[Main principals of clinical diagnosis formation in peritonitis].
Based on great clinical experience (more 1000 patients) the author makes attempt to standardize classification of peritonitis. Bearing in mind the critical analysis of available peritonitis classifications, it is proposed to divide toxic phase of peritonitis (by K.S. Simonyan) into two variants--with poliorganic insufficiency or without it. This elaboration permits to make the treatment of the patients with general peritonitis more detailed. Besides, the changes were made in division of peritonitis by degree of generalization along peritoneum, it is proposed to distinguish only 4 types by abdominal exudate character that also determine the actions of surgeon. Individual surgical situations in various forms and types of peritonitis are analyzed. The own model of peritonitis classification permits to receive comparable immediate results of treatment.


Long-term results of nonoperative treatment for uncomplicated acute appendicitis.
This study aimed to assess the long-term (>12 months) efficacy of nonoperative treatment (antibiotic administration) in the management of uncomplicated acute appendicitis (AA). We surveyed uncomplicated AA patients who elected to undergo nonoperative treatment between 2010 and 2012. A binary logistic regression analysis was performed to identify the critical predictors of recurrence. Age, gender, presence of appendicolith, and white blood cell count on admission were analyzed as possible predictors of recurrence. The median follow-up period of the study was 23 months. Twelve of 118 patients (10.2%) were diagnosed with recurrent appendicitis. Seven were retreated with the same antibiotic protocol and did not show further recurrence. The binary logistic regression analysis revealed statistical significance only for the presence of appendicolith [P=0.001, Exp (B)=0.058, B=-2.845]. Recurrence rate was lower in the presence of appendicolith. Nonoperative treatment of uncomplicated AA is an effective option. Recurrence is rare and it can be addressed efficiently with the administration of a second course of antibiotics. The presence of appendicolith should not discourage physicians from prescribing nonoperative treatment for patients with uncomplicated AA.


Determination of the Perception Level of Life Style Innovations in Type 2 Diabetes Mellitus.
In this tudy, our aim was to measure information and behaviors of our patients about their diseases, and to determine the level of compliance with their treatment and to investigate the causes of nonconformities. A total of 111 patients who applied to outpatient clinics between May-December 2017 were included in this prospective cross-sectional study. Sociodemographic, clinical data, diabetes, medical nutrition therapy and physical activity questionnaires were administered face to face by the researchers. About 68.5% of the 111 patients were females. While 64.9% were primary school graduates, 58.6% were housewives and 82.9% were low income level. Body Mass Index (BMI) was found to be significantly higher in women (p=0.041). It has been found that the awareness of the patients about themselves and their illnesses are 37.8% for HbA1c, 64.8% for fasting blood sugar level, 78.3% for their height and body weight. While males had a higher score than females in the diabetes survey, females scored higher than males in the medical nutrition therapy and physical activity questionnaires. On the other hand, 46.8% of patients showed additional health problems as a cause of non-compliance to physical activity. Level of knowledge and compliance with treatment were also found to be inadequate.


Treatment of sebopsoriasis. A clinical trial--an etiological approach.
1% Bifonazole cream and gel were used for the local therapy of sebopsoriasis and psoriasis in a pilot study with 20 patients. 3 of the 9 patients with psoriasis and 9 of the 11 patients with sebopsoriasis had improved markedly. The mechanisms of the effectiveness of this therapy will be discussed together with the results of some provocation tests with bacterial antigens.


Repair of scleral rupture and total retinal detachment in a self-injuring psychotic patient under local anesthesia: a case report.
Ocular self-injury by psychotic patients is an uncommon cause of ocular morbidity that poses peculiar problems. This report describes a schizophrenic self-injuring patient with scleral rupture and retinal detachment (RD), treated under loco-regional anesthesia. A 65-year-old man presented with scleral rupture, hyphema, traumatic lens luxation, vitreous prolapse, vitreous hemorrhage and total RD after deliberately hitting his head. The fellow eye had been successfully operated with scleral buckle surgery for the same reason two years earlier. The patient underwent a two-step surgical procedure under local anesthesia, with repositioning and resection of the uveal prolapse and scleral rupture repair and, separately, lens removal pars plana vitrectomy (PPV), membrane peeling, retinotomy, laser treatment and SiO tamponade. Twelve months after PPV, the cornea was clear, IOP was 16 mmHg, the retina was attached and VA was 20/200. The fellow eye maintained 20/30 VA. In psychotic patients the intrinsic difficulty of a traumatic RD is combined with systemic illness, no compliance and the risk of recurrence. Although ocular traumas usually require general anesthesia, this patient underwent both interventions under local anesthesia with sedation, because of his psychotic condition and chronic liver failure. Local anesthesia and sedation proved effective in controlling pain and intra-operative compliance even in such a difficult patient. Although it is reasonable to question operating on such patients, we nonetheless believe that every attempt should always be made at gaining useful vision in both eyes since these patients are at a high risk of recurrent ocular trauma.


