Objective: The aim of this study was to investigate the effectiveness of short wave diathermy (SWD) in patients with subacromial impingement syndrome. Design: In this double-blinded, randomized, placebo-controlled trial, 57 patients (aged 35-65 yrs) were classified into night pain positive (NP[+]) (n = 28) and night pain negative (NP[-]) (n = 29) groups. Both groups were randomly assigned to SWD (NP[+], n = 14; NP[-], n = 14) and sham (NP[+], n = 15; NP[-], n = 14) subgroups. Visual analog scale, Constant-Murley Scale (CS), and Shoulder Disability Questionnaire (SDQ) scores were used for evaluation. Results: There was only a significant difference in pain with activity at 1-mo (mean difference [MD], -1.65; 95% confidence interval, -3.01 to -0.28]) and 2-mo evaluations (MD, -2.1; 95% confidence interval, -3.51 to -0.69) between SWD versus sham groups. In the NP(+) SWD group, the CS pain score was significantly higher than in the NP(+) sham group at all evaluations after treatment. At 1 mo, the NP(-) SWD group showed significantly better pain, strength, total CS, and SDQ scores than the NP(-) sham group. At 2 mos, the pain, range of motion, strength, and total CS and SDQ scores were better in the NP(-) SWD group than in the NP(-) sham group (P
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Πέμπτη 7 Σεπτεμβρίου 2017
Factors Contributing to Chronic Ankle Instability: A Systematic Review and Meta-Analysis of Systematic Reviews
Abstract
Background
Many factors are thought to contribute to chronic ankle instability (CAI). Multiple systematic reviews have synthesised the available evidence to identify the primary contributing factors. However, readers are now faced with several systematic reviews that present conflicting findings.
Objective
The aim of this systematic review and meta-analysis was to establish the statistical significance and effect size of primary factors contributing to CAI and to identify likely reasons for inconsistencies in the literature.
Methods
Relevant health databases were searched: CINAHL, MEDLINE, PubMed, Scopus and SPORTDiscus. Systematic reviews were included if they answered a focused research question, clearly defined the search strategy criteria and study selection/inclusion and completed a comprehensive search of the literature. Included reviews needed to be published in a peer-reviewed journal and needed to review observational studies of factors and/or characteristics of persons with CAI, with or without meta-analysis. There was no language restriction. Studies using a non-systematic review methodology (e.g. primary studies and narrative reviews) were excluded. Methodological quality of systematic reviews was assessed using the modified R-AMSTAR tool. Meta-analysis on included primary studies was performed.
Results
Only 17% of primary studies measured a clearly defined CAI population. There is strong evidence to support the contribution of dynamic balance, peroneal reaction time and eversion strength deficits and moderate evidence for proprioception and static balance deficits to non-specific ankle instability.
Conclusions
Evidence from previous systematic reviews does not accurately reflect the CAI population. For treatment of non-specific ankle instability, clinicians should focus on dynamic balance, reaction time and strength deficits; however, these findings may not be translated to the CAI population. Research should be updated with an adequately controlled CAI population.
Systematic review registration
PROSPERO 2016, CRD42016032592.
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Analysis of the Delta and Theta Rhythms of a Conditioned Avoidance Reflex Using the Granger Causality Method
Frequency decomposition of conditional Granger causality was used to show that on execution of a conditioned avoidance reflex, the activity of the ventral hippocampus in the θ range had unidirectional influences on (predicted) the activity of the ventral tegmental area of the midbrain, the amygdala, and (directly and indirectly via the amygdala) the prefrontal cortex. During the period of expectation of the conditioned signal, activity in the prefrontal cortex in the δ range had one-way influences on activity in the ventral tegmental area and the amygdala.
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The Use of Agomelatine (Valdoxan) in the Treatment of Gambling: A Pilot Study
Objective. To study the antidepressant agomelatine (an M1/M2 agonist and 5-HT2C receptor antagonist) in pathological gambling (PG) (ICD-10, F63.0). Materials and methods. An 8-week, open, pilot study was performed. A total of 22 out-patients were treated (17 men and five women, mean age 38 ± 7 years). The severity of PG was assessed using the Yale–Brown obsessive-compulsive scale adapted for PG (PG-YBOCS); levels of anxiety and depression were measured using the Hospital Anxiety and Depression Scale (HADS). Results and conclusions. These studies showed that agomelatine significantly decreased PG-YBOCS scores from week 2 (from 24.2 ± 2.1 before treatment to 12.6 ± 3.0, p < 0.05) and further to the end of the study (5.3). HADS scores also decreased significantly: from 23.6 ± 2.9 to 11.4 ± 1.9 (p < 0.05). These changes corresponded to positive behavioral changes. The results indicated that agomelatine is effective in PG.
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Morphometric Characteristics of the Dorsal Nuclei of Clarke in the Rostral Segments of the Lumbar Part of the Spinal Cord on Cats
The morphometric characteristics and distribution of Clarke's nuclei in the gray matter of the spinal cord were studied in cats by histochemical detection of acetylcholinesterase, an immunohistochemical marker for non-phosphorylated domains of neurofilament heavy chains (SMI-32) and the Klüver–Barrera method for detection of myelinated fibers. Results averaged for five cats yielded metric maps of segments LI–IV of the spinal cord with superimposed spatial coordinates of the boundaries of Clarke's nuclei. These studies provide the information required for more precise stereotaxic access to Clarke's nuclei for investigations in future research and applied studies.
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Features of Platelet Hemostasis in Patients with Ischemic Stroke after Systemic Thrombolytic Therapy
Objective. To study the state of platelet aggregation (PA) in patients with ischemic stroke (II) after systemic thrombolytic therapy (TLT). Materials and methods. A total of 24 patients, 13 with atherothrombotic and 11 with cardioembolic II, receiving systemic TLT were studied. Investigations included assessment of spontaneous and adrenalin-induced PA, the international normalized ratio, the activated partial thromboplastin time, fibrinogen, and the severity of neurological deficit on the NIHSS on days 2, 6–7, 12–14, and 21 after TLT, along with computerized tomography (CT) brain scans before TLT and two days after TLT. Results. A relationship was found between the outcomes of TLT and the characteristics of spontaneous and adrenalin-induced PA. Patients with initially elevated PA (group 1, n = 7) showed the smallest NIHSS scores on day 21. Patients with initially decreased PA (group 2, n = 17) included a subgroup lacking spontaneous aggregation (n = 9) and another with dysregulation of the hemostasis system in the form of increases in spontaneous PA and fibrinogen (n = 8), in whom restoration of neurological functions was less complete than in group 1. Conclusions. The results obtained here can be used for the individual prophylaxis of antiaggregant and anticoagulant treatment after TLT.
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Nursing Across the Lifespan: Implications of Lifecourse Theory for Nursing Research
Despite the lifecourse focus of nursing clinical care, nursing research largely remains cross-sectional or process-oriented within silos determined by patient characteristics such as age, acuity, or disease process. Incorporating interdisciplinary lifecourse theory into pediatric nursing research provides the opportunity to expand nursing theories and research beyond practice, age, and disease silos. One such theory is the Lifecourse Health Development (LCHD) framework. LCHD takes a more expansive view of health development from preconception through old age based on the premise that health is a consequence of transactions between genetic, biological, behavioral, social, and economic contexts that change as a child develops over time (Halfon & Hochstein, 2002).
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Breath-to-breath variability of exhaled CO2 as a marker of lung dysmaturity in infancy
The concept of diffusional screening implies that breath-to-breath variations in CO2 clearance, when related to the variability of breathing, may contain information on the quality and utilization of the available alveolar surface. We explored the validity of the above hypothesis in a cohort of young infants of comparable post-menstrual age but born at different stages of lung maturity, namely, in term-born infants (N = 128), preterm-born infants without chronic lung disease of infancy (CLDI) (N = 53) and preterm infants with moderate/severe CLDI (N = 87). Exhaled CO2 volume (VE,CO2) and concentration (FE,CO2) were determined by volumetric capnography, while their variance was assessed by linear and non-linear variability metrics. The relationship between relative breath-to-breath change of VE,CO2 (VE,CO2) and the corresponding change of tidal volume (VT), was also analyzed. Non-linear FE,CO2 variability was lower in CLDI compared to term and non-CLDI preterm group (P<0.001 for both comparisons). In CLDI infants, most of the VE,CO2 variability was attributed to the variability of VT (R2 0.749), while in term and healthy preterm infants this relationship was weaker (R2 0.507 and 0.630, respectively). The VE,CO2-VT slope was less steep in the CLDI group (1.06 ± 0.07) compared to non-CLDI preterm (1.16 ± 0.07; P <0.001) and term infants (1.20 ± 0.10; P <0.001), suggesting that the more dysmature the infant lung the less efficiently it eliminates CO2 under tidal breathing conditions. We conclude that the temporal variation of CO2 clearance may be related to the degree of lung dysmaturity in early infancy.
