Hormonal and cellular interactions in follicular steroid biosynthesis by the sheep ovary.
Studies of isolated cell types from sheep follicles revealed several functional changes which occur during follicular maturation. Cyclic AMP production by granulosa cells from the smallest follicles studied (1-3 mm diameter) was stimulated by FSH but not by hCG, suggesting functional FSH receptors at this early stage of differentiation. Medium-sized follicles (4-6 mm) responded to both FSH and hCG. Granulosa cells were unable to synthesize androgens, but readily converted exogenous testosterone to oestradiol-17 beta. This conversion occurred to a limited extent in the cells from the smallest follicles, but was much greater in medium and large (greater than 6 mm) follicles. Oestradiol production by theca preparations from small follicles was barely detectable, but increased markedly with increasing follicle size. Androgen (androstenedione and testosterone) production by theca preparations was stimulated by hCG. This stimulation was short-lived, and levels declined to below control values after 6 h of culture. This decline could not be prevented by addition of cyclic AMP. The presence of granulosa cells with thecal preparations (i.e. follicle wall tissue) enhanced production of androgen by the theca, the effect being more marked for testosterone than for androstenedione. In-vivo studies in which granulosa cells and follicular fluid were removed during the preovulatory period suggested that granulosa cells and/or follicular fluid contributed to the oestradiol secreted into the ovarian vein during this period, but did not exclude a significant contribution by the theca as well.


[Chronobiological aspects of gerontology].
The hypothesis of the dynamics of aging on the chronobiological grounds is presented. The results of the original research are demonstrated as well as the conclusions made by the leading authorities in the human individual annual and perennial endogenous cycles are treated. Risk-zones, which tend to increase the possibility of "mistakes" in a genetic program that lead to aging of organism are proposed. The data obtained could provide an opinion of existing both the perennial and annual endogenous cycles, that begin from the moment of conception and include nine months of the embryo period and three months after the date of birth. The data available provide a ground for a hypothesis verifying the trimester time-genetic program of the endogenous year. The "mistakes" in the chronobiological program emerging as the reaction on the environment during the periods of intensive growth of metabolic process are supposed to be one of the essential causes of aging and early death.


Structure and binding interface of the cytosolic tails of αXβ2 integrin.
Integrins are signal transducer proteins involved in a number of vital physiological processes including cell adhesion, proliferation and migration. Integrin molecules are hetero-dimers composed of two distinct subunits, α and β. In humans, 18 α and 8 β subunits are combined into 24 different integrin molecules. Each of the subunit comprises a large extracellular domain, a single pass transmembrane segment and a cytosolic tail (CT). The CTs of integrins are vital for bidirectional signal transduction and in maintaining the resting state of the receptors. A large number of intracellular proteins have been found to interact with the CTs of integrins linking integrins to the cytoskeleton. In this work, we have investigated structure and interactions of CTs of the leukocyte specific integrin αXβ2. We determined the atomic resolution structure of a myristoylated CT of αX in perdeuterated dodecylphosphocholine (DPC) by NMR spectroscopy. Our results reveal that the 35-residue long CT of αX adopts an α-helical conformation for residues F4-N17 at the N-terminal region. The remaining residues located at the C-terminal segment of αX delineate a long loop of irregular conformations. A segment of the loop maintains packing interactions with the helical structure by an extended non-polar surface of the αX CT. Interactions between αX and β2 CTs are demonstrated by (15)N-(1)H HSQC NMR experiments. We find that residues constituting the polar face of the helical conformation of αX are involved in interactions with the N-terminal residues of β2 CT. A docked structure of the CT complex indicates that a network of polar and/or salt-bridge interactions may sustain the heteromeric interactions. The current study provides important insights into the conservation of interactions and structures among different CTs of integrins.


The African Pediatric Fellowship Training Program in Pediatric Pulmonology: A Model for Growing African Capacity in Child Lung Health.
Childhood respiratory diseases are the major cause of mortality and morbidity in African children. However, there is limited expertise in pediatric pulmonology in Africa. The African Pediatric Fellowship Program (APFP) was developed in the Department of Paediatrics and Child Health at the University of Cape Town in partnership with African academic institutions beyond South Africa to promote training of African child health professionals and to build capacity. From 2008 to 2016, 11 fellows have completed APFP training in pediatric pulmonology. Fellows have come from Kenya, Nigeria, Ghana, and Uganda. All but one returned to their home institutions, where they are building academic departments, improving clinical service delivery, growing research capacity, and advancing advocacy and policies to improve child lung health. In parallel, training of South African pediatric pulmonologists has been strengthened with a further nine South African fellows trained during this period. The African Pediatric Pulmonology program provides a highly successful model, with high retention of graduates in their home countries. The long-term goal is to grow African clinical capacity and strengthen services, research, training, and advocacy for child lung health in Africa.


[Determination of acrylamide content in potato products using GC-MS/MS and LC-MS/MS methods].
The aim of our study was to check a useful of GCQ-MS/MS and LC-MS/MS methods to determination of acrylamide in foodstuffs and determined acrylamide content in potato products randomly collected in Poland in 2007-2008. As a result of validation of these methods we found the both using methods were characterized by low quantification limit and well precision. The highest acrylamide level was in potato crisps--770 microg/kg (113 divided by 1890 microg/kg), but the lowest--was in French fries collected from bars and restaurants--401 microg/kg (134 divided by 679 microg/kg). Acrylamide content analyzed in 2008 in potato crisp and French fries ready to eat was higher than in 2007. The difference was not statistically significant. In French fries fried in laboratory from pre-cooked French fries in 2008 acrylamide level was lower that in these products analyzed in 2007.


[Treatment of the positional compression syndrome].
The experience with the treatment of 35 patients with the syndrome of positional compression is described, 29 of then having acute renal insufficiency. They were subjected to 116 operations of hemodialysis. Five patients died. The main caused of the death was acute renal insufficiency. The measures used for the prevention of acute renal insufficiency are considered by the authors to be ineffective while the timely treatment by hemodialysis can result in recovery almost in all the cases. The main cause of failure of the treatment of this type of acute renal insufficiency was hyperhydration of the pulmonary tissue.


An accessible and efficient autism screening method for behavioural data and predictive analyses.
Autism spectrum disorder is associated with significant healthcare costs, and early diagnosis can substantially reduce these. Unfortunately, waiting times for an autism spectrum disorder diagnosis are lengthy due to the fact that current diagnostic procedures are time-consuming and not cost-effective. Overall, the economic impact of autism and the increase in the number of autism spectrum disorder cases across the world reveal an urgent need for the development of easily implemented and effective screening methods. This article proposes a new mobile application to overcome the problem by offering users and the health community a friendly, time-efficient and accessible mobile-based autism spectrum disorder screening tool called ASDTests. The proposed ASDTests app can be used by health professionals to assist their practice or to inform individuals whether they should pursue formal clinical diagnosis. Unlike existing autism screening apps being tested, the proposed app covers a larger audience since it contains four different tests, one each for toddlers, children, adolescents and adults as well as being available in 11 different languages. More importantly, the proposed app is a vital tool for data collection related to autism spectrum disorder for toddlers, children, adolescent and adults since initially over 1400 instances of cases and controls have been collected. Feature and predictive analyses demonstrate small groups of autistic traits improving the efficiency and accuracy of screening processes. In addition, classifiers derived using machine learning algorithms report promising results with respect to sensitivity, specificity and accuracy rates.


[How Can we provide better services for demented nursing home residents suffering from apathy?].
Behavioural and psychological symptoms of Dementia include agitation, depression and apathy. Apathy is a common condition and a major challenge especially in nursing home residents. The development of a brief intervention for nursing home residents combining physical activation and reminiscence therapy in order to reactivating apathic residents and increasing their quality of life will be described.


A novel homozygous exon2 deletion of TRIM32 gene in a Chinese patient with sarcotubular myopathy: A case report and literature review.
Sarcotubular myopathy (STM) is a rare autosomal recessive myopathy caused by TRIM32 gene mutations. It is predominantly characterized by the weakness of the proximal limb and mild to moderate elevation of creatine kinase (CK) levels. In this study, we describe a 50-year-old Chinese man who exhibited a proximal-to-distal weakness in the muscles of the lower limbs and who had difficulty standing up from a squat position. The symptoms gradually became more severe. He denied a history of cognitive or cardiological problems. The patient's parents and children were healthy. Histopathological examination revealed dystrophic changes and irregular slit-shaped vacuoles containing amorphous materials. Whole-exome sequencing consisting of protein-encoding regions of 19,396 genes was performed, the results of which identified one novel homozygous 2kb deletion chr9.hg19: g.119460021_119461983del (exon2) in the TRIM32 gene. This was confirmed at the homozygous state with quantitative real-time PCR. Here, we present a Chinese case of STM with one novel mutation in TRIM32 and provide a brief summary of all known pathogenic mutations in TRIM32.


Otoconin-90, the mammalian otoconial matrix protein, contains two domains of homology to secretory phospholipase A2.
The ability to sense orientation relative to gravity requires dense particles, called otoconia, which are localized in the vestibular macular organs. In mammals, otoconia are composed of proteins (otoconins) and calcium carbonate crystals in a calcite lattice. Little is known about the mechanisms that regulate otoconial biosynthesis. To begin to elucidate these mechanisms, we have partially sequenced and cloned the major protein component of murine otoconia, otoconin-90 (OC90). The amino acid sequence identified an orphan chimeric human cDNA. Because of its similarity to secretory phospholipase A2 (sPLA2), this gene was referred to as PLA2-like (PLA2L) and enabled the identification of human Oc90. Partial murine cDNA and genomic clones were isolated and shown to be specifically expressed in the developing mouse otocyst. The mature mouse OC90 is composed of 453 residues and contains two domains homologous to sPLA2. The cloning of Oc90 will allow an examination of the role of this protein in otoconial biosynthesis and in diseases that affect the vestibular system.


Nascent stage of cellulose biosynthesis.
Freeze-etching of never-dried pellicles or of incubated suspensions of both Acetobacter xylinum and Acetobacter acetigenum show a nascent form of the cellulose microfibril which has a core surrounded by an amorphous sheath. Drying of the pellicle or suspension reduces the diameter of the sheath and changes the form of the microfibril to the one usually seen. This nascent form of the cellulose microfibril is consistent with previous postulations of an intermediate polymer or polymers in the biosynthesis of cellulose.


