The standard of care in the management of immune-mediated inflammatory conditions relies on immunomodulators, glucocorticoids, and biologicals (including anti-tumour necrosis factor −α and other monoclonal antibodies). These agents have an overall favourable benefit/risk ratio; however, they modulate the immune response as part of their mechanisms of action, and therefore they may increase the risk of developing infections, particularly in older patients or in patients with concomitant corticosteroids.
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Δευτέρα 11 Σεπτεμβρίου 2017
Screening, prophylaxis and counselling before the start of biological therapies: a practical approach focused on IBD patients
Ocular Dysfunctions Presenting in Tacrolimus-Induced Posterior Reversible Encephalopathy Syndrome: A Case Presentation
The constellation of ocular symptoms, known as Balint's syndrome, is a rare disorder seen in bilateral parieto-occipital lesions and is most frequently due to arterial occlusive disease or acute hypertension. Here we present a case of a patient with tacrolimus-induced posterior reversible encephalopathy syndrome (PRES) who presented with optic ataxia, simultanagnosia, and ocular apraxia. These ocular findings, consistent with Balint's syndrome, are rarely the initial presentation of PRES. This case highlights the importance of early recognition of this unusual phenomenon as well as the importance of an individualized rehabilitation plan to maximize functional independence in these patients.
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Epidemiology of Youth Boys' and Girls' Lacrosse Injuries in the 2015-2016 Seasons.
Purpose: Examinations of injury among younger populations of lacrosse players that are beginning their development is limited. This study describes the epidemiology of youth boys' and girls' lacrosse injuries during the 2015-2016 seasons. Methods: Surveillance data originated from a convenience sample of 10 leagues in five states with 1090 boys' and 480 girls' lacrosse players from the U9-U15 divisions. Athletic trainers reported injury and exposure data at games and practices. Time-loss (TL) injuries were defined as resulting in >=24 hours of participation restriction time. Injury counts and rates per 1000 athlete-games/practices were calculated. Injury rate ratios (IRR) with 95% confidence intervals (CI) compared rates by sex and age division. Results: Overall, 241 and 59 injuries were reported in boys' and girls' youth lacrosse, respectively, of which 17.0% and 18.6% were TL. Compared to girls, boys had a higher overall injury rate (12.7 vs. 8.7/1000 athlete-games/practices; IRR=1.5; 95%CI: 1.1-1.9). U13/U15 boys had a higher TL injury rate than U9/U11 boys (2.6 vs. 1.0/1000 athlete-game/practices; IRR=2.6; 95%CI: 1.1-6.1). Most injuries were diagnosed as contusions (boys: 53.7%; girls: 47.2%) and resulted from stick contact (boys: 34.1%; girls: 30.6%) and ball contact (boys: 17.1%; girls: 25.0%). Among girls, ball contact contributed to 75.0% (n=9) of all head/face injuries. Among the 14 concussions reported in boys, player contact was the most common injury mechanism (50.0%, n=7), followed by stick contact (35.7%, n=5). Conclusion: Boys' lacrosse has a higher injury incidence than girls' lacrosse, reflecting the contact nature of the boys' game. The high incidence of stick- and ball-related injuries suggests the need for youth specific rules to better protect youth players. (C) 2017 American College of Sports Medicine
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Work Rate during Self-paced Exercise is not Mediated by the Rate of Heat Storage.
PURPOSE: To date, there have been mixed findings on whether greater anticipatory reductions in self-paced exercise intensity in the heat are mediated by early differences in rate of body heat storage. The disparity may be due to an inability to accurately measure minute-to-minute changes in whole-body heat loss. Thus, we evaluated whether early differences in rate of heat storage can mediate exercise intensity during self-paced cycling at a fixed rate of perceived exertion (RPE of 16; hard-to-very-hard work effort) in COOL (15[degrees]C), NORMAL (25[degrees]C) and HOT (35[degrees]C) ambient conditions. METHODS: On separate days, nine endurance-trained cyclists exercised in COOL, NORMAL and HOT conditions at a fixed RPE until work rate (measured after first 5-min of exercise) decreased to 70% of starting values. Whole-body heat loss and metabolic heat production were measured by direct and indirect calorimetry respectively. RESULTS: Total exercise time was shorter in HOT (57+/-20 min) relative to both NORMAL (72+/-23 min, P=0.004) and COOL (70+/-26 min, P=0.045). Starting work rate was lower in HOT (153+/-31 W) compared to NORMAL (166+/-27 W, P=0.024) and COOL (170+/-33 W, P=0.037). Rate of heat storage was similar between conditions during the first 4 min of exercise (all P>0.05). Thereafter, rate of heat storage was lower in HOT relative to NORMAL and COOL until 30-min of exercise (last common time-point between conditions; all P
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Screening, prophylaxis and counselling before the start of biological therapies: a practical approach focused on IBD patients
The standard of care in the management of immune-mediated inflammatory conditions relies on immunomodulators, glucocorticoids, and biologicals (including anti-tumour necrosis factor −α and other monoclonal antibodies). These agents have an overall favourable benefit/risk ratio; however, they modulate the immune response as part of their mechanisms of action, and therefore they may increase the risk of developing infections, particularly in older patients or in patients with concomitant corticosteroids.