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Intrinsic Exercise Capacity in Rats Influences Dopamine Neuroplasticity Induced by Physical Training
The study evaluates whether the intrinsic capacity for physical exercise influences dopamine neuroplasticity induced by physical training. Male rats were submitted to 3 progressive tests until fatigue. Based on the maximal time of exercise (TE), rats were considered as low-performance (LP), standard-performance (SP) or high-performance (HP) to exercise. Eight animals from each group (LP, SP and HP) were randomly subdivided in sedentary (SED) or trained (TR). Physical training was performed during six weeks. After that, concentrations of dopamine (DA), serotonin (5-HT) and their metabolites and mRNA levels of D1 receptor (Drd1), D2 receptor (Drd2), dopamine transporter (Dat), tyrosine hydroxylase (Th), glia cell line-neurotrophic factor (Gdnf) and brain-derived neurotrophic factor (Bdnf) were determined in the caudate-putamen (CPu). TE was increased with training in all performance groups. However, the relative increase was markedly higher in LP rats and this was associated with a training-induced increase in dopaminergic activity in the CPu, determined by the 3,4-dihydroxyphenylacetic acid (DOPAC)/DA ratio. An opposite monoamine response was found in HP-TR rats, in which physical training decreased the DOPAC/DA ratio in the CPu. Moreover, LP-SED rats displayed higher levels of Drd2 in the CPu compared to the other SED groups, and this higher expression was decreased by physical training. Physical training also decreased Dat and increased Gdnf in the CPu of LP rats. Physical training decreased Bdnf in the CPu only in HP rats. Thus, we provide evidence that the intrinsic capacity to exercise affects the neuroplasticity of the dopaminergic system in response to physical training.
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CORP: Ultrasound Assessment of Vascular Function with the Passive Leg Movement Technique
As dysfunction of the vascular system is an early, modifiable step in the progression of many cardiovascular diseases, there is demand for methods to non-invasively monitor the health of the vascular system in clinical and research settings. Validated by very good agreement with more technical assessments of vascular function, like intra-arterial drug infusions and flow mediated dilation (FMD), the passive leg movement (PLM) technique has emerged as a powerful, yet relatively simple, test of peripheral vascular function. In the PLM technique, the change in leg blood flow elicited by the passive movement of the leg through a 90° range of motion is quantified with Doppler ultrasound. This relatively easy-to-learn test has proven to be up to 80% dependent upon nitric oxide (NO) bioavailability and is especially adept at determining peripheral vascular function across the spectrum of cardiovascular health. Indeed, multiple reports have documented that individuals with decreased cardiovascular health such as the elderly and those with heart failure tend to exhibit a substantially blunted PLM-induced hyperemic response (~50% and ~85% reduction, respectively) compared to populations with good cardiovascular health, such as young individuals. As specific guidelines have not yet been put forth, the purpose of this Cores of Reproducibility in Physiology (CORP) article is to provide a comprehensive reference for the assessment and interpretation of vascular function with PLM, with the aim to increase reproducibility and consistency among studies and facilitate the use of PLM as a research tool with clinical relevance.
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Case Studies in Physiology: Skeletal Muscle Mitochondrial Protein Synthesis and Respiration in Response to the Energetic Stress of an Ultra-Endurance Race
The 2016 Colorado Trail Race (CTR) was an ultra-endurance mountain bike race where competitors cycled for up to 24 hrs/day between altitudes of 1675 to 4025 meters to complete 800 kilometers and 21,000 meters of elevation gain. In one athlete, we had the unique opportunity to characterize skeletal muscle protein synthesis and mitochondrial respiration in response to a normal activity control period (CON) and the CTR. We hypothesized that mitochondrial protein synthesis would be elevated and mitochondrial respiration would be maintained during the extreme stresses of the CTR. Titrated and bolus doses of ADP were provided to determine substrate-specific oxidative phosphorylation (OXPHOS) and electron transport system (ETS) capacities in permeabilized muscle fibers via high-resolution respirometry. Protein synthetic rates were determined by daily oral consumption of deuterium oxide (2H2O). The endurance athlete had OXPHOS (226 pmol·s-1·mg tissue-1) and ETS (231 pmol·s-1·mg tissue-1) capacities that rank amongst the highest published to date in humans. Mitochondrial (3.2 fold), cytoplasmic (2.3 fold), and myofibrillar (1.5 fold) protein synthesis rates were greater during CTR compared to CON. With titrated ADP doses, the apparent Km of ADP, OXPHOS, and ETS increased after the CTR. With provision of ADP boluses after the CTR, the addition of fatty acids (-12 and -14%) mitigated the decline in OXPHOS and ETS capacity during carbohydrate-supported respiration (-26 and -31%). In the face of extreme stresses during the CTR, elevated rates of mitochondrial protein synthesis may contribute to rapid adaptations in mitochondrial bioenergetics.
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Beneficial effects of exercise training in heart failure are lost in male diabetic rats.
Exercise training has been demonstrated to have beneficial effects in patients with heart failure (HF) or diabetes. However, it is unknown whether diabetic patients with HF will benefit from exercise training. Male Wistar rats were fed either a standard (Sham, n= 53) or high-fat, high-sucrose (HFHS) diet (D, n=66) for 6 months. After 2 months of diet, the rats were already diabetic. Rats were then randomly subjected to either myocardial infarction by coronary artery ligation (MI) or sham operation (Sham). Two months later, heart failure was documented by echocardiography and animals were randomly subjected to exercise training with treadmill for eight additional weeks or remained sedentary. At the end, rats were euthanized and tissues were assayed by RT-PCR, immunoblotting, spectrophotometry and immunohistology. MI induced a similar decrease in ejection fraction in diabetic and lean animals but a higher premature mortality in the diabetic group. Exercise for 8 weeks resulted in a higher working power developed by MI animals with diabetes, and improved glycaemia but not ejection fraction or pathological phenotype. In contrast exercise improved the ejection fraction and increased adaptive hypertrophy after MI in the lean group. Trained diabetic rats with MI were nevertheless able to develop cardiomyocyte hypertrophy but without angiogenic responses. Exercise improved stress markers and cardiac energy metabolism in lean- but not diabetic-MI rats. Hence, following HF, the benefits of exercise training on cardiac function are blunted in diabetic animals. In conclusion, exercise training only improved the myocardial profile of infarcted lean rats fed the standard diet.
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Identifying subsets of patients with single-level degenerative disc disease for lumbar fusion: the value of prognostic tests in surgical decision making
Fusion surgery for degenerative disc disease (DDD) has become a standard of care, albeit not without controversy. Outcomes are inconsistent and a superiority over conservative treatment is debatable. Proper patient selection is key to clinical success, and a comprehensive understanding of prognostic tests does not currently exist.
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A new iPhone® application for measuring active craniocervical range of motion in patients with non-specific neck pain: a reliability and validity study
Measurement of cervical spine range of motion (ROM) is often considered to be an essential component of cervical spine physiotherapy assessment.
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Hostility and cognitive control: Evidence of increased cardiovascular reactivity as a function of exposure to affective stress using a dichotic listening paradigm
Source:International Journal of Psychophysiology
Author(s): Alissa K. Holland, Gina A. Mitchell, Angela Steele, Jessica Bunting, David W. Harrison
Indices of cognitive control were examined in men with high and low levels of trait hostility as a function of exposure to affective and cognitive stress. A dual concurrent task paradigm was used whereby participants intentionally directed focus to the left or right ear under dichotic listening conditions before and after exposure to angry infant vocalizations. Analysis of the behavioral data supports the prediction of reduced right frontal regulatory control in men with high levels of hostility as indicated by diminished capacity to suppress report of phonemes presented to the language dominant left hemisphere (right ear) in the Focus Left condition. This diminishment in the capacity to suppress report of phonemes presented to the right ear in the Focus Left condition is suggestive of reduced cognitive control. With respect to the neurophysiological data, heart rate increased for only men with high levels of hostility in the Focus Left condition, and this was especially evident in the post-affective stress condition. This increase in right hemisphere arousal provides additional evidence of reduced cognitive control and support for the capacity model of hostility by implicating poor right frontal regulatory control over right posterior cerebral regions under dual task conditions. The results are discussed in terms of integrating the construct of cognitive control into the capacity model as well as providing implications regarding reductions in the capacity to suppress predominant aggressive responses in domestic settings.
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Altered expression of the FMR1 splicing variants landscape in premutation carriers
Publication date: Available online 7 September 2017
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Elizabeth Tseng, Hiu-Tung Tang, Reem Rafik AlOlaby, Luke Hickey, Flora Tassone
FMR1 premutation carriers (55–200 CGG repeats) are at risk for developing Fragile X-associated Tremor/Ataxia Syndrome (FXTAS), an adult onset neurodegenerative disorder. In addition, 20% of female carriers will develop Fragile X-associated Primary Ovarian Insufficiency (FXPOI), in addition to a number of clinical problems affecting premutation carriers throughout their life span. Marked elevation in FMR1 mRNA levels have been observed with premutation alleles resulting in RNA toxicity, the leading molecular mechanism proposed for the FMR1 associated disorders observed in premutation carriers.The FMR1 gene undergoes alternative splicing and we have recently reported that the relative abundance of all FMR1 mRNA isoforms is significantly increased in premutation carriers.In this study, we further investigated the transcriptional FMR1 isoforms distribution pattern in different tissues and identified a total of 49 isoforms, some of which observed only in premutation carriers and which might play a role in the pathogenesis of FXTAS.Further, we investigated the distribution pattern and expression levels of the FMR1 isoforms in asymptomatic premutation carriers and in those with FXTAS and found no significant difference between the two groups.Our findings suggest that the characterization of the expression levels of the different FMR1 isoforms is fundamental for understanding the regulation of the FMR1 gene as imbalance in their expression could lead to an altered functional diversity with neurotoxic consequences. Their characterization will also help to elucidating the mechanism(s) by which "toxic gain of function" of the FMR1 mRNA may play a role in FXTAS and/or in the other FMR1-associated conditions.