Integration and excision of pMC7105 in Pseudomonas syringae pv. phaseolicola: involvement of repetitive sequences.
The site for integration of pMC7105 into the chromosome of Pseudomonas syringae pv. phaseolicola has been mapped to a 2.6-kilobase-pair (kb) Bg/II-EcoRI fragment on this 150-kb indigenous plasmid. Selected excision plasmids resulting from imprecise excision of pMC7105 were used to identify one of the plasmid-chromosome juncture fragments and to characterize the mechanism of recombination from the chromosome. A 14.2-kb BamHI plasmid-chromosome juncture fragment has been identified in pEX8060 (234 kb), an excision plasmid which carries approximately 90 kb of chromosomal sequences to the left of the site of integration. This fragment contains a portion of the 2.6-kb Bg/II-EcoRI fragment as well as chromosomal sequences. Blot hybridization with a probe made from selected fragments of pMC7105 revealed three distinct repetitive sequences, RS-I, RS-II, and RS-III, on this plasmid. The 2.6-kb fragment, to which the site of integration maps, also contains RS-II. Five copies of RS-II are present in pMC7105, and more than 20 copies are present in the chromosome. Eight small excision plasmids were shown to result from recombination among fragments of pMC7105 that contain common repetitive sequences. The results indicate that integration and excision of pMC7105 occur through general recombination at homologous repetitive sequences.


Towards defining the pathogenesis of the hairless phenotype.
Mutation of the hairless (hr) gene in mice causes severe abnormalities during the first hair follicle regression (catagen), resulting in complete baldness. Here, we further characterize how hairlessness develops in HRS/J hairless mouse skin (hr) by histology, histochemistry, immunohistology, and in situ hybridization. We show that, in hr skin, only two defined epithelial cell populations in the distal outer root sheath (ORS) retain their integrity, whereas the rest of the ORS disintegrates. The surviving distal ORS forms the characteristic utriculi, whereas the remnants of the bulge get isolated from other epithelial compartments, but retain the capacity to proliferate and to produce either columnar epithelial outgrowths or selected dermal cysts. Normal dermal papilla structures get lost during the development of hairlessness. Based on the patterns of keratin 17 mRNA and neural cell adhesion molecule antigen expression, and on the distribution of alkaline phosphatase activity, we propose that dermal cysts in hr skin arise from (i) the central ORS, (ii) bulge-derived cells, or (iii) the disintegrating proximal ORS under the influence of dermal papilla remnants. The hr mutation seems to disrupt the integrity of key functional tissue units in the hair follicle, possibly due to a dysregulation of normal, catagen-associated apoptosis and/or an impairment of cell adhesion, whereas the distal follicle epithelium (including its stem cell region) seems to be largely protected from this. Thus, hairless mice offer a unique model for dissecting the as yet obscure functional properties of the hr gene product in maintaining follicle integrity during normal catagen.


Obsessive-Compulsive Symptoms in Obsessive-Compulsive Disorder and in Generalized Anxiety Disorder: Occurrence and Correlations.
Because of the heterogeneity of obsessive-compulsive disorders (OCDs) and their co-occurrence with anxiety disorders, we investigated the prevalence, severity, and correlations between obsessive and compulsive symptoms reported by patients diagnosed with OCD or generalized anxiety disorder (GAD). A retrospective study was conducted in 2 groups of patients: 76 patients diagnosed with OCD [F42 according to the 10th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-10)], and 186 patients diagnosed with GAD (F41.1 according to ICD-10), who had presented for therapy at the day ward. The Symptom Questionnaire "O," based on the Symptom Checklist 90-Revised (SCL-90-R) questionnaire, was used to assess obsessive, compulsive, and anxiety symptoms. The analysis took into account the impact of sex and the presence or absence of cognitive dysfunction (as assessed using the Bender Benton Visual Retention and Bender-Gestalt tests) on the associations being investigated. We observed that obsessive and compulsive symptoms were more prevalent and more strongly expressed in the group with OCD than in the group with GAD. However, almost all patients with GAD (94%) confirmed the presence of some obsessive-compulsive symptoms. The study revealed differences in correlations with obsessions and compulsions between the OCD and GAD groups. In the group with OCD, no significant correlation between the severity of obsessions and compulsions was identified, whereas in the group with GAD, a significant positive correlation was found between the severity of those symptoms. In both the GAD and OCD groups, a greater intensity of obsessive-compulsive symptoms was accompanied by an increase in the severity of anxiety symptoms (with this effect noted to a greater extent with obsessions than compulsions). The study revealed that patients with GAD often have coexisting obsessive-compulsive symptoms, which may not be identified during routine psychiatric examination. Obsessive-compulsive symptoms observed in patients with GAD may show a different structure than obsessive-compulsive symptoms in patients with OCD. The results of this study suggest that compulsions are more specific for the diagnosis of OCD than obsessions. Compulsions, such as counting related to the need for order and symmetry, may be associated with some cognitive dysfunctions and male sex, a finding that requires further research.


Pionic carbon/oxygen capture ratios in blood and muscle tissue of pig.
The pionic carbon/oxygen capture ratio for the blood and muscle tissue of a pig was measured using an intrinsic Ge detector in order to investigate possible explanations for an enhanced lesion observed in the autopsy of pion-irradiated patients. Pure iron was also irradiated in order to determine the energies and intensities of pionic x-rays from iron. It was expected that some of them originated from haemoglobin and could be observed in the spectrum for a blood sample. TE plastic (Shonka A-150) and Lucite were also investigated for comparison with other work.


A case report of a new pulmonary embolism occurring in a patient receiving continuous infusion of recombinant activated protein C.
There are no guidelines governing the concomitant use of recombinant human activated protein C (rhAPC) and deep venous thrombosis/pulmonary embolism (DVT/PE) prophylaxis in critically ill patients. It is unknown if rhAPC provides any protection against DVT/PE in this population of patients. Case report. This report describes the first case of a radiographically demonstrated pulmonary embolism occurring in a patient receiving continuous therapeutic infusion of rhAPC. The administration of rhAPC alone may not be sufficient DVT/PE prophylaxis in high risk patients. The risks associated with concomitant anticoagulation and rhAPC therapy are unknown. Further research is necessary to determine the safest and most effective regimen for DVT/PE prophylaxis in patients receiving rhAPC.


The natural history of pineal cysts in children and young adults.
The authors reviewed their experience with pediatric pineal cysts to define the natural history and clinical relevance of this common intracranial finding. The authors identified all patients with pineal cysts who had been clinically evaluated at their institution over an 11.5-year interval and were < 25 years of age at the time of diagnosis. All inclusion criteria were met in 106 patients, and included repeated MR imaging as well as repeated clinical evaluation over at least a 6-month interval. The mean age at diagnosis was 11.7 +/- 7.2 years. Forty-two patients were male and 64 were female. On follow-up MR imaging evaluation at a mean interval of 3.0 years from the initial study, 98 pineal cysts had no increase in size and no change in imaging appearance. Six pineal cysts increased in size and 2 others had a change in imaging characteristics without associated growth. Younger age was associated with cyst change or growth on follow-up imaging (p = 0.02). The mean age of patients with cysts that changed or grew was 5.5 years, and the mean age of patients with stable pineal cysts was 12.2 years. Initial cyst size and appearance on MR imaging were not significant predictors of growth or change in imaging appearance at follow-up. Similarly, the patient's sex was not a significant predictor of growth or change in imaging characteristics. Follow-up imaging and neurosurgical evaluation may be considered optional in older children with pineal cysts.


Sequence variability of the alpha-chemokine UL146 from clinical strains of human cytomegalovirus.
Human cytomegalovirus (HCMV) is a ubiquitous pathogen that infects a variety of cell types in vivo. A region (referred to as UL/b') present in the Toledo strain of HCMV and low passage clinical isolates contains 22 additional genes, which are absent in the highly passaged laboratory strain AD169. One of these genes, UL146, encodes an alpha-chemokine. PCR amplification and sequencing of this gene from serial samples obtained from transplant recipients and samples from infants with suspected congenital HCMV infection, revealed that UL146 is a hypervariable gene in vivo. However, genetic changes were highly conserved in individuals and in renal transplant recipients multiple genotypes of UL146 were present. The majority of strains characterized maintained the conserved ELRCXC motif present in the Toledo strain of HCMV. These results provide further evidence that AD169 does not represent the authentic virus in vivo and although Towne and Toledo are more representative, major genetic differences still exist. Mixed populations of HCMV strains occur in vivo so cloning of these strains is essential if an authentic genotype is to be defined.


Measuring action understanding: Relations between goal prediction and imitation.
We explored the developmental course of goal prediction and imitation as two commonly used measures of action understanding. In particular, we investigated the relationships between the measures in two complex multistep actions (hammering and pulling action) in children between 12 and 30 months (n = 64) in a between-subjects design. The results showed that the prediction of an action goal was related to the imitation in the hammering action, but not in the pulling action. The results are discussed in the light of current theories on goal prediction and imitation.


Effect of low-dose theophylline plus beclometasone on lung function in smokers with asthma: a pilot study.
Smoking is common in asthma and is associated with worse asthma control and a reduced therapeutic response to corticosteroids. The present authors hypothesised that treating smokers with asthma with low-dose theophylline added to inhaled corticosteroids would enhance steroid sensitivity and thereby improve lung function and symptoms. In a double-blind, parallel group exploratory trial, 68 asthmatic smokers were randomised to one of three treatments for 4 weeks: inhaled beclometasone (200 microg day(-1)), theophylline (400 mg day(-1)) or both treatments combined. Outcome measures included change in lung function and Asthma Control Questionnaire (ACQ) scores. At 4 weeks, theophylline added to inhaled beclometasone produced an improvement in peak expiratory flow (39.9 L min(-1), 95% confidence intervals (CI) 10.9-68.8) and ACQ score (-0.47, 95% CI -0.91- -0.04) and a borderline improvement in pre-bronchodilator forced expiratory volume in one second (mean difference 165 mL, 95% CI -13-342) relative to inhaled corticosteroid alone. Theophylline alone improved the ACQ score (-0.55, 95% CI -0.99- -0.11), but not lung function. In the present pilot study, the combination of low-dose theophylline and inhaled beclometasone produced improvements in both lung function and symptoms in a group of smokers with asthma. Larger trials are required to extend and confirm these findings.