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Comparison of Single Genome and Allele Frequency Data Reveals Discordant Demographic Histories
Inference of demographic history from genetic data is a primary goal of population genetics of model and non-model organisms. Whole genome-based approaches such as the Pairwise/Multiple Sequentially Markovian Coalescent (PSMC/MSMC) methods use genomic data from one to four individuals to infer the demographic history of an entire population, while site frequency spectrum (SFS)-based methods use the distribution of allele frequencies in a sample to reconstruct the same historical events. Although both methods are extensively used in empirical studies and perform well on data simulated under simple models, there have been only limited comparisons of them in more complex and realistic settings. Here we use published demographic models based on data from three human populations (Yoruba (YRI), descendants of northwest-Europeans (CEU), and Han Chinese (CHB)) as an empirical test case to study the behavior of both inference procedures. We find that several of the demographic histories inferred by the whole genome-based methods do not predict the genome-wide distribution of heterozygosity nor do they predict the empirical SFS. However, using simulated data, we also find that the whole genome methods can reconstruct the complex demographic models inferred by SFS-based methods, suggesting that the discordant patterns of genetic variation are not attributable to a lack of statistical power, but may reflect unmodeled complexities in the underlying demography. More generally, our findings indicate that demographic inference from a small number of genomes, routine in genomic studies of non-model organisms, should be interpreted cautiously, as these models cannot recapitulate other summaries of the data.
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Highly Efficient, Rapid and Co-CRISPR Independent Genome Editing in Caenorhabditis elegans
We describe a rapid and highly efficient method to generate point mutations in C. elegans using direct injection of CRISPR-Cas9 ribonucleoproteins. This versatile method does not require sensitized genetic backgrounds or co-CRISPR selection-based methods, and represents a single strategy that can used for creating genomic point mutations, regardless of location. As proof-of-principle, we show that knock-in mutants more faithfully report variant-associated phenotypes compared to transgenic overexpression. Data for nine knock-in mutants across five genes are presented that demonstrate high editing efficiencies (60%), a reduced screening workload (24 F1 progeny), and a rapid timescale (4-5 days). This optimized method simplifies genome engineering and is readily adaptable to other model systems.
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IOP-details
Source:International Journal of Psychophysiology, Volume 120
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Full title with Editorial board members
Source:International Journal of Psychophysiology, Volume 120
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Instructions to Authors
Source:International Journal of Psychophysiology, Volume 120
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Childhood adversity predicts reduced physiological flexibility during the processing of negative affect among adolescents with major depression histories
Source:International Journal of Psychophysiology
Author(s): Shimrit Daches, Maria Kovacs, Charles George, Ilya Yaroslavsky, Eniko Kiss, Agnes Vetro, Roberta Dochnal, István Benak, Ildikó Baji, Kitti Halas, Attila Makai, Krisztina Kapornai, Jonathan Rottenberg
BackgroundAdversity during early development has been shown to have enduring negative physiological consequences. In turn, atypical physiological functioning has been associated with maladaptive processing of negative affect, including its regulation. The present study therefore explored whether exposure to adverse life events in childhood predicted maladaptive (less flexible) parasympathetic nervous system functioning during the processing of negative affect among adolescents with depression histories.MethodsAn initially clinic-referred, pediatric sample (N=189) was assessed at two time points. At Time 1, when subjects were 10.17years old (SD=1.42), on average, and were depressed, parents reported on adverse life events the offspring experienced up to that point. At Time 2, when subjects were 17.18years old (SD=1.28), and were remitted from depression, parents again reported on adverse life events in their offspring's lives for the interim period. At time 2, subjects' parasympathetic nervous system functioning (quantified as respiratory sinus arrhythmia) also was assessed at rest, during sad mood induction, and during instructed mood repair.ResultsExtent of adverse life events experienced by T1 (but not events occurring between T1 and T2) predicted less flexible RSA functioning 7years later during the processing of negative affect. Adolescents with more extensive early life adversities exhibited less vagal withdrawal following negative mood induction and tended to show less physiological recovery following mood repair.ConclusionsEarly adversities appear to be associated with less flexible physiological regulatory control during negative affect experience, when measured later in development. Stress-related autonomic dysfunction in vulnerable youths may contribute to the unfavorable clinical prognosis associated with juvenile-onset depression.
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Emergency Reporting and First Due Size-Up announce integration and partnership to serve Fire and EMS department operations
Never again will a first responder be injured or worse due to a lack of information
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CONSTRUCTION EMT / PARAMEDIC - Event Medic Service
Event Medic Service is looking for one or two EMT or Paramedics to work at construction sites in Ashburn and Leesburgh VA starting Saturday 9/16 Monday through Saturday each week. If you can commit to all days or some days each week until at least December 31st contact us immediately ! IF YOU KNOW OF AN EXPERIENCED EMT OR PARAMEDIC WHO WOULD BE INTERESTED WE ARE OFFERING A $150 finders fee! Have them ...
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LanguageMAPS adds to its medical advisory board
DALLAS — LanguageMAPS, creator of the 1st Minute App and leader in simplified language translation for emergencies, is pleased to announce the addition of Dr. Patti C. Huang and Dr. Tyler DeLange as new members of its medical advisory board. Dr. Patti Huang Dr. Huang runs Frisco Family ENT in North Texas and has won "Best Doctor" awards from D Magazine since 2012. She is also the creator ...
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Pain in cancer survivors; filling in the gaps
Abstract
Cancer survivorship represents a growing clinical challenge for pain clinicians. The population of cancer survivors is rapidly expanding and many of these patients experience pain as a sequelae of their disease and its treatment. The features, pathophysiology and natural history of some painful conditions observed in cancer survivors, such as direct tumour effects, cancer induced bone pain (CIBP) or chronic post-surgical pain have received extensive exposure elsewhere in the literature. In this narrative review, we attempt to 'fill in the gaps' in the knowledge, by providing a succinct outline of a range of less well known pain states encountered in the cancer survivor population. These include neuropathies as a result of graft versus host disease (GVHD), novel chemotherapeutic agents and monoclonal antibodies (mAb), and radiation induced pain states. The increasing prevalence of visceral post-surgical pain and aromatase inhibitor-induced arthralgia (AIA) is also detailed. Additionally an overview of suggested approaches to the assessment of pain in cancer survivors is provided and potential treatment strategies, with a focus on novel approaches are discussed.from Anaesthesiology via xlomafota13 on Inoreader http://ift.tt/2gZzPb9
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Erratum to: Per-oral endoscopic myotomy (POEM): mid-term efficacy and safety
The Given Names and Family Names were all inadvertently inverted. The correct order is: Jan Martinek, Hana Svecova, Zuzana Vackova, Radek Dolezel, Ondrej Ngo, Jana Krajciova, Eva Kieslichova, Radim Janousek, Alexander Pazdro, Tomas Harustiak, Lucie Zdrhova, Pavla Loudova, Petr Stirand, Julius Spicak. The original article was corrected.
