Vulvar Lichen Sclerosus Clinical Severity Scales and Histopathologic Correlation: A Case Series.

ABSTRACT: Several vulvar lichen sclerosus (VLS) clinical severity scales have recently been proposed. In this prospective case series, we characterized histopathology in the context of clinical severity in 6 treatment-naïve postmenopausal patients with VLS. The Vulvar Quality of Life Index (VQLI) and an adaptation of the 2018 International Society for the Study of Vulvovaginal Disease Delphi consensus VLS severity score were administered. Vulvar skin punch biopsies were obtained to measure inflammatory density, constituent inflammatory cells, thickness of the stratum corneum and other epidermal layers, dermal edema, and dermal sclerosis. Clinicopathologic correlations were assessed. Two cases demonstrated sparse inflammatory densities, 1 case demonstrated patchy and nodular inflammatory density, 1 case demonstrated dense lichenoid inflammatory density, and 2 cases demonstrated dense lichenoid and epitheliotropic inflammatory densities. Those patients who reported severe pruritus demonstrated the greatest lymphocytic inflammatory densities on histopathological examination. Both cases of ulceration or erosion were associated with severe VQLI scores. Severe VQLI scores were also associated with trends for higher average thickness of the epidermal layers and of dermal sclerosis. Altogether, histopathologic grading of biopsy sites may reflect clinical severity in patients with VLS.

Risk of Antibiotic-Resistant Staphylococcus aureus Dispersion from Hog Farms: A Critical Review.

The World Health Organization has declared antibiotic resistance "one of the biggest threats to global health." Mounting evidence suggests that antibiotic use in industrial-scale hog farming is contributing to the spread of antibiotic-resistant Staphylococcus aureus. To capture available evidence on these risks, we searched peer-reviewed studies published before June 2017 and conducted a meta-analysis of these studies' estimates of the prevalence of swine-associated, antibiotic-resistant S. aureus in animals, humans, and the environment. The 166 relevant studies revealed consistent evidence of livestock-associated methicillin-resistant S. aureus (MRSA) in hog herds (55.3%) raised with antibiotics. MRSA prevalence was also substantial in slaughterhouse pigs (30.4%), industrial hog operation workers (24.4%), and veterinarians (16.8%). The prevalence of swine-associated, multidrug-resistant S. aureus (MDRSA)-with resistance to three or more antibiotics-is not as well documented. Nonetheless, sufficient studies were available to estimate MDRSA pooled prevalence in conventional hog operation workers (15.0%), workers' household members (13.0%), and community members (5.37%). Evidence also suggests that antibiotic-resistant S. aureus can be present in air, soil, water, and household surface samples gathered in or near high-intensity hog operations. An important caveat is that prevalence estimates for humans reflect colonization, not active infection, and the health risks of colonization remain poorly understood. In addition, these pooled results may not represent risks in specific locations, due to wide geographic variation. Nonetheless, these results underscore the need for additional preventive action to stem the spread of antibiotic-resistant pathogens from livestock operations and a streamlined reporting system to track this risk.

C. elegans germ cells divide and differentiate in a folded tissue.

Knowing how stem cells and their progeny are positioned within their tissues is essential for understanding their regulation. One paradigm for stem cell regulation is the C. elegans germline, which is maintained by a pool of germline stem cells in the distal gonad, in a region known as the 'progenitor zone'. The C. elegans germline is widely used as a stem cell model, but the cellular architecture of the progenitor zone has been unclear. Here we characterize this architecture by creating virtual 3D models of the progenitor zone in both sexes. We show that the progenitor zone in adult hermaphrodites is organized like a folded epithelium. The progenitor zone in males is not folded. Analysis of germ cell division shows that daughter cells are born side-by-side along the epithelial-like surface of the germline tissue. Analysis of a key regulator driving differentiation, GLD-1, shows that germ cells in hermaphrodites differentiate along a folded path, with previously described "steps" in GLD-1 expression corresponding to germline folds. Our study provides a three-dimensional view of how C. elegans germ cells progress from stem cell to overt differentiation, with critical implications for regulators driving this transition.

