Delirium as a Predictor of Physical and Cognitive Function in Individuals Aged 80 and Older After Transcatheter Aortic Valve Implantation or Surgical Aortic Valve Replacement.
To determine how development of delirium after surgical aortic valve replacement (SAVR) or transcatheter aortic valve implantation (TAVI) could predict activity of daily living (ADL) and instrumental ADLs (IADL) disability, cognitive function, and self-reported health in individuals aged 80 and older. Prospective cohort study. Tertiary university hospital. Individuals aged 80 and older undergoing elective SAVR or TAVI (N = 136). Delirium was assessed for 5 days using the Confusion Assessment Method. The Barthel Index, Nottingham Extended ADL Scale, and SF-12 were used to determine ADL and IADL ability and self-reported health at baseline and 1- and 6-month follow-up. Cognition was assessed using the Mini-Mental State Examination at baseline and 6-month follow-up. Participants had lower IADL scores 1 month after SAVR than at baseline (baseline 58, 1 month: delirium 42, no delirium 50, P ≤ .02), but scores had returned to baseline levels at 6 months. The Medical Outcomes Study 12-item Short-Form Health Survey (SF-12) Physical Component Summary (PCS) score was higher at 6-month follow-up (48) than at baseline (39), especially in participants who did not develop delirium (P < .001). No differences in other outcomes were found. Regression models suggest that delirium may help predict IADL disability 1 month after baseline (P ≤ .07) but does not predict large differences in ADL disability, cognitive function, or SF-12-scores. Individuals who underwent TAVI and developed delirium had lower ADL (baseline 19, 1-month 16, P < .001) and IADL (baseline 49, 1-month 40, P = .003) scores at 1-month follow-up. SF-12 PCS score (baseline 30) increased from baseline to 1- (35, P = .04) and 6- (35, P = .02) month follow-up in individuals who underwent TAVI and did not develop delirium. Delirium after TAVI predicted greater ADL and IADL disability at 1-month but not at 6-month follow-up. Individuals who develop delirium after SAVR and TAVI have poorer short-term IADL function but do not seem to have long-term reductions in physical, mental, or self-reported health.


Management of prostate abscess in the absence of guidelines.
In contemporary practice, the number of patients presenting with prostatic abscess have significantly declined due to the widespread use of antibiotics. However, when faced with the pathology, prostatic abscess tends to pose a challenge to clinicians due to the difficulty of diagnosis and lack of guidelines for treatment. Treatment consists of an array of measures including parenteral broad-spectrum antibiotic administration and abscess drainage.


How quantitative is metabarcoding: A meta-analytical approach.
Metabarcoding has been used in a range of ecological applications such as taxonomic assignment, dietary analysis and the analysis of environmental DNA. However, after a decade of use in these applications there is little consensus on the extent to which proportions of reads generated corresponds to the original proportions of species in a community. To quantify our current understanding, we conducted a structured review and meta-analysis. The analysis suggests that a weak quantitative relationship may exist between the biomass and sequences produced (slope = 0.52 ± 0.34, p < 0.01), albeit with a large degree of uncertainty. None of the tested moderators, sequencing platform type, the number of species used in a trial or the source of DNA, were able to explain the variance. Our current understanding of the factors affecting the quantitative performance of metabarcoding is still limited: additional research is required before metabarcoding can be confidently utilized for quantitative applications. Until then, we advocate the inclusion of mock communities when metabarcoding as this facilitates direct assessment of the quantitative ability of any given study.


Systematic review of quantitative imaging biomarkers for neck and shoulder musculoskeletal disorders.
This study systematically summarizes quantitative imaging biomarker research in non-traumatic neck and shoulder musculoskeletal disorders (MSDs). There were two research questions: 1) Are there quantitative imaging biomarkers associated with the presence of neck and shoulder MSDs?, 2) Are there quantitative imaging biomarkers associated with the severity of neck and shoulder MSDs? PubMed and SCOPUS were used for the literature search. One hundred and twenty-five studies met primary inclusion criteria. Data were extracted from 49 sufficient quality studies. Most of the 125 studies were cross-sectional and utilized convenience samples of patients as both cases and controls. Only half controlled for potential confounders via exclusion or in the analysis. Approximately one-third reported response rates. In sufficient quality articles, 82% demonstrated at least one statistically significant association between the MSD(s) and biomarker(s) studied. The literature synthesis suggested that neck muscle size may be decreased in neck pain, and trapezius myalgia and neck/shoulder pain may be associated with reduced vascularity in the trapezius and reduced trapezius oxygen saturation at rest and in response to upper extremity tasks. Reduced vascularity in the supraspinatus tendon may also be a feature in rotator cuff tears. Five of eight studies showed an association between a quantitative imaging marker and MSD severity. Although research on quantitative imaging biomarkers is still in a nascent stage, some MSD biomarkers were identified. There are limitations in the articles examined, including possible selection bias and inattention to potentially confounding factors. Recommendations for future studies are provided.


Study Protocol: establishing good relationships between patients and health care providers while providing cardiac care. Exploring how patient-clinician engagement contributes to health disparities between indigenous and non-indigenous Australians in South Australia.
Studies that compare Indigenous Australian and non-Indigenous patients who experience a cardiac event or chest pain are inconclusive about the reasons for the differences in-hospital and survival rates. The advances in diagnostic accuracy, medication and specialised workforce has contributed to a lower case fatality and lengthen survival rates however this is not evident in the Indigenous Australian population. A possible driver contributing to this disparity may be the impact of patient-clinician interface during key interactions during the health care process. This study will apply an Indigenous framework to describe the interaction between Indigenous patients and clinicians during the continuum of cardiac health care, i.e. from acute admission, secondary and rehabilitative care. Adopting an Indigenous framework is more aligned with Indigenous realities, knowledge, intellects, histories and experiences. A triple layered designed focus group will be employed to discuss patient-clinician engagement. Focus groups will be arranged by geographic clusters i.e. metropolitan and a regional centre. Patient informants will be identified by Indigenous status (i.e. Indigenous and non-Indigenous) and the focus groups will be convened separately. The health care provider focus groups will be convened on an organisational basis i.e. state health providers and Aboriginal Community Controlled Health Services. Yarning will be used as a research method to facilitate discussion. Yarning is in congruence with the oral traditions that are still a reality in day-to-day Indigenous lives. This study is nestled in a larger research program that explores the drivers to the disparity of care and health outcomes for Indigenous and non-Indigenous Australians who experience an acute cardiac admission. A focus on health status, risk factors and clinical interventions may camouflage critical issues within a patient-clinician exchange. This approach may provide a way forward to reduce the appalling health disadvantage experienced within the Indigenous Australian communities.


Professional Caregivers' Oral Care Practices and Beliefs for Elderly Clients Aging In Place.
As recently as the 1990s long-term care facilities (LTCFs) were the main housing option for semi- or fully-dependent elders. Today, 90% of those 65 and older want to "age in place." The growth of the elderly population that want to "age in place" will require increasing numbers of professional caregivers to assist in oral care practices. The purpose of this study was to address the gap in the knowledge about the oral care practices and beliefs of professional caregivers who work for non-medical in-home care companies charged in the care of "aging in place" elders. The Nursing Dental Coping Belief Scale was used in a descriptive cross-sectional study. Professional caregivers (n=67) employed by 3 non-medical in-home care companies in South Texas completed the survey. The survey gathered demographic information, oral care practice questions and oral health belief questions. Statistics used for data analysis included chi-square contingency table analysis. The level of significance was set at p<0.05 for all analyses. Non-medical in-home care companies are not mandated by law to provide training, yet professional caregivers wanted more training in brushing and flossing (85%). A majority (60%) reported being trained. Most (85%) looked inside their client's mouth yet nearly 18% did not floss their client's teeth and only 31% knew if their clients wore dentures. While this was a small study, it provides preliminary information that professional caregivers, who serve clients aging in place, want more oral care training. Professional caregivers would be better served if there were more thorough and frequent training provided with managerial oversight.


Differential balance of prefrontal synaptic activity in successful versus unsuccessful cognitive aging.
Normal aging is associated with a variable decline in cognitive functions. Among these, executive function, decision-making, and working memory are primarily associated with the prefrontal cortex. Although a number of studies have examined the structural substrates of cognitive decline associated with aging within this cortical area, their functional correlates remain poorly understood. To fill this gap, we aimed to identify functional synaptic substrates of age-associated frontal-dependent deficits in layer 2/3 pyramidal neurons of medial prefrontal cortex of 3-, 9-, and ≥ 23-month-old Fischer 344 rats. We combined, in the same animals, novelty recognition and exploratory behavioral tasks with assessment of structural and functional aspects of prefrontal synaptic properties. We found that subsets of aged animals displayed stereotyped exploratory behavior or memory deficits. Despite an age-dependent dendritic spine loss, patch-clamp recording of synaptic activity revealed an increase in miniature EPSC frequency restricted to aged animals with preserved exploratory behavior. In contrast, we found a strong positive relationship between miniature IPSC frequency and the occurrence of both stereotyped exploratory behavior and novelty-related memory deficits. The enhanced miniature inhibitory tone was accompanied by a deficit in activity-driven inhibition, also suggesting an impaired dynamic range for modulation of inhibition in the aged, cognitively impaired animals. Together, our data indicate that differential changes in the balance of inhibitory to excitatory synaptic tone may underlie distinct trajectories in the evolution of cognitive performance during aging.