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Considerations in the Use of Body Mass Change to Estimate Change in Hydration Status During a 161-Kilometer Ultramarathon Running Competition
Abstract
Hydration guidelines found in the scientific and popular literature typically advise that body mass losses beyond 2% should be avoided during exercise. In this work, we demonstrate that these guidelines are not applicable to prolonged exercise of several hours where body mass loss does not reflect an equivalent loss of body water due to the effects of body mass change from substrate use, release of water bound with muscle and liver glycogen, and production of water during substrate metabolism. These effects on the body mass loss required to maintain body water balance are shown for a 161-km mountain ultramarathon running competition participant utilizing published data for the total energy cost, exogenous energy consumption and percentage from each fuel source, average participant body mass, and the extent of soft tissue fluid accumulation during an ultramarathon. We assumed that total energy derived from protein ranges from 5 to 10%, all exogenous energy is used to support the energy cost of the race, glycogen utilization ranges from 300 to 500 g, water linked with glycogen ranges from 1 to 3 g per g of glycogen, and the mass of the bladder and gastrointestinal tract is unchanged from pre-race to post-race body mass measurements. These calculations show that the average participant of 68.8 kg must lose 1.9–5.0% body mass to maintain the water supporting body water balance while also avoiding overhydration. Future hydration guidelines should consider these findings so that the proper hydration message is conveyed to those who participate in prolonged exercise.
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Psychometric evaluation of a motor control test battery of the craniofacial region
Abstract
Background
The primary objective of this study was to determine the structural and known-group validity as well as the inter-rater reliability of a test battery to evaluate the motor control of the craniofacial region.
Methods
70 volunteers without TMD and 25 subjects with TMD (Axes I) per the DC/TMD were asked to execute a test battery consisting of eight tests. The tests were videotaped in the same sequence in a standardized manner. Two experienced physical therapists participated in this study as blinded assessors. We used exploratory factor analysis in order to identify the underlying component structure of the 8 tests. Internal consistency (Cronbach α), inter-rater reliability (intraclass correlation coefficient), and construct validity (i.e. hypothesis testing-known-group validity) (receiver operating curves) were also explored for the test battery.
Results
The structural validity showed the presence of one factor underlying the construct of the test battery. The internal consistency was excellent (0.90) as well as the inter-rater reliability. All values of reliability were close to 0.9 or above indicating very high inter-rater reliability. The Area Under the Curve (AUC) was 0.93 for rater 1 and 0.94 for rater two respectively indicating excellent discrimination between subjects with TMD and healthy controls.
Conclusions
The results of the present study support the psychometric properties of test battery to measure motor control of the craniofacial region when evaluated through videotaping. This test battery could be used to differentiate between healthy subjects and subjects with musculoskeletal impairments in the cervical and orofacial regions. In addition, this test battery could be used to assess the effectiveness of management strategies in the craniofacial region.
This article is protected by copyright. All rights reserved.
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Top EMS Game Changers – #6: Computer-based training
As a paramedic on the high side of 60, I sometimes have to defer to my much younger colleagues for day-to-day perspectives on new medical technology. Ultrasound and ECMO (extracorporeal membrane oxygenation) were never found on ambulances when I joined EMS. Once in a while, though, I might surprise our newest and brightest with been-there-done-that tales reaffirming the notion of old medics as occasionally ...
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mTOR mutations in Smith-Kingsmore syndrome: four additional patients and a review
Smith-Kingsmore syndrome (SKS) OMIM #616638, also known as MINDS syndrome (ORPHA: 457485), is a rare autosomal dominant disorder reported so far in 23 patients. SKS is characterized by intellectual disability, macrocephaly/hemi/megalencephaly, and seizures. It is also associated with a pattern of facial dysmorphology and other non-neurological features. Germline or mosaic mutations of the mTOR gene have been detected in all patients. The mTOR gene is a key regulator of cell growth, cell proliferation, protein synthesis and synaptic plasticity, and the mTOR pathway (PI3K-AKT-mTOR) is highly regulated and critical for cell survival and apoptosis. Mutations in different genes in this pathway result in known rare diseases implicated in hemi/megalencephaly with epilepsy, as the tuberous sclerosis complex caused by mutations in TSC1 and TSC2, or the PIK3CA related overgrowth spectrum (PROS). We here present 4 new cases of SKS, review all clinical and molecular aspects of this disorder, as well as some characteristics of the patients with only brain mTOR somatic mutations.
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Novel spondyloepimetaphyseal dysplasia due to UFSP2 gene mutation
Beukes Hip Dysplasia is an autosomal dominant disease which has to date been described only in a large South African family of Dutch origin. The patients presented with progressive epiphyseal dysplasia limited to femoral capital epiphysis and their height was not significantly reduced. A unique variant of the ubiquitin-fold modifier 1 (Ufm1)-specific peptidase 2 (UFSP2) gene (c.868T>C) has been reported in all individuals from Beukes family with clinical and radiological diagnosis of Beukes Hip Dysplasia.
Three individuals, propositus, mother, and grandmother, presented with short stature, joint pain, genu vara and a novel spondyloepimetaphyseal dysplasia involving epiphyses predominantly at hips, but also at knees, ankles, wrists and hands, associated with variable degrees of metaphysis and spine involvement.
