The ketone bodies acetoacetate, β-hydroxybutyrate (βHB) and acetone are small, lipid-derived molecules that are generated during ketogenesis, a process that is amplified during fasting, starvation, ketogenic diets, and prolonged glycogen-depleting exercise.
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Genetic interaction analysis is a powerful approach to the study of complex biological processes that are dependent on multiple genes. Because of the largely diploid nature of the human fungal pathogen Candida albicans, genetic interaction analysis has been limited to a small number of large-scale screens and a handful for gene-by-gene studies. Complex haploinsufficiency, which occurs when a strain containing two heterozygous mutations at distinct loci shows a phenotype that is distinct from either of the corresponding single heterozygous mutants, is an expedient approach to genetic interactions analysis in diploid organisms. Here, we describe the construction of a barcoded-library of 133 heterozygous TF deletion mutants and deletion cassettes for designed to facilitate complex haploinsufficiency-based genetic interaction studies of the TF networks in C. albicans. We have characterized the phenotypes of these heterozygous mutants under a broad range of in vitro conditions using both agar-plate and pooled signature tag-based assays. Consistent with previous studies, haploinsufficiency is relative uncommon. In contrast, a set of 12 TFs enriched in mutants with a role in adhesion were found to have altered competitive fitness at early time points in a murine model of disseminated candidiasis. Finally, we characterized the genetic interactions of a set of biofilm related TFs in the first two steps of biofilm formation, adherence and filamentation of adherent cells. The genetic interaction networks at each stage of biofilm formation are significantly different indicating that the network is not static but dynamic.
To function properly, organisms must adjust their physiology, behavior and metabolism in response to a suite of varying environmental conditions. One of the central regulators of these changes is organisms' internal circadian clock, and recent evidence has suggested that the clock genes are also important in the regulation of seasonal adjustments. In particular, thermosensitive splicing of the core clock gene timeless in a cosmopolitan fly, Drosophila melanogaster, has implicated this gene to be involved in thermal adaptation. To further investigate this link we examined the splicing of timeless in a northern malt fly species, Drosophila montana, which can withstand much colder climatic conditions than its southern relative. We studied northern and southern populations from two different continents (North America and Europe) to find out whether and how the splicing of this gene varies in response to different temperatures and day lengths. Interestingly, we found that the expression of timeless splice variants was sensitive to differences in light conditions, and while the flies of all study populations showed a change in the usage of splice variants in constant light compared to LD 22:2, the direction of the shift varied between populations. Overall, our findings suggest that the splicing of timeless in northern Drosophila montana flies is photosensitive, rather than thermosensitive and highlights the value of studying multiple species and populations in order to gain perspective on the generality of gene function changes in different kinds of environmental conditions.
Ostreid herpesvirus (OsHV) can cause mass mortality events in Pacific oyster aquaculture. While various factors impact on the severity of outbreaks, it is clear that genetic resistance of the host is an important determinant of mortality levels. This raises the possibility of selective breeding strategies to improve the genetic resistance of farmed oyster stocks, thereby contributing to disease control. Traditional selective breeding can be augmented by use of genetic markers, either via marker-assisted or genomic selection. The aim of the current study was to investigate the genetic architecture of resistance to OsHV in Pacific oyster, to identify genomic regions containing putative resistance genes, and to inform the use of genomics to enhance efforts to breed for resistance. To achieve this, a population of ~1,000 juvenile oysters were experimentally challenged with a virulent form of OsHV, with samples taken from mortalities and survivors for genotyping and qPCR measurement of viral load. The samples were genotyped using a recently-developed SNP array, and the genotype data were used to reconstruct the pedigree. Using these pedigree and genotype data, the first high density linkage map was constructed for Pacific oyster, containing 20,353 SNPs mapped to the ten pairs of chromosomes. Genetic parameters for resistance to OsHV were estimated, indicating a significant but low heritability for the binary trait of survival and also for viral load measures (h2 0.12 - 0.25). A genome-wide association study highlighted a region of linkage group 6 containing a significant QTL affecting host resistance. These results are an important step towards identification of genes underlying resistance to OsHV in oyster, and a step towards applying genomic data to enhance selective breeding for disease resistance in oyster aquaculture.
Spinocerebellar ataxia type 2 (SCA2) is a severe and progressive autosomal dominant cerebellar ataxia caused by a dynamic mutation in the ATXN2 gene, consisting of an abnormal expansion of cytosine-adenine-guanine (CAG) triplets in the first codon of the gene, and leading to expression of long polyglutamine (PolyQ) stretches in the ataxin-2 protein (Auburger, 2012; Pulst et al., 1996). This protein seems to have global effects on mRNA metabolism, as well as on endocytosis, calcium signaling and control of metabolism and energy balance.