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Effects of hypergravity on gene levels in anti-gravity muscle and bone through the vestibular system in mice
Abstract
We recently reported that hypergravity with 3 g for 4 weeks affects muscle and bone through the vestibular system in mice. The purpose of this study was to investigate the effects of hypergravity with 2 g, which had no influence on circulating glucocorticoid level, on the gene levels in muscle and bone, as well as the roles of the vestibular system in those changes using vestibular lesioned (VL) mice. Hypergravity for 2 and 8 weeks or VL exerted little effects on the mRNA levels of muscle differentiation factors and myokines in the soleus muscle. Although hypergravity for 2 weeks significantly elevated alkaline phosphatase (ALP) and type I collagen mRNA levels in the tibia, VL significantly attenuated the levels of ALP mRNA enhanced by hypergravity. In conclusion, the present study suggests that a 2-g load for 2 weeks enhances osteoblast differentiation partly through the vestibular system in mice.
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Patterns of Alcohol Intake of Pregnant and Lactating Women in Rural Western Australia
Abstract
Objectives Monitoring surveys and research outline a paucity of alcohol consumption data for women in the period of lactation, particularly in rural areas of developed countries. Identifying the drinking profile of ante- and postnatal women in this population will aid in the effective dissemination of public health interventions. This paper will present the first alcohol consumption data of pregnant and breastfeeding women living in rural Western Australia (WA). Methods A prospective cohort of 489 mothers and their infants were recruited between April 2010 and November 2011. All women regardless of their infant feeding method were followed up at 4, 10, 16, 26, 32, 40 and 52 weeks postpartum. Data were analysed to ascertain the prevalence and patterns of alcohol consumption during pregnancy and lactation. Results Approximately 20% of women consumed alcohol during pregnancy, with a predominance of women from older age groups and smokers. At 4, 6 and 12 months postpartum; 45.9%, 47.0% and 51.9% of breastfeeding mothers were consuming alcohol respectively. Conclusions for Practice There remains a considerable proportion of women who continue to drink during pregnancy. Although proven successful, public health campaigns now need to target women who are older and who smoke. Women are continuing to consume alcohol during the period of lactation, with the majority doing so at low levels.
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Arrested for doing your job: Fallout from the arrest of a Utah nurse
The recent release of a video showing a nurse being arrested for doing her job has created quite a stir among EMS and other health care providers. The fallout has included police officer suspensions and changes in policy and procedure for both University Hospital and the Salt Lake City Police Department. While I am perplexed as to how this unfortunate turn of events came to pass, there are a several ...
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Impact of a Mental Health Based Primary Care Program on Quality of Physical Health Care
Abstract
We examine the impact of mental health based primary care on physical health treatment among community mental health center patients in New York State using propensity score adjusted difference in difference models. Outcomes are quality indicators related to outpatient medical visits, diabetes HbA1c monitoring, and metabolic monitoring of antipsychotic treatment. Results suggest the program improved metabolic monitoring for patients on antipsychotics in one of two waves, but did not impact other quality indicators. Ceiling effects may have limited program impacts. More structured clinical programs to may be required to achieve improvements in quality of physical health care for this population.
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Gastric cancer associated with refractory cytomegalovirus gastritis
Abstract
Cytomegalovirus (CMV) sometimes causes gastritis, especially in immunocompromised patients, but whether CMV gastritis promotes the development of gastric cancer is unknown. Here, we report a case of gastric cancer that developed in the presence of CMV gastritis, which had been present for at least 4 years and was refractory to treatment. An 80-year-old woman had noted epigastric discomfort and appetite loss. Esophagogastroduodenoscopy revealed a shallow geographical ulcer extending from the upper body to the pylorus. Histological findings of the biopsy and serology were suggestive of CMV gastritis. Serum anti-Helicobacter pylori antibody test was positive, suggesting co-infection with CMV and H. pylori. Her gastritis was unimproved with repeated antiviral therapy and eradication of H. pylori. Thirty months later, wide-spread gastric cancer had developed. We suggest the possibility that the addition of chronic inflammation of CMV infection to H. pylori-induced gastritis facilitated the development of gastric cancer.
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Disappearance of multiple hyperechoic liver nodules in sporadic porphyria cutanea tarda after treatment with ledipasvir/sofosbuvir for hepatitis C
Abstract
Ultrasonography in a 60-year-old man with chronic hepatitis C (CHC) demonstrated multiple hyperechoic nodules. Radiological investigations did not reveal any signs of malignancy. However, magnetic resonance chemical shift imaging showed multiple focal fatty changes in the liver. Urinary levels of uroporphyrin and coproporphyrin were elevated, and we made a diagnosis of porphyria cutanea tarda. Direct-acting antivirals, ledipasvir/sofosbuvir, were initiated for CHC, which led to sustained viral response, resolution of the liver nodules, and normalization of urinary porphyrin. Hepatitis C virus infection can cause porphyria cutanea tarda with multiple hyperechoic liver nodules, which might be cured by direct-acting antivirals.
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Elderly-Onset and Adult-Onset Ulcerative Colitis Are More Similar than Previously Reported in a Nationwide Cohort
Abstract
Background
Elderly-onset ulcerative colitis (EO-UC) is recognized as a distinct subpopulation of UC. To our knowledge, there have been no nationwide studies of EO-UC populations in the USA.
Aims
We aim to characterize differences in presentation at diagnosis and clinical course between EO-UC and adult-onset UC (AO-UC) patients in a national cohort.
Methods
Complete medical records of patients newly diagnosed with UC from October 2001 to October 2011 in the Veterans Affairs health system were obtained. Patients were followed until colectomy, death, or the end of the observation period on November 2015. EO-UC patients (age of diagnosis ≥65 years) were compared to AO-UC patients (age of diagnosis ≤40 years) with respect to demographic, severity, and therapeutic data. Statistical analysis was performed using JMP statistical software.
Results
We identified 836 newly diagnosed UC patients, of which 207 had EO-UC and 102 had AO-UC. The mean age of diagnosis was 72.4 years (EO-UC) and 32.9 years (AO-UC), with a mean 8-year follow-up period. The incidence of pancolitis at the time of diagnosis was similar between both groups (p = 0.67). There was no difference in steroid use (36.7 vs 45.1%, p = 0.1563), thiopurine use (19.3 vs 22.6%, p = 0.5081), and colectomy rates (6.3 vs 5.9%, p = 0.8911) between EO-UC and AO-UC populations. There was lower anti-TNF use in EO-UC patients compared to AO-UC patients (5.8 vs 14.7%, p = 0.0091).
Conclusion
In this nationwide cohort, we found that the use of steroids, thiopurines, and colectomy was similar in both populations, while anti-TNF use was lower among the elderly.
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Obstructive Sleep Apnea Increases the Risk of Cardiopulmonary Adverse Events Associated with Ambulatory Colonoscopy Independent of Body Mass Index
Abstract
Background
The relationship between body mass index (BMI) and cardiopulmonary adverse events (CAEs) for ambulatory colonoscopy is unclear.
Aim
To assess the association of BMI and CAEs associated with ambulatory colonoscopy.
Methods
This is a retrospective cohort analysis of 418 patients who underwent outpatient colonoscopy at the Durham Veterans Affairs Medical Center categorized as normal/overweight (BMI < 30), obese (BMI 30–34), or morbidly obese (BMI ≥ 35). Adjusted logistic regression analyses were performed.
Results
At least one CAE occurred in 46.4% of patients (220 events, 72.7% were hypoxia). The rate of CAEs (BMI < 30: 43.8%, BMI 30–34: 48.0%, BMI ≥ 35: 50.6%, p = 0.53) and rate of hypoxia (BMI < 30: 34.8%, BMI 30–34: 40.9%, BMI ≥ 35: 43.2%, p = 0.32) were numerically higher for obese and morbidly obese patients, but not statistically significant. Obese (OR 1.10, 95% CI 0.70–1.73) and morbidly obese (OR 1.07, 95% CI 0.61–1.85) patients did not have an increased risk of CAEs after adjusting for age, ASA class, obstructive sleep apnea (OSA), and type of sedation. OSA was independently associated with an increased risk of CAEs (OR 1.71, 95% CI 1.09–2.74, p = 0.02) after adjusting for BMI, age, ASA class, and type of sedation.
Conclusion
OSA confers a higher risk of CAEs independent of BMI and sedation type. Consideration of undiagnosed OSA is recommended for appropriate pre-procedure risk stratification. While not statistically significant in this study, there may be clinically significant increased risks of CAEs and hypoxia for patient with BMI > 30 that require further evaluation with larger studies.
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Direct-Acting Antivirals Decreased Tumor Recurrence After Initial Treatment of Hepatitis C Virus-Related Hepatocellular Carcinoma
Abstract
Background
Suppressive activity of recurrence by interferon-free direct-acting antivirals (DAA) is not elucidated after curative treatment of hepatocellular carcinoma (HCC).
Patients and Methods
A total of 177 patients received DAA after curative manners of HCC: 89 patients underwent DAA therapy after initial HCC treatment, and the other 88 patients after repeated therapy of 2–10 times. Among a cohort of HCC patients with surgery and radiofrequency ablation, 89 patients were chosen adjusting age, gender, and Barcelona Clinic Liver Cancer (BCLC) staging with 89 patients with initial HCC therapy.