Regulation of virulence and antibiotic resistance in Gram-positive microbes in response to cell wall-active antibiotics.

PURPOSE OF REVIEW: Antibiotic stress can evoke considerable genotypic and phenotypic changes in Gram-positive bacteria. Here, we review recent studies describing altered virulence expression in response to cell wall-acting antibiotics and discuss mechanisms that coordinate regulation of the antibiotic response. RECENT FINDINGS: Pleiotropic effects induced by antibiotic exposure include alterations to bacterial metabolism, cell wall structure and antibiotic resistance. In addition, subinhibitory concentrations of cell wall-active (CWA) antibiotics have increasingly been shown to induce the production of exotoxins and biofilm formation that may influence virulence. Remarkably, phenotypes associated with comparable antibiotic stresses can vary considerably, emphasizing the need to better understand the response to CWA antibiotics. Recent studies support both direct antibiotic recognition and recognition of antibiotic-induced stress to the bacterial cell wall. Specifically, bacterial two-component systems, penicillin-binding protein and serine/threonine kinase-associated kinases and conserved oxidative-stress sensors each contribute to modulating the antibiotic stress response. SUMMARY: Bacterial sensory systems and global regulators coordinate signaling in response to CWA antibiotics. Regulation of the antibiotic response is complex and involves integration of signals from multiple response pathways. A better definition of the antibiotic stress response among Gram-positive pathogens may yield novel therapeutic targets to counter antibiotic resistance and virulence factor expression.

Myristate-induced endoplasmic reticulum stress requires ceramide synthases 5/6 and generation of C14-ceramide in intestinal epithelial cells.

Saturated fatty acids (SFAs) have been shown to induce endoplasmic reticulum (ER) stress and chronic inflammatory responses, as well as alter sphingolipid metabolism. Disruptions in ER stress and sphingolipid metabolism have also been implicated in intestinal inflammation. Therefore, to elucidate the roles of SFAs in ER stress and inflammation in intestinal epithelial cells, we examined myristate (C14:0) and palmitate (C16:0). Myristate, but not palmitate, induced ER stress signaling, including activation of inositol-requiring enzyme 1 (IRE1) and X-box binding protein 1 (XBP1) signaling. Myristate significantly increased C14-ceramide levels, whereas palmitate increased several long-chain ceramides. To define the role of ceramide synthases (CerSs) in myristate-induced ER stress, we used the pharmacologic inhibitor, fumonisin B1 (FB1), and small interfering RNA (siRNA) for CerS5 and 6, the primary isoforms that are involved in C14-ceramide generation. FB1 and siRNA for CerS5 or 6 suppressed myristate-induced C14-ceramide generation and XBP1 splicing (XBP1s). Moreover, increased XBP1s induced the downstream expression of IL-6 in a CerS5/6-dependent manner. In addition, a myristate-enriched milk fat-based diet, but not a lard-based diet, increased C14-ceramide, XBP1s, and IL-6 expression in vivo. Taken together, our data suggest that myristate modulates ER stress and cytokine production in the intestinal epithelium via CerS5/6 and C14-ceramide generation.-Choi, S., Snider, J. M., Olakkengil, N., Lambert, J. M., Anderson, A. K., Ross-Evans, J. S., Cowart, L. A., Snider, A. J. Myristate-induced endoplasmic reticulum stress requires ceramide synthases 5/6 and generation of C14-ceramide in intestinal epithelial cells.

Biomechanical, Anthropometric, and Psychological Determinants of Barbell Back Squat Strength.