High serum YKL-40 level in patients with COPD is related to hypoxemia and disease severity.
Chronic obstructive pulmonary disease (COPD) is a major health problem with increasing morbidity and mortality throughout the world. YKL-40 is a chitin-binding glycoprotein consisting of 383 amino acids, with a molecular mass of 40 kDa, and its serum level is elevated in inflammatory diseases. YKL-40 is a newly recognized biomarker of inflammation and has not been thoroughly investigated in COPD. The aim of the study is to investigate the relationship between serum YKL-40 levels and severity of COPD. The study population consisted of 52 patients with COPD with the mean age of 60.2 ± 10.1 years. The serum YKL-40 level increased significantly with increasing age (p = 0.022, r = 0.346). In COPD patients, high serum YKL-40 level is correlated to low forced expiratory volume at 1 second (FEV₁, percent of predicted) (r = -0.277, p = 0.047). Moreover, high serum YKL-40 level is correlated to low arterial oxygen pressure (PaO₂, mmHg) (r = -0.387, p = 0.005). The mean serum YKL-40 level was found as 243.1 ± 129.2 ng/ml in COPD patients with desaturation during 6-minute walk test (6MWT) and this value was higher than the mean serum YKL-40 level (155.8 ± 59.1 ng/ml) of COPD patients without desaturation during 6MWT (p = 0.004). This study demonstrated that high serum YKL-40 levels were correlated to severity of COPD. We propose that circulating YKL-40 levels could be a biomarker for hypoxemia and decline in lung function.


Natural history of liver cirrhosis in 116 Nigerians.
One hundred and sixteen cirrhotic patients were prospectively studied over a ten year period. Hepatitis B surface antigen was positive in 70% of tested patients. The cirrhotic liver was mainly macronodular and primary hepatocellullar carcinoma was associated with 63% of the patients. Half of the patients were critically ill with high incidences of ascites, jaundice and encephalopathy. Cirrhotic patients had significantly lower body temperature onycholysis and hyperpigmented palmo-plantar macular areas. The mean survival time was three years from onset of the initial symptoms to death. Patients with concomitant liver cancer were usually dead within six months after onset of the illness. Gender did not substantially affect the course of the disease. The major causes of death were tumour development (63%), gastrointestinal bleeding (40%), haemoperitoneum (28%) and hepatic failure (25%).


A vegetation classification and description of white-winged flufftail (Sarothrura ayresi) habitat at selected high-altitude peatlands in South Africa.
The white-winged flufftail is listed as critically endangered, and limited knowledge about the species' ecology has been identified as a limiting factor to effectively conserving the bird. Little is known about the vegetation inhabited by the white-winged flufftail, which hampers the identification and management of its habitat. This study presents a fine-scale classification and description of the vegetation of wetland sites where the bird is known to be present. A plant phytosociological study was conducted to describe the plant communities and vegetation structure of the habitat. Three sites were selected at Verloren Valei Nature Reserve and two at Middelpunt Wetland, Mpumalanga, South Africa, shortly after the white-winged flufftail breeding season. A total of 60 sample plots were placed within the study sites, where all plant species present were recorded and identified. Other aspects such as plant height, water depth and anthropogenic influences were also documented. A modified TWINSPAN analysis resulted in the identification of three sub-communities that can be grouped into one major community. The Cyperaceae, Asteraceae and Poaceae families dominate the vegetation, with the sedges Carex austro-africana and Cyperus denudatus being dominant, and the grasses Leersia hexandra and Arundinella nepalensis co-dominant. The broad habitat structure consisted of medium to tall herbaceous plants (0.5-0.7 m) with shallow slow-flowing water.


Antimicrobial effect of herbal extract of Acacia arabica with triphala on the biofilm forming cariogenic microorganisms.
Dental caries is a biofilm-related infectious disease with a multifactorial etiology, over five billion inhabitants have affected worldwide due to this disease. Antimicrobial efficacy of a mixed herbal powder extract (MHPE) against cariogenic microorganisms was investigated. MIC, MBC, kinetics of killing, biofilm disruption and anticaries effect of MHPE were determined. For biofilm disruption, biofilms of Streptococcus mutans, Lactobacillus casei, Actinomyces viscosus and Candida albicans were treated with MHPE for 30 min and attached cells were quantified after staining. For live/dead staining biofilm assay, S. mutans biofilm treated with MHPE for 1min, 5min and 1 h was examined with confocal laser scanning system after live/dead staining. Efficacy was experimented by structural quality using Scanning Electron Microscope (SEM). Anticaries effect was determined by formation of caries-like lesion in continuous flow biofilm model. MHPE exhibited inhibition zones ranging from 12.5 to 24.0 mm. The highest inhibition zone was recorded at concentration of 50 μg/ml. MIC for S. mutans was between 12.23 and 36.7 μg/ml, while the MBC values ranged from 36.7 to 110.65 μg/ml. Inhibitory concentration of MHPE was three fold higher than CHLX. Significant reduction of cell count (49-95%) was observed with increasing time and higher concentration. Percentage biofilm reduction compare with negative control was 96.9% (A. viscosus), 94% (C. albicans), 99.8% (L. casei) and 91.7% (S. mutans). For MHPE-treated biofilm, live/dead staining demonstrated significant (p < 0.05) higher in deceased red fluorescence areas in all kinetics points from 53.6% (1min) to 85% (1h). SEM confirmed the damage in the outer layers of S. mutans. MHPE has components with effective antibacterial activity against caries-inducing microorganisms. The anti-adherence and anti-biofilm effect as well as the faster killing activity suggests that MHPE formula has effective antibacterial activity and could be a useful source of anti-cariogenic agents in near future.


Residents Take the Lead: A Modern Collaborative Approach to Research During Residency.
Participation in scholarship is a requirement for Internal Medicine (IM) residencies, but programs struggle to successfully integrate research into busy clinical schedules. In 2013, the IM residency at Brigham and Women's Hospital implemented the Housestaff Research Project (HRP)- a novel residency-wide research initiative designed to facilitate participation in scholarship. The HRP had two components-a formal research curriculum and an infrastructure that provided funding and mentorship for resident-led, housestaff wide projects. This is a mixed-methods study of 190 IM residents and two HRP-supported research projects. Seventy-seven residents responded to an electronic survey about their interests in research exposure in residency. Fifty-six residents responded to an electronic survey about their participation in the HRP. The success of HRP-supported projects was evaluated through resident comments, interviews with three residents leading the first two HRPs and a description of the success of the projects based on resident involvement and dissemination of the results. Eighty-seven percent (n= 67/77) of residents were interested in additional research exposure during residency. Ninety-five percent (n = 53/56) of residents had heard of the HRP, and 77% had participate in at least one aspect of it. Approximately 20 residents were directly involved in the two resident-led projects. HRP-supported projects resulted in presentations at three local and three national conferences, one manuscript in press, and one manuscript in preparation. The resident project leaders felt that a strength and unique aspect of the HRP was the collaboration with co-residents. The HRP successfully created a culture of research and scholarship within the residency. The HRP leaders and residents that participated in HRP-supported projects expressed the most direct benefits from the program. All residents were exposed to research concepts and methods. Future directions for the HRP include selecting projects that maximize the number of resident participants and integrating a more robust research curriculum.


Stem Cell-Based or Cell-Free Gene Therapy in Chondrocyte Regeneration: Synovial Fluid-Derived Mesenchymal Stem Cell Exosomes.
Cartilage injuries are currently the most prevalent joint disease. Previous studies have emphasized the use of stem cells as the effective treatment for regenerating cartilage damage. In this study, considering the difficulties of the cellular therapy method, it was hypothesized that human synovial fluid-derived mesenchymal stem cell (hSFMSC) exosomes as a SC source could be used to treat these injuries as a safer and cell-free therapeutic alternative procedure due to its direct relevance to cartilage regeneration. Moreover, this study aimed to determine the miRNA and target genes required for the formation of SC treatment combined with gene therapy in order to reveal the mechanism of cartilage regeneration and increase its effectiveness. MSCs were characterized by flow cytometry, and immunocytochemical and differentiation analyses were done. To characterize functionally isolated exosomes, in vitro uptake analysis was performed. RT-qPCR was used to examine in terms of the advantages of cellular and cell-free therapy, mature human chondroblasts derived by differentiation from hSF-MSCs and human chondrocyte profiles were compared in order to demonstrate the above profile of hSF-MSCs and exosomes isolated from them, and the effectiveness of SC therapy in repairing cartilage damage. According to our findings, the expression level of hsa-miR-155-5p was found to be considerably higher in chondrocytes differentiated from human synovial fluid MSCs than in mature human chondrocytes. These findings were also supported by the TGF-signalling pathway and chondrogenesis marker genes. It was concluded that hSF-MSCs and exosomes can be used in the treatment of cartilage damage, and hsa-miR-155-5p can be used as a target miRNA in a new gene therapy approach because it increases the therapeutic effect on cartilage damage.


Symptom dimensions of anxiety and their association with mortality, hospitalization and quality of life in dialysis patients.
Symptoms of anxiety are highly prevalent in dialysis patients and are associated with adverse clinical outcomes. Identifying symptom dimensions may help to understand the pathophysiology, improve screening and guide treatment. Currently, there are no data on symptom dimensions of anxiety in dialysis patients. This study aimed to identify the best fitting dimensional model for anxiety in dialysis patients and assess the association between symptom dimensions of anxiety and adverse clinical outcomes. This study is a prospective observational cohort study including patients from 10 urban dialysis centers between 2012 and 2017. Anxiety symptoms were measured using the self-reported questionnaire Beck Anxiety Inventory. Confirmatory factor analysis was used to identify symptom dimensions. The association between dimensions and mortality, hospitalization and quality of life was investigated using stepwise cox, poisson and lineair regression models. Multivariable models included demographic, social, laboratory and clinical variables to adjust for possible confounding. In total 687 chronic dialysis patients were included. A Somatic and Subjective anxiety dimension were identified. Only Somatic anxiety symptoms showed an association with increased risk of hospitalization and mortality (Rate Ratio 1.73 (1.45-2.06) p = .007 and Hazard Ratio 1.65 (1.15-2.37) p = .007 respectively). These associations were independent from somatic comorbidity. All symptom dimensions of anxiety showed an association with Quality of Life. This study shows that anxiety is common in chronic dialysis patients and comprises of a somatic, subjective, and a total score. The discrimination between anxiety dimensions can be useful for clinical practice, as they are related to different clinical outcomes.