Results
HCC recurrence rates at the end of first and second year were 18.1 and 22.1% in patients with once of HCC therapy, 28.2 and 41.6% in those with 2–3 times of therapy, and 60.2 and 74.5% in those with 4 or more times of therapy, respectively (P < 0.0001). Recurrence rates were compared between 89 patients with DAA therapy after initial HCC therapy and 89 age-, gender-, and BCLC staging-matched patients without antiviral therapy after initial HCC therapy. HCC recurrence rates at first and second year were 18.1 and 25.0% in patients with DAA therapy and 21.8 and 46.5% in those without DAA therapy, respectively (P = 0.003). Multivariate analysis showed DAA therapy significantly decreased recurrence rate with a hazard ratio of 0.353 (confidence interval: 0.191–0.651) after adjustment with covariates of tumor multiplicity, alpha-fetoprotein value, and prothrombin time.
Conclusions
DAA therapy significantly decreased recurrence rate when it was performed after initial HCC therapy.
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Ethnicity and Language Proficiency Differences in the Provision of and Intention to Use Prenatal Screening for Down’s Syndrome and Congenital Anomalies. A Prospective, Non-selected, Register-Based Study in the Netherlands
Abstract
Objective We aimed to conduct an analysis of the associations between the information provision procedure of prenatal screening for Down's syndrome and congenital anomalies and the intention to participate in prenatal screening (PS) of ethnicity groups and Dutch language proficiency groups. Design Using a prospective web-based registration form, we asked counselors (midwives, general practitioners, nurses and gynecologists) to report whether and how they offered information about PS to pregnant women. Duration The study was conducted from 2008 to 2010. Participants We collected data on the characteristics of the women who received an information offer about PS from counselors. Measurements Measures included socio-demographic and language proficiency level (LPL) characteristics, key elements of the provision procedure of PS, and intentional participation in PS. Findings The dataset represents 37% of the total population in the study area. Women with a non-native Dutch background and/or insufficient Dutch LPL received fewer information offers about PS, faced a reduced chance of receiving counseling, and showed lower intentional participation rates for PS. Key Conclusions Women with a non-native Dutch background and/or with an insufficient LPL are underserved in the Dutch PS program. These findings present evidence indicating that the fundamental principle of the Dutch Population Screening Act, namely, equal access to PS for all pregnant women, is not being realized. Implications for Practice Therefore, the study findings are important for national and international healthcare, policy makers and governmental professionals to allow ethnic and LPL-related differences in the provision and intentional uptake of PS.
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Honeywell donates $2M in PPE to help Hurricane Harvey responders
The safety product company donated almost 100,000 PPE pieces to support responders in the region impacted by the storm
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Expansion and further delineation of the SETD5 phenotype leading to global developmental delay, variable dysmorphic features, and reduced penetrance
Diagnostic exome sequencing (DES) has aided delineation of the phenotypic spectrum of rare genetic etiologies of intellectual disability (ID). A SETD5 phenotype of ID and dysmorphic features has been previously described in relation to patients with 3p25.3 deletions and in a few individuals with de novo sequence alterations. Herein, we present additional patients with pathogenic SETD5 sequence alterations. The majority of patients in this cohort and previously reported have developmental delay, behavioral/psychiatric issues, and variable hand and skeletal abnormalities. We also present an apparently unaffected carrier mother of an affected individual and a carrier mother with normal intelligence and affected twin sons. We suggest that the phenotype of SETD5 is more complex and variable than previously presented. Therefore, many features and presentations need to be considered when evaluating a patient for SETD5 alterations through DES.
Case series and review of literature of patients with pathogenic SETD5 alterations. Phenotype is variable but encompasses developmental delay, behavioral/psychiatric issues, and variable hand and skeletal abnormalities and highly variable dysmorphic features
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Trans-ancestry Fine Mapping and Molecular Assays Identify Regulatory Variants at the ANGPTL8 HDL-C GWAS Locus
Recent genome-wide association studies (GWAS) have identified variants associated with high-density lipoprotein cholesterol (HDL-C) located in or near the ANGPTL8 gene. Given the extensive sharing of GWAS loci across populations, we hypothesized that at least one shared variant at this locus affects HDL-C. The HDL-C–associated variants are coincident with expression quantitative trait loci for ANGPTL8 and DOCK6 in subcutaneous adipose tissue; however, only ANGPTL8 expression levels are associated with HDL-C levels. We identified a 400-bp promoter region of ANGPTL8 and enhancer regions within 5 kb that contribute to regulating expression in liver and adipose. To identify variants functionally responsible for the HDL-C association, we performed fine-mapping analyses and selected 13 candidate variants that overlap putative regulatory regions to test for allelic differences in regulatory function. Of these variants, rs12463177-G increased transcriptional activity (1.5-fold, P = 0.004) and showed differential protein binding. Six additional variants (rs17699089, rs200788077, rs56322906, rs3760782, rs737337, and rs3745683) showed evidence of allelic differences in transcriptional activity and/or protein binding. Taken together, these data suggest a regulatory mechanism at the ANGPTL8 HDL-C GWAS locus involving tissue-selective expression and at least one functional variant.
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A Functional Link Between Bir1 and the Saccharomyces cerevisiae Ctf19 Kinetochore Complex Revealed Through Quantitative Fitness Analysis
Accelerating Wright-Fisher Forward Simulations on the Graphics Processing Unit
Forward Wright–Fisher simulations are powerful in their ability to model complex demography and selection scenarios, but suffer from slow execution on the Central Processor Unit (CPU), thus limiting their usefulness. However, the single-locus Wright–Fisher forward algorithm is exceedingly parallelizable, with many steps that are so-called "embarrassingly parallel," consisting of a vast number of individual computations that are all independent of each other and thus capable of being performed concurrently. The rise of modern Graphics Processing Units (GPUs) and programming languages designed to leverage the inherent parallel nature of these processors have allowed researchers to dramatically speed up many programs that have such high arithmetic intensity and intrinsic concurrency. The presented GPU Optimized Wright–Fisher simulation, or "GO Fish" for short, can be used to simulate arbitrary selection and demographic scenarios while running over 250-fold faster than its serial counterpart on the CPU. Even modest GPU hardware can achieve an impressive speedup of over two orders of magnitude. With simulations so accelerated, one can not only do quick parametric bootstrapping of previously estimated parameters, but also use simulated results to calculate the likelihoods and summary statistics of demographic and selection models against real polymorphism data, all without restricting the demographic and selection scenarios that can be modeled or requiring approximations to the single-locus forward algorithm for efficiency. Further, as many of the parallel programming techniques used in this simulation can be applied to other computationally intensive algorithms important in population genetics, GO Fish serves as an exciting template for future research into accelerating computation in evolution. GO Fish is part of the Parallel PopGen Package available at: http://ift.tt/2vrgFUF.
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Ras/MAPK Modifier Loci Revealed by eQTL in Caenorhabditis elegans
The oncogenic Ras/MAPK pathway is evolutionarily conserved across metazoans. Yet, almost all our knowledge on this pathway comes from studies using single genetic backgrounds, whereas mutational effects can be highly background dependent. Therefore, we lack insight in the interplay between genetic backgrounds and the Ras/MAPK-signaling pathway. Here, we used a Caenorhabditis elegans RIL population containing a gain-of-function mutation in the Ras/MAPK-pathway gene let-60 and measured how gene expression regulation is affected by this mutation. We mapped eQTL and found that the majority (~73%) of the 1516 detected cis-eQTL were not specific for the let-60 mutation, whereas most (~76%) of the 898 detected trans-eQTL were associated with the let-60 mutation. We detected six eQTL trans-bands specific for the interaction between the genetic background and the mutation, one of which colocalized with the polymorphic Ras/MAPK modifier amx-2. Comparison between transgenic lines expressing allelic variants of amx-2 showed the involvement of amx-2 in 79% of the trans-eQTL for genes mapping to this trans-band. Together, our results have revealed hidden loci affecting Ras/MAPK signaling using sensitized backgrounds in C. elegans. These loci harbor putative polymorphic modifier genes that would not have been detected using mutant screens in single genetic backgrounds.
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The Stress-Inducible Peroxidase TSA2 Underlies a Conditionally Beneficial Chromosomal Duplication in Saccharomyces cerevisiae
Although chromosomal duplications are often deleterious, in some cases they enhance cells' abilities to tolerate specific genetic or environmental challenges. Identifying the genes that confer these conditionally beneficial effects to particular chromosomal duplications can improve our understanding of the genetic and molecular mechanisms that enable certain aneuploidies to persist in cell populations and contribute to disease and evolution. Here, we perform a screen for spontaneous mutations that improve the tolerance of haploid Saccharomyces cerevisiae to hydrogen peroxide. Chromosome IV duplication is the most frequent mutation, as well as the only change in chromosomal copy number seen in the screen. Using a genetic mapping strategy that involves systematically deleting segments of a duplicated chromosome, we show that the chromosome IV's duplication effect is largely due to the generation of a second copy of the stress-inducible cytoplasmic thioredoxin peroxidase TSA2. Our findings add to a growing body of literature that shows the conditionally beneficial effects of chromosomal duplication are typically mediated by a small number of genes that enhance tolerance to specific stresses when their copy numbers are increased.