A systematic review and economic evaluation of diagnostic strategies for Lynch syndrome.
Lynch syndrome (LS) is an inherited autosomal dominant disorder characterised by an increased risk of colorectal cancer (CRC) and other cancers, and caused by mutations in the deoxyribonucleic acid (DNA) mismatch repair genes. To evaluate the accuracy and cost-effectiveness of strategies to identify LS in newly diagnosed early-onset CRC patients (aged < 50 years). Cascade testing of relatives is employed in all strategies for individuals in whom LS is identified. Systematic reviews were conducted of the test accuracy of microsatellite instability (MSI) testing or immunohistochemistry (IHC) in individuals with CRC at risk of LS, and of economic evidence relating to diagnostic strategies for LS. Reviews were carried out in April 2012 (test accuracy); and in February 2012, repeated in February 2013 (economic evaluations). Databases searched included MEDLINE (1946 to April week 3, 2012), EMBASE (1980 to week 17, 2012) and Web of Science (inception to 30 April 2012), and risk of bias for test accuracy was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) quality appraisal tool. A de novo economic model of diagnostic strategies for LS was developed. Inconsistencies in study designs precluded pooling of diagnostic test accuracy results from a previous systematic review and nine subsequent primary studies. These were of mixed quality, with significant methodological concerns identified for most. IHC and MSI can both play a part in diagnosing LS but neither is gold standard. No UK studies evaluated the cost-effectiveness of diagnosing and managing LS, although studies from other countries generally found some strategies to be cost-effective compared with no testing. The de novo model demonstrated that all strategies were cost-effective compared with no testing at a threshold of £20,000 per quality-adjusted life-year (QALY), with the most cost-effective strategy utilising MSI and BRAF testing [incremental cost-effectiveness ratio (ICER) = £5491 per QALY]. The maximum health benefit to the population of interest would be obtained using universal germline testing, but this would not be a cost-effective use of NHS resources compared with the next best strategy. When the age limit was raised from 50 to 60 and 70 years, the ICERs compared with no testing increased but remained below £20,000 per QALY (except for universal germline testing with an age limit of 70 years). The total net health benefit increased with the age limit as more individuals with LS were identified. Uncertainty was evaluated through univariate sensitivity analyses, which suggested that the parameters substantially affecting cost-effectiveness: were the risk of CRC for individuals with LS; the average number of relatives identified per index patient; the effectiveness of colonoscopy in preventing metachronous CRC; the cost of colonoscopy; the duration of the psychological impact of genetic testing on health-related quality of life (HRQoL); and the impact of prophylactic hysterectomy and bilateral salpingo-oophorectomy on HRQoL (this had the potential to make all testing strategies more expensive and less effective than no testing). The absence of high-quality data for the impact of prophylactic gynaecological surgery and the psychological impact of genetic testing on HRQoL is an acknowledged limitation. Results suggest that reflex testing for LS in newly diagnosed CRC patients aged < 50 years is cost-effective. Such testing may also be cost-effective in newly diagnosed CRC patients aged < 60 or < 70 years. Results are subject to uncertainty due to a number of parameters, for some of which good estimates were not identified. We recommend future research to estimate the cost-effectiveness of testing for LS in individuals with newly diagnosed endometrial or ovarian cancer, and the inclusion of aspirin chemoprevention. Further research is required to accurately estimate the impact of interventions on HRQoL. This study is registered as PROSPERO CRD42012002436. The National Institute for Health Research Health Technology Assessment programme.


Increasing caloric contribution from sugar-sweetened beverages and 100% fruit juices among US children and adolescents, 1988-2004.
We sought to document increases in caloric contributions from sugar-sweetened beverages and 100% fruit juice among US youth during 1988-2004. We analyzed 24-hour dietary recalls from children and adolescents (aged 2-19) in 2 nationally representative population surveys: National Health and Nutrition Examination Survey III (1988-1994, N = 9882) and National Health and Nutrition Examination Survey 1999-2004 (N = 10 962). We estimated trends in caloric contribution, type, and location of sugar-sweetened beverages and 100% fruit juice consumed. Per-capita daily caloric contribution from sugar-sweetened beverages and 100% fruit juice increased from 242 kcal/day (1 kcal = 4.2 kJ) in 1988-1994 to 270 kcal/day in 1999-2004; sugar-sweetened beverage intake increased from 204 to 224 kcal/day and 100% fruit juice increased from 38 to 48 kcal/day. The largest increases occurred among children aged 6 to 11 years ( approximately 20% increase). There was no change in per-capita consumption among white adolescents but significant increases among black and Mexican American youths. On average, respondents aged 2 to 5, 6 to 11, and 12 to 19 years who had sugar-sweetened beverages on the surveyed day in 1999-2004 consumed 176, 229, and 356 kcal/day, respectively. Soda contributed approximately 67% of all sugar-sweetened beverage calories among the adolescents, whereas fruit drinks provided more than half of the sugar-sweetened beverage calories consumed by preschool-aged children. Fruit juice drinkers consumed, on average, 148 (ages 2-5), 136 (ages 6-11), and 184 (ages 12-19) kcal/day. On a typical weekday, 55% to 70% of all sugar-sweetened beverage calories were consumed in the home environment, and 7% to 15% occurred in schools. Children and adolescents today derive 10% to 15% of total calories from sugar-sweetened beverages and 100% fruit juice. Our analysis indicates increasing consumption in all ages. Schools are a limited source for sugar-sweetened beverages, suggesting that initiatives to restrict sugar-sweetened beverage sales in schools may have an only marginal impact on overall consumption. Pediatricians' awareness of these trends is critical for helping children and parents target suboptimal dietary patterns that may contribute to excess calories and obesity.


The effect of listening to music on human transcriptome.
Although brain imaging studies have demonstrated that listening to music alters human brain structure and function, the molecular mechanisms mediating those effects remain unknown. With the advent of genomics and bioinformatics approaches, these effects of music can now be studied in a more detailed fashion. To verify whether listening to classical music has any effect on human transcriptome, we performed genome-wide transcriptional profiling from the peripheral blood of participants after listening to classical music (n = 48), and after a control study without music exposure (n = 15). As musical experience is known to influence the responses to music, we compared the transcriptional responses of musically experienced and inexperienced participants separately with those of the controls. Comparisons were made based on two subphenotypes of musical experience: musical aptitude and music education. In musically experiencd participants, we observed the differential expression of 45 genes (27 up- and 18 down-regulated) and 97 genes (75 up- and 22 down-regulated) respectively based on subphenotype comparisons (rank product non-parametric statistics, pfp 0.05, >1.2-fold change over time across conditions). Gene ontological overrepresentation analysis (hypergeometric test, FDR < 0.05) revealed that the up-regulated genes are primarily known to be involved in the secretion and transport of dopamine, neuron projection, protein sumoylation, long-term potentiation and dephosphorylation. Down-regulated genes are known to be involved in ATP synthase-coupled proton transport, cytolysis, and positive regulation of caspase, peptidase and endopeptidase activities. One of the most up-regulated genes, alpha-synuclein (SNCA), is located in the best linkage region of musical aptitude on chromosome 4q22.1 and is regulated by GATA2, which is known to be associated with musical aptitude. Several genes reported to regulate song perception and production in songbirds displayed altered activities, suggesting a possible evolutionary conservation of sound perception between species. We observed no significant findings in musically inexperienced participants.


Validity of rheumatoid arthritis diagnoses in the Danish National Patient Registry.
Discharge diagnoses following hospital admissions in Denmark are recorded in the Danish National Patient Registry (NPR). Such routine hospitalization records may serve as useful research tools in epidemiological studies. The aim of the study was to provide measures of the validity and completeness of rheumatoid arthritis (RA) diagnoses recorded in the NPR. We identified medical records for 217 patients recorded as having RA in the NPR between 1977 and 2001. Using two definitions of RA (clinically confirmed RA and fulfilment of the American College of Rheumatology (ACR) 1987 diagnostic criteria for RA), a rheumatologist assessed the proportion of RA diagnoses recorded in the NPR that could be confirmed by scrutiny of the original medical records. The completeness of RA diagnoses in the NPR was estimated by a two-sample capture-recapture method. Overall, 59% of the 217 RA diagnoses in the NPR were confirmed by information in the medical records. However, major differences were seen according to characteristics of the underlying hospital registrations. Generally, RA diagnoses were most often confirmed for patients registered as inpatients and for patients with more than one hospital registration with RA. Specifically, only 42% of patients with one RA registration from a rheumatology department were confirmed as having RA. In contrast, 91% of patients treated at a rheumatology department and having three or more hospital registrations with RA were confirmed as having RA. The completeness of the NPR with respect to RA satisfying the ACR 1987 classification criteria was estimated to 26%. Our conclusion is that with careful attention to the limitations in the data, discharge diagnoses for patients with records of RA in the Danish NPR can be used for epidemiological research purposes; however, our findings prompt general carefulness when using non-audited registries for research in RA.


Transcriptomic changes in the plant pathogenic fungus Rhizoctonia solani AG-3 in response to the antagonistic bacteria Serratia proteamaculans and Serratia plymuthica.
Improved understanding of bacterial-fungal interactions in the rhizosphere should assist in the successful application of bacteria as biological control agents against fungal pathogens of plants, providing alternatives to chemicals in sustainable agriculture. Rhizoctonia solani is an important soil-associated fungal pathogen and its chemical treatment is not feasible or economic. The genomes of the plant-associated bacteria Serratia proteamaculans S4 and Serratia plymuthica AS13 have been sequenced, revealing genetic traits that may explain their diverse plant growth promoting activities and antagonistic interactions with R. solani. To understand the functional response of this pathogen to different bacteria and to elucidate whether the molecular mechanisms that the fungus exploits involve general stress or more specific responses, we performed a global transcriptome profiling of R. solani Rhs1AP anastomosis group 3 (AG-3) during interaction with the S4 and AS13 species of Serratia using RNA-seq. Approximately 104,504 million clean 75-100 bp paired-end reads were obtained from three libraries, each in triplicate (AG3-Control, AG3-S4 and AG3-AS13). Transcriptome analysis revealed that approximately 10% of the fungal transcriptome was differentially expressed during challenge with Serratia. The numbers of S4- and AS13-specific differentially expressed genes (DEG) were 866 and 292 respectively, while there were 1035 common DEGs in the two treatment groups. Four hundred and sixty and 242 genes respectively had values of log2 fold-change > 3 and for further analyses this cut-off value was used. Functional classification of DEGs based on Gene Ontology enrichment analysis and on KEGG pathway annotations revealed a general shift in fungal gene expression in which genes related to xenobiotic degradation, toxin and antioxidant production, energy, carbohydrate and lipid metabolism and hyphal rearrangements were subjected to transcriptional regulation. This RNA-seq profiling generated a novel dataset describing the functional response of the phytopathogen R. solani AG3 to the plant-associated Serratia bacteria S4 and AS13. Most genes were regulated in the same way in the presence of both bacterial isolates, but there were also some strain-specific responses. The findings in this study will be beneficial for further research on biological control and in depth exploration of bacterial-fungal interactions in the rhizosphere.