Exome sequencing allowed us to identify the heterozygous variant c.1277A>C of the UFSP2 gene, leading to the missense change p.D426A, in all three patients. This mutation is predicted as damaging and, similarly to the mutation originally described in the Beukes family (p. Y290H), directly affects one of the catalytic residues participating in the active site of the protein. This supports the novel notion that loss of catalytic UFSP2 activity, observed in association with different mutants and already experimentally proven in vitro, may have different clinical outcomes.
UFSP2 gene, reported in one family as cause of isolated hip dysplasia is responsible of a novel spondyloepimetaphyseal dysplasia
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Adaptability and specificity of inhibition processes in distractor-induced blindness
Abstract
In a rapid serial visual presentation task, inhibition processes cumulatively impair processing of a target possessing distractor properties. This phenomenon—known as distractor-induced blindness—has thus far only been elicited using dynamic visual features, such as motion and orientation changes. In three ERP experiments, we used a visual object feature—color—to test for the adaptability and specificity of the effect. In Experiment I, participants responded to a color change (target) in the periphery whose onset was signaled by a central cue. Presentation of irrelevant color changes prior to the cue (distractors) led to reduced target detection, accompanied by a frontal ERP negativity that increased with increasing number of distractors, similar to the effects previously found for dynamic targets. This suggests that distractor-induced blindness is adaptable to color features. In Experiment II, the target consisted of coherent motion contrasting the color distractors. Correlates of distractor-induced blindness were found neither in the behavioral nor in the ERP data, indicating a feature specificity of the process. Experiment III confirmed the strict distinction between congruent and incongruent distractors: A single color distractor was embedded in a stream of motion distractors with the target consisting of a coherent motion. While behavioral performance was affected by the distractors, the color distractor did not elicit a frontal negativity. The experiments show that distractor-induced blindness is also triggered by visual stimuli predominantly processed in the ventral stream. The strict specificity of the central inhibition process also applies to these stimulus features.
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Top EMS Game Changers – #6: Computer-based training
Convenience, cost and the flexibility of self-directed learning continue to propel online learning initiatives in EMS
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Company designs futuristic off-road rescue truck
There are no plans for production any time soon, but Polish firm 2sympleks collaborated with search and rescue teams for the design
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Biologic Agents Are Associated with Excessive Weight Gain in Children with Inflammatory Bowel Disease
Abstract
Background
Children with active inflammatory bowel disease (IBD) are frequently underweight. Anti-tumor necrosis factor (anti-TNF) agents may induce remission and restore growth. However, its use in other autoimmune diseases has been associated with excess weight gain. Our aim was to examine whether children with IBD could experience excess weight gain.
Methods
A centralized diagnostic index identified pediatric IBD patients evaluated at our institution who received anti-TNF therapy for at least 1 year between August 1998 and December 2013. Anthropometric data were collected at time of anti-TNF initiation and annually. Excess weight gain was defined as ΔBMI SDS (standard deviation score) where patients were (1) reclassified from "normal" to "overweight/obese," (2) "overweight" to "obese," or (2) a final BMI SDS >0 and ΔSDS >0.5.
Results
During the study period, 268 children received anti-TNF therapy. Of these, 69 had sufficient follow-up for a median of 29.3 months. Median age at first anti-TNF dose was 12.8 years. At baseline, mean weight SDS was −0.7 (SD 1.4), while mean BMI SDS was −0.6 (1.3). Using baseline BMI SDS, 11.6% were overweight/obese. At last follow-up (LFU), however, the mean ΔBMI SDS was 0.50 (p < 0.0001). However, 10 (17%) patients had excess weight gain at LFU; 3 patients were reclassified from "normal" to "obese," and 7 had a final BMI SDS >0 and ΔSDS >0.5.
Conclusions
Pediatric patients with IBD may experience excess weight gain when treated with anti-TNF agents. Monitoring for this side effect is warranted.
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Changes in microvascular density differentiate metabolic health outcomes in monkeys with prior radiation exposure and subsequent skeletal muscle ECM remodeling
Radiation exposure accelerates the onset of age-related diseases such as diabetes, cardiovascular disease, and neoplasia and, thus, lends insight into in vivo mechanisms common to these disorders. Fibrosis and extracellular matrix (ECM) remodeling, which occur with aging and overnutrition and following irradiation, are risk factors for development of type 2 diabetes mellitus. We previously demonstrated an increased incidence of skeletal muscle insulin resistance and type 2 diabetes mellitus in monkeys that had been exposed to whole body irradiation 5–9 yr prior. We hypothesized that irradiation-induced fibrosis alters muscle architecture, predisposing irradiated animals to insulin resistance and overt diabetes. Rhesus macaques (Macaca mulatta, n = 7–8/group) grouped as nonirradiated age-matched controls (Non-Rad-CTL), irradiated nondiabetic monkeys (Rad-CTL), and irradiated monkeys that subsequently developed diabetes (Rad-DM) were compared. Prior radiation exposure resulted in persistent skeletal muscle ECM changes, including a relative overabundance of collagen IV and a trend toward increased transforming growth factor-β1. Preservation of microvascular markers differentiated the irradiated diabetic and nondiabetic groups. Microvascular density and plasma nitrate and heat shock protein 90 levels were lower in Rad-DM than Rad-CTL. These results are consistent with a protective effect of abundant microvasculature in maintaining glycemic control within radiation-induced fibrotic muscle.