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The Integrated Genomic Architecture and Evolution of Dental Divergence in East African Cichlid Fishes (Haplochromis chilotes x H. nyererei)
The independent evolution of the two toothed jaws of cichlid fishes is thought to have promoted their unparalleled ecological divergence and species richness. However, dental divergence in cichlids could exhibit substantial genetic covariance and this could dictate how traits like tooth numbers evolve in different African Lakes and on their two jaws. To test this hypothesis, we used a hybrid mapping cross of two trophically divergent Lake Victoria species (Haplochromis chilotes x Haplochromis nyererei) to examine genomic regions associated with cichlid tooth diversity. Surprisingly, a similar genomic region was found to be associated with oral jaw tooth numbers in cichlids from both Lake Malawi and Lake Victoria. Likewise, this same genomic location was associated with variation in pharyngeal jaw tooth numbers. Similar relationships between tooth numbers on the two jaws in both our Victoria hybrid population and across the phylogenetic diversity of Malawi cichlids additionally suggests that tooth numbers on the two jaws of haplochromine cichlids might generally coevolve owing to shared genetic underpinnings. Integrated, rather than independent, genomic architectures could be key to the incomparable evolutionary divergence and convergence in cichlid tooth numbers.
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The Douglas-Fir Genome Sequence Reveals Specialization of the Photosynthetic Apparatus in Pinaceae
A reference genome sequence for Pseudotsuga menziesii var. menziesii (Mirb.) Franco (Coastal Douglas-fir) is reported, thus providing a reference sequence for a third genus of the family Pinaceae. The contiguity and quality of the genome assembly far exceeds that of other conifer reference genome sequences (contig N50 = 44,136 bp and scaffold N50 = 340,704 bp). Incremental improvements in sequencing and assembly technologies are in part responsible for the higher quality reference genome, but it may also be due to a slightly lower exact repeat content in Douglas-fir vs. pine and spruce. Comparative genome annotation with angiosperm species reveals gene-family expansion and contraction in Douglas-fir and other conifers which may account for some of the major morphological and physiological differences between the two major plant groups. Notable differences in the size of the NDH-complex gene family and genes underlying the functional basis of shade tolerance/intolerance were observed. This reference genome sequence not only provides an important resource for Douglas-fir breeders and geneticists but also sheds additional light on the evolutionary processes that have led to the divergence of modern angiosperms from the more ancient gymnosperms.
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Evolutionary Dynamics of Male Reproductive Genes in the Drosophila virilis Subgroup
Postcopulatory sexual selection (PCSS) is a potent evolutionary force that can drive rapid changes of reproductive genes within species, and thus has the potential to generate reproductive incompatibilities between species. Male seminal fluid proteins (SFPs) are major players in postmating interactions, and are important targets of PCSS in males. The virilis subgroup of Drosophila exhibits strong interspecific gametic incompatibilities, and can serve as a model to study the genetic basis of PCSS and gametic isolation. However, reproductive genes in this group have not been characterized. Here we utilize short-read RNA sequencing of male reproductive organs to examine the evolutionary dynamics of reproductive genes in members of the virilis subgroup: D. americana, D. lummei, D. novamexicana, and D. virilis. We find that the majority of male reproductive transcripts are testes-biased, accounting for ~15% of all annotated genes. Ejaculatory bulb (EB)-biased transcripts largely code for lipid metabolic enzymes, and contain orthologs of the D. melanogaster EB protein, Peb-me, which is involved in mating-plug formation. In addition, we identify 71 candidate SFPs, and show that this gene set has the highest rate of nonsynonymous codon substitution relative to testes- and EB-biased genes. Furthermore, we identify orthologs of 35 D. melanogaster SFPs that have conserved accessory gland expression in the virilis group. Finally, we show that several of the SFPs that have the highest rate of nonsynonymous codon substitution reside on chromosomal regions, which contributes to paternal gametic incompatibility between species. Our results show that SFPs rapidly diversify in the virilis group, and suggest that they likely play a role in PCSS and/or gametic isolation.
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Genome-Wide SNP Discovery and Analysis of Genetic Diversity in Farmed Sika Deer (Cervus nippon) in Northeast China Using Double-Digest Restriction Site-Associated DNA Sequencing
Sika deer are an economically valuable species owing to their use in traditional Chinese medicine, particularly their velvet antlers. Sika deer in northeast China are mostly farmed in enclosure. Therefore, genetic management of farmed sika deer would benefit from detailed knowledge of their genetic diversity. In this study, we generated over 1.45 billion high-quality paired-end reads (288 Gbp) across 42 unrelated individuals using double-digest restriction site-associated DNA sequencing (ddRAD-seq). A total of 96,188 (29.63%) putative biallelic SNP loci were identified with an average sequencing depth of 23x. Based on the analysis, we found that the majority of the loci had a deficit of heterozygotes (FIS >0) and low values of Hobs, which could be due to inbreeding and Wahlund effects. We also developed a collection of high-quality SNP probes that will likely be useful in a variety of applications in genotyping for cervid species in the future.
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Sequence-Based Mapping and Genome Editing Reveal Mutations in Stickleback Hps5 Cause Oculocutaneous Albinism and the casper Phenotype
Here, we present and characterize the spontaneous X-linked recessive mutation casper, which causes oculocutaneous albinism in threespine sticklebacks (Gasterosteus aculeatus). In humans, Hermansky-Pudlak syndrome results in pigmentation defects due to disrupted formation of the melanin-containing lysosomal-related organelle (LRO), the melanosome. casper mutants display not only reduced pigmentation of melanosomes in melanophores, but also reductions in the iridescent silver color from iridophores, while the yellow pigmentation from xanthophores appears unaffected. We mapped casper using high-throughput sequencing of genomic DNA from bulked casper mutants to a region of the stickleback X chromosome (chromosome 19) near the stickleback ortholog of Hermansky-Pudlak syndrome 5 (Hps5). casper mutants have an insertion of a single nucleotide in the sixth exon of Hps5, predicted to generate an early frameshift. Genome editing using CRISPR/Cas9 induced lesions in Hps5 and phenocopied the casper mutation. Injecting single or paired Hps5 guide RNAs revealed higher incidences of genomic deletions from paired guide RNAs compared to single gRNAs. Stickleback Hps5 provides a genetic system where a hemizygous locus in XY males and a diploid locus in XX females can be used to generate an easily scored visible phenotype, facilitating quantitative studies of different genome editing approaches. Lastly, we show the ability to better visualize patterns of fluorescent transgenic reporters in Hps5 mutant fish. Thus, Hps5 mutations present an opportunity to study pigmented LROs in the emerging stickleback model system, as well as a tool to aid in assaying genome editing and visualizing enhancer activity in transgenic fish.
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A Large Deletion in the NSDHL Gene in Labrador Retrievers with a Congenital Cornification Disorder
In heterozygous females affected by an X-linked skin disorder, lesions often appear in a characteristic pattern, the so-called Blaschko's lines. We investigated a female Labrador Retriever and her crossbred daughter, which both showed similar clinical lesions that followed Blaschko's lines. The two male littermates of the affected daughter had died at birth, suggesting a monogenic X-chromosomal semidominant mode of inheritance. Whole genome sequencing of the affected daughter, and subsequent automated variant filtering with respect to 188 nonaffected control dogs of different breeds, revealed 332 hetero-zygous variants on the X-chromosome private to the affected dog. None of these variants was protein-changing. By visual inspection of candidate genes located on the X-chromosome, we identified a large deletion in the NSDHL gene, encoding NAD(P) dependent steroid dehydrogenase-like, a 3β-hydroxysteroid dehydrogenase involved in cholesterol biosynthesis. The deletion spanned >14 kb, and included the last three exons of the NSDHL gene. By PCR and fragment length analysis, we confirmed the presence of the variant in both affected dogs, and its absence in 50 control Labrador Retrievers. Variants in the NSDHL gene cause CHILD syndrome in humans, and the bare patches (Bpa) and striated (Str) phenotypes in mice. Taken together, our genetic data and the known role of NSDHL in X-linked skin disorders strongly suggest that the identified structural variant in the NSDHL gene is causative for the phenotype in the two affected dogs.
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Ankyrin-1 Gene Exhibits Allelic Heterogeneity in Conferring Protection Against Malaria
Allelic heterogeneity is a common phenomenon where a gene exhibits a different phenotype depending on the nature of its genetic mutations. In the context of genes affecting malaria susceptibility, it allowed us to explore and understand the intricate host–parasite interactions during malaria infections. In this study, we described a gene encoding erythrocytic ankyrin-1 (Ank-1) which exhibits allelic-dependent heterogeneous phenotypes during malaria infections. We conducted an ENU mutagenesis screen on mice and identified two Ank-1 mutations, one resulting in an amino acid substitution (MRI95845), and the other a truncated Ank-1 protein (MRI96570). Both mutations caused hereditary spherocytosis-like phenotypes and confer differing protection against Plasmodium chabaudi infections. Upon further examination, the Ank-1(MRI96570) mutation was found to inhibit intraerythrocytic parasite maturation, whereas Ank-1(MRI95845) caused increased bystander erythrocyte clearance during infection. This is the first description of allelic heterogeneity in ankyrin-1 from the direct comparison between two Ank-1 mutations. Despite the lack of direct evidence from population studies, this data further supported the protective roles of ankyrin-1 mutations in conferring malaria protection. This study also emphasized the importance of such phenomena in achieving a better understanding of host–parasite interactions, which could be the basis of future studies.