Patient-reported outcomes and considerations in the management of COPD: focus on aclidinium.
Chronic obstructive pulmonary disease (COPD) is a complex heterogeneous disease, in which several factors combine to give the final clinical expression. Both early and more recent studies have shown that forced expiratory volume in one second (FEV1), despite being an extremely important parameter to predict the progression of the disease, is a poor surrogate marker for symptoms perception. Accordingly, patient-reported outcomes (PROs) have gained popularity as a measure of the impact of treatment from the patients' perspective, since they represent the individuals' perception of their health status, beyond any physiological limitations. Several such PROs, therefore, are currently included in multidimensional COPD evaluation. This multidimensional approach helps identify different patient types and individualize, up to a certain point, pharmacological treatment. In this multidimensional approach it is important to highlight the importance of long-acting bronchodilators in COPD treatment strategies. Long-acting bronchodilators are cost-effective and have been shown to achieve the greatest functional and clinical improvements in COPD. As a result, long-acting bronchodilators are now the main pharmacological treatment for COPD at all stages of the disease. Until recently, tiotropium was the leading bronchodilator for the treatment of COPD. The clinical development of this medication, unprecedented in inhaled therapy, involved tens of thousands of patients and yielded consistent outcomes in terms of lung function, symptoms, quality of life, exacerbations, and prognosis. However, new long-acting bronchodilators have recently been developed or are currently under development. In this review, we evaluate the effects of aclidinium bromide, a novel long-acting bronchodilator, on PROs in COPD. Aclidinium is a novel long-acting muscarinic antagonist with a good safety profile for the treatment of COPD, and has proven efficacy in both objective functional measurements and PROs. Comparison studies with tiotropium have shown it to have similar lung function improvement and a similar impact on PROs, including quality of life or symptom perception.


Zebrafish models of dyslipidemia: relevance to atherosclerosis and angiogenesis.
Lipid and lipoprotein metabolism in zebrafish and in humans are remarkably similar. Zebrafish express all major nuclear receptors, lipid transporters, apolipoproteins and enzymes involved in lipoprotein metabolism. Unlike mice, zebrafish express cetp and the Cetp activity is detected in zebrafish plasma. Feeding zebrafish a high cholesterol diet, without any genetic intervention, results in significant hypercholesterolemia and robust lipoprotein oxidation, making zebrafish an attractive animal model to study mechanisms relevant to early development of human atherosclerosis. These studies are facilitated by the optical transparency of zebrafish larvae and the availability of transgenic zebrafish expressing fluorescent proteins in endothelial cells and macrophages. Thus, vascular processes can be monitored in live animals. In this review article, we discuss recent advances in using dyslipidemic zebrafish in atherosclerosis-related studies. We also summarize recent work connecting lipid metabolism with regulation of angiogenesis, the work that considerably benefited from using the zebrafish model. These studies uncovered the role of aibp, abca1, abcg1, mtp, apoB, and apoC2 in regulation of angiogenesis in zebrafish and paved the way for future studies in mammals, which may suggest new therapeutic approaches to modulation of excessive or diminished angiogenesis contributing to the pathogenesis of human disease.


The genetic and molecular basis of haploinsufficiency in flowering plants.
In diploid organisms, haploinsufficiency can be defined as the requirement for more than one fully functional copy of a gene. In contrast to most genes, whose loss-of-function alleles are recessive, loss-of-function alleles of haploinsufficient genes are dominant. However, forward and reverse genetic screens are biased toward obtaining recessive, loss-of-function mutations, and therefore, dominant mutations of all types are underrepresented in mutant collections. Despite this underrepresentation, haploinsufficient loci have intriguing implications for studies of genome evolution, gene dosage, stability of protein complexes, genetic redundancy, and gene expression. Here we review examples of haploinsufficiency in flowering plants and describe the underlying molecular mechanisms and evolutionary forces driving haploinsufficiency. Finally, we discuss the masking of haploinsufficiency by genetic redundancy, a widespread phenomenon among angiosperms.


Fractal free energy landscapes in structural glasses.
Glasses are amorphous solids whose constituent particles are caged by their neighbours and thus cannot flow. This sluggishness is often ascribed to the free energy landscape containing multiple minima (basins) separated by high barriers. Here we show, using theory and numerical simulation, that the landscape is much rougher than is classically assumed. Deep in the glass, it undergoes a 'roughness transition' to fractal basins, which brings about isostaticity and marginal stability on approaching jamming. Critical exponents for the basin width, the weak force distribution and the spatial spread of quasi-contacts near jamming can be analytically determined. Their value is found to be compatible with numerical observations. This advance incorporates the jamming transition of granular materials into the framework of glass theory. Because temperature and pressure control what features of the landscape are experienced, glass mechanics and transport are expected to reflect the features of the topology we discuss here.


Protective effects of medicinal plant breviscapine on postcerebral hemorrhage in rats.
Medicinal plant breviscapine is shown to exhibit a protective role in tissue damage after cerebral hemorrhage. The effects of breviscapine on neurological deficit score, brain tissue water content, brain pathological tissue changes, blood-brain barrier bidirectional regulation, and inflammatory factors after cerebral hemorrhage in rats were observed. Western blot and real-time quantitative polymerase chain reaction were performed to explore how Periostin and nuclear factor kappa-B pathway-related factors protein expression contribute to the protective effects of breviscapine on brain injury. Breviscapine inhalation could reduce neurological deficit scores and brain tissue water content. Hematoxylin-eosin staining showed that breviscapine could improve the pathological changes of brain tissue and alleviate brain damage. Breviscapine reduced the abnormal increase of Evans blue content caused by a cerebral hemorrhage, and could significantly inhibit the levels of inflammatory factors interleukin-6 and tumor necrosis factor-α. Also, breviscapine significantly inhibited the expressions of Periostin and nuclear factor kappa-B pathway-related factors after cerebral hemorrhage, and alleviate brain damage by down-regulating Periostin expression and inhibiting nuclear factor kappa-β signaling pathway.