Patient dose simulations for scanning-beam digital x-ray tomosynthesis of the lungs.
An improved method of image guidance for lung tumor biopsies could help reduce the high rate of false negatives. The aim of this work is to optimize the geometry of the scanning-beam digital tomography system (SBDX) for providing real-time 3D tomographic reconstructions for target verification. The unique geometry of the system requires trade-offs between patient dose, imaging field of view (FOV), and tomographic angle. Tomosynthetic angle as a function of tumor-to-detector distance was calculated. Monte Carlo Software (PCXMC) was used to calculate organ doses and effective dose for source-to-detector distances (SDDs) from 90 to 150 cm, patient locations with the tumor at 20 cm from the source to 20 cm from the detector, and FOVs centered on left lung and right lung as well as medial and distal peripheries of the lungs. These calculations were done for two systems, a SBDX system and a GE OEC-9800 C-arm fluoroscopic unit. To evaluate the dose effect of the system geometry, results from PCXMC were calculated using a scan of 300 mAs for both SBDX and fluoroscopy. The Rose Criterion was used to find the fluence required for a tumor SNR of 5, factoring in scatter, air-gap, system geometry, and patient position for all models generated with PCXMC. Using the calculated fluence for constant tumor SNR, the results from PCXMC were used to compare the patient dose for a given SNR between SBDX and fluoroscopy. Tomographic angle changes with SDD only in the region near the detector. Due to their geometry, the source array and detector have a peak tomographic angle for any given SDD at a source to tumor distance that is 69.7% of the SDD assuming constant source and detector size. Changing the patient location in order to increase tomographic angle has a significant effect on organ dose distribution due to geometrical considerations. With SBDX and fluoroscopy geometries, the dose to organs typically changes in an opposing manner with changing patient location. When tumor SNR is held constant (i.e., x-ray fluence is scaled appropriately), SBDX gives 2-10 times less dose than fluoroscopy for the same conditions within the typical range of patient locations. The relative position of the patient (as a percent of SDD) has a much more significant impact on dose than either SDD or patient position. The patient position providing the minimum dose for a given tumor SNR and SDD is approximately the same as the position of maximum tomographic angle. SBDX offers a significant dose advantage over currently used C-arm fluoroscopy. The patient location with lowest dose coincides with the location of maximum tomographic angle. In order to provide adequate space for the patient and for the pulmonologists' equipment, a SDD of 100 cm is recommended.


Vascular tone and angiogenesis modulation by catecholamine coordinated to ruthenium.
Catecholamines participate in angiogenesis, an important tumor development process. However, the way catecholamines interact with their receptors has not been completely elucidated, and doubts still remain as to whether these interactions occur between catechol and/or amine sites and particular amino acid residues on the catecholamine receptors. To evaluate how catechol and amine groups contribute to angiogenesis, we immobilized the catechol site through ruthenium ion (Ru) coordination, to obtain species with the general formula [Ru(NH3)4(catecholamine-R)]Cl. We then assessed the angiogenic activity of the complexes in a chorioallantoic membrane model (CAM) and examined vascular reactivity and calcium mobilization in rat aortas and vascular cells. [Ru(NH3)4(catecholamine-R)]Cl acted as partial agonists and/or antagonists of their respective receptors and induced calcium mobilization. [Ru(NH3)4(isoproterenol)]+ [Ru(NH3)4(noradrenaline)]+, and [Ru(NH3)4(adrenaline)]+ behaved as antiangiogenic complexes, whereas [Ru(NH3)4(dopamine)]+ proved to be a proangiogenic complex. In conclusion, catecholamines and [Ru(NH3)4(catecholamine-R)]Cl can modulate angiogenesis, and catechol group availability can modify the way these complexes impact the vascular tone, suggesting that catecholamines and their receptors interact differently after catecholamine coordination to ruthenium.


Control method for bio-actuators based on muscle contraction model.
For the practical application of bio-actuators, it is desired to develop a precise control method for skeletal muscles. In this study, a novel model-based control method has been proposed. The control method enables skeletal muscles to exert an arbitrary magnitude of contraction force, rather than just the conventional on/off control. First, we proposed a control system to obtain the optimized electrical stimulation voltage, that can reproduce reference force. In order to actually apply the method, a bio-actuator consisting of a skeletal muscle of a frog was manufactured for a verification experiment. First, muscle contraction model parameters that could reproduce the contractile response of the gastrocnemius muscle were identified from the experimental data. Next, based on this model, the proposed control method was used to calculate the stimulation voltage to exert the reference force. The voltage was applied to the bio-actuator to control the contraction force. As a results, the output of the actuator was able to follow the stepwise reference force. Our proposed control method demonstrates the feasibility of precise control of bio-actuators.Clinical Relevance- If skeletal muscles could be used as actuators for power-assistive suits, it would be possible to develop power-assistive suits that are more compatible with people and reduce the burden on caregivers in the field of nursing care. The method proposed in this study will enable the control of skeletal muscle contraction force by electrical stimulation, bringing skeletal muscle actuators closer to practical application.


Mutations in MYB3R1 and MYB3R4 cause pleiotropic developmental defects and preferential down-regulation of multiple G2/M-specific genes in Arabidopsis.
R1R2R3-Myb proteins represent an evolutionarily conserved class of Myb family proteins important for cell cycle regulation and differentiation in eukaryotic cells. In plants, this class of Myb proteins are believed to regulate the transcription of G2/M phase-specific genes by binding to common cis-elements, called mitosis-specific activator (MSA) elements. In Arabidopsis (Arabidopsis thaliana), MYB3R1 and MYB3R4 act as transcriptional activators and positively regulate cytokinesis by activating the transcription of KNOLLE, which encodes a cytokinesis-specific syntaxin. Here, we show that the double mutation myb3r1 myb3r4 causes pleiotropic developmental defects, some of which are due to deficiency of KNOLLE whereas other are not, suggesting that multiple target genes are involved. Consistently, microarray analysis of the double mutant revealed altered expression of many genes, among which G2/M-specific genes showed significant overrepresentation of the MSA motif and a strong tendency to be down-regulated by the double mutation. Our results demonstrate, on a genome-wide level, the importance of the MYB3R-MSA pathway for regulating G2/M-specific transcription. In addition, MYB3R1 and MYB3R4 may have diverse roles during plant development by regulating G2/M-specific genes with various functions as well as genes possibly unrelated to the cell cycle.


Effects of butanol on Clostridium acetobutylicum.
The internal pH of Clostridium acetobutylicum was determined at various stages during the growth of the organism. Even in the presence of significant quantities of acetic, butyric, and lactic acids, an internal pH of 6.2 was maintained. Experiments using N,N'-dicyclohexylcarbodiimide indicated that a functioning H+-ATPase is necessary for internal pH control. Butanol, one of the end products of the fermentation, had numerous harmful effects on C. acetobutylicum. At a concentration high enough to inhibit growth, butanol destroyed the ability of the cell to maintain internal pH, lowered the intracellular level of ATP, and inhibited glucose uptake. Experiments done at two different external pH values suggested that the butanol-mediated decrease in ATP concentration was independent of the drop in internal pH. Glucose uptake was not affected by arsenate, suggesting that uptake was not ATP dependent. The effects of butanol on C. acetobutylicum are complex, inhibiting several interrelated membrane processes.


Children and adolescents admitted to a university-level trauma centre in Denmark 2002-2011.
The epidemiology of children or adolescents admitted to a Scandinavian trauma centre is largely unknown. The aim of this paper was to describe the epi-demiology and severity of potentially severely injured children and adolescents admitted to a university hospital trauma centre. This was a descriptive study of all children and adolescents aged 0-17 admitted to the university level trauma centre at Odense University Hospital, Denmark in the 2002-2011 period. Data were extracted from the Southern Danish Trauma Register and from medical records. A total of 950 children and adolescents were included. The median age was 13 (range: 0-17) years. Boys accounted for 60.6% of the cases. Accidents accounted for 97.2%, violence 1.4% and self-inflicted injuries 0.4%. More than three fourths of the injuries occurred either in traffic or at home. The occurrence was greatest in the summer (34.0%), during weekends (48.9%) and in the hours between 12.00 and 20.00 (59.2%). Overall, 58.5% of the in-juries were due to traffic. Of these injuries, 39.7% were in-juries suffered by passengers in motor vehicles, 27.5% drivers/passengers of a scooter/MC, 21.8% bicyclists and 10.3% pedestrians. The median Injury Severity Score (ISS) and Abbreviated Injury Scale was 4 (range: 1-75) and 2 (range: 1-6), respectively. Head/face injuries accounted for 36.5% and injuries to the extremities for 30.9% of all injuries. A total of 153 (16.1%) suffered from severe injuries (ISS > 15). Overall, 49 (5.2%) died due to their injuries. Based on a local trauma register, we described the epidemiology and severity of potentially se-verely injured children and adolescents admitted to a university trauma centre. none. not relevant.


Palliative dual iliac screw fixation for lumbosacral metastasis. Technical note.
Spinal fixation for destructive metastatic lesions at the lumbosacral junction is challenging because of the large and unique load-bearing characteristics present. In particular, caudal fixation is difficult in cases of sacral destruction because of insufficient S-1 pedicle screw anchorage. The authors describe their surgical technique for secure iliac screw placement and the clinical results obtained in five patients with metastatic spinal disease. All patients in this study underwent palliative operations with dual iliac screw fixation between April 1999 and October 2002, and the clinical and radiological findings were assessed. In all five patients, spinal metastases extended into the sacrum. The metastases were from renal cell carcinomas in two patients, lung cancer in two, and a paraganglioma in one patient. Postoperative follow-up periods ranged from 3 months to 6 years (mean 28.4 months). Preoperatively, four patients could not walk due to severe pain or neurological compromise. Postoperatively, all patients reported a reduction in pain and regained the ability to walk. Complications included one case of early wound infection. In the patients with long survival after the operation, there was one case of iliac screw loosening and one case of rod breakage. The dual iliac screw fixation technique provided sufficient immediate stability for destructive lumbosacral metastasis.