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Application of Response Surface Methods To Determine Conditions for Optimal Genomic Prediction
An epistatic genetic architecture can have a significant impact on prediction accuracies of genomic prediction (GP) methods. Machine learning methods predict traits comprised of epistatic genetic architectures more accurately than statistical methods based on additive mixed linear models. The differences between these types of GP methods suggest a diagnostic for revealing genetic architectures underlying traits of interest. In addition to genetic architecture, the performance of GP methods may be influenced by the sample size of the training population, the number of QTL, and the proportion of phenotypic variability due to genotypic variability (heritability). Possible values for these factors and the number of combinations of the factor levels that influence the performance of GP methods can be large. Thus, efficient methods for identifying combinations of factor levels that produce most accurate GPs is needed. Herein, we employ response surface methods (RSMs) to find the experimental conditions that produce the most accurate GPs. We illustrate RSM with an example of simulated doubled haploid populations and identify the combination of factors that maximize the difference between prediction accuracies of best linear unbiased prediction (BLUP) and support vector machine (SVM) GP methods. The greatest impact on the response is due to the genetic architecture of the population, heritability of the trait, and the sample size. When epistasis is responsible for all of the genotypic variance and heritability is equal to one and the sample size of the training population is large, the advantage of using the SVM method vs. the BLUP method is greatest. However, except for values close to the maximum, most of the response surface shows little difference between the methods. We also determined that the conditions resulting in the greatest prediction accuracy for BLUP occurred when genetic architecture consists solely of additive effects, and heritability is equal to one.
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RNA-seq of Rice Yellow Stem Borer Scirpophaga incertulas Reveals Molecular Insights During Four Larval Developmental Stages
The yellow stem borer (YSB), Scirpophaga incertulas, is a prominent pest in rice cultivation causing serious yield losses. The larval stage is an important stage in YSB, responsible for maximum infestation. However, limited knowledge exists on the biology and mechanisms underlying the growth and differentiation of YSB. To understand and identify the genes involved in YSB development and infestation, so as to design pest control strategies, we performed de novo transcriptome analysis at the first, third, fifth, and seventh larval developmental stages employing Illumina Hi-seq. High-quality reads (HQR) of ~229 Mb were assembled into 24,775 transcripts with an average size of 1485 bp. Genes associated with various metabolic processes, i.e., detoxification mechanism [CYP450, GSTs, and carboxylesterases (CarEs)], RNA interference (RNAi) machinery (Dcr-1, Dcr-2, Ago-1, Ago-2, Sid-1, Sid-2, Sid-3, and Sid-1-related gene), chemoreception (CSPs, GRs, OBPs, and ORs), and regulators [transcription factors (TFs) and hormones] were differentially regulated during the developmental stages. Identification of stage-specific transcripts made it possible to determine the essential processes of larval development. Comparative transcriptome analysis revealed that YSB has not evolved much with respect to the detoxification mechanism, but showed the presence of distinct RNAi machinery. The presence of strong specific visual recognition coupled with chemosensory mechanisms supports the monophagous nature of YSB. Designed expressed sequenced tags-simple-sequence repeats (EST-SSRs) will facilitate accurate estimation of the genetic diversity of YSB. This is the first report on characterization of the YSB transcriptome and the identification of genes involved in key processes, which will help researchers and industry to devise novel pest control strategies. This study also opens up a new avenue to develop next-generation resistant rice using RNAi or genome editing approaches.
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Regulation of Small Mitochondrial DNA Replicative Advantage by Ribonucleotide Reductase in Saccharomyces cerevisiae
Small mitochondrial genomes can behave as selfish elements by displacing wild-type genomes regardless of their detriment to the host organism. In the budding yeast Saccharomyces cerevisiae, small hypersuppressive mtDNA transiently coexist with wild-type in a state of heteroplasmy, wherein the replicative advantage of the small mtDNA outcompetes wild-type and produces offspring without respiratory capacity in >95% of colonies. The cytosolic enzyme ribonucleotide reductase (RNR) catalyzes the rate-limiting step in dNTP synthesis and its inhibition has been correlated with increased petite colony formation, reflecting loss of respiratory function. Here, we used heteroplasmic diploids containing wild-type (rho+) and suppressive (rho–) or hypersuppressive (HS rho–) mitochondrial genomes to explore the effects of RNR activity on mtDNA heteroplasmy in offspring. We found that the proportion of rho+ offspring was significantly increased by RNR overexpression or deletion of its inhibitor, SML1, while reducing RNR activity via SML1 overexpression produced the opposite effects. In addition, using Ex Taq and KOD Dash polymerases, we observed a replicative advantage for small over large template DNA in vitro, but only at low dNTP concentrations. These results suggest that dNTP insufficiency contributes to the replicative advantage of small mtDNA over wild-type and cytosolic dNTP synthesis by RNR is an important regulator of heteroplasmy involving small mtDNA molecules in yeast.
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Two Types of Etiological Mutation in the Limb-Specific Enhancer of Shh
An enhancer named MFCS1 regulates Sonic hedgehog (Shh) expression in the posterior mesenchyme of limb buds. Several mutations in MFCS1 induce ectopic Shh expression in the anterior limb bud, and these result in preaxial polydactyly (PPD). However, the molecular basis of ectopic Shh expression remains elusive, although some mutations are known to disrupt the negative regulation of Shh expression in the anterior limb bud. Here, we analyzed the molecular mechanism of ectopic Shh expression in PPD including in a mouse mutation—hemimelic extra toes (Hx)—and in other MFCS1 mutations in different species. First, we generated transgenic mouse lines with a LacZ reporter cassette flanked with tandem repeats of 40 bp MFCS1 fragments harboring a mutation. The transgenic mouse line with the Hx-type fragment showed reporter expression exclusively in the anterior, but not in the posterior margins of limb buds. In contrast, no specific LacZ expression was observed in lines carrying the MFCS1 fragment with other mutations. Yeast one-hybrid assays revealed that the msh-like homeodomain protein, MSX1, bound specifically to the Hx sequence of MFCS1. Thus, PPD caused by mutations in MFCS1 has two major types of molecular etiology: loss of a cis-motif for negative regulation of Shh, and acquisition of a new cis-motif binding to a preexisting transcription factor, as represented by the Hx mutation.
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Genome-Wide Transcriptional Dynamics in the Companion Bacterial Symbionts of the Glassy-Winged Sharpshooter (Cicadellidae: Homalodisca vitripennis) Reveal Differential Gene Expression in Bacteria Occupying Multiple Host Organs
The agricultural pest known as the glassy-winged sharpshooter (GWSS) or Homalodisca vitripennis (Hemiptera: Cicadellidae) harbors two bacterial symbionts, "Candidatus Sulcia muelleri" and "Ca. Baumannia cicadellinicola," which provide the 10 essential amino acids (EAAs) that are limited in the host plant-sap diet. Although they differ in origin and symbiotic age, both bacteria have experienced extensive genome degradation resulting from their ancient restriction to specialized host organs (bacteriomes) that provide cellular support and ensure vertical transmission. GWSS bacteriomes are of different origins and distinctly colored red and yellow. While Sulcia occupies the yellow bacteriome, Baumannia inhabits both. Aside from genomic predictions, little is currently known about the cellular functions of these bacterial symbionts, particularly whether Baumannia in different bacteriomes perform different roles in the symbiosis. To address these questions, we conducted a replicated, strand-specific RNA-seq experiment to assay global gene expression patterns in Sulcia and Baumannia. Despite differences in genomic capabilities, the symbionts exhibit similar profiles of their most highly expressed genes, including those involved in nutrition synthesis and protein stability (chaperonins dnaK and groESL) that likely aid impaired proteins. Baumannia populations in separate bacteriomes differentially express genes enriched in essential nutrient synthesis, including EAAs (histidine and methionine) and B vitamins (biotin and thiamine). Patterns of differential gene expression further reveal complexity in methionine synthesis. Baumannia's capability to differentially express genes is unusual, as ancient symbionts lose the capability to independently regulate transcription. Combined with previous microscopy, our results suggest that the GWSS may rely on distinct Baumannia populations for essential nutrition and vertical transmission.
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Genome-Wide Sequence and Expression Analysis of the NAC Transcription Factor Family in Polyploid Wheat
Many important genes in agriculture correspond to transcription factors (TFs) that regulate a wide range of pathways from flowering to responses to disease and abiotic stresses. In this study, we identified 5776 TFs in hexaploid wheat (Triticum aestivum) and classified them into gene families. We further investigated the NAC family exploring the phylogeny, C-terminal domain (CTD) conservation, and expression profiles across 308 RNA-seq samples. Phylogenetic trees of NAC domains indicated that wheat NACs divided into eight groups similar to rice (Oryza sativa) and barley (Hordeum vulgare). CTD motifs were frequently conserved between wheat, rice, and barley within phylogenetic groups; however, this conservation was not maintained across phylogenetic groups. Three homeologous copies were present for 58% of NACs, whereas evidence of single homeolog gene loss was found for 33% of NACs. We explored gene expression patterns across a wide range of developmental stages, tissues, and abiotic stresses. We found that more phylogenetically related NACs shared more similar expression patterns compared to more distant NACs. However, within each phylogenetic group there were clades with diverse expression profiles. We carried out a coexpression analysis on all wheat genes and identified 37 modules of coexpressed genes of which 23 contained NACs. Using gene ontology (GO) term enrichment, we obtained putative functions for NACs within coexpressed modules including responses to heat and abiotic stress and responses to water: these NACs may represent targets for breeding or biotechnological applications. This study provides a framework and data for hypothesis generation for future studies on NAC TFs in wheat.