Phase I and pharmacokinetic study of LM985 (flavone acetic acid ester).
We have conducted a Phase I and initial clinical pharmacological evaluation of LM985, the first of a series of compounds based on the flavone ring structure to be considered for clinical trial in malignant disease. The drug was administered i.v. to 26 patients with advanced cancer on an every-21-day schedule. Patients were treated at 14 dosage levels ranging from 10 to 1500 mg/m2. Dose limiting toxicity was identified as acute reversible hypotension occurring during drug infusion; no leukopenia, alopecia, hepatic toxicity, or renal toxicity was observed, but at the higher dose range, mild sedation was apparent. Twenty patients had measurable disease and were evaluable for response. One patient with colorectal carcinoma had stable disease after three courses of LM985; however, no other responses were seen. Pharmacokinetic and in vitro drug degradation studies imply that the ester LM985 is hydrolyzed to LM975 (flavone acetic acid) rapidly in vivo. LM975 is active in a variety of animal tumor models, but it does not have the cardiovascular side effects seen with LM985 (hypotension and bradycardia) in pithed or anesthetized rats. We would recommend that LM975 be considered for clinical trial, because it seems likely that substantially higher doses of LM975 than of LM985 can be given without dose limiting cardiovascular toxicity.


Systematic Review: Guideline-Based Approach for the Management of Asthma and Subtypes via Chinese Medicine.
Asthma is a chronic condition that results in the inflammation and narrowing of airways, often clinically presenting as wheeze and shortness of breath. Little is known of the mechanisms of action (MOA) of herbs used to treat asthma. The aim of this study is to review existing data regarding known MOA of traditional Chinese medicine which will aid in the understanding of possible interactions between Western drugs and Chinese herbs as well as the standardization of management via a proposed guideline to improve patient safety and possible synergism in the long term. We searched through 5 databases for commonly prescribed herbs and formulas for asthma and narrowed down the search to identify the underlying MOA of individual herbs that could specifically target asthma symptoms. We included studies that stated the MOA of individual herbs when used for treating symptoms of asthma, excluding them if they are described as part of a formula. A total of 26 herbs commonly prescribed for asthma with known mechanism of action were identified. Herbs used for asthma were found to have similar MOA as that for drugs. Based on existing GINA guidelines, a guideline is proposed which includes a total of 5 steps depending on the severity of asthma and the herbs' MOA. 16 formulas were subsequently identified for the management of asthma, which consist of 12 "stand-alone" and 4 "add-on" formulas. "Stand-alone" formulas used independently for asthma generally follow the GINA guidelines but do not proceed beyond step 3. These formulas consist mainly of beta-agonist and steroid-like effects. "Add-on" formulas added as adjunct to "stand-alone" formulas, however, mainly act on T helper cells or have steroid-like effects. Through the understanding of MOA of herbs and their respective formulas, it will ensue greater patient safety and outcomes.


Vitamin D-binding protein in cerebrospinal fluid is associated with multiple sclerosis progression.
Multiple sclerosis is a neurological disorder that presents with symptoms including inflammation, neurodegeneration, and demyelination of the central nervous system (CNS). Secondary progressive multiple sclerosis (SPMS) manifests with serious physical disability. To quantitatively analyze differential protein expression in patients with SPMS, we performed two-dimensional fluorescence difference in-gel electrophoresis, followed by mass spectrometry on the cerebrospinal fluid of these patients and patients with other neurological diseases. Vitamin D-binding protein (DBP), gelsolin, albumin, etc. showed more than a 1.5-fold difference between the two groups. Based on these results, an experimental allergic encephalomyelitis (EAE) model of multiple sclerosis in Lewis rats was used to investigate DBP's role in the disease. Protein levels, mRNA transcripts, and ligands of DBP in different regions of the CNS were evaluated under various vitamin D intake levels. Here, DBP levels increased in the experimental rat groups compared to the control groups regardless of vitamin D intake. Moreover, DBP mRNA levels varied in different parts of the CNS including spinal cords in the experimental groups. The observed differences between DBP protein and mRNA levels in the experimental groups' spinal cords could be derived from the disruption of the blood-brain barrier. Furthermore, an interaction between DBP and actin was confirmed using coimmunoprecipitation and western blot. These results indicate a role for DBP in the actin scavenge system. Moreover, in the experimental group that received oral vitamin D3 supplement, we observed both delayed onset and diminished severity of the disease. When DBP was upregulated, however, the benefits from the vitamin D3 supplements were lost. Thus, we inferred that high levels of DBP were adverse to recovery. In conclusion, here we observed upregulated DBP in the cerebrospinal fluid could serve as a specific diagnostic biomarker for the progression of multiple sclerosis. Next, we demonstrate the vital function of increased levels of free vitamin D metabolites for multiple sclerosis treatment. Finally, vitamin D supplements may be particularly beneficial for SPMS patients.