Effect of priming with granulocyte colony-stimulating factor on the outcome of chemotherapy for acute myeloid leukemia.
Sensitization of leukemic cells with hematopoietic growth factors may enhance the cytotoxicity of chemotherapy in acute myeloid leukemia (AML). In a multicenter randomized trial, we assigned patients (age range, 18 to 60 years) with newly diagnosed AML to receive cytarabine plus idarubicin (cycle 1) and cytarabine plus amsacrin (cycle 2) with granulocyte colony-stimulating factor (G-CSF) (321 patients) or without G-CSF (319). G-CSF was given concurrently with chemotherapy only. Idarubicin and amsacrin were given at the end of a cycle to allow the cell-cycle-dependent cytotoxicity of cytarabine in the context of G-CSF to have a greater effect. The effect of G-CSF on disease-free survival was assessed in all patients and in cytogenetically distinct prognostic subgroups. After induction chemotherapy, the rates of response were not significantly different in the two groups. After a median follow-up of 55 months, patients in complete remission after induction chemotherapy plus G-CSF had a higher rate of disease-free survival than patients who did not receive G-CSF (42 percent vs. 33 percent at four years, P=0.02), owing to a reduced probability of relapse (relative risk, 0.77; 95 percent confidence interval, 0.61 to 0.99; P=0.04). G-CSF did not significantly improve overall survival (P=0.16). Although G-CSF did not improve the outcome in the subgroup with an unfavorable prognosis, the 72 percent of patients with standard-risk AML benefited from G-CSF therapy (overall survival at four years, 45 percent, as compared with 35 percent in the group that did not receive G-CSF [relative risk of death, 0.75; 95 percent confidence interval, 0.59 to 0.95; P=0.02]; disease-free survival, 45 percent vs. 33 percent [relative risk, 0.70]; 95 percent confidence interval, 0.55 to 0.90; P=0.006). Sensitization of leukemic cells with growth factors is a clinically applicable means of enhancing the efficacy of chemotherapy in patients with AML.


Nutrition in general practice: role and workforce preparation expectations of medical educators.
Nutrition advice from general practitioners (GPs) is held in high regard by the general public, yet the literature investigating the role of GPs in the provision of nutrition care is limited. This qualitative study aimed to explore the perceptions of general practice medical educators (GPMEs) regarding the role of GPs in general practice nutrition care, the competencies required by GPs to provide effective nutrition care and the learning and teaching strategies best suited to develop these competencies. Twenty medical educators from fourteen Australian and New Zealand universities participated in an individual semi-structured telephone interview, guided by an inquiry logic informed by the literature. Interviews were transcribed verbatim and thematically analysed. Medical educators identified that nutrition was an important but mostly superficially addressed component of health care in general practice. Numerous barriers to providing nutrition care in general practice were identified. These include a lack of time and associated financial disincentives, perceptions of inadequate skills in nutrition counselling associated with inadequate training, ambiguous attitudes and differing perceptions about the role of GPs in the provision of nutrition care. Further research is required to identify strategies to improve nutrition care and referral practices provided in the general practice setting, in order to utilise the prime position of GPs as gatekeepers of integrated care to the general public.


Tick-borne bacterial diseases emerging in Europe.
Since the identification of Borrelia burgdorferi as the agent of Lyme disease in 1982, 11 tick-borne human bacterial pathogens have been described throughout Europe. These include five spotted fever rickettsiae, the agent of human granulocytic ehrlichiosis, four species of the B. burgdorferi complex and a new relapsing fever borrelia. We present these emerging diseases and focus on the factors that play a role in the recognition of new tick-borne diseases.


Cbl: many adaptations to regulate protein tyrosine kinases.
Responses to extracellular stimuli are often transduced from cell-surface receptors to protein tyrosine kinases which, when activated, initiate the formation of protein complexes that transmit signals throughout the cell. A prominent component of these complexes is the product of the proto-oncogene c-Cbl, which specifically targets activated protein tyrosine kinases and regulates their signalling. How, then, does this multidomain protein shape the responses generated by these signalling complexes?


Impairment prevention in the training years. A new mental health program at UCLA.
The new Mental Health Program for Physicians in Training, at UCLA, offers free psychiatric evaluation and short-term psychotherapy to UCLA medical students and house officers, utilizing a large group of physician volunteers from the clinical and regular faculties. The program features complete confidentiality and an off-campus setting and provides help in a number of specialized areas. It also conducts research on stress in medical education. A basic aim is to promote a sense of community in the medical profession by demonstrating the concern of mature practitioners for their young colleagues. It also seeks to foster greater sensitivity among young physicians by educating them about the importance of their own psychological needs. The UCLA program provides a model for mental health services that are low in cost, both to medical trainees and to the training institution, at a time of severe budget shrinkage.


Building a new conceptual framework for receptor heteromers.
Receptor heteromers constitute a new area of research that is reshaping our thinking about biochemistry, cell biology, pharmacology and drug discovery. In this commentary, we recommend clear definitions that should facilitate both information exchange and research on this growing class of transmembrane signal transduction units and their complex properties. We also consider research questions underlying the proposed nomenclature, with recommendations for receptor heteromer identification in native tissues and their use as targets for drug development.


Early transcriptomic responses associated with the membrane-initiated action of cortisol in the skeletal muscle of rainbow trout (Oncorhynchus mykiss).
Cortisol is a critical neuroendocrine regulator of the stress response in fish. Cortisol practically affects all tissues by interacting with an intracellular receptor and modulating target gene expression. However, cortisol also interacts with components of the plasma membrane in a nongenomic process that activates rapid signaling. Until now, the implication of this novel cortisol signaling for the global transcriptional response has not been explored. In the present work, we evaluated the effects of the membrane-initiated actions of cortisol on the in vivo transcriptome of rainbow trout (Oncorhynchus mykiss) skeletal muscle. RNA-Seq analyses were performed to examine the transcriptomic changes in rainbow trout stimulated by physiological concentrations of cortisol and cortisol coupled with bovine serum albumin (cortisol-BSA), a membrane-impermeable analog of cortisol. A total of 660 million paired-ends reads were generated. Reads mapped onto the reference genome revealed that 1,737; 897; and 1,012 transcripts were differentially expressed after 1, 3, and 9 h of cortisol-BSA treatment, respectively. Gene Ontology analysis showed that this novel action of cortisol modulates several biological processes, such as mRNA processing, ubiquitin-dependent protein catabolic processes, and transcription regulation. In addition, a KEGG analysis revealed that focal adhesion was the main signaling pathway that was upregulated at all the times tested. Taking these results together, we propose that the membrane-initiated cortisol action contributes significantly in the regulation of stress-mediated gene expression.


Emotion Recognition and Traffic-Related Risk-Taking Behavior in Patients with Neurodegenerative Diseases.
Neurodegenerative diseases (NDDs), such as Alzheimer's disease, frontotemporal dementia, dementia with Lewy bodies, and Huntington's disease, inevitably lead to impairments in higher-order cognitive functions, including the perception of emotional cues and decision-making behavior. Such impairments are likely to cause risky daily life behavior, for instance, in traffic. Impaired recognition of emotional expressions, such as fear, is considered a marker of impaired experience of emotions. Lower fear experience can, in turn, be related to risk-taking behavior. The aim of our study was to investigate whether impaired emotion recognition in patients with NDD is indeed related to unsafe decision-making in risky everyday life situations, which has not been investigated yet. Fifty-one patients with an NDD were included. Emotion recognition was measured with the Facial Expressions of Emotions: Stimuli and Test (FEEST). Risk-taking behavior was measured with driving simulator scenarios and the Action Selection Test (AST). Data from matched healthy controls were used: FEEST (n = 182), AST (n = 36), and driving simulator (n = 18). Compared to healthy controls, patients showed significantly worse emotion recognition, particularly of anger, disgust, fear, and sadness. Furthermore, patients took significantly more risks in the driving simulator rides and the AST. Only poor recognition of fear was related to a higher amount of risky decisions in situations involving a direct danger. To determine whether patients with an NDD are still fit to drive, it is crucial to assess their ability to make safe decisions. Measuring emotion recognition may be a valuable contribution to this judgment.


Resilience of experimentally seeded dietary traditions in wild vervets: Evidence from group fissions.
Controlled laboratory experiments have delivered extensive and compelling evidence for the diffusion and maintenance of socially learned behavior in primates and other animals. Such evidence is rarer in the wild, but we show that a behavior seeded in a majority of individuals within vervet monkey (Chlorocebus pygerythus) groups may be sustained across several years. Here, we report results of two natural fission events in such groups that offer novel evidence of the resilience of socially transmitted group norms of behavior. Before fission, high ranked females exhibited an almost exclusive adherence to a group preference among two food options, originally introduced through a distasteful additive in one option, but no longer present in repeated later tests. Because of rank-dependent competition, low-ranked females ate more of the formerly distasteful food and so discovered it was now as palatable as the alternative. Despite this experience, low ranked females who formed the splinter groups then expressed a 100% bias for the preferred option of their original parent group, revealing these preferences to be resilient. We interpret this effect as conformity to either the preferences of high rankers or of a majority in the parent group, or both. However, given fissioned individuals' familiarity with their habitat and experimental options, we question the adequacy of the informational function usually ascribed to conformity and discuss alternatives under a concept of "social conformity".


COVID-19 Neurological Manifestations and Underlying Mechanisms: A Scoping Review.
In the Corona Virus Disease 2019 (COVID-19) pandemic, the primary problem is respiratory-related, but there also is increasing evidence of central nervous system (CNS) involvement. This study aims to summarize the literature on neurological manifestations of COVID-19, underlying mechanisms of CNS involvement and cognitive consequences. A scoping review was conducted with multiple searches in PubMed, PsycInfo, and CINAHL databases. Full text articles in English were included if they involved humans with COVID-19. The search was updated twice, the latest on 19 May 2020. After screening 266 records and cross referencing, 85 articles were included. The articles were case studies, opinion papers, letters to editors, and a few observational studies. No articles were found regarding cognitive consequences in COVID-19 patients. All reported on neurological manifestations and/or underlying mechanisms of CNS involvement in COVID-19. Neurological manifestations of COVID-19 vary from mild (e.g. loss of taste and smell, dizziness, headache) to severe (e.g. ischemic stroke, encephalitis). Underlying pathways are suggested to be both indirect (as a result of thrombotic complication, inflammatory consequences, hypoxia, blood pressure dysregulation), and direct (neurotropic properties of the virus). Since most articles were opinion papers and no studies have been conducted on cognitive consequences, further research is warranted.