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Enduring effects of perinatal nicotine exposure on murine sleep in adulthood
The long-term consequences of early life nicotine exposure are poorly defined. Approximately 8–10% of women report smoking during pregnancy, and this may promote aberrant development in the offspring. To this end, we investigated potential enduring effects of perinatal nicotine exposure on murine sleep and affective behaviors in adulthood (~13–15 wk of age) in C57Bl6j mice. Mothers received a water bottle containing 200 µg/ml nicotine bitartrate dihydrate in 2% wt/vol saccharin or pH-matched 2% saccharin with 0.2% (vol/vol) tartaric acid throughout pregnancy and before weaning. Upon reaching adulthood, offspring were tested in the open field and elevated plus maze, as well as the forced swim and sucrose anhedonia tests. Nicotine-exposed male (but not female) mice had reduced mobility in the open field, but no differences were observed in anxiety-like or depressive-like responses. Upon observing this male-specific phenotype, we further assessed sleep-wake states via wireless EEG/EMG telemetry. Following baseline recording, we assessed whether mice exposed to nicotine altered their homeostatic response to 5 h of total sleep deprivation and whether nicotine influenced responses to a powerful somnogen [i.e., lipopolysaccharides (LPS)]. Males exposed to perinatal nicotine decreased the percent time spent awake and increased time in non-rapid eye movement (NREM) sleep, without changes to REM sleep. Nicotine-exposed males also displayed exaggerated responses (increased time asleep and NREM spectral power) to sleep deprivation. Nicotine-exposed animals additionally had blunted EEG slow-wave responses to LPS administration. Together, our data suggest that perinatal nicotine exposure has long-lasting effects on normal sleep and homeostatic sleep processes into adulthood.
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Upregulation of circulating myomiR following short-term energy restriction is inversely associated with whole body protein synthesis
The objective of the present investigation was to determine whether energy restriction (ER) influences expression of skeletal muscle-specific microRNA (miRNA) in circulation (c-myomiR) and whether changes in c-myomiR are associated with rates of whole body protein synthesis. Sixteen older (64 ± 2 yr) overweight (28.5 ± 1.2 kg/m2) men enrolled in this 35-day controlled feeding trial. A 7-day weight maintenance (WM) period was followed by 28 days of 30% ER. Whole body protein turnover was determined from [15N]glycine enrichments in 24-h urine collections, and c-myomiR (miR-1-3p, miR-133a-3p, miR-133b, and miR-206) expression was assessed from serum samples by RT-quantitative PCR upon completion of the WM and ER periods. Participants lost 4.4 ± 0.3 kg body mass during ER (P < 0.05). After 28 days of ER, miR-133a and miR-133b expression was upregulated (P < 0.05) compared with WM. When all four c-myomiR were grouped as c-myomiR score (sum of the median fold change of all myomiR), overall expression of c-myomiR was higher (P < 0.05) at ER than WM. Backward linear regression analysis of whole body protein synthesis and breakdown and carbohydrate, fat, and protein oxidation determined protein synthesis to be the strongest predictor of c-myomiR score. An inverse association (P < 0.05) was observed with ER c-myomiR score and whole body protein synthesis (r = –0.729, r2 = –0.530). Findings from the present investigation provide evidence that upregulation of c-myomiR expression profiles in response to short-term ER is associated with lower rates of whole body protein synthesis.
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Normobaric hypoxic conditioning to maximize weight loss and ameliorate cardio-metabolic health in obese populations: a systematic review
Normobaric hypoxic conditioning (HC) is defined as exposure to systemic and/or local hypoxia at rest (passive) or combined with exercise training (active). HC has been previously used by healthy and athletic populations to enhance their physical capacity and improve performance in the lead up to competition. Recently, HC has also been applied acutely (single exposure) and chronically (repeated exposure over several weeks) to overweight and obese populations with the intention of managing and potentially increasing cardio-metabolic health and weight loss. At present, it is unclear what the cardio-metabolic health and weight loss responses of obese populations are in response to passive and active HC. Exploration of potential benefits of exposure to both passive and active HC may provide pivotal findings for improving health and well being in these individuals. A systematic literature search for articles published between 2000 and 2017 was carried out. Studies investigating the effects of normobaric HC as a novel therapeutic approach to elicit improvements in the cardio-metabolic health and weight loss of obese populations were included. Studies investigated passive (n = 7; 5 animals, 2 humans), active (n = 4; all humans) and a combination of passive and active (n = 4; 3 animals, 1 human) HC to an inspired oxygen fraction (FIO2) between 4.8 and 15.0%, ranging between a single session and daily sessions per week, lasting from 5 days up to 8 mo. Passive HC led to reduced insulin concentrations (–37 to –22%) in obese animals and increased energy expenditure (+12 to +16%) in obese humans, whereas active HC lead to reductions in body weight (–4 to –2%) in obese animals and humans, and blood pressure (–8 to –3%) in obese humans compared with a matched workload in normoxic conditions. Inconclusive findings, however, exist in determining the impact of acute and chronic HC on markers such as triglycerides, cholesterol levels, and fitness capacity. Importantly, most of the studies that included animal models involved exposure to severe levels of hypoxia (FIO2 = 5.0%; simulated altitude >10,000 m) that are not suitable for human populations. Overall, normobaric HC demonstrated observable positive findings in relation to insulin and energy expenditure (passive), and body weight and blood pressure (active), which may improve the cardio-metabolic health and body weight management of obese populations. However, further evidence on responses of circulating biomarkers to both passive and active HC in humans is warranted.
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Nkx2.5 is essential to establish normal heart rate variability in the zebrafish embryo
Heart rate variability (HRV) has become an important clinical marker of cardiovascular health and a research measure for the study of the cardiac conduction system and its autonomic controls. While the zebrafish (Danio rerio) is an ideal vertebrate model for understanding heart development, HRV has only recently been investigated in this system. We have previously demonstrated that nkx2.5 and nkx2.7, two homologues of Nkx2–5 expressed in zebrafish cardiomyocytes, play vital roles in maintaining cardiac chamber-specific characteristics. Given observed defects in ventricular and atrial chamber identities in nkx2.5–/– embryos coupled with conduction system abnormalities in murine models of Nkx2.5 insufficiency, we postulated that reduced HRV would serve as a marker of poor cardiac health in nkx2.5 mutants and in other zebrafish models of human congenital heart disease. Using live video image acquisition, we derived beat-to-beat intervals to compare HRV in wild-type and nkx2.5–/– embryos. Our data illustrate that the nkx2.5 loss-of-function model exhibits increased heart rate and decreased HRV when compared with wild type during embryogenesis. These findings validate HRV analysis as a useful quantitative tool for assessment of cardiac health in zebrafish and underscore the importance of nkx2.5 in maintaining normal heart rate and HRV during early conduction system development.