Vigotsky, AD, Bryanton, MA, Nuckols, G, Beardsley, C, Contreras, B, Evans, J, and Schoenfeld, BJ. Biomechanical, anthropometric, and psychological determinants of barbell back squat strength. J Strength Cond Res 33(7S): S26-S35, 2019-Previous investigations of strength have only focused on biomechanical or psychological determinants, while ignoring the potential interplay and relative contributions of these variables. The purpose of this study was to investigate the relative contributions of biomechanical, anthropometric, and psychological variables to the prediction of maximum parallel barbell back squat strength. Twenty-one college-aged participants (male = 14; female = 7; age = 23 ± 3 years) reported to the laboratory for 2 visits. The first visit consisted of anthropometric, psychometric, and parallel barbell back squat 1 repetition maximum (1RM) testing. On the second visit, participants performed isometric dynamometry testing for the knee, hip, and spinal extensors in a sticking point position-specific manner. Multiple linear regression and correlations were used to investigate the combined and individual relationships between biomechanical, anthropometric, and psychological variables and squat 1RM. Multiple regression revealed only 1 statistically predictive determinant: fat-free mass normalized to height (standardized estimate ± SE = 0.6 ± 0.3; t(16) = 2.28; p = 0.037). Correlation coefficients for individual variables and squat 1RM ranged from r = -0.79 to 0.83, with biomechanical, anthropometric, experiential, and sex predictors showing the strongest relationships, and psychological variables displaying the weakest relationships. These data suggest that back squat strength in a heterogeneous population is multifactorial and more related to physical rather than psychological variables.

The impact of reducing intensive care unit length of stay on hospital costs: evidence from a tertiary care hospital in Canada.

PURPOSE: To use theoretical modelling exercises to determine the effect of reduced intensive care unit (ICU) length of stay (LOS) on total hospital costs at a Canadian centre. METHODS: We conducted a retrospective cost analysis from the perspective of one tertiary teaching hospital in Canada. Cost, demographic, clinical, and LOS data were retrieved through case-costing, patient registry, and hospital abstract systems of The Ottawa Hospital Data Warehouse for all new in-patient ward (30,483) and ICU (2,239) encounters between April 2012 and March 2013. Aggregate mean daily variable direct (VD) costs for ICU vs ward encounters were summarized by admission day number, LOS, and cost centre. RESULTS: The mean daily VD cost per ICU patient was $2,472 (CAD), accounting for 67.0% of total daily ICU costs per patient and $717 for patients admitted to the ward. Variable direct cost is greatest on the first day of ICU admission ($3,708), and then decreases by 39.8% to plateau by the fifth day of admission. Reducing LOS among patients with ICU stays ≥ four days could potentially result in an annual hospital cost saving of $852,146 which represents 0.3% of total in-patient hospital costs and 1.2% of ICU costs. CONCLUSION: Reducing ICU LOS has limited cost-saving potential given that ICU costs are greatest early in the course of admission, and this study does not support the notion of reducing ICU LOS as a sole cost-saving strategy.

Comparison between MRI and pathology in the assessment of tumour regression grade in rectal cancer.

BACKGROUND: Limited data exist regarding the correlation between MRI tumour regression grade (mrTRG) and pathological TRG (pTRG) in rectal cancer. METHODS: mrTRG and pTRG were compared in rectal cancer patients from two phase II trials (EXPERT and EXPERT-C). The agreement between radiologist and pathologist was assessed with the weighted κ test while the Kaplan-Meier method was used to estimate survival outcomes. RESULTS: One hundred ninety-one patients were included. Median time from completion of neoadjuvant treatment to pre-operative MRI and surgery was 4.1 weeks (interquartile range (IQR): 3.7-4.7) and 6.6 weeks (IQR: 5.9-7.6), respectively. Fair agreement was found between mrTRG and pTRG when regression was classified according to standard five-tier systems (κ=0.24) or modified three-tier systems (κ=0.25). Sensitivity and specificity of mrTRG 1-2 (complete/good radiological regression) for the prediction of pathological complete response was 74.4% (95% CI: 58.8-86.5) and 62.8% (95% CI: 54.5-70.6), respectively. Survival outcomes of patients with intermediate pathological regression (pTRG 2) were numerically better if complete/good regression was also observed on imaging (mrTRG 1-2) compared to poor regression (mrTRG 3-5) (5-year recurrence-free survival 76.9% vs 65.9%, P=0.18; 5-year overall survival 80.6% vs 68.8%, P=0.22). CONCLUSIONS: The agreement between mrTRG and pTRG is low and mrTRG cannot be used as a surrogate of pTRG. Further studies are warranted to assess the ability of mrTRG to identify pathological complete responders for the adoption of non-operative management strategies and to provide complementary prognostic information to pTRG for better risk-stratification after surgery.