Update on meniscus debridement and resection.
Arthroscopic treatment of meniscal pathology is among the most common procedures performed by orthopedic surgeons, and has evolved from open total meniscectomy to arthroscopic partial meniscectomy and repair. With knowledge of the importance of the meniscus to articular cartilage preservation, efforts to preserve the meniscus with repair have been increasing, but this is not appropriate for all patients. The decision of whether to perform meniscal debridement or repair must be made on an individual basis, and characteristics of both the patient and tear should be considered. Important patient characteristics include age, cartilage status, concomitant anterior cruciate ligament reconstruction, and compliance. Tear characteristics that influence healing ability include location, morphology, acuity, and stability. Results from the literature indicate that outcomes of partial meniscectomy are superior to total, and that arthroscopic debridement of the meniscus is an effective treatment in appropriate patients. Symptomatic meniscal tears that are not likely to heal are better treated with partial meniscectomy than repair. The determination of which patients and meniscal tears are appropriate for meniscal debridement or repair should be made on an individual basis, in consultation with the patient, based on the factors presented.


Optical reflection from cholesteric liquid crystal films.
The reflection spectrum of light from the surface of a cholesteric liquid crystal film has been theoretically studied by including the absorption of light by the material. The intensity of reflection is found as a function of the wavelength and the angle of incidence as well as the angle of reflection near the circular dichroism region. A good agreement has been obtained with the available experimental data.


Adaptation of the osmotolerant yeast Zygosaccharomyces rouxii to an osmotic environment through copy number amplification of FLO11D.
Copy number variations (CNVs) contribute to the adaptation process in two possible ways. First, they may have a direct role, in which a certain number of copies often provide a selective advantage. Second, CNVs can also indirectly contribute to adaptation because a higher copy number increases the so-called "mutational target size." In this study, we show that the copy number amplification of FLO11D in the osmotolerant yeast Zygosaccharomyces rouxii promotes its further adaptation to a flor-formative environment, such as osmostress static culture conditions. We demonstrate that a gene, which was identified as FLO11D, is responsible for flor formation and that its expression is induced by osmostress under glucose-free conditions, which confer unique characteristics to Z. rouxii, such as osmostress-dependent flor formation. This organism possesses zero to three copies of FLO11D, and it appears likely that the FLO11D copy number increased in a branch of the Z. rouxii tree. The cellular hydrophobicity correlates with the FLO11D copy number, and the strain with a higher copy number of FLO11D exhibits a fitness advantage compared to a reference strain under osmostress static culture conditions. Our data indicate that the FLO gene-related system in Z. rouxii has evolved remarkably to adapt to osmostress environments.


Identification of neoxanthin synthase as a carotenoid cyclase paralog.
Neoxanthin, a precursor of the plant hormone abscisic acid, is an allenic xanthophyll recognized as the last product of carotenoid synthesis in green plants. A cDNA for neoxanthin synthase (NSY) was isolated from tomato using a molecular approach based on the mechanistic and structural similarities of NSY to two other closely related carotenogenic enzymes, lycopene cyclase (LCY) and capsanthin-capsorubin synthase (CCS). The identified tomato NSY cDNA (T.NSY) encodes a 56-kDa plastid-targeted protein that when expressed in Escherichia coli, catalyzes the conversion of violaxanthin to neoxanthin. In tobacco leaves that transiently express T.NSY, an increase in neoxanthin content with a concomitant decrease in violaxanthin is observed. NSY is structurally similar to LCY and CCS. However, in Cyanobacteria, the generally accepted progenitor of plastids, both CCS and NSY are absent while LCY is present. LCY catalyzes a simplified version of the reaction catalyzed by NSY and CCS suggesting that these two enzymes were remodeled from LCY during higher plant evolution to create new forms of oxidized carotenoids.


Anti-peptide antibody blocks peptide binding to MHC class I molecules in the endoplasmic reticulum.
The finding that MHC class I molecules are physically associated with the TAP transporter has suggested that peptides may be directly transported into the binding groove of the class I molecules rather than into the lumen of the endoplasmic reticulum (ER) where they subsequently would encounter class I molecules by diffusion. Such a mechanism would protect peptides from peptidases in the ER and/or escaping back into the cytoplasm. However, we find that an anti-peptide Ab that is cotranslationally transported into the ER prevents TAP-transported peptides from being presented on class I molecules. The Ab only blocks the binding of its cognate peptide (SIINFEKL) but not other peptides (KVVRFKDL, ASNENMETM, and FAPGNYPAL). Therefore, most TAP-transported peptides must diffuse through the lumen of the ER before binding stably to MHC class I molecules.


Neurologic status of human immunodeficiency virus 1-infected infants and their controls: a prospective study from birth to 2 years. Mothers and Infants Cohort Study.
To determine the timing, extent, severity, and persistence of neurologic abnormalities in children with perinatally acquired human immunodeficiency virus 1 (HIV-1) infection compared with similar uninfected children of HIV-1-infected women and control children. Serial neurologic examinations and head circumference measurements were performed on a cohort of HIV-1-infected children born to HIV-1-infected women, seroreverting children born to HIV-1-infected women, and control children born to uninfected women. Examination data from 32 HIV-1-infected children, 99 reverters, and 116 control children were summarized by eight neurologic domains. Data were analyzed by longitudinal analysis. Reverter children were not different from control children in neurologic function for any of the eight domains or head circumference. HIV-1-infected children had significantly more neurologic problems than the control and reverter children for seven of the eight domains. The HIV-1-infected children were further classified by whether they had acquired immunodeficiency syndrome (AIDS)-defining clinical conditions (other than lymphoid interstitial pneumonitis) in the first 24 months of life (the AIDS-opportunistic infection group) or did not (the infected-other group). Neurologic abnormalities were early, severe, pervasive, and persistent in the AIDS-opportunistic infection group, and nearly all in this group had head circumference measurements below the 10th percentile. The infected-other group had no statistically significant differences from the uninfected children, although individual children in the infected-other group had some abnormalities. In utero exposure to HIV-1 without infection seems to have no negative impact on neurologic function in children in the first 2 years of life. Among children with perinatally acquired HIV-1 infection, the most severe and pervasive neurologic problems occur in those children who have early serious HIV-1 clinical disease. Most children without serious AIDS-defining clinical conditions in the first 2 years of life are also free from serious neurologic problems during that period.


Design of New Bridge-Ring Energetic Compounds Obtained by Diels-Alder Reactions of Tetranitroethylene Dienophile.
The density functional theory method was employed to calculate three-dimensional structures for a series of novel explosophores. The design of new molecules (DA1-DA12) was based on the bridge-ring structures that could be formed via Diels-Alder (DA) reaction of selected nitrogen-rich dienes and tetranitroethylene dienophile. The feasibility of the proposed DA reactions was predicted on the basis of the molecular orbital theory. The strong interactions between the HOMO of dienes, with electron-donating groups (Diene2, Diene6, and Diene8), and the LUMO of tetranitroethylene dienophile suggested thermodynamically favorable formation of the desired DA reaction products. In addition to molecular structures of the explored DA compounds, their physicochemical and energetic properties were also calculated in detail. Due to compact bridge-ring structures, new energetic molecules have highly positive heats of formation (up to 1124.90 kJ·mol-1) and high densities (up to 2.04 g·cm-3). Also, as a result of all-right ratios of nitrogen and oxygen, most of the new compounds possess high detonation velocities (8.28-10.02 km·s-1) and high detonation pressures (30.87-47.83 GPa). Energetic compounds DA1, DA4, and DA12 exhibit a superior detonation performance over widely used HMX explosive, and DA5, DA7, and DA10 could be comparable to the state-of-the-art CL-20 and ONC explosives. Our proposed designs and synthetic methodology should provide a platform for the development of novel energetic materials with superior performance.


First alternative method validated by a retrospective weight-of-evidence approach to replace the Draize eye test for the identification of non-irritant substances for a defined applicability domain.
A replacement alternative to the rabbit eye irritation test has been sought for many years. First published in 1944 by FDA toxicologist J. H. Draize, the test, now known as the Draize Eye Test, has been used extensively to assess eye safety. It has also been a focal point for concern regarding its animal use. In 1992, Molecular Devices developed the Cytosensor Microphysiometer (CM) technology, an automated potentiometric online measurement of pH changes in cells, and evaluated it also for chemically induced irritation. The method was included in some of the six major validation studies for eye irritation from 1991-1997. The results for CM were inconclusive as were those from other tests evaluated as stand-alone methods to fully replace the animal test. In 2002, the European Centre for the Validation of Alternative Methods (ECVAM) started applying concepts from evidence-based medicine, and opened validation to retrospective meta-analysis. This activity was done in collaboration with US counterpart ICCVAM/NICEATM, and the European Cosmetics Association, Colipa. After a new, comprehensive evaluation of the prior available data, the ECVAM scientific advisory committee (ESAC) has recently accepted the CM as capable of identifying non-irritants for testing limited to water-soluble surfactants and water-soluble surfactant-containing mixtures. This 25-year development is remarkable and instructive in many respects. The authors see this as opening the door, at last, for an end to the use of animals as a standard requirement for eye irritation. Here, several of the people critically involved in this processes have summarized the important aspects of this history.


[Color adaptation in a yellow-blue system: proof of a simple numerical relationship].
Three axes in color space are specified: a (unique) yellow - (unique) blue axis, a (unique) green - magenta axis and brightness. Based on the two chromatic axes two linear opponent colors systems are defined: a red/green-system and a yellowish/bluish-system. A numerical relation is presented to describe color adaptation for the yellowish/bluish-system under adaptation to (unique) yellow and (unique) blue: two pairs of color stimuli are equivalent with regard to the yellowish/bluish-system - consisting of a test stimulus and an adaptation stimulus, respectively - if the ratios from the yellowish/bluish-coordinates of test stimulus and adaptation stimulus are identical. A control of brightness and the red/green-system is presupposed. For several (unique) yellow and (unique) blue adaptation stimuli it is examined how a test stimulus that appears neither yellowish nor bluish changes its location on the (unique) yellow - (unique) blue axis within color space. Three observers take part in the experiment. For each observer a plane of constant brightness and the opponent colors axes are estimated experimentally. The data show that the ratios from the yellowish/bluish coordinates of test stimulus and adaptation stimulus are essentially constant. The results are compared with analogous data for the red/green-system. The findings provide evidence for the specification of the three phenomenal axes. The specification is discussed with regard to Hering's opponent colors theory and Krauskopf's three "cardinal" axes [1982, Vision Research, 22, 1123-1131].