Enhanced diabetic wound healing by electrospun core-sheath fibers loaded with dimethyloxalylglycine.
The destabilization and dysfunction of hypoxia-inducible factor 1 α (HIF-1α) caused by hyperglycemia are important reasons for delayed healing of diabetic chronic wounds. Hence, it is worth designing HIF-1α-stabilizing wound dressings to counteract the effects of a hyperglycemic microenvironment. Dimethyloxalylglycine (DMOG), a competitive inhibitor of prolyl hydroxylases (PHDs), can stabilize HIF-1α by inhibiting its degradation. Therefore, in this study, we developed DMOG releasing nanofibrous wound dressings for diabetic wound healing. We systematically evaluated the regulation of DMOG-releasing nanofibers on human foreskin fibroblasts (HFFs) with in vitro biological assessments. The results showed that the release of DMOG from nanofibers can be effectively controlled by the co-axial structure of nanofibers. The sustained release of DMOG in co-axial nanofibers enhanced the migration and expression of wound healing-related genes in HFFs. In addition, we conducted an in vivo study using a diabetic wound model in rat to examine the effects of DMOG-loaded nanofibrous wound dressings on the wound healing process. The in vivo study confirmed that the DMOG incorporated in nanofibers stabilized local HIF-1α levels in wounds and subsequently improved the diabetic wound regeneration by accelerating re-epithelialization, angiogenesis and wound closure, which was consistent with the in vitro evaluation. The results suggest that DMOG-releasing nanofibers may be promising functional wound dressings for diabetic wounds.


Surgical management and outcome of schwannomas in the craniocervical region.
Schwannomas occupying the craniocervical junction (CCJ) are rare and usually originate from the jugular foramen, hypoglossal nerves, and C-1 and C-2 nerves. Although they may have different origins, they may share the same symptoms, surgical approaches, and complications. An extension of these lesions along the posterior fossa cisterns, foramina, and spinal canal--usually involving various cranial nerves (CNs) and the vertebral and cerebellar arteries--poses a surgical challenge. The primary goals of both surgical and radiosurgical management of schwannomas in the CCJ are the preservation and restoration of function of the lower CNs, and of hearing and facial nerve function. The origins of schwannomas in the CCJ and their clinical presentation, surgical management, adjuvant stereotactic radiosurgery, and outcomes in 36 patients treated at Barrow Neurological Institute (BNI) are presented. Between 1989 and 2009, 36 patients (mean age 43.6 years, range 17-68 years) with craniocervical schwannomas underwent surgical resection at BNI. The records were reviewed retrospectively regarding clinical presentation, radiographic assessment, surgical approaches, adjuvant therapies, and follow-up outcomes. Headache or neck pain was present in 72.2% of patients. Cranial nerve impairments, mainly involving the vagus nerve, were present in 14 patients (38.9%). Motor deficits were found in 27.8% of the patients. Sixteen tumors were intra- and extradural, 15 were intradural, and 5 were extradural. Gross-total resection was achieved in 25 patients (69.4%). Adjunctive radiosurgery was used in the management of residual tumor in 8 patients; tumor control was ultimately obtained in all cases. Surgical removal, which is the treatment of choice, is curative when schwannomas in the CCJ are excised completely. The far-lateral approach and its variations are our preferred approaches for managing these lesions. Most common complications involve deficits of the lower CNs, and their early recognition and rehabilitation are needed. Stereotactic radiosurgery, an important tool for the management of these tumors as adjuvant therapy, can help decrease morbidity rates.


BTG3 tumor suppressor gene promoter demethylation, histone modification and cell cycle arrest by genistein in renal cancer.
BTG3/ANA/APRO4 has been reported to be a tumor suppressor gene in some malignancies. It constitutes important negative regulatory mechanism for Src-mediated signaling, a negative regulator of the cell cycle and inhibits transcription factor E2F1. We report that BTG3 is downregulated in renal cancer and that the mechanism of inactivation is through promoter hypermethylation. Quantitative real-time polymerase chain reaction (PCR) showed that BTG3 was downregulated in cancer tissues and cells. Genistein and 5-aza-2'-deoxycytidine (5Aza-C) induced BTG3 messenger RNA (mRNA) expression in A498, ACHN and HEK-293 renal cell carcinoma (RCC) cell lines. Bisulfite-modified PCR and DNA sequencing results showed complete methylation of BTG3 promoter in tumor samples and cancer cell lines. Genistein and 5Aza-C treatment significantly decreased promoter methylation, reactivating BTG3 expression. Chromatin immunoprecipitation assay revealed that genistein and 5Aza-C increased levels of acetylated histones 3, 4, 2H3K4, 3H3K4 and RNA polymerase II at the BTG3 promoter indicative of active histone modifications. Enzymatic assays showed genistein and 5Aza-C decreased DNA Methyltransferase, methyl-CpG-binding domain 2 activity and increased HAT activity. Cell cycle and 3-(4,5-dimethylthiazole-2-yl)-2,5-biphenyl tetrazolium bromide cell proliferation assays showed that genistein has antiproliferative effect on cancer cell growth through induction of cell cycle arrest. This is the first report to show that BTG3 is epigenetically silenced in RCC and can be reactivated by genistein-induced promoter demethylation and active histone modification. Genistein had similar effects to that of 5Aza-C, which is a potent demethylating agent with high toxicity and instability. Genistein being a natural, non-toxic, dietary isoflavone is effective in retarding the growth of RCC cells, making it a promising candidate for epigenetic therapy in renal carcinoma.


Retinal Development and Ommin Pigment in the Cranchiid Squid Teuthowenia pellucida (Cephalopoda: Oegopsida).
The cranchiid Teuthowenia pellucida, like many deep-sea squid species, possesses large eyes that maximise light sensitivity in a nearly aphotic environment. To assess ontogenetic changes in the visual system, we conducted morphometric and histological analyses of the eyes using specimens from New Zealand collections. While the ratio between eye diameter and mantle length maintained a linear relationship throughout development, histological sections of the retina revealed that the outer photoreceptor layer became proportionally longer as the animal aged, coincident with a habitat shift into deeper, darker ocean strata. Other retinal layers maintained the same absolute thickness as was observed in paralarvae. Granules of the pigment ommin, normally located in the screening layer positioned at the base of the photoreceptors, were also observed at the outer end of the photoreceptor segments throughout the retina in young and mid-sized specimens. Early developmental stages of this species, dwelling in shallow waters, may therefore rely on migratory ommin to help shield photoreceptors from excess light and prevent over-stimulation. The oldest, deeper-dwelling specimens of T. pellucida examined had longer photoreceptors, and little or no migrated ommin was observed; we suggest therefore that short-term adaptive mechanisms for bright light conditions may be used primarily during epipelagic, early life stages in this species.


Characterization of the Widely Distributed Novel ECF42 Group of Extracytoplasmic Function σ Factors in Streptomyces venezuelae.
Extracytoplasmic function σ factors (ECFs) represent the third most abundant fundamental principle of bacterial signal transduction, outranked only by one- and two-component systems. A recent census of ECFs revealed a large number of novel groups whose functions and regulatory mechanisms have not yet been elucidated. Here, we report the characterization of members of the novel group ECF42. ECF42 is a highly abundant and widely distributed ECF group that is present in 11 phyla but is predominantly found in Actinobacteria Analysis of the genomic context conservation did not identify a putative anti-σ factor. Instead, ECF42 genes are cotranscribed with genes encoding a conserved DGPF protein. We have experimentally verified the target promoter of these ECFs (TGTCGA in the -35 region and CGA/TC in the -10 region), which was found upstream of the ECF42-encoding operons in Streptomyces venezuelae, suggesting that ECF42s are positively autoregulated. RNA sequencing (RNA-seq) was performed to define the regulons of the three ECF42 proteins in S. venezuelae, which identified mostly genes encoding DGPF proteins. In contrast to typical ECFs, ECF42 proteins harbor a long C-terminal extension, which is crucial for their activity. Our work provides the first analysis of the function and regulatory mechanism of this novel ECF group that contains a regulatory C-terminal extension.IMPORTANCE In contrast to the one- and two-component signal transduction systems in bacteria, the importance and diversity of ECFs have only recently been recognized in the course of comprehensive phylogenetic and comparative genomics studies. Thus, most of the ECFs still have not been experimentally characterized regarding their physiological functions and regulation mechanisms so far. The physiological roles, target promoter, and target regulons of a novel group of ECFs, ECF42, in S. venezuelae have been investigated in this work. More importantly, members of this group are characterized by a C-terminal extension, which has been verified to harbor a regulatory role in ECF42s. Hence, our work provides an important source for further research on such C-terminal extension containing ECFs.


Supporting anticoagulant treatment decision making to optimise stroke prevention in complex patients with atrial fibrillation: a cluster randomised trial.
Anticoagulation for preventing stroke in atrial fibrillation is under-utilised despite evidence supporting its use, resulting in avoidable death and disability. We aimed to evaluate an intervention to improve the uptake of anticoagulation. We carried out a national, cluster randomised controlled trial in the Australian primary health care setting. General practitioners received an educational session, delivered via telephone by a medical peer and provided information about their patients selected either because they were not receiving anticoagulation or for whom anticoagulation was considered challenging. General practitioners were randomised to receive feedback from a medical specialist about the cases (expert decisional support) either before or after completing a post-test audit. The primary outcome was the proportion of patients reported as receiving oral anticoagulation. A secondary outcome assessed antithrombotic treatment as appropriate against guideline recommendations. One hundred and seventy-nine general practitioners participated in the trial, contributing information about 590 cases. At post-test, 152 general practitioners (84.9%) completed data collection on 497 cases (84.2%). A 4.6% (Adjusted Relative Risk = 1.11, 95% CI = 0.86-1.43) difference in the post-test utilization of anticoagulation between groups was not statistically significant (p = 0.42). Sixty-one percent of patients in both groups received appropriate antithrombotic management according to evidence-based guidelines at post-test (Adjusted Relative Risk = 1.0; 95% CI = 0.85 to 1.19) (p = 0.97). Specialist feed-back in addition to an educational session did not increase the uptake of anticoagulation in patients with AF. ANZCTRN12611000076976 Retrospectively registered.