Ecoimmunology and microbial ecology: Contributions to avian behavior, physiology, and life history.

Bacteria have had a fundamental impact on vertebrate evolution not only by affecting the evolution of the immune system, but also generating complex interactions with behavior and physiology. Advances in molecular techniques have started to reveal the intricate ways in which bacteria and vertebrates have coevolved. Here, we focus on birds as an example system for understanding the fundamental impact bacteria have had on the evolution of avian immune defenses, behavior, physiology, reproduction and life histories. The avian egg has multiple characteristics that have evolved to enable effective defense against pathogenic attack. Microbial risk of pathogenic infection is hypothesized to vary with life stage, with early life risk being maximal at either hatching or fledging. For adult birds, microbial infection risk is also proposed to vary with habitat and life stage, with molt inducing a period of increased vulnerability. Bacteria not only play an important role in shaping the immune system as well as trade-offs with other physiological systems, but also for determining digestive efficiency and nutrient uptake. The relevance of avian microbiomes for avian ecology, physiology and behavior is highly topical and will likely impact on our understanding of avian welfare, conservation, captive breeding as well as for our understanding of the nature of host-microbe coevolution.

PATHOPHYSIOLOGIC EVALUATION OF THE TRANSGENIC CFTR "GUT-CORRECTED" PORCINE MODEL OF CYSTIC FIBROSIS.

This study evaluated the pulmonary pathophysiology of the transgenic CFTR "gut-corrected" cystic fibrosis (CF) pigs. Four sows produced 18 piglets of which 11 were stillborn with only 2 animals surviving beyond 2 weeks. Failure to survive beyond the neonatal period by 5 piglets was judged to result from metabolic dysfunction related to genetic manipulation for CFTR gut expression or due to cloning artifact. Plasma analysis showed very low plasma proteins, highly elevated liver enzymes, and severe acidosis. All surviving offspring received furosemide for systemic edema. Physiologic evaluation was performed with lung tissues from the two surviving pigs. Both acetylcholine and forskolin induced mucous liquid secretion that was significantly lower in CF bronchi than non-CF bronchi. The percent non-volatile solids in mucus secreted from CF bronchi was elevated following acetylcholine or forskolin. Mucociliary transport in excised tracheas was reduced in the CF tracheas relative to nonCF tracheas. The diameter of CF tracheas was less than that of non-CF pigs in spite of their greater body weight. Despite exhibiting severe metabolic dysfunction during the neonatal period, this CF animal model appears to express important characteristics of human CF pulmonary disease.

Impact of nest sanitation on the immune system of parents and nestlings in a passerine bird.

Bacterial communities are thought to have fundamental effects on the growth and development of nestling birds. The antigen exposure hypothesis suggests that, for both nestlings and adult birds, exposure to a diverse range of bacteria would select for stronger immune defences. However, there are relatively few studies that have tested the immune/bacterial relationships outside of domestic poultry. We therefore sought to examine indices of immunity (microbial killing ability in naive birds, which is a measure of innate immunity, and the antibody response to sheep red blood cells, which measures adaptive immunity) in both adult and nestling zebra finches (Taeniopygia guttata). We did this throughout breeding and between reproductive attempts in nests that were experimentally manipulated to change the intensity of bacterial exposure. Our results suggest that nest sanitation and bacterial load affected measures of the adaptive immune system, but not the innate immune parameters tested. Adult finches breeding in clean nests had a lower primary antibody response to sheep red blood cells, particularly males, and a greater difference between primary and secondary responses. Adult microbial killing of Escherichia coli decreased as parents moved from incubation to nestling rearing for both nest treatments; however, killing of Candida albicans remained consistent throughout. In nestlings, both innate microbial killing and the adaptive antibody response did not differ between nest environments. Together, these results suggest that exposure to microorganisms in the environment affects the adaptive immune system in nesting birds, with exposure upregulating the antibody response in adult birds.