Faster Movement Speed Results in Greater Tendon Strain during the Loaded Squat Exercise.
Tendon dynamics influence movement performance and provide the stimulus for long-term tendon adaptation. As tendon strain increases with load magnitude and decreases with loading rate, changes in movement speed during exercise should influence tendon strain. Ten resistance-trained men [squat one repetition maximum (1RM) to body mass ratio: 1.65 ± 0.12] performed parallel-depth back squat lifts with 60% of 1RM load at three different speeds: slow fixed-tempo (TS: 2-s eccentric, 1-s pause, 2-s concentric), volitional-speed without a pause (VS) and maximum-speed jump (JS). In each condition joint kinetics, quadriceps tendon length (LT), patellar tendon force (FT), and rate of force development (RFDT) were estimated using integrated ultrasonography, motion-capture, and force platform recordings. Peak LT, FT, and RFDT were greater in JS than TS (p < 0.05), however no differences were observed between VS and TS. Thus, moving at faster speeds resulted in both greater tendon stress and strain despite an increased RFDT, as would be predicted of an elastic, but not a viscous, structure. Temporal comparisons showed that LT was greater in TS than JS during the early eccentric phase (10-14% movement duration) where peak RFDT occurred, demonstrating that the tendon's viscous properties predominated during initial eccentric loading. However, during the concentric phase (61-70 and 76-83% movement duration) differing FT and similar RFDT between conditions allowed for the tendon's elastic properties to predominate such that peak tendon strain was greater in JS than TS. Based on our current understanding, there may be an additional mechanical stimulus for tendon adaptation when performing large range-of-motion isoinertial exercises at faster movement speeds.


Marsupial tammar wallaby delivers milk bioactives to altricial pouch young to support lung development.
Our research is exploiting the marsupial as a model to understand the signals required for lung development. Marsupials have a unique reproductive strategy, the mother gives birth to altricial neonate with an immature lung and the changes in milk composition during lactation in marsupials appears to provide bioactives that can regulate diverse aspects of lung development, including branching morphogenesis, cell proliferation and cell differentiation. These effects are seen with milk collected between 25 and 100days postpartum. To better understand the temporal effects of milk composition on postnatal lung development we used a cross-fostering technique to restrict the tammar pouch young to milk composition not extending beyond day 25 for 45days of its early postnatal life. These particular time points were selected as our previous study showed that milk protein collected prior to ~day 25 had no developmental effect on mouse embryonic lungs in culture. The comparative analysis of the foster group and control young at day 45 postpartum demonstrated that foster pouch young had significantly reduced lung size. The lungs in fostered young were comprised of large intermediate tissue, had a reduced size of airway lumen and a higher percentage of parenchymal tissue. In addition, expression of marker genes for lung development (BMP4, WNT11, AQP-4, HOPX and SPB) were significantly reduced in lungs from fostered young. Further, to identify the potential bioactive expressed by mammary gland that may have developmental effect on pouch young lungs, we performed proteomics analysis on tammar milk through mass-spectrometry and listed the potential bioactives (PDGF, IGFBP5, IGFBPL1 and EGFL6) secreted in milk that may be involved in regulating pouch young lung development. The data suggest that postnatal lung development in the tammar young is most likely regulated by maternal signalling factors supplied through milk.


Genome-wide identification and expression analysis of glutathione S-transferase gene family in tomato: Gaining an insight to their physiological and stress-specific roles.
Glutathione S-transferase (GST) refers to one of the major detoxifying enzymes that plays an important role in different abiotic and biotic stress modulation pathways of plant. The present study aimed to a comprehensive genome-wide functional characterization of GST genes and proteins in tomato (Solanum lycopersicum L.). The whole genome sequence analysis revealed the presence of 90 GST genes in tomato, the largest GST gene family reported till date. Eight segmental duplicated gene pairs might contribute significantly to the expansion of SlGST gene family. Based on phylogenetic analysis of tomato, rice, and Arabidopsis GST proteins, GST family members could be further divided into ten classes. Members of each orthologous class showed high conservancy among themselves. Tau and lambda are the major classes of tomato; while tau and phi are the major classes for rice and Arabidopsis. Chromosomal localization revealed highly uneven distribution of SlGST genes in 13 different chromosomes, where chromosome 9 possessed the highest number of genes. Based on publicly available microarray data, expression analysis of 30 available SlGST genes exhibited a differential pattern in all the analyzed tissues and developmental stages. Moreover, most of the members showed highly induced expression in response to multiple biotic and abiotic stress inducers that could be harmonized with the increase in total GST enzyme activity under several stress conditions. Activity of tomato GST could be enhanced further by using some positive modulators (safeners) that have been predicted through molecular docking of SlGSTU5 and ligands. Moreover, tomato GST proteins are predicted to interact with a lot of other glutathione synthesizing and utilizing enzymes such as glutathione peroxidase, glutathione reductase, glutathione synthetase and γ-glutamyltransferase. This comprehensive genome-wide analysis and expression profiling would provide a rational platform and possibility to explore the versatile role of GST genes in crop engineering.