Simultaneous analysis of the bidirectional African cassava mosaic virus promoter activity using two different luciferase genes.
The expression of geminivirus genes is controlled by bidirectional promoters which are located in the large intergenic region of the circular DNA genomes and specifically regulated by virus encoded proteins. In order to study the simultaneous regulation of both orientations of the DNA A and DNA B promoters of African cassava mosaic virus (ACMV), they were cloned between two different luciferase genes with the firefly luciferase gene in complementary-sense and the Renilla luciferase gene in virion-sense orientation. The regulation of the ACMV promoters by proteins encoded by the complete DNA A, as well as by the individually expressed transactivator (TrAP) or replication-associated (Rep) proteins was assessed in tobacco and cassava protoplasts using dual luciferase assays. In addition, the regulation of the DNA A promoter integrated into tobacco genome was also assessed. The results show that TrAP activates virion-sense expression strongly both in cassava and tobacco protoplasts, but not in transgenic tobacco plants. In contrast to this, DNA A encoded proteins activate virion-sense expression both in protoplasts and in transgenic plants. At the same time they reduce the expression of the complementary-sense Rep gene on DNA A but activate the expression of the complementary-sense movement protein (MPB) gene on DNA B. The degree of MBP activation is higher in cassava than in tobacco protoplasts, indicating that the plant host also influences the promoter strength. Transient transformation experiments using linearized DNA indicate that the different regulation of the ACMV DNA A promoter in protoplasts and transgenic plants could be due to different DNA curvature in free plasmids and in genes integrated in plant genomic DNA.


Ultrastructural abnormalities in CA1 hippocampus caused by deletion of the actin regulator WAVE-1.
By conveying signals from the small GTPase family of proteins to the Arp2/3 complex, proteins of the WAVE family facilitate actin remodeling. The WAVE-1 isoform is expressed at high levels in brain, where it plays a role in normal synaptic processing, and is implicated in hippocampus-dependent memory retention. We used electron microscopy to determine whether synaptic structure is modified in the hippocampus of WAVE-1 knockout mice, focusing on the neuropil of CA1 stratum radiatum. Mice lacking WAVE-1 exhibited alterations in the morphology of both axon terminals and dendritic spines; the relationship between the synaptic partners was also modified. The abnormal synaptic morphology we observed suggests that signaling through WAVE-1 plays a critical role in establishing normal synaptic architecture in the rodent hippocampus.


Herpes simplex virus type 1 deletion variants 1714 and 1716 pinpoint neurovirulence-related sequences in Glasgow strain 17+ between immediate early gene 1 and the 'a' sequence.
Dideoxynucleotide sequence analysis of a spontaneously isolated deletion variant (1714) of Glasgow strain 17+ of herpes simplex virus type 1 (HSV-1) demonstrates that the deletion is 759 bp in length and is located within each copy of the BamHI s fragment (0 to 0.02 and 0.81 to 0.83 map units) of the long repeat region of the genome. The deletion removes one complete copy of the 18 bp DR1 element of the 'a' sequence and terminates 1105 bp upstream of the 5' end of immediate early (IE) gene 1. The variant grows to high titre, is not temperature-sensitive and is not host cell type-restricted in vitro. In vivo studies demonstrate that 1714 is totally avirulent for BALB/c mice following intracerebral inoculation, with an LD50 of 7 x 10(6) p.f.u./mouse compared to less than 10 p.f.u./mouse for the parental wild-type strain 17+. In vivo growth kinetics show that the non-neurovirulent phenotype is due to an inability to replicate in mouse brain. Because 1714 was in a genomic background in which the four XbaI sites had been removed and because the phenotype was thymidine kinase-negative, the 759 bp deletion was introduced into an otherwise totally wild-type background. The resulting variant (1716) is non-neurovirulent for mice, with an LD50 of 7 x 10(6) p.f.u./mouse. The deletion does not prevent the virus from establishing a latent infection or reactivating from it in vitro. The results demonstrate that sequences between IE-1 and the 'a' sequence produce neurovirulence in Glasgow strain 17+ and, in conjunction with the non-neurovirulence of the HSV-2 HG52 variant JH2604, identify a common function conserved in HSV-1 and -2.


Cutaneous Protothecosis as an Unusual Complication Following Dermal Filler Injection: A Case Report.
A 77-year-old female patient presented with bilateral tender, swollen, erythematous, focally crusted cheeks with a discharge of pus and necrotic material, which had developed one month after autologous fat transfer and a corrective injection procedure conducted to correct an overdone fat transfer. Histopathological examination of the discharged material using routine hematoxylin and eosin staining revealed degenerated collagen admixed with three different filler materials. Scattered all throughout the specimen were numerous thick-walled, basophilic, nonbudding spherical bodies of variable sizes. The bodies stained positively with Periodic acid-Schiff and Alcian blue and showed internal septation and sporangia with a morula-like appearance. The morphology of these bodies was characteristic of a Prototheca infection. The patient was treated by surgical drainage accompanied by itraconazole 200mg daily for six months, ultimately showing marked improvement.


Hierarchical assembly of plasmonic nanostructures using virus capsid scaffolds on DNA origami templates.
Building plasmonic nanostructures using biomolecules as scaffolds has shown great potential for attaining tunable light absorption and emission via precise spatial organization of optical species and antennae. Here we report bottom-up assembly of hierarchical plasmonic nanostructures using DNA origami templates and MS2 virus capsids. These serve as programmable scaffolds that provide molecular level control over the distribution of fluorophores and nanometer-scale control over their distance from a gold nanoparticle antenna. While previous research using DNA origami to assemble plasmonic nanostructures focused on determining the distance-dependent response of single fluorophores, here we address the challenge of constructing hybrid nanostructures that present an organized ensemble of fluorophores and then investigate the plasmonic response. By combining finite-difference time-domain numerical simulations with atomic force microscopy and correlated scanning confocal fluorescence microscopy, we find that the use of the scaffold keeps the majority of the fluorophores out of the quenching zone, leading to increased fluorescence intensity and mild levels of enhancement. The results show that the degree of enhancement can be controlled by exploiting capsid scaffolds of different sizes and tuning capsid-AuNP distances. These bioinspired plasmonic nanostructures provide a flexible design for manipulating photonic excitation and photoemission.


Firsthand in situ observation of active fine laser tuning by combining a temperature gradient and a CLC wedge cell structure.
In situ direct observation of the lasing process in a cholesteric liquid crystal (CLC) laser array using a CMOS camera was used to investigate discontinuous laser tuning in a parallel CLC cell. In accordance with the discontinuous pitch change by thermal energy transfer, at the same time the laser wavelength undergoes an immediate and discontinuous shift. And we found out the reason why the CLC phase has domain textures. And this work develops a simple active tunable laser array by forming a spatial temperature gradient along a wedge CLC cell. With this new strategy, only just about 7 nm laser tuning range at room temperature is extremely widened over the 105 nm wavelength range with about 0.2 nm tuning resolution. Furthermore, there is no aging effect because the employed CLC array has only one chiral molecular concentration. This strategy could be used in a practical CLC laser device application.


Enumeration of Bacteroides species in human faeces by fluorescent in situ hybridisation combined with flow cytometry using 16S rRNA probes.
Bacteroides is a predominant group of the faecal microbiota in healthy adults. To investigate the species composition of Bacteroides by fluorescent in situ hybridisation (FISH) combined with flow cytometry, we developed five species-specific probes targeting the 16S rRNA. Probes were designed to identify cells belonging to Bacteroides distasonis, B. fragilis, B. ovatus, B. vulgatus and B. putredinis. The species-specificity of the probes was assessed against a collection of reference strains from the Cytophaga-Flavobacterium-Bacteroides group. The results of the FISH experiments showed that the probes were specific as they only detected strains of the target species. Determining the fluorescence intensity of each probe relative to that of the EUB 338 probe (domain bacteria) further showed that each species probe easily accessed the targeted site. The probes were applied to quantify the Bacteroides species in faeces collected from 20 healthy adults. All five species were detected in the faecal samples. Cells hybridised with Bfra 998 were the most frequent as they were observed in 90% of individuals (18/20 samples, mean proportion of 3.9 +/- 2.2%). The cells hybridised with Bvulg 1017 were observed in 85% of individuals (17/20 samples) and represented with a mean proportion of 4.2 +/- 6.1%, the most abundant Bacteroides species in human faeces. Cells hybridising with probes for B. ovatus, B. distasonis and B. putredinis were less frequently detected. The large distribution of B. vulgatus and B. fragilis in human faeces is in accordance with previous reports based on culture or molecular studies. This work showed that fluorescent in situ hybridisation is a tool appropriate for a high-resolution analysis of the species composition of complex ecosystems and especially of the Bacteroides group within the faecal microbiota.


A new archosauriform (Reptilia: Diapsida) from the Manda beds (Middle Triassic) of southwestern Tanzania.
Archosauria and their closest relatives, the non-archosaurian archosauriforms, diversified in the Early and Middle Triassic, soon after the end-Permian extinction. This diversification is poorly documented in most Lower and Middle Triassic rock sequences because fossils of early groups of archosauriforms are relatively rare compared to those of other amniotes. The early Middle Triassic (? late Anisian) Manda beds of southwestern Tanzania form an exception, with early archosaur skeletons being relatively common and preserved as articulated or associated specimens. The Manda archosaur assemblage is exceptionally diverse for the Middle Triassic. However, to date, no non-archosaurian archosauriforms have been reported from these rocks. Here, we name a new taxon, Asperoris mnyama gen. et sp. nov., from the Manda beds and thoroughly describe the only known specimen. The specimen consists of a well-preserved partial skull including tooth-bearing elements (premaxilla, maxilla), the nasal, partial skull roof, and several incomplete elements. All skull elements are covered in an autapomorphic highly rugose sculpturing. A unique combination of character states indicates that A. mnyama lies just outside Archosauria as a stem archosaur within Archosauriformes, but more precise relationships of A. mnyama relative to other early archosauriform clades (e.g., Erythrosuchidae) cannot be determined currently. Asperoris mnyama is the first confirmed non-archosaurian archosauriform from the Manda beds and increases the morphological and taxonomic diversity of early archosauriforms known from the Middle Triassic. The direct association of A. mnyama with species referable to Archosauria demonstrates that non-archosaurian archosauriforms were present during the rise and early diversification of Archosauria. Non-archosaurian archosauriforms and archosaurs co-occur in fossil reptile assemblages across Pangaea from the late Early Triassic to the end of the Late Triassic.