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Interleukin-33 induces growth-regulated oncogene-{alpha} expression and secretion in human umbilical vein endothelial cells
Although interleukin-33 (IL-33), a member of the IL-1 cytokine family, plays proinflammatory roles in immune cells as an "alarmin," little is known regarding the biological actions of IL-33 on vascular endothelial cells. To investigate the effects of IL-33 on vascular endothelial cells, we first screened the IL-33-regulated proteins in human umbilical vein endothelial cells (HUVECs) using a dot blot array and observed that IL-33 markedly increased growth-regulated oncogene-α (GRO-α), a chemokine that is also known as chemokine (C-X-C motif) ligand 1 (CXCL1). Real-time reverse transcription PCR and ELISA demonstrated that IL-33 induced GRO-α expression and secretion in HUVECs in a dose- and a time-dependent manner. Western immunoblot assay revealed that IL-33 activated the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun NH2-terminal kinase (JNK). In addition, translocation of nuclear factor-B (NF-B) p65 to the nucleus of HUVECs was observed by IL-33 stimulation. Furthermore, treatment with pharmacological inhibitors against ERK1/2 (PD98059), JNK (SP600125), or NF-B (BAY11-7085) significantly suppressed IL-33-induced GRO-α gene expression and secretion from HUVECs. Moreover, immunohistochemical staining demonstrated that IL-33 and GRO-α coexpressed in the endothelium of human carotid atherosclerotic plaque. Taken together, the present study indicates that IL-33 localized in the human atherosclerotic plaque increases GRO-α mRNA expression and protein secretion via activation of ERK1/2, JNK, and NF-B in HUVECs, suggesting that IL-33 plays an important role in the pathophysiology and development of atherosclerosis.
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The effect of bolus volume on laryngeal closure and UES opening in swallowing: Kinematic analysis using 320-row area detector CT Study
Abstract
This study investigated the effects of three different volumes of honey-thick liquid on the temporal characteristics of swallowing. Twenty six healthy subjects (15 males, 11 females) underwent 320-Row Area Detector CT scan while swallowing 3, 10, and 20ml of honey-thick liquid barium. Three-dimensional images were created at 10 images/s. Kinematic events involving six structures (velopharynx, hyoid bone, epiglottis, laryngeal vestibule (LV), true vocal cords (TVC), upper esophageal sphincter (UES)) and timing of bolus movement were timed using frame by frame analysis. The overall sequence of events did not differ across three volumes, however, increasing bolus volume significantly changed the onset and termination of events. The bolus head reached to pharynx and esophagus earlier and the duration of bolus passing through UES was significantly longer in 10 ml and 20ml compared to 3ml (p<0.05). Consequently, the onset of UES opening was significantly earlier with increased volume (p<0.05). LV and TVC closure occurred later in 20ml compared to 3ml (p<0.05). These changes in motion of pharynx and larynx appeared to promote swallow safety by preventing aspiration, suggesting that anatomical structure movements adapt in response to bolus volume. Our findings also suggest that the pharyngeal swallow behaviors may be modified by afferents in the oral cavity. The three-dimensional visualization and quantitative measurements provided by 320-ADCT provide essential benchmarks for understanding swallowing, both normal and abnormal.
This article is protected by copyright. All rights reserved.
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Decreased GABA Levels in the Brainstem in Patients with Possible Sleep Bruxism: A Pilot Study
Abstract
Background
An increasing number of studies have indicated that the central and autonomic nervous systems play roles in the genesis of sleep bruxism (SB). The role of specific neurochemicals in SB has been a subject of interest.
Objective
In this study, we use proton magnetic resonance spectroscopy (1H-MRS) to determine whether the levels of γ-aminobutyric acid (GABA) and glutamate (Glu) are different in the brainstem and bilateral cortical masticatory area (CMA) between possible sleep bruxism (SB) patients and controls, and discuss whether the brainstem or cortical networks which may affect the central masticatory pathways are under the genesis of SB.
Methods
Twelve possible SB patients and twelve age- and gender-matched controls underwent 1H-MRS using the "MEGA-Point Resolved Spectroscopy Sequence" (MEGA-PRESS) technique in the brainstem and bilateral CMA. 1H-MRS data were processed using LCModel. Because the signal detected by MEGA-PRESS includes contributions from GABA, macromolecules (primarily proteins) and homocarnosine, the GABA signal is referred to as "GABA+". The glutamate complex (Glx) signal contains both glutamate (Glu) and glutamine (Gln), which mainly reflect glutamatergic metabolism.
Results
Edited spectra were successfully obtained from the bilateral CMA in all subjects. There were no significant differences in neurochemical levels between the left and right CMA in possible SB patients and controls. In the brainstem, significantly lower GABA+ levels were found in possible SB patients than in controls (P=0.011), whereas there was no significant difference (P=0.307) in Glx levels between the two groups.
Conclusions
SB patients may possess abnormalities in the GABAergic system of brainstem networks.
This article is protected by copyright. All rights reserved.
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Training and acute exercise modulates mitochondrial dynamics in football players’ blood mononuclear cells
Abstract
Purpose
Regular physical activity induces oxidative stress but also causes adaptations in antioxidant defences including the nuclear factor κB (NF-κB) pathway, which activates target genes related to antioxidant defences such as uncoupling proteins (UCPs), and mitochondrial biogenesis mediated by peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). The aim of the study was to determine the effect of long-term training and acute exercise on oxidant/antioxidant status and the expression of mitochondrial biogenesis genes in peripheral blood mononuclear cells (PBMCs).