Six-Minute Walk Test Vs. Three-Minute Step Test for Measuring Functional Endurance.
The purpose of this study was to compare 2 practical measures of functional endurance. Specifically, the six-minute walk test (SMWT) and three-minute step test (TMST) were compared to determine their appropriateness for use as field tests and inclusion in the NIH Toolbox for the assessment of neurological and behavioral function. Individuals between 14 and 85 years performed both the SMWT and TMST in random order. We documented completion rates, criterion performance, heart rate responses, and subjective exertion associated with the 2 tests. All 189 participants completed the SMWT, but only 73.0% completed the TMST. Those completing the TMST were more likely to be male, report better health, and have a younger age and lower body mass index. The SMWT distance was greater for those who did vs. those who did not complete the TMST. For those completing both tests, the average distance walked in 6 minutes was 595.9 m; the average cumulative heart beats during the minute after the TMST was 107.4. Distance walked and cumulative heart beats correlated weakly. Average heart rate and perceived exertion were significantly higher after the TMST than the SMWT. Posttest heart rate and perceived exertion for the 2 tests correlated significantly but not strongly. We conclude that the SMWT is more likely to be completed and is usually less stressful physiologically than the TMST and therefore may be a better option for field testing functional endurance and inclusion in the NIH Toolbox.


Risk Factors for Urgent or Emergent Cholecystectomy Mid-workup for Symptomatic Cholelithiasis.
Patients who undergo cholecystectomy often do so for diagnoses related to the sequelae of gallstones. Many patients present acutely, requiring urgent removal due to complications of cholelithiasis. This study aims to characterize the patient population likely to present acutely during ongoing workup for cholelithiasis to better identify those who may benefit from expedited care. Medical records of all adult patients who underwent cholecystectomy for indications related to cholelithiasis between 2015 and 2016 were reviewed retrospectively. Qualitative data was analyzed using Chi square test and quantitative data was analyzed using independent t-tests. One hundred and seventy-four cholecystectomies were performed. Overall, 74.2% of the procedures were done electively while 25.8% were done urgently. And 42.2% of patients who underwent acute surgical intervention had evidence of prior workup. Patients requiring urgent intervention during ongoing diagnostic evaluation were more likely to have initially presented to an emergency department (ED) than another provider (68.4% vs 31.3%, P < .001) and had an odds ratio of 4.7 for undergoing acute intervention if they initially presented to the ED. They also tended to be more temporally remote from their initial diagnosis (119 ± 142 vs 74.6 ± 68.2 days, P < .19) relative to those who underwent elective operations. Patients who require urgent intervention during ongoing workup for cholelithiasis have prolonged courses of care and present to the ED more often for initial evaluation when compared to those who undergo elective intervention. These findings suggest that an emphasis on expedited workup of cholelithiasis and early surgical referral may be warranted, especially for those who initially present in the ED.


The cloning and mapping of ADR6, a gene required for sporulation and for expression of the alcohol dehydrogenase II isozyme from Saccharomyces cerevisiae.
The alcohol dehydrogenase II (ADH2) gene of the yeast, Saccharomyces cerevisiae, is not transcribed during growth on fermentable carbon sources such as glucose. Growth of yeast cells in a medium containing only nonfermentable carbon sources leads to a marked increase or derepression of ADH2 expression. The recessive mutation, adr6-1, leads to an inability to fully derepress ADH2 expression and to an inability to sporulate. The ADR6 gene product appears to act directly or indirectly on ADH2 sequences 3' to or including the presumptive TATAA box. The upstream activating sequence (UAS) located 5' to the TATAA box is not required for the Adr6- phenotype. Here, we describe the isolation of a recombinant plasmid containing the wild-type ADR6 gene. ADR6 codes for a 4.4-kb RNA which is present during growth both on glucose and on nonfermentable carbon sources. Disruption of the ADR6 transcription unit led to viable cells with decreased ADHII activity and an inability to sporulate. This indicates that both phenotypes result from mutations within a single gene and that the adr6-1 allele was representative of mutations at this locus. The ADR6 gene mapped to the left arm of chromosome XVI at a site 18 centimorgans from the centromere.


Invasive non-typhoidal Salmonella (iNTS) aminoglycoside-resistant ST313 isolates feature unique pathogenic mechanisms to reach the bloodstream.
Invasive non-typhoidal Salmonella (iNTS) from the clonal type ST313 (S. Typhimurium ST313) is the primary cause of invasive salmonellosis in Africa. Recently, in Brazil, iNTS ST313 strains have been isolated from different sources, but there is a lack of understanding of the mechanisms behind how these gut bacteria can break the gut barrier and reach the patient's bloodstream. Here, we compare 13 strains of S. Typhimurium ST313, previously unreported isolates, from human blood cultures, investigating aspects of virulence and mechanisms of resistance. Initially, RNAseq analyses between ST13-blood isolate and SL1344 (ST19) prototype revealed 15 upregulated genes directly related to cellular invasion and replication, such as sopD2, sifB, and pipB. Limited information is available about S. Typhimurium ST313 pathogenesis and epidemiology, especially related to the global distribution of strains. Herein, the correlation of strains isolated from different sources in Brazil was employed to compare clinical and non-clinical isolates, a total of 22 genomes were studied by single nucleotide polymorphism (SNPs). The epidemiological analysis of 22 genomes of S. Typhimurium ST313 strains grouped them into three distinct clusters (A, B, and C) by SNP analysis, where cluster A comprised five, group B six, and group C 11. The 13 clinical blood isolates were all resistant to streptomycin, 92.3% of strains were resistant to ampicillin and 15.39% were resistant to kanamycin. The resistance genes acrA, acrB, mdtK, emrB, emrR, mdsA, and mdsB related to the production of efflux pumps were detected in all (100%) strains studied, similar to pathogenic traits investigated. In conclusion, we evidenced that S. Typhimurium ST313 strains isolated in Brazil have unique epidemiology. The elevated frequencies of virulence genes such as sseJ, sopD2, and pipB are a major concern in these Brazilian isolates, showing a higher pathogenic potential.