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Focal Cortical Dysplasia (FCD) is one of the most common etiology of medically intractable seizures in adults (Kabat and Król, 2012). Patients with this type of lesion often have drug-resistant epilepsy and become candidate for a surgical treatment. The area responsible to generate seizure, or the Epileptogenic Zone (EZ), however may be difficult to define, even in patients with identifiable lesions on MRI. Non-congruent semiology, scalp EEG and imaging findings often indicate poor localization of the EZ, and invasive EEG studies may help to define the EZ in patients with FCDs (Chassoux et al., 2000).
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"The Lion was so tickled at the idea of the Mouse being able to help him, that he lifted up his paw and let him go." ~ Aesop
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Studies over the last 20 years have revealed that there are fibrous connective tissues between the suboccipital muscles, nuchal ligament and cervical spinal dura mater(SDM). This fibrous connection with the SDM is through the posterior atlanto-occipital and/or atlanto-axial interspaces and is called the Myodural Bridge(MDB). Researches have inferred that the MDB might have important functions. It was speculated that the function of MDB might be related to proprioception transmission, keeping the subarachnoid space and the cerebellomedullary cistern unobstructed, and affecting the dynamic circulation of the cerebrospinal fluid (CSF).
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Objectives Studies suggest that parents tend to misperceive their child's actual weight status and typically underestimate their child's weight. Since few studies examine the factors that influence parental misperception, this study aims to assess the influence of parent and child factors with parental misperception of their child's actual weight status who were either at their recommended weight or overweight/obese in South Carolina in 2013 and 2014. Methods Secondary data were obtained from the Behavioral Risk Factor Surveillance System (BRFSS) and the Children's Health Assessment Survey (CHAS) in 2013 and 2014 in SC. Parental misperception of child's actual weight status was measured by comparing parental perception to their child's actual weightstatus measured via BMI. Logistic regression was conducted to assess the association between parental and child factors with parental misperception of child's weight status. Results In the adjusted multivariate analysis, only child's age was significantly and positively associated with parental misperception of their child's actual weight status. Conclusions for Practice This cross sectional analysis showed an association between child's age and parental misperception of child's actual weight status. It is essential to educate parents about their children's weight status, especially among young children.
Dextromethorphan 20mg /quinidine 10mg (DM/Q) was approved to treat pseudobulbar affect (PBA) based upon phase 3 trials conducted in participants with amyotrophic lateral sclerosis or multiple sclerosis. PRISM II evaluated DM/Q effectiveness, safety and tolerability for PBA following stroke, dementia or traumatic brain injury (TBI). Objective. To report results from the TBI cohort of PRISM II, including a TBI-specific functional scale. Design. Open-label trial evaluating twice daily DM/Q over 90 days.
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Suspension systems are designed to reduce shock and vibration exposure. An aftermarket rear-wheel suspension system is now available for manual tilt-in-space wheelchairs.
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Publication date: February 2018
Source:Journal of Human Evolution, Volume 115
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Publication date: Available online 21 February 2018
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Nam G. Lee, H. You Joshua Sung, Chung H. Yi, Hye S. Jeon, Bong S. Choi, Dong R. Lee, Jae M. Park, Tae H. Lee, In T. Ryu, Hyun S. Yoon
ObjectivesTo compare the effects of conventional core stabilization (CCS) and dynamic neuromuscular stabilization (DNS) on anticipatory postural adjustment (APA) time, balance performance, and fear of falls in chronic hemiparetic stroke.DesignTwo-group randomized controlled trial with pretest-posttest designSettingHospital's rehabilitation center.ParticipantsTwenty-eight adults with chronic hemiparetic strokeInterventionParticipants were randomly divided into either CCS (n=14) or DNS (n=14) groups. Both groups received a total of 20 sessions of CCS or DNS training for 30 minutes per session 5 times a week during the 4-week period.Main Outcome MeasuresElectromyography was used to measure the APA time for bilateral external oblique (EO), transverse abdominis/internal oblique (TrA/IO), and erector spinae (ES) activation during rapid shoulder flexion. Trunk Impairment Scale (TIS), Berg Balance Scale (BBS), and Falls Efficacy Scale (FES) were used to measure trunk movement control, balance performance, and fear of falling.ResultsBaseline APA times were delayed and fear of falling was moderately high in both the CCS and DNS groups. After the interventions, the APA times for EO, TrA/IO, and ES were shorter in the DNS group than in the CCS group (P<0.008). The BBS and TIS scores (P<0.008) as well as FES score (P<0.003) were improved compared to baseline in both groups, but FES remained stable through the two-year follow-up period only in the DNS group (P<0.003).ConclusionsThis is the first clinical evidence highlighting the importance of core stabilization exercises for improving APA control, balance, and fear of falls in individuals with hemiparetic stroke.