Methods
Twelve professional football players performed an 8-week exercise programme comprising a daily 2-h football training session. Blood samples were taken before and after the training season.
Results
The results reported a significant increase in antioxidant protein levels and in mitochondrial proteins in resting conditions after the 8-week training period. PGC1α, UCP-2 and mitofusin 2 protein levels also increased after acute exercise compared to pre-exercise levels. After the training, the expression of PGC1α, cytochrome c oxidase subunit IV and mitochondrial NADH dehydrogenase subunit 5 messenger RNA (mRNA) significantly augmented after the acute physical activity compared to pre-exercise levels; while no changes occurred in these mRNA in basal conditions. NF-κB activation and ROS production reported a significant increase after acute exercise.
Conclusions
Training increases the levels of proteins related to mitochondrial biogenesis and improves the antioxidant capabilities of mitochondria in PBMCs among well-trained football players. Acute exercise may act as an inducer of mitochondrial biogenesis through NF-κB activation and PGC1α gene expression.
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Fatigability, oxygen uptake kinetics and muscle deoxygenation in incomplete spinal cord injury during treadmill walking
Abstract
Purpose
The purpose of the present study was to characterize hypothesized relationships among fatigability and cardiorespiratory fitness in individuals with chronic motor-incomplete SCI (iSCI) during treadmill walking. The theoretical framework was that exacerbated fatigability would occur concomitantly with diminished cardiorespiratory fitness in people with iSCI.
Methods
Subjects with iSCI (n = 8) and an able-bodied reference group (REF) (n = 8) completed a 6-min walking bout followed by a walking bout of 30-min or until volitional exhaustion, both at a self-selected walking speed. Fatigability was assessed using both perceived fatigability and performance fatigability measures. Pulmonary oxygen uptake kinetics (VO2 on-kinetics) was measured breath-by-breath and changes in deoxygenated hemoglobin/myoglobin concentration (∆[HHb]) of the lateral gastrocnemius was measured by near-infrared spectroscopy. Adjustment of VO2 and ∆[HHb] on-kinetics were modeled using a mono-exponential equation.
Results
Perceived fatigability and performance fatigability were 52% and 44% greater in the iSCI group compared to the REF group (p = 0.003 and p = 0.004). Phase II time constant (τp) of VO2 on-kinetics and ∆[HHb] ½ time during resting arterial occlusion were 55.4% and 16.3% slower in iSCI vs REF (p < 0.01 and p = 0.047, respectively).
Conclusions
The results of the present study may suggest that compromised O2 delivery and/or utilization may have contributed to the severity of fatigability in these individuals with iSCI. The understanding of the extent to which fatigability and VO2 and Δ[HHb] on-kinetics impacts locomotion after iSCI will assist in the future development of targeted interventions to enhance function.
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Classical experiments in whole-body metabolism: closed-circuit respirometry
Abstract
As part of a series of reviews aimed at providing historical context to the study of whole-body metabolism, this article focuses on the technique of closed-circuit respirometry. Developed by nineteenth century physiologists Henri-Victor Regnault and Jules de Reiset, a constant-pressure closed-circuit calorimeter capable of measuring oxygen consumption and carbon dioxide production in small animals became the framework for future experiments on whole-body metabolism in humans. The volume-loss and volume-replenishment techniques can be used to indirectly assess energy expenditure using an oxygen reservoir; spirometers are simplistic in design but difficult to operate. Leaks, calibration errors, equilibration of gases and dead space are some of the major limitations of the methodology. Despite operational difficulties, closed-circuit respirometry is highly accurate and reproducible. Due to the bespoke nature of many closed-circuit systems, maintenance and repair is often troublesome. Compounded by technological advancement, closed-circuit techniques have become progressively outdated. Nevertheless, the classical experiments in whole-body metabolism played a pivotal role in furthering our understanding of basic human physiology and paved the way for current methodologies used in the field.
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Increase in echo intensity and extracellular-to-intracellular water ratio is independently associated with muscle weakness in elderly women
Abstract
Purpose
The changes in muscle composition and its heterogeneity during aging are associated with muscle weakness in elderly persons independent of decreases in muscle mass or muscle thickness (MT). Both the assessment of echo intensity (EI) with ultrasound imaging and the evaluation of the extracellular water/intracellular water (ECW/ICW) ratio with segmental bioelectrical impedance spectroscopy (BIS) are non-invasive and convenient methods and seem valuable for muscle quality determination. However, no previous study has evaluated both EI and the ECW/ICW ratio simultaneously to investigate their relationship to muscle strength. The purpose of the present study was to investigate whether both EI and the ECW/ICW ratio are independently associated with muscle strength in elderly women.
Methods
A total of 179 elderly women with a mean age of 74.1 ± 4.9 years, living independently in the community, were enrolled. The MT and EI of the quadriceps femoris were measured using transverse ultrasound imaging. The ECW/ICW ratio in the upper thigh was calculated from segmental BIS. The maximum knee extensor strength and the presence of knee pain were also assessed.
Results
Knee extensor strength showed a significant positive correlation with MT, and significant negative correlations with EI, the ECW/ICW ratio, and age. Stepwise regression analysis revealed that knee extensor strength in elderly women was predicted by MT, EI, and the ECW/ICW ratio.
Conclusions
This study suggests that the simultaneous application of EI and the ECW/ICW ratio is useful in assessing muscle strength, and accurately estimates the changes in muscle quality related to muscle weakness.
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Acute effects of heated resistance exercise in female and male power athletes
Abstract
Purpose
To determine the effects of heated resistance exercise on thermal strain, neuromuscular function and hormonal responses in power athletes.