Use of Fertility Awareness-Based Methods for Pregnancy Prevention Among Ghanaian Women: A Nationally Representative Cross-Sectional Survey.
Few studies in low- and middle-income countries have examined the use of fertility awareness-based methods (FABMs) for pregnancy prevention. Understanding the prevalence of FABM use among Ghanaian contraceptors and the characteristics and practices of users is essential. Our 2018 nationally representative survey of Ghanaian women included detailed questions on the use of rhythm and Standard Days Method/Cycle Beads (SDM). After considering multimethod use patterns, we estimated likely FABM prevalence among contraceptors, identified characteristics associated with current use of an FABM (vs. current use of a hormonal method/intrauterine device [IUD]), and described how women report using FABMs. At least 18% of contracepting Ghanaian women likely use an FABM, though this may be underreported. Among FABM users, 57% reported current use of an FABM alone; the remainder reported concurrent use of other methods. Women who were older, richer, more educated, and had fewer children had higher odds of current FABM use versus IUD/hormonal method. Although FABM users were more likely than other contraceptors to correctly identify the approximate fertile time, only 50% of FABM users did so correctly. Most (92%) rhythm users were interested in making their method use more effective. While 72% had heard of SDM, less than 25% had heard of various other ways to make the rhythm method more effective. Only 17% of rhythm users had ever discussed the method with a health professional. Rhythm users indicated substantial willingness to track additional biomarkers (e.g., daily temperature or cervical mucus) or to use a phone to enhance the effectiveness of their method, and most indicated no substantial difficulty getting partners to abstain or withdraw on fertile days. A nontrivial proportion of reproductive age Ghanaian women are using an FABM, nearly all of whom are interested in learning how to improve its effectiveness. The family planning field should better address these women's contraceptive needs in commitment to reproductive autonomy and choice.


Binocular Therapy for Childhood Amblyopia Improves Vision Without Breaking Interocular Suppression.
Amblyopia is a common developmental visual impairment characterized by a substantial difference in acuity between the two eyes. Current monocular treatments, which promote use of the affected eye by occluding or blurring the fellow eye, improve acuity, but are hindered by poor compliance. Recently developed binocular treatments can produce rapid gains in visual function, thought to be as a result of reduced interocular suppression. We set out to develop an effective home-based binocular treatment system for amblyopia that would engage high levels of compliance but that would also allow us to assess the role of suppression in children's response to binocular treatment. Balanced binocular viewing therapy (BBV) involves daily viewing of dichoptic movies (with "visibility" matched across the two eyes) and gameplay (to monitor compliance and suppression). Twenty-two children (3-11 years) with anisometropic (n = 7; group 1) and strabismic or combined mechanism amblyopia (group 2; n = 6 and 9, respectively) completed the study. Groups 1 and 2 were treated for a maximum of 8 or 24 weeks, respectively. The treatment elicited high levels of compliance (on average, 89.4% ± 24.2% of daily dose in 68.23% ± 12.2% of days on treatment) and led to a mean improvement in acuity of 0.27 logMAR (SD 0.22) for the amblyopic eye. Importantly, acuity gains were not correlated with a reduction in suppression. BBV is a binocular treatment for amblyopia that can be self-administered at home (with remote monitoring), producing rapid and substantial benefits that cannot be solely mediated by a reduction in interocular suppression.


Neuropathy target esterase and a homologous Drosophila neurodegeneration-associated mutant protein contain a novel domain conserved from bacteria to man.
The N-terminal amino acid sequences of proteolytic fragments of neuropathy target esterase (NTE), covalently labelled on its active-site serine by a biotinylated organophosphorus ester, were determined and used to deduce the location of this serine residue and to initiate cloning of its cDNA. A putative NTE clone, isolated from a human foetal brain cDNA library, encoded a 1327 residue polypeptide with no homology to any known serine esterases or proteases. The active-site serine of NTE (Ser-966) lay in the centre of a predicted hydrophobic helix within a 200-amino-acid C-terminal domain with marked similarity to conceptual proteins in bacteria, yeast and nematodes; these proteins may comprise a novel family of potential serine hydrolases. The Swiss Cheese protein which, when mutated, leads to widespread cell death in Drosophila brain [Kretzschmar, Hasan, Sharma, Heisenberg and Benzer (1997) J. Neurosci. 17, 7425-7432], was strikingly homologous to NTE, suggesting that genetically altered NTE may be involved in human neurodegenerative disease.


Scalable Database Indexing and Fast Image Retrieval Based on Deep Learning and Hierarchically Nested Structure Applied to Remote Sensing and Plant Biology.
Digitalisation has opened a wealth of new data opportunities by revolutionizing how images are captured. Although the cost of data generation is no longer a major concern, the data management and processing have become a bottleneck. Any successful visual trait system requires automated data structuring and a data retrieval model to manage, search, and retrieve unstructured and complex image data. This paper investigates a highly scalable and computationally efficient image retrieval system for real-time content-based searching through large-scale image repositories in the domain of remote sensing and plant biology. Images are processed independently without considering any relevant context between sub-sets of images. We utilize a deep Convolutional Neural Network (CNN) model as a feature extractor to derive deep feature representations from the imaging data. In addition, we propose an effective scheme to optimize data structure that can facilitate faster querying at search time based on the hierarchically nested structure and recursive similarity measurements. A thorough series of tests were carried out for plant identification and high-resolution remote sensing data to evaluate the accuracy and the computational efficiency of the proposed approach against other content-based image retrieval (CBIR) techniques, such as the bag of visual words (BOVW) and multiple feature fusion techniques. The results demonstrate that the proposed scheme is effective and considerably faster than conventional indexing structures.


CAFM Educational Research Alliance (CERA) 2011 Residency Director survey: background, methods, and respondent characteristics.
Due to the scarcity of funds for educational research it is difficult for many clinician educators to conduct meaningful educational research. The Council of Academic Family Medicine Educational Research Alliance (CERA) was created to provide an infrastructure to facilitate educational research in family medicine. CERA's first major initiative was an omnibus survey of family medicine residency directors. This survey incorporated several distinct subprojects focusing on different topic areas. Members of the Association of Family Medicine Residency Directors (AFMRD) were surveyed electronically in 2011 using the infrastructure of the Society of Teachers of Family Medicine. The response rate for the survey was 38% (172/452). The majority of the programs were community based, university affiliated, and well established, with a mean of 31.2 years of providing residency training. Program directors were predominantly male (72%) and had a mean duration of 6.8 years in that role. This 2011 Family Medicine Residency Director survey is the first step in building the CERA infrastructure. Several more CERA surveys of other distinct populations have already been put into the field. CERA represents an important conduit for academic family physicians to produce high-quality educational research. The creation of CERA is a key step toward making educational research in family medicine more achievable, more rigorous, and more generalizable.


Erythropoietin as a novel brain and kidney protective agent.
Erythropoietin is a 30.4 kDa glycoprotein produced by the kidney, which is mostly known for its physiological function in regulating red blood cell production in the bone marrow Accumulating evidence, however suggests that erythropoietin has additional organ protective effects, which may specifically be useful in protecting the brain and kidneys from injury. Experimental evidence suggests that these protective mechanisms are multi-factorial in nature and may include inhibition of apoptotic cell death, stimulation of cellular regeneration, inhibition of deleterious pathways and promotion of recovery. In this article we review the physiology of erythropoietin, assess previous work that supports the role of erythropoietin as a general tissue protective agent and explain the mechanisms by which it may achieve this tissue protective effect. We then focus on specific laboratory and clinical data that suggest that erythropoietin has a strong brain protective and kidney protective effect. In addition, we comment on the implications of these studies for clinicians at the bedside and for researchers designing controlled trials to further elucidate the true clinical utility of erythropoietin as a neuroprotective and nephroprotective agent. Finally, we describe EPO-TBI, a double-blinded multi-centre randomised controlled trial involving the authors that is being conducted to investigate the organ protective effects of erythropoietin on the brain, and also assesses its effect on the kidneys.


Phased diploid genome assembly with single-molecule real-time sequencing.
While genome assembly projects have been successful in many haploid and inbred species, the assembly of noninbred or rearranged heterozygous genomes remains a major challenge. To address this challenge, we introduce the open-source FALCON and FALCON-Unzip algorithms (https://github.com/PacificBiosciences/FALCON/) to assemble long-read sequencing data into highly accurate, contiguous, and correctly phased diploid genomes. We generate new reference sequences for heterozygous samples including an F1 hybrid of Arabidopsis thaliana, the widely cultivated Vitis vinifera cv. Cabernet Sauvignon, and the coral fungus Clavicorona pyxidata, samples that have challenged short-read assembly approaches. The FALCON-based assemblies are substantially more contiguous and complete than alternate short- or long-read approaches. The phased diploid assembly enabled the study of haplotype structure and heterozygosities between homologous chromosomes, including the identification of widespread heterozygous structural variation within coding sequences.