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3'-Terminated Overhangs Regulate DNA Double-Strand Break Processing in Escherichia coli
Double-strand breaks (DSBs) are lethal DNA lesions, which are repaired by homologous recombination in Escherichia coli. To study DSB processing in vivo, we induced DSBs into the E. coli chromosome by -irradiation and measured chromosomal degradation. We show that the DNA degradation is regulated by RecA protein concentration and its rate of association with single-stranded DNA (ssDNA). RecA decreased DNA degradation in wild-type, recB, and recD strains, indicating that it is a general phenomenon in E. coli. On the other hand, DNA degradation was greatly reduced and unaffected by RecA in the recB1080 mutant (which produces long overhangs) and in a strain devoid of four exonucleases that degrade a 3' tail (ssExos). 3'–5' ssExos deficiency is epistatic to RecA deficiency concerning DNA degradation, suggesting that bound RecA is shielding the 3' tail from degradation by 3'–5' ssExos. Since 3' tail preservation is common to all these situations, we infer that RecA polymerization constitutes a subset of mechanisms for preserving the integrity of 3' tails emanating from DSBs, along with 3' tail's massive length, or prevention of their degradation by inactivation of 3'–5' ssExos. Thus, we conclude that 3' overhangs are crucial in controlling the extent of DSB processing in E. coli. This study suggests a regulatory mechanism for DSB processing in E. coli, wherein 3' tails impose a negative feedback loop on DSB processing reactions, specifically on helicase reloading onto dsDNA ends.
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Gene Expression Networks in the Murine Pulmonary Myocardium Provide Insight into the Pathobiology of Atrial Fibrillation
The pulmonary myocardium is a muscular coat surrounding the pulmonary and caval veins. Although its definitive physiological function is unknown, it may have a pathological role as the source of ectopic beats initiating atrial fibrillation. How the pulmonary myocardium gains pacemaker function is not clearly defined, although recent evidence indicates that changed transcriptional gene expression networks are at fault. The gene expression profile of this distinct cell type in situ was examined to investigate underlying molecular events that might contribute to atrial fibrillation. Via systems genetics, a whole-lung transcriptome data set from the BXD recombinant inbred mouse resource was analyzed, uncovering a pulmonary cardiomyocyte gene network of 24 transcripts, coordinately regulated by chromosome 1 and 2 loci. Promoter enrichment analysis and interrogation of publicly available ChIP-seq data suggested that transcription of this gene network may be regulated by the concerted activity of NKX2-5, serum response factor, myocyte enhancer factor 2, and also, at a post-transcriptional level, by RNA binding protein motif 20. Gene ontology terms indicate that this gene network overlaps with molecular markers of the stressed heart. Therefore, we propose that perturbed regulation of this gene network might lead to altered calcium handling, myocyte growth, and contractile force contributing to the aberrant electrophysiological properties observed in atrial fibrillation. We reveal novel molecular interactions and pathways representing possible therapeutic targets for atrial fibrillation. In addition, we highlight the utility of recombinant inbred mouse resources in detecting and characterizing gene expression networks of relatively small populations of cells that have a pathological significance.
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Convergence of fMRI and ERP measures of emotional face processing in combat-exposed U. S. military veterans
Abstract
The late positive potential (LPP) and fMRI blood-oxygen-level dependent (BOLD) activity can provide complementary measures of the processing of affective and social stimuli. Separate lines of research using these measures have often employed the same stimuli, paradigms, and samples; however, there remains relatively little understanding of the way in which individual differences in one of these measures relates to the other, and all prior research has been conducted in psychiatrically healthy samples and using emotional scenes (not faces). Here, 32 combat-exposed U. S. military veterans with varying levels of posttraumatic stress symptomatology viewed affective social stimuli (angry, fearful, and happy faces) and geometric shapes during separate EEG and fMRI BOLD recordings. Temporospatial principal component analysis was used to quantify the face-elicited LPP in a data-driven manner, prior to conducting whole-brain correlations between resulting positivities and fMRI BOLD elicited by faces. Participants with larger positivities to fearful faces (> shapes) showed increased activation in the amygdala; larger positivities to angry and happy faces (> shapes) were associated with increased BOLD activation in the posterior fusiform gyrus and inferior temporal gyrus, respectively. Across all face types, larger positivities were associated with increased activation in the fusiform "face" area. Correlations using mean area amplitude LPPs showed an association with increased activation in the anterior insula for angry faces (> shapes). LPP-BOLD associations were not moderated by PTSD. Findings provide the first evidence of correspondence between face-elicited LPP and BOLD activation across a range of (normal to disordered) psychiatric health.
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Startle reflex modulation during threat of shock and “threat” of reward
Abstract
During threat of shock, the startle reflex is potentiated, suggesting modulation by defensive mobilization. To determine whether startle potentiation is specific to aversive anticipation, startle reflexes were measured in the context of either aversive or appetitive anticipation in a between-subject study. Participants wore a device on the wrist that could deliver electrical shock (n = 49), or vibrotactile stimulation indicating monetary reward (n = 48). Cues signaling "threat" or "safe" periods were presented alone, or accompanied by presentation of affective and neutral pictures on half of the trials. Results indicated that the startle reflex was significantly potentiated when anticipating either shock or reward, compared to safe periods, both when no picture was presented, as well as during picture viewing. The difference between threat and safety in both reflex magnitude and skin conductance changes was larger for those anticipating shock, suggesting that the aversive context was more motivationally engaging. The pattern of reflex modulation as a function of picture valence varied under threat and safety, but was identical in the shock and reward groups, consistent with a hypothesis that anticipation of either aversive or appetitive events prompts heightened perceptual vigilance, potentiating the acoustic startle reflex.
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Microarray analysis after adipose derived mesenchymal stem cells injection in monosodium iodoacetate-induced osteoarthritis rats
Abstract
Osteoarthritis (OA) is a degenerative joint disease characterized by abrasion, and ultimately, destruction of the articular cartilage and trabecular bone loss. OA is still considered a devastating disease, which requires an aggressive therapeutic approach. Despite the therapeutic potential of human adipose-derived mesenchymal stem cells (AD-MSCs), the molecular parameters needed to define the "stemness" remain largely unknown. Using high-density oligonucleotide microarrays, the differential gene expression profiles between a fraction of human adipose-derived (AD) mononuclear cells and its MSC subpopulation were obtained. Of particular interest was a subset of 58 genes preferentially expressed at sevenfold or higher in the group treated with human AD-MSCs. This subset contained numerous genes involved in the inflammatory response, immune response, lipid metabolism, cell death, cell proliferation, and DNA repair. Additionally, four protein networks were constructed. The interaction network consisted of 46 proteins encoded by up-regulated genes. However, the interaction network also consisted of 38 proteins encoded by down-regulated genes. My results provide a basis for a more reproducible and reliable quality control using genotypic analysis for the definition of human AD-MSCs. Therefore, these results will provide a basis for studies on molecular mechanisms controlling the core properties of human MSCs.
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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
Abstract
Background
Diagnosis of low-grade dysplasia (LGD) is important in the management of ulcerative colitis (UC), but it is often difficult to distinguish LGD from inflammatory regenerative epithelium. The unfolded protein response (UPR) is activated in inflammatory bowel disease and malignancies. We aimed to identify a UPR-related gene that is involved in the development of non-UC and UC-associated colorectal cancer (CRC), and to investigate whether the target gene is useful for the diagnosis of LGD.
Methods
Using our microarray gene expression database of 152 CRCs, we identified activating transcription factor 6 (ATF6) as a target gene. Immunohistochemistry (IHC) of ATF6 were analyzed in 137 surgically resected CRCs, 95 endoscopically resected adenomas and pTis cancers, and 136 samples from 51 UC patients (93 colitis without neoplasia, 31 dysplasia, and 12 UC-associated CRC). The diagnostic accuracy of ATF6 and p53 as markers of LGD was assessed.
Results
ATF6 expression was detectable in all CRCs but not in normal colonic mucosa, was elevated with increase in cellular atypia (adenoma with moderate atypia < severe atypia < pTis CRC, p < 0.001), and higher in dysplasia and CRC than in non-neoplastic colitis (p < 0.001). Notably, the difference between colitis and LGD was significant. Compared to p53-IHC, ATF6-IHC had better diagnostic accuracy for distinguishing LGD from background inflammatory mucosa (sensitivity 70.8 vs. 16.7%, specificity 78.5 vs.71.0%, respectively).
Conclusions
ATF6 was expressed in lesions undergoing pre-cancerous atypical change in both non-UC and UC-associated CRC and may be used to distinguish LGD from inflammatory regenerative epithelium in UC patients.
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Pouch functional outcomes after restorative proctocolectomy with ileal-pouch reconstruction in patients with ulcerative colitis: Japanese multi-center nationwide cohort study
Abstract
Background
Although several complications capable of causing pouch failure may develop after restorative proctocolectomy (RPC) for ulcerative colitis (UC), the incidences and causes are conflicting and vary according to country, race and institution. To avoid pouch failure, this study aimed to evaluate the rate of pouch failure and its risk factors in UC patients over the past decade via a nationwide cohort study.
Methods
We conducted a retrospective, observational, multicenter study that included 13 institutions in Japan. Patients who underwent RPC between January 2005 and December 2014 were included. The characteristics and backgrounds of the patients before and during surgery and their postoperative courses and complications were reviewed.
Results
A total of 2376 patients were evaluated over 6.7 ± 3.5 years of follow-up. Twenty-seven non-functional pouches were observed, and the functional pouch rate was 98.9% after RPC. Anastomotic leakage (odds ratio, 9.1) was selected as a risk factor for a non-functional pouch. The cumulative pouch failure rate was 4.2%/10 years. A change in diagnosis to Crohn's disease/indeterminate colitis (hazard ratio, 13.2) was identified as an independent risk factor for pouch failure.