Methods
Sixteen (n = 8 female; 8 male) highly trained power athletes completed a combined strength and power resistance exercise session in hot (HOT ~30 °C) and temperate (CON ~20 °C) conditions. Human growth hormone (hGH), cortisol and testosterone concentrations in plasma, peak power (counter-movement jump, CMJ) and peak force (isometric mid-thigh pull) were measured before and after each training session; thermoregulatory responses were monitored during training.
Results
Skin temperature, thermal sensation and thermal discomfort were higher in HOT compared with CON. Sweat rate was higher in HOT for males only. Compared with CON, HOT had trivial effects on core temperature and heart rate. During HOT, there was a possible increase in upper-body power (medicine ball throw) in females [3.4% (90% CL −1.5, 8.6)] and males [(3.3% (−0.1, 6.9)], while lower-body power (vertical jump) was enhanced in males only [3.2% (−0.4, 6.9)]. Following HOT, CMJ peak power [4.4% (2.5; 6.3)] and strength [8.2% (3.1, 13.6)] were enhanced in female athletes, compared with CON, while effects in males were unclear. Plasma hGH concentration increased in females [83% (18; 183)] and males [107% (−21; 444)] in HOT compared with CON, whereas differential changes occurred for cortisol and testosterone.
Conclusion
Heated resistance exercise enhanced power and increased plasma hGH concentration in female and males power athletes. Further research is required to assess the ergogenic potential of resistance exercise in the heat.
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Impact of rotavirus vaccines in low and middle-income countries
Current Opinion in Infectious Diseases
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Drinks industry distorts alcohol cancer risk
Reuters Health News
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Expression of ATF6 as a marker of pre-cancerous atypical change in ulcerative colitis-associated colorectal cancer: A potential role in the management of dysplasia
Journal of Gastroenterology
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Antimicrobial scrubs do not protect ICU nurses from contamination
Reuters Health News
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Optimal timing for a second ERCP after failure of initial biliary cannulation following precut sphincterotomy: An analysis of experience at two tertiary centers
Surgical Endoscopy
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Significance of measurement of serum trough level and anti-drug antibody of adalimumab as personalised pharmacokinetics in patients with Crohn's disease: A subanalysis of the DIAMOND trial
Alimentary Pharmacology and Therapeutics
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Rectal water contrast transvaginal ultrasound versus double-contrast barium enema in the diagnosis of bowel endometriosis
BMJ Open
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The cost-effectiveness of one-time hepatitis C screening strategies among adolescents and young adults in primary care settings
Clinical Infectious Diseases
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A Japanese population-based meta-analysis of vonoprazan versus PPI for Helicobacter pylori eradication therapy: Is superiority an illusion?
Helicobacter
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Direct-acting antiviral therapy for chronic HCV infection results in liver stiffness regression over 12 months post-treatment
Digestive Diseases and Sciences
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Endoscopic mucosal resection is superior to rectal suction biopsy for analysis of enteric ganglia in constipation and dysmotility
Gastrointestinal Endoscopy
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Immune responses in DAA treated chronic hepatitis C patients with and without prior RG-101 dosing
Antiviral Research
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New York top court rejects right to doctor-assisted suicide
Reuters Health News
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The prognostic value of derived neutrophil to lymphocyte ratio in oesophageal cancer treated with definitive chemoradiotherapy
Radiotherapy & Oncology
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Cancer of the esophagus and asbestos exposure
American Journal of Industrial Medicine
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Absolute quantification of microparticles by flow cytometry in ascites of patients with decompensated cirrhosis: A cohort study
Journal of Translational Medicine
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Contribution of virtual biopsy to the screening of microvascular invasion in hepatocellular carcinoma: A pilot study
Liver International
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A randomized double-blind placebo-controlled crossover-style trial of buspirone in functional dysphagia and ineffective esophageal motility
Neurogastroenterology & Motility
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Randomized trial of cholangioscopy-guided laser lithotripsy versus conventional therapy for large bile duct stones
Gastrointestinal Endoscopy
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Sofosbuvir-based interferon-free direct acting antiviral regimens for heart transplant recipients with chronic hepatitis C virus infection
Clinical Infectious Diseases
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Effects on jaw function shortly after whiplash trauma
Abstract
Normal jaw function involves muscles and joints of both jaw and neck. A whiplash trauma may disturb the integrated jaw-neck sensory-motor function and thereby impair chewing ability, however, it is not known if such impairment is present shortly after a neck trauma or develops over time. The aim was to evaluate jaw function after a recent whiplash trauma. Eighty cases (47 women) were examined within one month after a whiplash trauma and compared to 80 controls (47 women) without neck trauma. Participants completed the Jaw disability checklist (JDC) and Neck Disability Index (NDI) questionnaires and performed a 5-minute chewing test. Elicited fatigue and pain during chewing was noted and group differences were evaluated with Fisher's exact test and Mann-Whitney U-test. Compared to controls, cases had higher JDC (P<0.0001) and NDI scores (15% vs. 2%, P<0.0001), and reported more fatigue (53% vs 31%, P=0.006) and pain (30% vs 10%, P=0.003) during the chewing test. Cases also had a shorter onset time for fatigue and pain (both P=0.001) Furthermore, cases reporting symptoms during chewing had higher JDC and NDI scores compared to cases not reporting symptoms (both P=0.01). Symptoms mainly occurred in the trigeminal area for both groups, but also in spinal areas more often for cases than for controls. Taken together, the results indicate that jaw-neck sensory-motor function is impaired already within one month after a whiplash trauma. The association between neck disability and jaw impairment underlines the close functional relationship between the regions, and stresses the importance of multidisciplinary assessment.
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Chromatin: Probing a piRNA paradox
Nature Reviews Genetics. doi:10.1038/nrg.2017.76
Author: Darren J. Burgess
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Harnessing ancient genomes to study the history of human adaptation
Nature Reviews Genetics. doi:10.1038/nrg.2017.65
Authors: Stephanie Marciniak & George H. Perry
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