Superfluous neuroscience information makes explanations of psychological phenomena more appealing.

Does the presence of irrelevant neuroscience information make explanations of psychological phenomena more appealing? Do fMRI pictures further increase that allure? To help answer these questions, 385 college students in four experiments read brief descriptions of psychological phenomena, each one accompanied by an explanation of varying quality (good vs. circular) and followed by superfluous information of various types. Ancillary measures assessed participants' analytical thinking, beliefs on dualism and free will, and admiration for different sciences. In Experiment 1, superfluous neuroscience information increased the judged quality of the argument for both good and bad explanations, whereas accompanying fMRI pictures had no impact above and beyond the neuroscience text, suggesting a bias that is conceptual rather than pictorial. Superfluous neuroscience information was more alluring than social science information (Experiment 2) and more alluring than information from prestigious "hard sciences" (Experiments 3 and 4). Analytical thinking did not protect against the neuroscience bias, nor did a belief in dualism or free will. We conclude that the "allure of neuroscience" bias is conceptual, specific to neuroscience, and not easily accounted for by the prestige of the discipline. It may stem from the lay belief that the brain is the best explanans for mental phenomena.

The prognostic significance of postchemoradiotherapy high-resolution MRI and histopathology detected extramural venous invasion in rectal cancer.

OBJECTIVE: This study aimed to determine the prognostic significance of extramural venous invasion (EMVI) after chemoradiotherapy (CRT) by both magnetic resonance imaging (MRI) (ymrEMVI) and histopathology (ypEMVI). BACKGROUND: EMVI is a prognostic factor in rectal cancer but whether this remains so after CRT preoperative is unknown. Histopathological definitions of EMVI are variable and lead to underreporting particularly after CRT. METHODS: All consecutive patients staged on initial MRI as EMVI-positive undergoing preoperative CRT and curative surgery between Jan 2006 and Jan 2012 were included. Posttreatment EMVI status (yEMVI) was reevaluated for both MRI and pathology. The primary endpoint of disease-free survival (DFS) for ymrEMVI and ypEMVI was calculated using the Kaplan-Meier product limit and compared with a Mantel-Cox log-rank test. A P < 0.05 was considered significant. Hazard ratios (HRs) for disease recurrence were generated using Cox proportional hazard regression for MRI and histopathology tumor characteristics. RESULTS: A total of 188 patients who had evidence of EMVI on initial baseline MRI staging were included. MRI detected significantly more patients with persistent EMVI than histopathology (53% vs 19%) but both were prognostic for worse survival-ymrEMVI (HR 1.97) and ypEMVI (HR 2.39). Patients with persistent ymrEMVI-positivity had significantly worse DFS at 3 years (42.7%) compared with ymrEMVI-negative tumors (79.8%); DFS for was 36.9% versus 65.9% positive and negative ypEMVI, respectively. CONCLUSIONS: Detection of EMVI post-CRT is prognostically significant whether detected by MRI or histopathology. EMVI status after treatment may be used to counsel patients regarding ongoing risks of metastatic disease, implications for surveillance, and systemic chemotherapy.

Impaired cognitive flexibility in amyotrophic lateral sclerosis.

BACKGROUND AND OBJECTIVE: Up to half of patients with amyotrophic lateral sclerosis (ALS) may have cognitive difficulty, but most cognitive measures are confounded by a motor component. Studies relating impaired cognition in ALS to disease in gray matter and white matter are rare. Our objective was to assess executive function in patients with ALS using a simple, untimed measure with minimal motor demands, and to relate performance to structural disease. METHODS: We gave the Visual-Verbal Test to 56 patients with ALS and 29 matched healthy controls. This brief, untimed measure of cognitive flexibility first assesses participants' ability to identify a feature shared by 3 of 4 simple geometric designs. The participants' cognitive flexibility is challenged when they are next asked to identify a different feature shared by another combination of 3 of the same 4 geometric designs. In a subset of 17 patients who underwent magnetic resonance imaging, regression analyses related test performance to gray matter atrophy and reduced white matter fractional anisotropy. RESULTS: The patients with ALS showed significant impairment in cognitive flexibility (P<0.01), with 48.2% making an error on the test. Regression analyses related impaired cognitive flexibility to gray matter atrophy in inferior frontal and insular regions, and to reduced fractional anisotropy in white matter projections in the inferior fronto-occipital and uncinate fasciculi and corpus callosum. CONCLUSIONS: Our patients with ALS had impaired cognitive flexibility on an untimed measure with minimal motor demands, a finding related in part to a large-scale frontal network that is degraded in ALS.