EMS Provider assessment of vehicle damage compared with assessment by a professional crash reconstructionist.
To determine the accuracy of emergency medical services (EMS) provider assessments of motor vehicle damage when compared with measurements made by a professional crash reconstructionist. EMS providers caring for adult patients injured during a motor vehicle crash and transported to the regional trauma center in a midsized community were interviewed upon emergency department arrival. The interview collected provider estimates of crash mechanism of injury. For crashes that met a preset severity threshold, the vehicle's owner was asked to consent to having a crash reconstructionist assess the vehicle. The assessment included measuring intrusion and external automobile deformity. Vehicle damage was used to calculate change in velocity. Paired t-test, correlation, and kappa were used to compare EMS estimates and investigator-derived values. Ninety-one vehicles were enrolled; of these, 58 were inspected and 33 were excluded because the vehicle was not accessible. Six vehicles had multiple patients. Therefore, a total of 68 EMS estimates were compared with the inspection findings. Patients were 46% male, 28% were admitted to hospital, and 1% died. The mean EMS-estimated deformity was 18 inches and the mean measured deformity was 14 inches. The mean EMS-estimated intrusion was 5 inches and the mean measured intrusion was 4 inches. The EMS providers and the reconstructionist had 68% agreement for determination of external automobile deformity (kappa 0.26) and 88% agreement for determination of intrusion (kappa 0.27) when the 1999 American College of Surgeons Field Triage Decision Scheme criteria were applied. The mean (± standard deviation) EMS-estimated speed prior to the crash was 48 ± 13 mph and the mean reconstructionist-estimated change in velocity was 18 ± 12 mph (correlation -0.45). The EMS providers determined that 19 vehicles had rolled over, whereas the investigator identified 18 (kappa 0.96). In 55 cases, EMS and the investigator agreed on seat belt use; for the remaining 13 cases, there was disagreement (five) or the investigator was unable to make a determination (eight) (kappa 0.40). This study found that EMS providers are good at estimating rollover. Vehicle intrusion, deformity, and seat belt use appear to be more difficult for EMS to estimate, with only fair agreement with the crash reconstructionist. As expected, the EMS provider -estimated speed prior to the crash does not appear to be a reasonable proxy for change in velocity.


Open-path atmospheric transmission for a diode-pumped cesium laser.
A tunable diode laser absorption spectroscopy device was developed to study atmospheric propagation for emerging high-energy laser weapons. The cesium diode-pumped alkali laser operates near 895 nm in the vicinity of several water-vapor absorption lines. Temperature, pressure, and water vapor concentration were determined for 150 m and 1 km open paths with statistical errors of ∼0.2%. Comparison with meteorological instruments yields agreement for the 1 km path to within 0.6% for temperature, 3.7% for pressure, and 2.4% for concentration.


Inequalities in mortality by social class in men in Barcelona, Spain.
Most of the studies of inequalities in mortality carried out in Spain have been ecological, due to the difficulty of obtaining good quality socioeconomic information at individual level. The objective of this study was to describe inequalities in mortality by social class, based on occupation, among men residents of Barcelona in 1993. A representative sample was obtained of men residents of Barcelona who died during the year 1993, aged between 15 and 65 years. It was a retrospective interview given to relatives of the deceased, or other closely related persons. The variables analysed were: age, education level, underlying cause of death, and social class based on occupation (manual and non-manual workers). Rates, relative risks (RRs) and their 95% confidence intervals (95% CIs) are presented by age groups and cause of death. The main results show that among young people, the excess of mortality due to infectious diseases is notable (RR: 1.9; 95% CI: 1.6-2.2), and also due to external causes (RR: 2.1; 95% CI: 1.8-2.4) among manual workers with respect to non-manual workers, mainly due to AIDS and drug overdose. No significant differences were found in mortality due to tumours. For respiratory and cardiovascular causes, there is an increase in mortality in the less favoured social classes, as also occurs for mortality due to diseases of the digestive system, particularly among young manual workers, with an RR: 2.6 (95% CI: 1.5-3.6) compared to non-manual workers. This study shows that it is necessary to continue exploring inequalities in health, but above all it is necessary to implement efficient preventive measures addressed mainly at young people in situations of disadvantage, in order to avoid the excess of avoidable mortality which is found.


Housing, Transportation, And Food: How ACOs Seek To Improve Population Health By Addressing Nonmedical Needs Of Patients.
Addressing nonmedical needs-such as the need for housing-is critical to advancing population health, improving the quality of care, and lowering the costs of care. Accountable care organizations (ACOs) are well positioned to address these needs. We used qualitative interviews with ACO leaders and site visits to examine how these organizations addressed the nonmedical needs of their patients, and the extent to which they did so. We developed a typology of medical and social services integration among ACOs that disentangles service and organizational integration. We found that the nonmedical needs most commonly addressed by ACOs were the need for transportation and housing and food insecurity. ACOs identified nonmedical needs through processes that were part of the primary care visit or care transformation programs. Approaches to meeting patients' nonmedical needs were either individualized solutions (developed patient by patient) or targeted approaches (programs developed to address specific needs). As policy makers continue to provide incentives for health care organizations to meet a broader spectrum of patients' needs, these findings offer insights into how health care organizations such as ACOs integrate themselves with nonmedical organizations.


Diagnostic yield of repeat capsule endoscopy and the effect on subsequent patient management.
Capsule endoscopy (CE) has been shown to produce a high diagnostic yield in patients with obscure gastrointestinal bleeding (OGIB); however, in those with negative studies, management is controversial. Very few studies have reported on repeat CE in the same patient; data regarding this diagnostic strategy are limited. To determine the diagnostic yield of repeated CE studies and how this yield affects subsequent patient management. A retrospective chart review of all patients who underwent CE at St Paul's Hospital (Vancouver, British Columbia) between December 2001 and June 2009 was conducted. Patients who underwent subsequent repeat CE were identified and divided into one of four subgroups. Findings were classified as positive or negative. Eighty-two of 676 patients underwent more than one CE study. Group 1 (incomplete study) included 22 patients (27%) and yielded 10 positive findings (45%). Group 2 (screening) comprised four patients (5%) and yielded two positive findings (50%). Group 3 (ongoing symptoms despite previous negative study) totalled 26 patients (32%) and yielded 10 positive findings (38%). Group 4 (previous positive study with treatment/investigation) included 30 patients (37%) and yielded 23 positive findings (77%). Overall, the present study found positive findings in 55% (45 of 82) of repeated CE cases, which resulted in a change in management in 39% (n=32) of the patients. Due to the high diagnostic yield and noninvasive nature of CE, repeat CE appears to be of benefit and should be considered for specific patients before other types of small bowel studies.


Dual role of delta-like 1 homolog (DLK1) in skeletal muscle development and adult muscle regeneration.
Muscle development and regeneration is tightly orchestrated by a specific set of myogenic transcription factors. However, factors that regulate these essential myogenic inducers remain poorly described. Here, we show that delta-like 1 homolog (Dlk1), an imprinted gene best known for its ability to inhibit adipogenesis, is a crucial regulator of the myogenic program in skeletal muscle. Dlk1(-/-) mice were developmentally retarded in their muscle mass and function owing to inhibition of the myogenic program during embryogenesis. Surprisingly however, Dlk1 depletion improves in vitro and in vivo adult skeletal muscle regeneration by substantial enhancement of the myogenic program and muscle function, possibly by means of an increased number of available myogenic precursor cells. By contrast, Dlk1 fails to alter the adipogenic commitment of muscle-derived progenitors in vitro, as well as intramuscular fat deposition during in vivo regeneration. Collectively, our results suggest a novel and surprising dual biological function of DLK1 as an enhancer of muscle development, but as an inhibitor of adult muscle regeneration.


Depressive symptoms and 3-year mortality in older hospitalized medical patients.
Depressive symptoms are common in hospitalized older persons. However, their relation to long-term mortality is unclear because few studies have rigorously considered potential confounders of the relation between depression and mortality, such as comorbid illness, functional impairment, and cognitive impairment. To measure the association between depressive symptoms and long-term mortality in hospitalized older persons. Prospective cohort study. General medical service of a teaching hospital. 573 patients 70 years of age or older. Depressive symptoms (Geriatric Depression Scale score), severity of acute illness (Acute Physiology and Chronic Health Evaluation II score), burden of comorbid illness (Charlson comorbidity index score), physical function (a nurse assessed dependence in six activities of daily living), and cognitive function (modified Mini-Mental State Examination) were measured at hospital admission. Mortality over the 3 years after admission was determined from the National Death Index. Mortality rates among patients with six or more depressive symptoms were compared with those among patients with five or fewer symptoms. The mean age of the patients was 80 years; 68% of patients were women. Patients with six or more depressive symptoms had greater comorbid illness, functional impairment, and cognitive impairment at admission than patients with fewer depressive symptoms. Three-year mortality was higher in patients with six or more depressive symptoms (56% compared with 40%; hazard ratio, 1.56 [95% CI, 1.22 to 2.00]; P < 0.001). After adjustment for age, acute illness severity, comorbid illness, functional impairment, and cognitive impairment at the time of admission, patients with six or more depressive symptoms continued to have a higher mortality rate during the 3 years after admission (hazard ratio, 1.34 [CI, 1.03 to 1.73]). Although depressive symptoms contributed less to the mortality rate than did the total burden of comorbid medical illnesses, the excess mortality rate associated with depressive symptoms was greater than that conferred by one additional comorbid medical condition. Depressive symptoms are associated with long-term mortality in older patients hospitalized with medical illnesses. This association is not fully explained by greater levels of comorbid illness, functional impairment, and cognitive impairment in patients with more depressive symptoms.


High-dose biotin in progressive multiple sclerosis: A prospective study of 178 patients in routine clinical practice.
A recent controlled trial suggested that high-dose biotin supplementation reverses disability progression in patients with progressive multiple sclerosis. To analyze the impact of high-dose biotin in routine clinical practice on disability progression at 12 months. Progressive multiple sclerosis patients who started high-dose biotin at Nantes or Rennes Hospital between 3 June 2015 and 15 September 2017 were included in this prospective study. Disability outcome measures, patient-reported outcome measures, relapses, magnetic resonance imaging (MRI) data, and adverse events were collected at baseline, 6, and 12 months. A total of 178 patients were included. At baseline, patients were 52.0 ± 9.4 years old, mean Expanded Disability Status Scale (EDSS) score was 6.1 ± 1.3, mean disease duration was 16.9 ± 9.5 years. At 12 months, 3.8% of the patients had an improved EDSS score. Regarding the other disability scales, scores either remained stable or increased significantly. In total, 47.4% of the patients described stability, 27.6% felt an improvement, and 25% described a worsening. Four patients (2.2%) had a relapse. Of the 74 patients (41.6%) who underwent an MRI, 20 (27.0%) had new T2 lesions, 8 (10.8%) had gadolinium-enhancing lesions. Twenty-five (14%) reported adverse event. In this study, high-dose biotin did not seem to be associated with a clear improvement in disability.