The pentachlorophenol-dehalogenating Desulfitobacterium hafniense strain PCP-1.
In this report, a complete description of Desulfitobacterium hafniense strain PCP-1 is presented. The D. hafniense strain PCP-1 was isolated from a methanogenic consortium for its capacity to dehalogenate pentachlorophenol (PCP) into 3-chlorophenol. This strain is also capable of dehalogenating several other chloroaromatic compounds and tetrachloroethene into trichloroethene. Four gene loci encoding putative chlorophenol-reductive dehalogenases (CprA2 to CprA5) were detected, and the products of two of these loci have been demonstrated to dechlorinate different chlorinated phenols. Strain PCP-1 was used in laboratory-scale bioprocesses to degrade PCP present in contaminated environments. Desulfitobacterium hafniense PCP-1 is an excellent candidate for the development of efficient bioprocesses to degrade organohalide compounds.


Rehabilitation Following Hip Arthroscopy - A Systematic Review.
Rehabilitation following hip arthroscopy is an integral component of the clinical outcome of the procedure. Given the increase in quantity, complexity, and diversity of procedures performed, a need exists to define the role of rehabilitation following hip arthroscopy. (1) To determine the current rehabilitation protocols utilized following hip arthroscopy in the current literature, (2) to determine if clinical outcomes are significantly different based on different post-operative rehabilitation protocols, and (3) to propose the best-available evidence-based rehabilitation program following hip arthroscopy. Per PRISMA guidelines and checklist, Medline, SciVerse Scopus, SportDiscus, and Cochrane Central Register of Controlled Trials were searched. Level I-IV evidence clinical studies with minimum 2-year follow-up reporting outcomes of hip arthroscopy with post-operative rehabilitation protocols described were included. All study, subject, and surgery parameters were collected. All elements of rehabilitation were extracted and analyzed. Descriptive statistics were calculated. Study methodological quality was analyzed using the modified Coleman methodology score. Eighteen studies were included (2,092 subjects; 52% male, mean age 35.1 ± 10.6 years, mean follow-up 3.2 ± 1.0 years). Labral tear and femoroacetabular impingement were the most common diagnoses treated and labral debridement and femoral/acetabular osteochondroplasty the most common surgical techniques performed. Rehabilitation protocol parameters (weight-bearing, motion, strengthening, and return to sport) were poorly reported. Differences in clinical outcomes were unable to be assessed given heterogeneity in study reporting. Time-, phase-, goal-, and precaution-based guidelines were extracted and reported. The current literature of hip arthroscopy rehabilitation lacks high-quality evidence to support a specific protocol. Heterogeneity in study, subject, and surgical demographics precluded assimilation of protocols and/or outcomes to generate evidence-based guidelines. Strengths and limitations in the literature were identified. Future studies should recognize and report the essentials of rehabilitation following hip arthroscopy.


Management and Recommendations for Future Pregnancy in Patients with Early-Stage Endometrial Cancer: A Survey of Gynecologic Oncologists and Reproductive Endocrinology and Infertility Specialists.
Purpose: To determine how young patients with early-stage endometrial cancer are counseled regarding fertility preserving therapy and pregnancy options by gynecologic oncology and reproductive endocrinology and infertility (REI) providers. Methods: Anonymous online survey of Society of Gynecology Oncology (SGO) and the Society for Reproductive Endocrinology and Infertility (SREI) members; data were analyzed using chi-square and t-tests. Results: Twelve percent (169/1433) of SGO and 6.5% (60/927) of SREI members responded to the survey request. Most providers manage fewer than 10 fertility preservation patients annually. All gynecologic oncologists offer conservative management to patients with grade 1 endometrial cancer without evidence of invasion, and 40% would offer it to patients with grade 2 or <50% invasion. Magnetic resonance imaging was the most common method of assessing invasion, and the progesterone intrauterine device was the preferred first-line treatment. Two-thirds of providers would recommend hysterectomy if no endometrial response was noted by 12 months, two-thirds would continue conservative management for more than a year if a partial response was noted, and 70% would recommend hysterectomy after a patient completes childbearing. Comparatively, 60% of REI providers would recommend hysterectomy after childbearing. More gynecologic oncologists than REI providers recommend attempting spontaneous conception and for longer durations before initiating fertility treatments. Conclusion: Heterogeneous management styles exist among and between gynecologic oncology and REI providers for patients with early-stage endometrial cancer desiring future pregnancy. Improved guidelines are needed regarding treatment and monitoring surrounding trials of conception and pregnancy.