A modern learning theory perspective on the etiology of panic disorder.
Several theories of the development of panic disorder (PD) with or without agoraphobia have emerged in the last 2 decades. Early theories that proposed a role for classical conditioning were criticized on several grounds. However, each criticism can be met and rejected when one considers current perspectives on conditioning and associative learning. The authors propose that PD develops because exposure to panic attacks causes the conditioning of anxiety (and sometimes panic) to exteroceptive and interoceptive cues. This process is reflected in a variety of cognitive and behavioral phenomena but fundamentally involves emotional learning that is best accounted for by conditioning principles. Anxiety, an anticipatory emotional state that functions to prepare the individual for the next panic, is different from panic, an emotional state designed to deal with a traumatic event that is already in progress. However, the presence of conditioned anxiety potentiates the next panic, which begins the individual's spiral into PD. Several biological and psychological factors create vulnerabilities by influencing the individual's susceptibility to conditioning. The relationship between the present view and other views, particularly those that emphasize the role of catastrophic misinterpretation of somatic sensations, is discussed.


Engaging heart failure patients from a clinical data research network: A survey on willingness to participate in different types of research.
The willing participation of patients in clinical research is a critical element in national efforts to collect health data for precision medicine and large cohort studies. However, recruiting patients is challenging. Clinical data research networks (CDRN) have primarily been used for observational studies, but may be able to enhance recruitment efforts. We need a better understanding of patient motivation and preferences for research participation and their interest in different types of research activities, particularly among those who are already represented in CDRNs. We surveyed a heart failure patient cohort constructed from EHRs in a CDRN to assess research participation. Results showed that CDRN recruitment is feasible. Respondents were most interested in completing a one-time survey and giving a blood sample one time. They were least interested in a study about weight control that require surgery. We found statistically significant associations between race and research activity interests.


Evaluation of a large-scale aptamer proteomics platform among patients with kidney failure on dialysis.
Patients with kidney failure suffer high mortality, and we currently lack markers for risk stratification for these patients. We carried out a quality control study of a modified aptamer assay (SomaScan v.4.0) that measures ~ 5000 proteins, in preparation for a larger study using this platform in cohorts with kidney failure. Forty participants from the Cardiac, Endothelial Function and Arterial Stiffness in End-Stage Renal Disease (CERES study) were selected to analyze technical and short-term biological variability, orthogonal correlations and differential protein expression in plasma from patients who died during 2.5 year follow-up. Long-term (one year) variability was studied in 421 participants in the Chronic Renal Insufficiency Cohort. We evaluated 4849 aptamers (4607 unique proteins) using data formats including raw data and data formatted using Adaptive Normalization by Maximum Likelihood (ANML), an algorithm developed for SomaScan data in individuals with normal kidney function. In ANML format, median[IQR] intra-assay coefficient of variation (CV) was 2.38%[1.76, 3.40] and inter-assay CV was 7.38%[4.61, 13.12]. Short-term within-subject CV was 5.76% [3.35, 9.72]; long-term CV was 8.71%[5.91, 13.37]. Spearman correlations between aptamer and traditional assays for PTH, NT-proBNP, FGF-23 and CRP were all > 0.7. Fold-change (FC) in protein levels among non-survivors, significant after Bonferroni correction, included SVEP1 (FC[95% CI] 2.14 [1.62, 2.82]), keratocan (1.74 [1.40, 2.15]) and LanC-like protein 1 (0.56 [0.45, 0.70]). Compared to raw aptamer data, technical and short-term biological variability in paired samples was lower in ANML-formatted data. ANML formatting had minimal impact on orthogonal correlations with traditional assays or the associations of proteins with the phenotype of mortality. SomaScan had excellent technical variability and low within-subject short-term variability. ANML formatting could facilitate comparison of biomarker results with other studies that utilize this format. We expect SomaScan to provide novel and reproducible information in patients with kidney failure on dialysis.


Increased risk of dislocation after primary total hip arthroplasty in inflammatory arthritis: a prospective observational study of 410 hips.
It is unclear whether patients with inflammatory arthritis have a higher risk of dislocation after hip replacement. We carried out a prospective study assessing the incidence of dislocation within 2 years after surgery for patients diagnosed with inflammatory arthritis (IA) and osteoarthrosis (OA). One single type of prosthesis was implanted using a lateral approach. Both diagnostic groups were compared by univariate analysis with respect to dislocation, sex, age, diagnosis, prior hip surgery, experience of the surgeon and malposition of the acetabular component. In a multivariate logistic regression approach, the difference in dislocation incidence was assessed after adjusting for the effect of the potential confounders given above. Between 1996 and 1999, 410 THA were performed: 70 in IA and 340 in OA. After 2 years no patients were lost to follow-up, but 12 patients had died, and 5 revisions were carried out for reasons other than dislocation. The dislocation rate in patients with IA was higher than in patients with OA: 10% (7 hips) in the IA group and 3% (10 hips) in the OA group (p = 0.006). No significant differences were found among the risk factors for dislocation between the two groups. Multivariate logistic regression analysis showed that IA is an independent risk factor for dislocation (odds ratio (OR) 3.7, 95% CI 1.3-11), together with malposition of the cup in more than 55 degrees abduction (OR 7.7, CI 2.3-26) and increased anteversion (OR 7.6, CI 1.4-42.4). Our findings clearly suggest that inflammatory arthritis has to be considered as an independent risk factor for dislocation after primary THA.


Quantitation of corneal neovascularization using computerized image analysis.
We have developed a method for quantitating corneal neovascularization, induced in anesthetized rats by silver nitrate/potassium nitrate cauterization, using a LeMont OASYS video input image analyzer. Corneal vessels are visualized by perfusing the upper half of deeply anesthetized animals with a mixture of 10% india ink, 11% gelatin in lactated Ringer's solution. The eyes are then rapidly cooled using a stream of compressed dichlorodifluoromethane (Freon) to solidify the gelatin mixture. Magnified images of flat preparations of the corneas are acquired using a television camera attached to a dissecting microscope. The images are electronically converted to digital form and the digitized data are stored in the image analyzer. The area of the cornea and blood vessels are independently determined by analyzing the digitized data as discrete values of varying shades of gray (gray-scale analysis). The area and gray scale of the injury and its distance from the corneoscleral limbus can also be measured to determine variability of location and intensity of the injury in different animals. This technique allows the area occupied by new blood vessels during studies on corneal neovascularization in rats to be rapidly quantitated.


Clinical features and management outcomes of severe hand, foot and mouth disease.
This study was designed to describe the clinical features and management outcomes of severe hand, foot and mouth disease (HFMD). Data on 147 severe HFMD patients during an outbreak in 2009 were analyzed. Most patients were under 3 years of age; 102 (69.4%) were boys. All had skin rashes and fever of ≥38°C. All (n = 147, 100%) showed signs of central nervous system involvement, such as lethargy (n = 124, 84.4%), myoclonic jerks (n = 76, 51.7%), or drowsiness (n = 34, 23.1%). Respiratory symptoms were mainly tachypnea (n = 112, 76.2%) or bradypnea (n = 21, 14.3%). Common cardiovascular symptoms included tachycardia (n = 134, 91.2%) and hypertension (n = 23, 15.5%). Chest X-ray showed increased markings in 76 (51.7%) or consolidation in 44 (29.9%). Hyperglycemia and elevated blood lactic acid levels were found in 127 (86.4%) and 130 (88.4%), respectively. Positive enterovirus EV71-PCR was found in 113 (76.9%). All patients were treated with mechanical ventilation for 61.2 ± 12.8 h (range, 40-96 h), as well as mannitol, dexamethasone, gamma globulin and ribavirin. Dopamine, dobutamine or amrinone was administered in 58.5, 51.0 and 21.8%, respectively. Three patients (2%) died during hospitalization. All others had a full recovery and were discharged after 14.2 ± 1.6 days (range, 12-17 days). Central nervous and cardiorespiratory systems were involved in the patients with severe HFMD. Fasting blood glucose and lactic acid levels increased in the majority of patients. Mechanical ventilation and supportive pharmacotherapy were associated with a good clinical outcome in these patients.


Temporal variations of health indicators in Iran comparing with other Eastern Mediterranean Region countries in the last two decades.
The recent significant improvement in most health indicators in Iran has not been explored deeply particularly in comparison with other countries in Eastern Mediterranean Region (EMR). We aimed to explore the temporal variations of five main indicators in Iran and compare their variations in EMR countries. Data on DPT vaccination and birth weight were obtained from EMR office reports, and total fertility rate, under 5 mortality rate (U5MR) and adult literacy rate (ALR) were obtained from WHO sources for the time period 1995-2005. Using linear regression, we modeled the temporal variations in Iran and other EMR countries classified by their human development index (HDI) levels. The estimated annual decline rate of U5MR in Iran as a middle HDI country was 2.5 per 1000 live birth which was much greater than the corresponding number in countries with medium HDI (1.85) and very close to countries with high HDI (2.67). The WHO data showed that Iran was very successful in increasing ALR. It seems that most health indicators in Iran have improved more rapidly compared with countries with low and medium HDI in EMR. The improvement rates were also very close to countries with high HDI in the region.


The oppD Gene and Putative Peptidase Genes May Be Required for Virulence in Mycoplasma gallisepticum.
Relatively few virulence genes have been identified in pathogenic mycoplasmas, so we used signature-tagged mutagenesis to identify mutants of the avian pathogen Mycoplasma gallisepticum with a reduced capacity to persist in vivo and compared the levels of virulence of selected mutants in experimentally infected chickens. Four mutants had insertions in one of the two incomplete oppABCDF operons, and a further three had insertions in distinct hypothetical genes, two containing peptidase motifs and one containing a member of a gene family. The three hypothetical gene mutants and the two with insertions in oppD1 were used to infect chickens, and all five were shown to have a reduced capacity to induce respiratory tract lesions. One oppD1 mutant and the MGA_1102 and MGA_1079 mutants had a greatly reduced capacity to persist in the respiratory tract and to induce systemic antibody responses against M. gallisepticum The other oppD1 mutant and the MGA_0588 mutant had less capacity than the wild type to persist in the respiratory tract but did elicit systemic antibody responses. Although M. gallisepticum carries two incomplete opp operons, one of which has been acquired by horizontal gene transfer, our results suggest that one of the copies of oppD may be required for full expression of virulence. We have also shown that three hypothetical genes, two of which encode putative peptidases, may be required for full expression of virulence in M. gallisepticum. None of these genes has previously been shown to influence virulence in pathogenic mycoplasmas.