Effect of caffeine ingestion on muscular strength and endurance: a meta-analysis.
Our objective was to perform a systematic review and meta-analysis of the research literature assessing the effect of caffeine ingestion on maximal voluntary contraction (MVC) strength and muscular endurance. Thirty-four relevant studies between 1939 and 2008 were included in the meta-analyses of caffeine's effects on MVC strength (n = 27 studies) and muscular endurance (n = 23 studies). Effect sizes (ES) were calculated as the standardized mean difference and meta-analyses were completed using a random-effects model. Overall, caffeine ingestion was found to result in a small beneficial effect on MVC strength (overall ES = 0.19, P = 0.0003). However, caffeine appears to improve MVC strength primarily in the knee extensors (i.e., by approximately 7%, ES = 0.37) and not in other muscle groups such as the forearm or the knee flexors. In an attempt to offer a physiological mechanism behind caffeine's ability to improve MVC strength, a meta-analysis was run on ES from nine studies that measured percent muscle activation during MVC in trials comparing caffeine versus placebo; the overall ES (0.67) was highly significant (P = 0.00008) and of moderate to large size, thus implicating an effect of caffeine on the CNS. Caffeine ingestion was also found to exert a small beneficial effect on muscular endurance (overall ES = 0.28, P = 0.00005). However, it appears caffeine improves muscular endurance only when it is assessed using open (i.e., by approximately 18%, ES = 0.37) and not fixed end point tests. Overall, caffeine ingestion improves MVC strength and muscular endurance. The effect on strength appears exclusively in the knee extensors, and the effect on muscular endurance appears only detectable with open end point tests.


A ligand for the erbB-2 oncogene product (gp30) induces differentiation of human breast cancer cells.
The human erbB-2 oncogene encodes a tyrosine kinase receptor. A ligand for the erbB-2 receptor (gp30), with an apparent molecular weight of 30,000, was reported to modulate the growth of cells overexpressing erbB-2. Whereas low concentrations of gp30 induced proliferation of these cells, higher concentrations inhibited their growth. To elucidate the cellular mechanisms underlying cell growth inhibition by gp30, we tested the effect of this ligand on cell growth and differentiation of the human breast cancer cells AU-565 and MDA-MB-453 (which overexpress erbB-2) and MCF-7 cells (which express low levels of this protooncogene). Ligand concentrations that inhibited growth in cells overexpressing erbB-2 induced apparent differentiation of cells with a more mature phenotype, i.e., with characteristics such as inhibited cell growth, altered cytoplasmic and nuclear morphology, and increased synthesis of milk components (casein and lipids). No significant effect of the ligand was observed in the human breast cancer cell line MCF-7. Concomitant with the induction of differentiation in AU-565 and MDA-MB-453 cells, the erbB-2 protein was translocated from membrane to the cytoplasm and perinuclear sites. These findings indicate that ligand-induced growth inhibition in cells overexpressing erbB-2 is associated with an apparent induction of differentiation.


Coagulation of a giant hemangioma in glans penis with holmium laser.
A 21-year-old man presented with an enlarged giant hemangioma on glans penis which also causes an erectile dysfunction (ED) that partially responded to the intracavernous injection stimulation test. Although the findings in magnetic resonance imaging (MRI) indicated a glandular hemangioma, penile colored Doppler ultrasound revealed an invaded cavernausal hemangioma to the glans. Surgical excision was avoided according to the broad extension of the gland lesion. Holmium laser coagulation was applied to the lesion due to the cosmetically concerns. However, the cosmetic results after holmium laser application was not impressive as expected without an improvement in intracavernous injection stimulation test. In conclusion, holmium laser application should not be used to the hemangiomas of glans penis related to the corpus cavernosum, but further studies are needed to reveal the effects of holmium laser application in small hemangiomas restricted to the glans penis.


Trauma-induced coagulopathy in severely injured patients: knowledge lost in translation?
Many guidelines exist on how to treat patients with multiple injuries correctly in an accident and emergency setting. The aim of the present work was to find out how well patients are treated focusing on trauma induced coagulopathy (TIC), and what anaesthetists involved in trauma care think about their own experiences with TIC. In a retrospective chart review of patients with an Injury Severity Score (ISS) > or = 16 between October 2007 and October 2008. A total of 172 patients with multiple injuries (134 men, 38 women) were treated in the resuscitation room and underwent complete coagulation screening (international normalised ratio (INR), activated partial thromboplastin time (aPTT), thrombin time (TT)). The presence of TIC was defined as INR>1.5 and aPTT>60 s or TT>15 s. Additionally, during the weekly anaesthesia and critical care grand round, a short questionnaire about TIC management was distributed to all anaesthetists involved in trauma care. Of the 172 patients with multiple injuries, 56 (32.6%) had TIC at admission to the resuscitation bay and 7 of these 56 (12.5%) received fresh-frozen plasma in the first hour of treatment. The mean of 55 anaesthetists thought that TIC could be corrected within about 30 min, although a chart review shows that it takes about 60 min to get complete laboratory based coagulation screening results. However, 70% of the doctors are not satisfied with the laboratory results they receive concerning TIC. There is an obvious discrepancy between the content of guidelines and the everyday practice. Future academic efforts in the area of trauma care should therefore focus more on the translational approach and the implementation of existing knowledge rather than on simply formulating guidelines.


'Candidatus Rhabdochlamydia porcellionis', an intracellular bacterium from the hepatopancreas of the terrestrial isopod Porcellio scaber (Crustacea: Isopoda).
Intracellular bacteria were observed in the hepatopancreas of the terrestrial isopod Porcellio scaber. Comparative 16S rRNA gene sequence analysis and electron microscopic observations were used to determine the taxonomic position of these intracellular bacteria. Phylogenetic analysis and a complex developmental cycle affiliate these bacteria to the order Chlamydiales, within which they form a distinctive lineage, close to the family Simkaniaceae. They share <92 % 16S rRNA gene sequence similarity with their closest relative and <88 % similarity with other members of the order Chlamydiales. A specific signature oligonucleotide sequence was identified and used as a probe, enabling the identification of intracellular bacteria in infected hepatopancreatic tissue. According to the distinctive morphology of their elementary bodies, which are rod-shaped rather than spherical and contain translucent oblong structures, their genomic properties and their crustacean host, the name 'Candidatus Rhabdochlamydia porcellionis' is proposed for intracellular bacteria in the hepatopancreas of P. scaber.


Analysis of the 5' region of PMS2 reveals heterogeneous transcripts and a novel overlapping gene.
The PMS2 gene encodes a protein that is involved in DNA mismatch repair and is mutated in a subset of patients with hereditary nonpolyposis colon cancer (HNPCC). The previously published PMS2 cDNA sequence lacks an upstream in-frame stop codon preceding the presumptive initiating methionine. To evaluate the 5' terminus of the PMS2 coding region further, we isolated additional cDNA clones, RT-PCR products, and the corresponding 5' genomic segment of the PMS2 locus. The PMS2 gene transcripts were found to have heterogeneous but colinear 5' termini, one of which contained an in-frame termination codon preceding the initiating methionine. In addition, a novel gene encoding a 34.5-kDa polypeptide was found to initiate transcriptionally within PMS2 from the opposite strand.


Mutual coherence function determination from a double point source propagating through a transversely and longitudinally inhomogeneous aero-optic turbulence layer.
The mutual coherence function (MCF) that results when a double point source illuminates a transversely and longitudinally inhomogeneous turbulence layer is considered. The analysis was carried out by (1) decomposition of the free-space MCF from the double point source into four separate interference terms, (2) calculation of the MCF that resulted from each of these terms when the optical wave that arose from these terms propagated through the inhomogeneous turbulence layer, and (3) addition of the solutions together to form the overall MCF solution of the optical system. The analysis was carried out in a transverse center-difference coordinate system. Two of the four terms were shown to vary rapidly in the center coordinate variables, and the other two were shown to vary rapidly in the difference coordinate variables. Because two of the terms showed rapid interference effects in the center coordinate variable and the other two in the difference coordinate variable, two different spatial-spectral algorithms were developed in the paper to analyze the MCF's that arose from each of the two types of rapid interference variation. The spatial-spectral MCF equations that arose from the analysis were solved numerically by the Lax-Wendroff finite-difference method. Several numerical plots of the center and difference interference MCF's that resulted when a double point source was incident upon a transversely inhomogeneous aero-optic layer were given. Plots of the variation of the interference MCF's with angular separation of the double point source are shown.


Depression and cancer mortality: a meta-analysis.
The goal of the present study was to analyze associations between depression and mortality of cancer patients and to test whether these associations would vary by study characteristics. Meta-analysis was used for integrating the results of 105 samples derived from 76 prospective studies. Depression diagnosis and higher levels of depressive symptoms predicted elevated mortality. This was true in studies that assessed depression before cancer diagnosis as well as in studies that assessed depression following cancer diagnosis. Associations between depression and mortality persisted after controlling for confounding medical variables. The depression-mortality association was weaker in studies that had longer intervals between assessments of depression and mortality, in younger samples and in studies that used the Beck Depression Inventory as compared with other depression scales. Screening for depression should be routinely conducted in the cancer treatment setting. Referrals to mental health specialists should be considered. Research is needed on whether the treatment of depression could, beyond enhancing quality of life, extend survival of depressed cancer patients.


The isolated tubal torsion: an insidious pediatric and adolescent pelvic urgency.
Isolated tubal torsion (ITT) is a rare cause of acute abdominal pain. Preoperative diagnosis is difficult because of a lack of specific signs. Surgery is recommended to preserve the integrity of the tube. Seven patients of median age of 13 years (range 9 to 15) came to our observation for worsening abdominal pain, nausea and vomiting. On admission, all girls had blood tests and ultrasound. Laparoscopy was performed for diagnosis in all cases. The girls had one-month and one-year ultrasound and clinic follow up. In all cases diagnosis was delayed, median 66 hours after the onset of symptoms and laparoscopy showed necrosis of the Fallopian tube. In five girls a laparoscopic salpingectomy was performed. In the other two, an open salpingectomy was necessary because of pelvic adhesions. Histology showed a hemorrhagic infarction of the Fallopian tubes. At follow up all patients were asymptomatic with normal ovaries, but one ovarian cyst. In the differential diagnosis of acute abdominal pain in children or female adolescents the possibility of ITT should be considered for a conservative treatment. Laparoscopy allows for definitive diagnosis and treatment.