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Circulating microparticles (MPs) are biological vectors of information within the cardiovascular system, eliciting both deleterious and beneficial effects on the vasculature. Acute exercise has been shown to alter MP concentrations, likely through a shear stress-dependent mechanism, however evidence is limited. Therefore, we investigated the effect of exercise intensity on plasma levels of CD34+ and CD62E+ MPs in young, healthy men and women. Blood samples were collected before, during, and after two energy-matched bouts of acute treadmill exercise: interval exercise (10 × 1-minute intervals at ∼95% VO2max) and continuous exercise (65% VO2max). Continuous exercise, but not interval, reduced CD62E+ MP concentrations in men and women by 18% immediately after exercise (from 914.5 ± 589.6 MPs μL−1 to 754.4 ± 390.5 MPs μL−1, P < 0.05), suggesting that mechanisms underlying exercise-induced CD62E+ MP dynamics are intensity dependent. Furthermore, continuous exercise reduced CD62E+ MPs in women by 19% (from 1030.6 ± 688.1 MPs μL−1 to 829.9 ± 435.4 MPs μL−1, P < 0.05), but not men. While interval exercise did not alter CD62E+ MPs per se, the concentrations after interval exercise were higher than that observed after continuous exercise (p < 0.05). Conversely, CD34+ MPs did not fluctuate in response to short-duration acute continuous or interval exercise in men or women. Our results suggest that exercise-induced MP alterations are intensity dependent, sex-specific, and differentially impact MP populations.
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Objectives Training healthcare professionals in emergency maternal healthcare is a critical component of improving overall maternal health in developing countries like Rwanda. This paper explored the challenges that healthcare professionals who participated in a Continuing Professional Development (CPD) program on Advanced Life Support in Obstetrics® (ALSO) face in putting the learned knowledge and skills into practice in hospitals of Rwanda. Methods This study used a mixed methods approach to understand the challenges/barriers to applying new knowledge and skills in the hospitals of Rwanda. We conducted thirteen purposive in-depth interviews with ALSO® trainees (nurses, midwives and physicians) complemented with a cross-sectional survey on staff turnover in eight of the nine hospitals in the Eastern province of Rwanda. Results Our study found that trainees do not get enough opportunity to apply the new knowledge and skills in their hospitals and expand to health centers. In part because they are frequently rotating to different departments of the hospital and are not getting the opportunity to train their colleagues to share the learned knowledge and skills. The lack of refresher trainings/mentorship and the high personnel turnover were also reported as a barrier to applying new knowledge and skills. Reasons for staff turnover included pursuing further studies, a better opportunity (job/remuneration), low morale, and family related motives including joining a spouse or better schools for children. Conclusions for Practice Expanding and formalizing CPD training to all the healthcare professionals involved in providing maternal care services would improve the provision of emergency maternal healthcare in Rwanda.
Objectives Pacific Islanders are disproportionately burdened by poorer perinatal health outcomes with higher rates of pre-term births, low birth weight babies, infant mortality, and inadequate or no prenatal care. The aim of this study is to examine Marshallese mothers' beliefs, perceptions, and experiences of prenatal care and to identify potential barriers. Methods Three focus groups were conducted with Marshallese mothers, who were 18 years or older, and living in Arkansas. Focus groups focused on mothers' beliefs, perceptions, and experiences of prenatal care. A thematic qualitative analysis was conducted to identify salient themes within the data. Results The results demonstrated that negotiating health insurance, transportation, and language barriers were all major structural barriers that constrain prenatal care. The social–cultural barriers that emerged included a lack of understanding of the importance of seeking early and consistent prenatal care, as well as how to navigate the healthcare process. The more complicated challenges that emerged were the feelings of shame and embarrassment due to the perception of their age or being unmarried during pregnancy not being acceptable in American culture. Furthermore, the participants described perceived discrimination from prenatal care providers. Lastly, the participants described fear as a barrier to seeking out prenatal care. Conclusions for Practice This study identified both structural and socio-cultural barriers that can be incorporated into suggestions for policy makers to aid in alleviating maternal health disparities among Pacific Islander women. Further research is needed to address the Marshallese mothers' perceived discrimination from maternal health care providers.
Temple syndrome (TS14, #616222) is a rare imprinting disorder characterised by phenotypic features including pre- and postnatal growth retardation, muscular hypotonia and feeding difficulties in infancy, early puberty and short stature with small hands and feet and often truncal obesity. It is caused by maternal uniparental disomies, paternal deletions and primary imprinting defects that affect the chromosomal region 14q32 and lead to a disturbed expression of imprinted genes in this region.
Here we present detailed clinical data of eight patients with Temple syndrome, four with an imprinting defect, two with an imprinting defect in a mosaic state as well as one complete and one segmental maternal uniparental disomy of chromosome 14.
Temple syndrome is a rare imprinting disorder caused by genetic and epigenetic disturbances of the imprinted region on chromosome 14q32. Detailed clinical description of eight patients with Temple syndrome due to different molecular causes (imprinting defects, mosaic imprint defects, maternal uniparental disomy of chromosome 14) and first description of a segmental maternal uniparental disomy of chromosome14q32 causing Temple syndrome.