Detection and Typing of Norovirus from Frozen Strawberries Involved in a Large-Scale Gastroenteritis Outbreak in Germany.
During September/October 2012, a norovirus gastroenteritis outbreak affecting about 11,000 people occurred in Germany. Epidemiological studies suggested that frozen strawberries represented the vehicle of infection. We describe here the analysis of frozen strawberries for the presence of norovirus. Samples were taken by applying a stratified subsampling scheme. Two different methods for virus extraction from strawberries were compared. First, viruses were eluted from strawberries under alkaline conditions and concentrated using a polyethylene glycol precipitation. Second, ultrafiltration was applied for concentration of viruses rinsed off of the berries. In both cases, RNA was extracted and analyzed by real-time RT-PCR. Application of the ultrafiltration method generally resulted in a lower detection rate. Noroviruses were detected in 7/11 samples derived from the lot of strawberries implicated in the outbreak using the precipitation method. Typing of norovirus revealed three different genotypes including a combination of norovirus genotype II.16 (viral polymerase) and II.13 (viral capsid). This genotype combination was also found in some of the patients that were involved in the outbreak, but that had not been reported in Germany so far. In conclusion, heterogeneously distributed noroviruses in frozen strawberries can be detected by applying an optimized combination of sampling procedures, virus extraction methods, and real-time RT-PCR protocols. The detection of several different genotypes in the strawberries may suggest contamination from sewage rather than from a single infected food handler.


Comparative Efficacy of Red Beetroot Extract and Ozonated Olive Oil on Wound Healing in Rats.
To compare and assess the effect of red beetroot extract and ozonated olive oil on wound healing in rats. Experimental study. Place and Duration of the Study: Department of Experimental Animal Research Laboratory, Faculty of Medicine, Aydin Adnan Menderes University, from June to July 2021. Twenty-one, female Wistar albino rats were divided into 3 groups; red beetroot extract group (RBG, n=7), ozonated olive oil group (OOG, n=7), and physiological saline group (CG). Three round wound areas of similar shapes were produced on the back areas. Skin incisions with a diameter of 15 mm were made in rats with a scalpel under anaesthesia protocol. Beetroot extract was applied to RBG, ozonated olive oil to OOG, and saline to CG, once a day for 21 days. Tissue samples were taken from the wounds on the 3rd, 10th, and 21st day of the study, and a histopathological examination (Hematoxylin eosin staining) was performed for haemorrhage, congestion, necrosis, inflammation and fibrosis levels. Wound healing was also determined macroscopically by photography on same days. Serum oxidant (TOS, μmol H2O2 equivalents/L), antioxidant status (TAS, mmol trolox equivalents/L), serum total thiol (μmol/L), serum native thiol (μmol/L) and paraoxonase (PON, U/L) were determined from blood samples on the 21st day. Lower inflammation and higher blood antioxidant levels were determined in the RGB and OOG groups compared to the CG. A better wound healing on histology was observed in the OOG group compared to RGB. Red beetroot extract and ozonated olive oil enhanced wound healing in female rats. Ozonated olive oil had more effective wound-healing effect than beetroot extract. Wound healing, Ozonated olive oil, Red beetroot extract, Antioxidant effect.


Mixed arteriovenous occlusive disease of the fundus.
Sudden loss of vision occurred in two young healthy patients who had the clinical findings of partial retinal artery and partial retinal vein occlusion. This might represent a severe variant of papillophlebitis.


Macroscopic Alignment of Block Copolymers on Silicon Substrates by Laser Annealing.
Laser annealing is a competitive alternative to conventional oven annealing of block copolymer (BCP) thin films enabling rapid acceleration and precise spatial control of the self-assembly process. Localized heating by a moving laser beam (zone annealing), taking advantage of steep temperature gradients, can additionally yield aligned morphologies. In its original implementation it was limited to specialized germanium-coated glass substrates, which absorb visible light and exhibit low-enough thermal conductivity to facilitate heating at relatively low irradiation power density. Here, we demonstrate a recent advance in laser zone annealing, which utilizes a powerful fiber-coupled near-IR laser source allowing rapid BCP annealing over a large area on conventional silicon wafers. The annealing coupled with photothermal shearing yields macroscopically aligned BCP films, which are used as templates for patterning metallic nanowires. We also report a facile method of transferring laser-annealed BCP films onto arbitrary surfaces. The transfer process allows patterning substrates with a highly corrugated surface and single-step rapid fabrication of multilayered nanomaterials with complex morphologies.


Chromatin accessibility and pioneer factor FOXA1 restrict glucocorticoid receptor action in prostate cancer.
Treatment of prostate cancer relies predominantly on the inhibition of androgen receptor (AR) signaling. Despite the initial effectiveness of the antiandrogen therapies, the cancer often develops resistance to the AR blockade. One mechanism of the resistance is glucocorticoid receptor (GR)-mediated replacement of AR function. Nevertheless, the mechanistic ways and means how the GR-mediated antiandrogen resistance occurs have remained elusive. Here, we have discovered several crucial features of GR action in prostate cancer cells through genome-wide techniques. We detected that the replacement of AR by GR in enzalutamide-exposed prostate cancer cells occurs almost exclusively at pre-accessible chromatin sites displaying FOXA1 occupancy. Counterintuitively to the classical pioneer factor model, silencing of FOXA1 potentiated the chromatin binding and transcriptional activity of GR. This was attributed to FOXA1-mediated repression of the NR3C1 (gene encoding GR) expression via the corepressor TLE3. Moreover, the small-molecule inhibition of coactivator p300's enzymatic activity efficiently restricted GR-mediated gene regulation and cell proliferation. Overall, we identified chromatin pre-accessibility and FOXA1-mediated repression as important regulators of GR action in prostate cancer, pointing out new avenues to oppose steroid receptor-mediated antiandrogen resistance.


Fecal Dysbiosis and Inflammation in Intestinal-Specific Cftr Knockout Mice on Regimens Preventing Intestinal Obstruction.
Chronic intestinal inflammation is a poorly understood manifestation of Cystic Fibrosis (CF), which may be refractory to ion channel CFTR modulator therapy. People with CF exhibit intestinal dysbiosis which has potential for stimulating intestinal and systemic inflammation. CFTR is expressed in organ epithelia and in the leukocyte population. Here, we investigate the contribution of intestinal epithelial-specific loss of Cftr (iCftr KO) to dysbiosis and inflammation in mice treated with either of two anti-obstructive dietary regimens necessary to maintain CF mouse models (PEG laxative or a liquid diet, LiqD). Feces collected from iCftr KO mice and their wildtype (WT) sex-matched littermates were used to measure fecal calprotectin and to perform 16S rRNA sequencing to characterize the gut microbiome. Fecal calprotectin was elevated in iCftr KO relative to WT samples of mice consuming either PEG or LiqD. PEG iCftr KO mice did not show a change in a-diversity versus WT but demonstrated a significant difference in microbial composition (b-diversity) with increases in phylum Proteobacteria, family Peptostreptococcaceae, four genera of Clostridia including C. innocuum, and mucolytic genus Akkermansia. Fecal microbiome analysis of LiqD iCftr KO mice showed both decreased a-diversity and differences in microbial composition with increases in Proteobacteria family Enterobacteriaceae, Firmicutes families Clostridiaceae and Peptostreptococcaceae, and enrichment of Clostridium perfringens, C. innocuum, C. difficile, mucolytic Ruminococcus gnavus, and reduction of Akkermansia. It was concluded that epithelial-specific loss of Cftr is a major driver of CF intestinal dysbiosis and inflammation with significant similarities to previous studies of global Cftr KO mice.


Brorin is required for neurogenesis, gliogenesis, and commissural axon guidance in the zebrafish forebrain.
Bmps regulate numerous neural functions with their regulators. We previously identified Brorin, a neural-specific secreted antagonist of Bmp signaling, in humans, mice, and zebrafish. Mouse Brorin has two cysteine-rich domains containing 10 cysteine residues in its core region, and these are located in similar positions to those in the cysteine-rich domains of Chordin family members, which are secreted Bmp antagonists. Zebrafish Brorin had two cysteine-rich domains with high similarity to those of mouse Brorin. We herein examined zebrafish brorin in order to elucidate its in vivo actions. Zebrafish brorin was predominantly expressed in developing neural tissues. The overexpression of brorin led to the inactivation of Bmp signaling. On the other hand, the knockdown of brorin resulted in the activation of Bmp signaling and brorin morphants exhibited defective development of the ventral domain in the forebrain. Furthermore, the knockdown of brorin inhibited the generation of γ-aminobutyric acid (GABA)ergic interneurons and oligodendrocytes and promoted the generation of astrocytes in the forebrain. In addition, brorin was required for axon guidance in the forebrain. The present results suggest that Brorin is a secreted Bmp antagonist predominantly expressed in developing neural tissues and that it plays multiple roles in the development of the zebrafish forebrain.


Impacts of dung combustion on the carbon cycle of alpine grassland of the north Tibetan plateau.
Alpine grassland of Tibet is a frangible ecosystem in terms of carbon (C) emission. Yak dung is an important resident energy with about 80 % of yak dung combusted for energy in the north Tibetan plateau. This paper investigated the impact of dung combustion on the C cycle of the alpine grassland ecosystem in north Tibet, China. During the growing season of 2011, from a field survey and household questionnaires, the main impacts of dung collection for fuel on the C cycle of the ecosystem were identified. (1) The C sequestration and storage capacity, including the dung-derived C stored in soil and C captured by vegetation, decreased. The net primary production decreased remarkably because of the reduction of dung returned to soil. (2) In a given period, more C was emitted to the atmosphere in the dung combustion situation than that in the dung returned to soil situation. (3) The energy grazing alpine meadow ecosystem changed into a net C source, and the net biome production of the ecosystem dropped to -15.18 g C/m2 year in the dung combustion situation, 42.95 g C/m2 year less than that in the dung returned situation. To reduce the CO2 emission derived from dung use, the proportion of dung combustion should be reduced and alternative renewable energy such as solar, wind, or hydro energy should be advocated, which is suitable for, and accessible to, the north Tibetan plateau.