A systematic study of yeast sterol biosynthetic protein-protein interactions using the split-ubiquitin system.
Sterol biosynthesis occurs in the ER and most sterol biosynthetic enzymes have transmembrane domains. However, due to difficulties in characterizing membrane protein-protein interactions, the nature of the sterol biosynthetic complex as well as in vivo interactions between various enzymes have not been described. We employed a split-ubiquitin membrane protein yeast two-hybrid system to characterize interactions between sterol biosynthetic proteins. Fourteen bait constructs were co-transformed into a reporter yeast strain with 14 prey constructs representing all sterol enzymatic reactions beginning with the synthesis of squalene. Our results not only confirmed several previous interactions, but also allowed us to identify novel interactions. Based on these results, ergosterol biosynthetic enzymes display specific protein-protein interactions forming a functional complex we designate, the ergosome. In this complex, Erg11p, Erg25p, Erg27p, and Erg28p appear to form a core center that can interact with other enzymes in the pathway. Also Erg24p and Erg2p, two enzymes that are sensitive to morpholine antifungals, appear to interact with one another; however, the profile of protein interaction partners appears to be unique. Erg2p and Erg3p, two enzymes catalyzing sequential reactions also appear to have different interaction partners. Our results provide a working model as to how sterol biosynthetic enzymes are topologically organized not only in yeast but in plant and animal systems that share many of these biosynthetic reactions.


Gamma knife surgery for trigeminal neuralgia: improved initial response with two isocenters and increasing dose.
The authors sought to evaluate the initial response of trigeminal neuralgia (TN) to gamma knife surgery (GKS) based on the number of shots delivered and radiation dose. Between September 1998 and September 2003, some 63 patients with TN refractory to medical or surgical management underwent GKS at Upstate Medical University. Ten patients had multiple sclerosis and 25 patients had undergone prior invasive treatment. Gamma knife surgery was delivered to the trigeminal nerve root entry zone in one shot in 27 patients or two shots in 36 patients. The radiation dose was escalated to less than or equal to 80 Gy in 20 patients, 85 Gy in 21 patients, and greater than or equal to 90 Gy in 22 patients. Pain before and after GKS was assessed using the Barrow Neurological Institute Pain Scale and the improvement score was analyzed as a function of dose grouping and number of shots. Sixty patients were available for evaluation, with an initial overall and complete response rate of 90% and 27%, respectively. There was a greater improvement score for patients who were treated with two shots compared with one shot, mean 2.83 compared with 1.72 (p < 0.001). There was an increased improvement in score at each dose escalation level: less than or equal to 80 Gy (p = 0.017), 85 Gy (p < 0.001), and greater than or equal to 90 Gy (p < 0.001). Linear regression analysis also indicated that there was a greater response with an increased dose (p = 0.021). Patients treated with two shots were more likely to receive a higher dose (p < 0.001). There were no severe complications. Five patients developed mild facial numbness. Gamma knife surgery is an effective therapy for TN. Initial response rates appear to correlate with the number of shots and dose.


Variation in Expression of the HECT E3 Ligase UPL3 Modulates LEC2 Levels, Seed Size, and Crop Yields in Brassica napus.
Identifying genetic variation that increases crop yields is a primary objective in plant breeding. We used association analyses of oilseed rape/canola (Brassica napus) accessions to identify genetic variation that influences seed size, lipid content, and final crop yield. Variation in the promoter region of the HECT E3 ligase gene BnaUPL3 C03 made a major contribution to variation in seed weight per pod, with accessions exhibiting high seed weight per pod having lower levels of BnaUPL3 C03 expression. We defined a mechanism in which UPL3 mediated the proteasomal degradation of LEC2, a master transcriptional regulator of seed maturation. Accessions with reduced UPL3 expression had increased LEC2 protein levels, larger seeds, and prolonged expression of lipid biosynthetic genes during seed maturation. Natural variation in BnaUPL3 C03 expression appears not to have been exploited in current B napus breeding lines and could therefore be used as a new approach to maximize future yields in this important oil crop.


HERES, a lncRNA that regulates canonical and noncanonical Wnt signaling pathways via interaction with EZH2.
Wnt signaling through both canonical and noncanonical pathways plays a core role in development. Dysregulation of these pathways often causes cancer development and progression. Although the pathways independently contribute to the core processes, a regulatory molecule that commonly activates both of them has not yet been reported. Here, we describe a long noncoding RNA (lncRNA), HERES, that epigenetically regulates both canonical and noncanonical Wnt signaling pathways in esophageal squamous cell carcinoma (ESCC). For this study, we performed RNA-seq analysis on Korean ESCC patients and validated these results on a larger ESCC cohort to identify lncRNAs commonly dysregulated in ESCCs. Six of the dysregulated lncRNAs were significantly associated with the clinical outcomes of ESCC patients and defined 4 ESCC subclasses with different prognoses. HERES reduction repressed cell proliferation, migration, invasion, and colony formation in ESCC cell lines and tumor growth in xenograft models. HERES appears to be a transacting factor that regulates CACNA2D3, SFRP2, and CXXC4 simultaneously to activate Wnt signaling pathways through an interaction with EZH2 via its G-quadruple structure-like motif. Our results suggest that HERES holds substantial potential as a therapeutic target for ESCC and probably other cancers caused by defects in Wnt signaling pathways.


Prevalence of dementia in older latinos: the influence of type 2 diabetes mellitus, stroke and genetic factors.
To estimate dementia prevalence in older Mexican Americans, determine the distribution of dementia by etiology, and evaluate the contribution of type 2 diabetes mellitus, stroke, and apolipoprotein E (ApoE) genotype to dementia. Analysis of baseline data from an epidemiological cohort study. Sacramento Valley, California. One thousand seven hundred eighty-nine Latinos aged 60 and older residing in targeted census tracts during 1998-99. Each subject was interviewed and screened for dementia and cardiovascular risk factors and diseases. Fasting blood samples were drawn for glucose, insulin, and lipids. Buccal cells were obtained for genetic analysis of ApoE. A three-stage process of screening was used to diagnose dementia, including cognitive testing, a clinical examination, and imaging to determine etiology. Presence of dementia was established according to National Institute of Neurological Disorders and Stroke/Alzheimers and Related Disorders Association criteria and California Alzheimer's Disease Diagnostic and Treatment Criteria. Overall dementia prevalence was 4.8%. Prevalence in those aged 85 and older was 31%. Education and Anglo cultural orientation was negatively associated with dementia risk. Risk of dementia was nearly eight times higher in those with both type 2 diabetes mellitus and stroke. Forty-three percent of dementia was attributable to type 2 diabetes mellitus, stroke, or a combination of the two. ApoE allele frequency was E2 5.9%, E3 90.1%, and E4 4%. Those with any E4 and 4-4 combinations had a higher risk for dementia than those with the E3-3 combination. Dementia prevalence in this ethnic group is similar to that reported in Canadian and European studies but lower than in Caribbean-Hispanics residing in the United States. The etiological fraction of dementia attributable to type 2 diabetes mellitus and stroke is substantial and points toward the need for intervention research and treatment with the goal of reducing neurological sequelae in groups with high prevalence of type 2 diabetes mellitus. The allele frequency of ApoE was similar to that in other published studies on Mexican Americans. The low frequency of the E4 allele may contribute to the difference in etiology of dementia in older Mexican Americans and older people of European background. Dementia in this ethnic group may be related to preventable causes, with a smaller genetic component than in Europeans.


Vitamin D: a brief overview of its importance and role in inflammatory bowel disease.
Vitamin D has traditionally been known for its regulation of bone metabolism and homeostasis, but emerging evidence suggests that it also has a broad function in immune regulation, and inflammatory bowel disease (IBD). The etiology of IBD is thought to be multifactorial but stems in part due to the deregulation of the immune response to environmental factors in the setting of a pre-existing genetic disposition. Vitamin D, based on its mechanistic role at the cellular level in T-cell trafficking, had been postulated to have a direct effect on the immune system, This alludes to the fact that vitamin D may have the ability to not only potentiate the IBD phenotype, but also in doing so, its supplementation may serve a therapeutic role in amelioration of the diseased state. We review in this article the current literature as it pertains to the basic mechanism of Vitamin D, its role in the pathogenicity of IBD, how it regulates our immune system, interpretation and accuracy of obtaining levels, and the role there may be in supplementation in IBD.


Evaluation of mean platelet volume (MPV) levels in patients with synovitis associated with knee osteoarthritis.
Platelet count, C-reactive protein (CRP) and neutrophile countings are markers those reflect the inflammatory response. Mean platelet volume (MPV) is a simple indicator of platelet size and has been known to be a marker of platelet activity. Some platelet markers, including MPV, have been investigated to have relation with inflammation. MPV is inversely correlated with inflammation in inflammatory bowel diseases, rheumatoid arthritis, and ankylosing spondylitis, as shown in the previous studies. In this study, we aimed to investigate the levels of MPV in patients with synovitis of knee osteoarthritis. 147 patients diagnosed with synovitis associated to osteoarthritis, 191 patients with knee osteoarthritis, and 121 patients between the same age range who did not have joint complaints (control group), totally 459 participants were included to our study. MPV results of these groups were compared. We found a significant difference between the patient group with synovitis associated with osteoarthritis of knee and patients with knee osteoarthritis in MPV blood level (p < 0.0001), similarly a significant difference was found between the patient group with synovitis associated with osteoarthritis of knee and the control group (p < 0.0001). There was no significant difference between the knee osteoarthritis patient group and the control group (p = 0.78). We found a significant relation between MPV and ESR in the patient group with synovitis of osteoarthritis (p = 0.004). According to the Pearson correlation, it is found that there is a negative relationship between CRP and MPV variables in those of knee osteoarthritis patients. This correlation coefficient is statistically significant at the 10% level (p = 0.058). We could not find a relation between CRP and MPV in patients with the osteoarthritis group, but we found negative correlation (p = 0.65). Significant relationship was not found between ESR and MPV variables at the 10% level; the p value is 0.34. In the control group no correlation was found between CRP-MPV (p = 0.69) and ESR-MPV (p = 0.798). MPV levels may be beneficial in osteoarthritis with synovitis patients. MPV levels may be considered as a marker of inflammation but further comprehensive prospective trials are needed in osteoarthritis associated with synovitis patients.