Estimating the prevalence of COPD in Canada: Reported diagnosis versus measured airflow obstruction.

BACKGROUND: Estimates of chronic obstructive pulmonary disease (COPD) prevalence based on self-reports of a diagnosis are thought to underestimate the prevalence of COPD in Canada. DATA AND METHODS: Pre-bronchodilator spirometry measures were obtained from the 2007 to 2009 Canadian Health Measures Survey for 2,487 individuals aged 35 to 79. The prevalence of self-reported chronic bronchitis symptoms and self-reported diagnosis of COPD by a health care professional was compared with the prevalence of measured airflow obstruction according to seven definitions, including the Global Initiative for Obstructive Lung Disease (GOLD) criteria. RESULTS: The prevalence of measured airflow obstruction compatible with COPD was two to six times greater than estimates based on self-reports of a diagnosis. An estimated 16.6% (95% CI: 14.3%-18.9%) of people aged 35 to 79 had pre-bronchodilator airflow obstruction as defined by ≥ GOLD stage I, and 8.1% (95% CI: 6.0%-10.2%) had ≥ GOLD stage II. INTERPRETATION: This study suggests that the prevalence of COPD in Canada has been underestimated.

Assessment of the Cutaneous Hormone Landscapes and Microbiomes in Vulvar Lichen Sclerosus.

Vulvar lichen sclerosus (VLS) is a progressive skin disease of unknown etiology. In this longitudinal case-control exploratory study, we evaluated the hormonal and microbial landscapes in 18 postmenopausal females (mean [SD] age: 64.4 [8.4] years) with VLS and controls. We reevaluated the patients with VLS after 10-14 weeks of daily topical class I steroid. We found that groin cutaneous estrone was lower in VLS than in controls (-22.33, 95% confidence interval [CI] = -36.96 to -7.70; P = .006); cutaneous progesterone was higher (5.73, 95% CI = 3.74-7.73; P < .0001). Forehead 11-deoxycortisol (-0.24, 95% CI = -0.42 to -0.06; P = .01) and testosterone (-7.22, 95% CI = -12.83 to -1.62; P = .02) were lower in disease. With treatment, cutaneous estrone (-7.88, 95% CI = -44.07 to 28.31; P = .62), progesterone (2.02, 95% CI = -2.08 to 6.11; P = .29), and 11-deoxycortisol (-0.13, 95% CI = -0.32 to 0.05; P = .15) normalized; testosterone remained suppressed (-7.41, 95% CI = -13.38 to -1.43; P = .02). 16S ribosomal RNA V1-V3 and ITS1 amplicon sequencing revealed bacterial and fungal microbiome alterations in disease. Findings suggest that cutaneous sex hormone and bacterial microbiome alterations may be associated with VLS in postmenopausal females.

Estimates of global mortality attributable to particulate air pollution using satellite imagery.