Phenolic Acids in Jerusalem Artichoke (Helianthus tuberosus L.): Plant Organ Dependent Antioxidant Activity and Optimized Extraction from Leaves.
Phenolic acids including chlorogenic acids are major polyphenolic compounds found in Jerusalem artichoke (Helianthus tuberosus L.). The plant itself is an emerging biorefinery crop due to the inulin-rich tubers, a bioethanol feedstock, but the aerial parts represent a rich source of bioactive compounds. We have determined the level of major phenolic acids in extracts of four plant organs: tuber, leaf, flower, and stem. Employing three heating conditions (20 °C, 60 °C, and microwaving), corrected total phenolic content (TPC) was highest in the leaves (4.5-5.7 mg gallic acid equivalents g-1 dry substance), followed by flower (2.1-2.9), tuber (0.9-1.4), and lowest in stem extracts (0.1-0.2). A previously overlooked interference of the Folin-Ciocalteu assay, namely a signal contribution from ascorbic acid, caused overestimation of TPC in various organs ranging from 65% to 94%. Radical scavenging activity of extracts correlated significantly with TPC, both on corrected (R2 = 0.841) and uncorrected (R2 = 0.884) values. Out of the identified phenolic acids determined by quantitative HPLC-UV analysis, chlorogenic and dicaffeoylquinic acids accounted for 72-82% of corrected TPC in leaf and tuber extracts. Optimization of leaf extraction was tested in a 23-factorial Central Composite Face (CCF) design. Temperature was the most important model term, and a solvent strength of less than 50% ethanol promoted the highest TPC yields. Further developments in extraction processing of crop residues may open avenues for improving the utilization of Jerusalem artichoke in valuable products.


Establishment of EMab-134, a Sensitive and Specific Anti-Epidermal Growth Factor Receptor Monoclonal Antibody for Detecting Squamous Cell Carcinoma Cells of the Oral Cavity.
Epidermal growth factor receptor (EGFR), a receptor tyrosine kinase, activates downstream signaling cascades in many tumors. In this study, we established novel anti-EGFR monoclonal antibodies (mAbs) and characterized their efficacy in flow cytometry, Western blot, and immunohistochemical analyses. We immunized mice with a combination of the extracellular domain of EGFR and EGFR-overexpressing LN229 glioblastoma cells (LN229/EGFR) and performed the first screening using enzyme-linked immunosorbent assay. Next, we selected mAbs using flow cytometry. Among 156 established clones, two mAbs, EMab-51 (IgG1, kappa) and EMab-134 (IgG1, kappa), reacted with EGFR in Western blot analysis; EMab-134 showed a much higher sensitivity compared with EMab-51. We compared the binding affinities of EMab-51 and EMab-134 using flow cytometry; the calculated KD values for EMab-51 and EMab-134 against SAS cells/HSC-2 cells were 9.2 × 10-9 M/9.9 × 10-9 M and 2.6 × 10-9 M/8.3 × 10-9 M, respectively, indicating that EMab-134 has a higher affinity to EGFR-expressing cells. Immunohistochemical analysis of EMab-51 and EMab-134 showed sensitive and specific reactions against oral cancer cells; EMab-134 demonstrated a much higher sensitivity (36/38 cases; 94.7%) to oral squamous cell carcinomas compared with EMab-51 (6/38 cases; 15.8%). This novel anti-EGFR mAb, EMab-134, could be advantageous for detecting EGFR in the pathological analysis of EGFR-expressing cancers.


Upper airway resistance syndrome and its treatment.
Although upper airway resistance syndrome (UARS) is being recognized by a growing number of specialists, its prevalence remains unknown. UARS is associated with nocturnal and daytime complaints and oro-naso-maxillo-mandibular signs. Spectrum analysis of the nocturnal sleep EEG from the central leads indicates significant differences in absolute power in the 12-14 Hz and the 7-9 Hz bands of UARS patients compared to controls. The 0.5-2.0 Hz band also appears to be involved when analyses performed on matched controls are compared to results obtained in subjects treated with nasal CPAP. Several treatment avenues--nasal CPAP, dental devices, surgical procedures, and radiofrequency thermal ablation--have been used for the treatment of UARS. The number of subjects treated have been too low and the protocols too limited to arrive at appropriate outcome recommendations, but many of the approaches have shown positive results, suggesting the possibility of several treatment avenues.


Identification of thioredoxin-2 as a regulator of the mitochondrial permeability transition.
Thioredoxin-2 (Trx2) is a multifunctional, mitochondria-specific protein, which inhibits cell death. The mitochondrial permeability transition (MPT) is a distinct mechanism for cell death activated by oxidants and linked to both necrotic and apoptotic morphologies. We studied mitochondria from Trx2 transgenic mice to determine whether Trx2 protects against oxidant-induced MPT. All experiments were performed in isolated mitochondria. Results showed that Trx2 protected against MPT induced by exogenously added peroxide. Unexpectedly, Trx2 also protected against the MPT induced by Ca(2+) in the absence of added peroxide. The results indicate that in addition to protecting against oxidative stress, Trx2 is an endogenous regulator of the MPT.