Conclusion
The significant risk factor for a non-functional pouch was anastomotic leakage. The optimal staged surgical procedure should be selected according to a patient's condition to avoid anastomotic failure during RPC. Changes in diagnosis after RPC confer a substantial risk of pouch failure. Additional cohort studies are needed to obtain an understanding of the long-standing clinical course of and proper treatment for pouch failure.
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Genome-wide abnormal DNA methylome of human blastocyst in assisted reproductive technology
Source:Journal of Genetics and Genomics
Author(s): Guoqiang Li, Yang Yu, Yong Fan, Congru Li, Xiaocui Xu, Jialei Duan, Rong Li, Xiangjin Kang, Xin Ma, Xuepeng Chen, Yuwen Ke, Jie Yan, Ying Lian, Ping Liu, Yue Zhao, Hongcui Zhao, Yaoyong Chen, Xiaofang Sun, Jianqiao Liu, Jie Qiao, Jiang Liu
Proper reprogramming of parental DNA methylomes is essential for mammalian embryonic development. However, it is unknown whether abnormal methylome reprogramming occurs and is associated with the failure of embryonic development. Here we analyzed the DNA methylomes of 57 blastocysts and 29 trophectoderm samples with different morphological grades during assisted reproductive technology (ART) practices. Our data reveal that the global methylation levels of high-quality blastocysts are similar (0.30 ± 0.02, mean ± SD), while the methylation levels of low-quality blastocysts are divergent and away from those of high-quality blastocysts. The proportion of blastocysts with a methylation level falling within the range of 0.30 ± 0.02 in different grades correlates with the live birth rate for that grade. Moreover, abnormal methylated regions are associated with the failure of embryonic development. Furthermore, we can use the methylation data of cells biopsied from trophectoderm to predict the blastocyst methylation level as well as to detect the aneuploidy of the blastocysts. Our data indicate that global abnormal methylome reprogramming often occurs in human embryos, and suggest that DNA methylome is a potential biomarker in blastocyst selection in ART.
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Cardiovascular and thermal strain during 3–4 days of a metabolically demanding cold-weather military operation
Cardiovascular (CV) and thermal responses to metabolically demanding multi-day military operations in extreme cold-weather environments are not well described. Characterization of these operations will provide...
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Neutrophil infiltration is a favorable prognostic factor in early stages of colon cancer
Human Pathology
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Clinicians urged to weigh antidepressants’ risks, benefits in young people
Reuters Health News
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A comparison of laparoscopic and open D3 lymphadenectomy for transverse colon cancer
International Journal of Colorectal Disease
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Novo Nordisk settles US probe over diabetes drug for nearly $58.7 million
Reuters Health News
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Bilirubin Uridine Diphosphate-glucuronosyltransferase Polymorphism as a Risk Factor for Prolonged Hyperbilirubinemia in Japanese Preterm Infants
The Journal of Pediatrics
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AMA: Reversing DACA puts patient care at risk, could worsen doctor shortage
Healthcare Finance News
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Expression of human cathelicidin peptide ll-37 in inflammatory bowel disease
Clinical and Experimental Immunology
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Managing ulcerative colitis patients with endoscopically invisible low-grade dysplasia
Gastrointestinal Endoscopy
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Relating gastric scintigraphy and symptoms to motility capsule transit and pressure findings in suspected gastroparesis
Neurogastroenterology & Motility
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Food elimination diets are effective for long-term treatment of adults with eosinophilic oesophagitis
Alimentary Pharmacology and Therapeutics
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Mortality after emergent trauma laparotomy: A multicenter, retrospective study
The Journal of Trauma and Acute Care Surgery
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HCV eradication induced by direct-acting antiviral agents reduces the risk of hepatocellular carcinoma
Journal of Hepatology
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Intimidated patients may act like hostages
Reuters Health News
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Prospective study on the incidence, prevalence and 5-year pancreatic-related mortality of pancreatic cysts in a population-based study
Gut
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Influence of gut microbiota on the development and progression of nonalcoholic steatohepatitis
European Journal of Nutrition
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Time course of cellular HIV-DNA and low-level HIV viremia in HIV–HCV co-infected patients whose HCV infection had been successfully treated with directly acting antivirals
Medical Microbiology and Immunology
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Treatment response and outcome with two different prednisolone regimens in autoimmune hepatitis
Digestive Diseases and Sciences
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Development of chronic kidney disease in patients with non-alcoholic fatty liver disease: A cohort study
Journal of Hepatology
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MicroRNA-155 modulates bile duct inflammation by targeting the suppressor of cytokine signaling 1 in biliary atresia
Pediatric Research
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How many deaths from colorectal cancer can be prevented by 2030? A scenario-based quantification of risk factor modification, screening, and treatment in Norway
Cancer Epidemiology, Biomarkers & Prevention
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Case report of perineal hernia after laparoscopic abdominoperineal resection
Abstract
Perineal hernia (PH) is a rare complication following laparoscopic abdominoperineal resection (APR) for rectal cancer. We present a case report of perineal hernia after laparoscopic APR and discuss its management. The patient was a 77-year-old man who was diagnosed with lower rectal cancer. He underwent laparoscopic APR and bilateral lateral lymph node dissection. Two months after the surgery, pain and bulging in the perineal region developed, and PH was diagnosed by CT. Repair with a polypropylene mesh was performed using a combination of laparoscopic abdominal and transperineal approaches. Reportedly, the incidence of secondary PH after APR has increased along with the rate of laparoscopic surgery. Treatment of secondary PH with transperineal repair alone may cause injuries to other organs because of adhesion of the pelvic viscera. In the present case, we safely repaired the hernia repair using a laparoscopy-assisted perineal approach.
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Getting help from Frank & Starling (& Coats & Bowditch) to augment blood flow in heat-stressed older adults
Abstract
Otto Frank and Ernest Starling are credited with the first observations that led to Starling's law of the heart, namely that the strength of cardiac contraction during systole is proportional to end-diastolic volume, or the amount of stretch on the myocardial muscle cells during diastole.
This article is protected by copyright. All rights reserved
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Risk Factors for Knee Injury in Golf: A Systematic Review
Abstract
Background
Golf is commonly considered a low-impact sport that carries little risk of injury to the knee and is generally allowed following total knee arthroplasty (TKA). Kinematic and kinetic studies of the golf swing have reported results relevant to the knee, but consensus as to the loads experienced during a swing and how the biomechanics of an individual's technique may expose the knee to risk of injury is lacking.
Objectives
Our objective was to establish (1) the prevalence of knee injury resulting from participation in golf and (2) the risk factors for knee injury from a biomechanical perspective, based on an improved understanding of the internal loading conditions and kinematics that occur in the knee from the time of addressing the ball to the end of the follow-through.
Methods
A systematic literature search was conducted to determine the injury rate, kinematic patterns, loading, and muscle activity of the knee during golf.
Results
A knee injury prevalence of 3–18% was established among both professional and amateur players, with no clear dependence on skill level or sex; however, older players appear at greater risk of injury. Studies reporting kinematics indicate that the lead knee is exposed to a complex series of motions involving rapid extension and large magnitudes of tibial internal rotation, conditions that may pose risks to the structures of a natural knee or TKA. To date, the loads experienced by the lead knee during a golf swing have been reported inconsistently in the literature. Compressive loads ranging from 100 to 440% bodyweight have been calculated and measured using methods including inverse dynamics analysis and instrumented knee implants. Additionally, the magnitude of loading appears to be independent of the club used.
Conclusions
This review is the first to highlight the lack of consensus regarding knee loading during the golf swing and the associated risks of injury. Results from the literature suggest the lead knee is subject to a higher magnitude of stress and more demanding motions than the trail knee. Therefore, recommendations regarding return to golf following knee injury or surgical intervention should carefully consider the laterality of the injury.
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Illness Representations of Pertussis and Predictors of Child Vaccination Among Mothers in a Strict Vaccination Exemption State
Abstract
Background Vaccine preventable diseases are making a comeback in the US. However, research is lacking on illness representations of vaccine preventable diseases and their application in improving childhood immunization. Objective We utilized the common sense model of self-regulation to examine illness representations of pertussis and their associations with child's receipt of any vaccine, up-to-date vaccination status, and mothers' intentions to follow the recommended vaccination schedule in the future. Methods We developed vaccine worry and vaccine hassles scales to assess mothers' worries and hassles for child vaccination, and used an open ended question to assess mother's illness representations of pertussis. We surveyed mothers with children <3 years old (N = 160) in the Appalachian state of West Virginia, which only allows medical vaccine exemptions. Results Some children (5.0%) had received no vaccination, 15.0% were not up-to-date with the recommended vaccination schedule, and 13.8% mothers reported no intention to follow the recommended schedule in future (future intention). Illness representations included identity (17.8%), timeline (61.8%), consequences (58.6%), cause (35.0%), and cure/control (56.7%). Higher vaccine worry was associated with child receiving no vaccine. Not using daycare, higher vaccine worry, and difficulty breathing (identity) were associated with child not being up-to-date. Higher vaccine worry, cough (identity), and belief that vaccines are ineffective (cure/control) were associated with no future intention. Conclusions Vaccination interventions need to address mothers' worry regarding vaccine safety. 'Common Sense' beliefs regarding vaccines need to be reconciled with scientific data about vaccine safety and effectiveness, even among those with high socio-economic status in a strict vaccination state.
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