BACKGROUND: Epidemiological studies of the health effects of air pollution have traditionally relied upon ground-monitoring stations to measure ambient concentrations. Satellite derived air pollution measures offer the advantage of providing global coverage. OBJECTIVE: To undertake a global assessment of mortality associated with long-term exposure to fine particulate air pollution using remote sensing data. METHODS: Global PM(2.5) exposure levels were derived from the MODIS and MISR satellite instruments. Relative risks and attributable fractions of mortality were modeled using previously developed concentration-response functions for the association between PM(2.5) and mortality. RESULTS: The global fraction of adult mortality attributable to the anthropogenic component of PM(2.5) (95% CI) was 8.0% (5.3-10.5) for cardiopulmonary disease, 12.8% (5.9-18.5) for lung cancer, and 9.4% (6.6-11.8) for ischemic heart disease. CONCLUSION: This study demonstrates the feasibility of using satellite derived pollution concentrations in assessing the population health impacts of air pollution at the global scale. This approach leads to global estimates of mortality attributable to PM(2.5) that are greater than those based on fixed site ground-level measures of urban PM(2.5), but more similar to estimates based on global chemical transport model simulations of anthropogenic PM(2.5).

Is there a role for referral of high-risk patients seen in preoperative medical consultation for postoperative inpatient follow-up?

The potential benefit of referring select high-risk surgical patients who are seen during a preoperative medical consultation for postoperative inpatient medical follow-up is uncertain. Over a seven-year period, our internal medicine perioperative clinic referred 5% of 4642 preoperative consults for postoperative follow-up. A retrospective chart review found that although reasons for referral were heterogeneous, those assessed by the medical consult team postoperatively were more comorbid, had more adverse medical complications and had longer hospital admissions compared to those not referred. Physicians were best able to predict adverse cardiac and diabetes-related complications. Half of the patients who were referred for postoperative assessment were lost to follow-up, and there was a trend towards increased hospital readmissions in this group. Further research is required to identify the subset of patients who might benefit from postoperative inpatient medical assessment.

Variability in the clinical management of fatty acid oxidation disorders: results of a survey of Canadian metabolic physicians.

INTRODUCTION: There is little robust empirical evidence on which to base treatment recommendations for fatty acid oxidation disorders. While consensus guidelines are important, understanding areas where there is a lack of consensus is also critical to inform priorities for future evaluative research. METHODS: We surveyed Canadian metabolic physicians on the treatment of medium-chain acyl-CoA dehydrogenase (MCAD) deficiency, very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency, long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency, and mitochondrial trifunctional protein (MTP) deficiency. We ascertained physicians' opinions on the use of different interventions for the long-term management of patients as well as for the management of acute illness, focusing on identifying interventions characterized by high variability in opinions. We also investigated factors influencing treatment decisions. RESULTS: We received 18 responses (response rate 45%). Participants focused on avoidance of fasting and increased meal frequency as interventions for the management of MCAD deficiency. For the long-chain disorders, avoidance of fasting remained the most consistently endorsed intervention, with additional highly endorsed treatments differing for VLCAD versus LCHAD/MTP deficiency. L-carnitine supplementation and restriction of dietary fat were characterized by high variability in physicians' opinions, as were several interventions specific to long-chain disorders. Social factors and patient characteristics were important influences on treatment decisions. CONCLUSIONS: Based on our findings we suggest that high priority treatments for rigorous effectiveness studies could include L-carnitine supplementation (MCAD and LCHAD/MTP deficiencies), restriction of dietary fat, and, for the long-chain disorders, feeding practices for breastfed infants and the use of various supplements (essential fatty acids, carbohydrates, cornstarch, multivitamins).

Comparative compositions of metabolites and dietary fibre components in doughs and breads produced from bread wheat, emmer and spelt and using yeast and sourdough processes.

Wholemeal flours from blends of bread wheat, emmer and spelt were processed into bread using yeast-based and sourdough fermentation. The bread wheat flour contained significantly higher concentrations of total dietary fibre and fructans than the spelt and emmer flours, the latter having the lowest contents. Breadmaking using sourdough and yeast systems resulted in changes in composition from flour to dough to bread including increases in organic acids and mannitol in the sourdough system and increases in amino acids and sugars (released by hydrolysis of proteins and starch, respectively) in both processing systems. The concentrations of fructans and raffinose (the major endogenous FODMAPs) were reduced by yeast and sourdough fermentation, with yeast having the greater effect. Both systems resulted in greater increases in sugars and glycerol in emmer than in bread wheat and spelt, but the significance of these differences for human health has not been established.