, bowel diary and Patient Assessment of Constipation Quality of Life (PAC-QOL) were evaluated pre- and post-treatment. RESULTS: Wexner constipation score improved significantly with treatment (median 18 pre-treatment, range 10-24, to median 14 post-treatment, range 7-22; P = 0.003). The PAC-QOL also showed significant improvement (median 2.31, range 1.36-3.61, to median 1.43, range 0.39-3.78; P = 0.008). Stool frequency increased (P = 0.048) and the use of laxatives decreased (P = 0.025). There was no change in colonic transit time (P = 0.45). CONCLUSION: Percutaneous tibial nerve stimulation has potential as an affordable and minimally invasive treatment for slow transit constipation.

The impact of nisin on sensitive and resistant mutants of Listeria monocytogenes in cottage cheese.

AIMS: Listeria monocytogenes ΔgadD1 and ΔlisK mutants display enhanced and reduced sensitivity, respectively, to the food preservative nisin in laboratory media. However, the behaviour of these strains in a nisin-containing food has not been assessed. Here we use cottage cheese as a model food to address this issue. MATERIALS AND RESULTS: Antibiotic-resistant forms of the wild-type and mutant strains were employed to investigate the behaviour of multiple strains in a single food sample, thereby eliminating the problem of intersample variation. Using this approach, it was established that percentage survival of the ΔlisK mutant was greater than the parent strain in the absence of nisin and that this relative difference became even more dramatic in cottage cheese supplemented with nisin. The numbers of the ΔgadD1 mutant decreased more rapidly than the parent in cottage cheese without nisin, but surprisingly this trend was reversed in nisin-supplemented cheese. Upon the addition of 10 mmol l(-1) monosodium glutamate, a substrate for the glutamate decarboxylase (GAD) system, the wild-type LO28 strain regained its relative advantage over ΔgadD1. CONCLUSIONS: Care needs to be taken when predicting the behaviour of mutants of L. monocytogenes with altered resistance to nisin in food as experiments in laboratory media are not always a good indicator of how the strains will behave in such food environments. SIGNIFICANCE AND IMPACT OF THE STUDY: This study further emphasizes the importance of utilizing food matrices to confirm observations made using laboratory media.