To Reinstate or to Not Reinstate? An Exploratory Study of Student Perspectives on the Death Penalty in Michigan.
The U.S. state of Michigan abolished the death penalty in 1846. Since then, several abortive efforts have been made by state legislators to re-establish the death sentence to deal with convicted murderers. Concurrently, some support exists among Michigan residents for the restoration of capital punishment in the state. This article presents the results of the analysis of an attitudinal survey of 116 college students enrolled in three criminal justice courses in a Michigan public university concerning the reinstatement of the death sentence in the state. The data from this exploratory study show that a slight majority (52.6%) of respondents favored reinstatement whereas 45.7% opposed restoration. Advocates and opponents of re-establishment of the death penalty in Michigan provided similar religious, moral and economic arguments proffered by others in previous surveys on capital punishment available in the death penalty literature. The current study makes a contribution to the scant extant literature on attitudes toward the death penalty in abolitionist jurisdictions. As this body of literature grows, it can provide baseline data or information with which to compare attitudes in retentionist states.


Brief communication: dental development and enamel thickness in the Lakonis Neanderthal molar.
Developmental and structural affinities between modern human and Neanderthal dental remains continue to be a subject of debate as well as their utility for informing assessments of life history and taxonomy. Excavation of the Middle Paleolithic cave site Lakonis in southern Greece has yielded a lower third molar (LKH 1). Here, we detail the crown development and enamel thickness of the distal cusps of the LKH 1 specimen, which has been classified as a Neanderthal based on the presence of an anterior fovea and mid-trigonid crest. Crown formation was determined using standard histological techniques, and enamel thickness was measured from a virtual plane of section. Developmental differences include thinner cuspal enamel and a lower periodicity than modern humans. Crown formation in the LKH 1 hypoconid is estimated to be 2.6-2.7 years, which is shorter than modern human times. The LKH 1 hypoconid also shows a more rapid overall crown extension rate than modern humans. Relative enamel thickness was approximately half that of a modern human sample mean; enamel on the distal cusps of modern human third molars is extremely thick in absolute and relative terms. These findings are consistent with recent studies that demonstrate differences in crown development, tissue proportions, and enamel thickness between Neanderthals and modern humans. Although overlap in some developmental variables may be found, the results of this and other studies suggest that Neanderthal molars formed in shorter periods of time than modern humans, due in part to thinner enamel and faster crown extension rates.


The Preparation and Properties of Thermo-reversibly Cross-linked Rubber Via Diels-Alder Chemistry.
A method for using Diels Alder thermo-reversible chemistry as cross-linking tool for rubber products is demonstrated. In this work, a commercial ethylene-propylene rubber, grafted with maleic anhydride, is thermo-reversibly cross-linked in two steps. The pending anhydride moieties are first modified with furfurylamine to graft furan groups to the rubber backbone. These pendant furan groups are then cross-linked with a bis-maleimide via a Diels-Alder coupling reaction. Both reactions can be performed under a broad range of experimental conditions and can easily be applied on a large scale. The material properties of the resulting Diels-Alder cross-linked rubbers are similar to a peroxide-cured ethylene/propylene/diene rubber (EPDM) reference. The cross-links break at elevated temperatures (> 150 °C) via the retro-Diels-Alder reaction and can be reformed by thermal annealing at lower temperatures (50-70 °C). Reversibility of the system was proven with infrared spectroscopy, solubility tests and mechanical properties. Recyclability of the material was also shown in a practical way, i.e., by cutting a cross-linked sample into small parts and compression molding them into new samples displaying comparable mechanical properties, which is not possible for conventionally cross-linked rubbers.


Mild stimulation improves neuronal survival in an in vitro model of the ischemic penumbra.
In the core of a brain infarct, characterized by severely reduced blood supply, loss of neuronal function is rapidly followed by neuronal death. In peripheral areas of the infarct, the penumbra, damage is initially reversible, and neuronal activity is typically reduced due to ischemia-induced synaptic failure. There is limited understanding of factors governing neuronal recovery or the transition to irreversible damage. Neuronal activity has been shown to be crucial for survival. Consequently, hypoxia induced neuronal inactivity may contribute to cell death, and activation of penumbral neurons possibly improves survival. Adversely, activation increases ATP demand, and a balance should be found between the available energy and sufficient activity. We monitored activity and viability of neurons in an in vitro model of the penumbra, consisting of (rat) neuronal networks on micro electrode arrays (MEAs) under controlled hypoxic conditions. We tested effects of optogenetic and electrical activation during hypoxia. Mild stimulation yielded significantly better recovery of activity immediately after re-oxygenation, compared with no stimulation, and a 60%-70% higher survival rate after 5 d. Stronger stimulation was not associated with better recovery than no stimulation, suggesting that beneficial effects depend on a delicate balance between sufficient activity and available energy. We show that mild activation during hypoxia/ischemia is beneficial for cell survival in an in vitro model of the penumbra. This finding opposes the current common belief that suppression of neuronal activity is the cornerstone of neuroprotection during cerebral ischemia, and may open new possibilities for the treatment of secondary brain damage after stroke.


The Future of Telehealth in Human Immunodeficiency Virus Care: A Qualitative Study of Patient and Provider Perspectives in South Carolina.
To ensure care continuity during the COVID-19 pandemic, telehealth has been widely implemented in human immunodeficiency virus (HIV) care. However, participation in and benefits from telehealth were unequal. This study aims to assess the willingness of people living with HIV (PWH) and HIV care providers to use telehealth and perceptions of the future role of telehealth. In-depth interviews with 18 PWH and 10 HIV care providers from South Carolina assessed their willingness to use telehealth, their perspectives on the future of telehealth in HIV care, and recommendations to improve telehealth. Interviews were analyzed using thematic analysis. Most PWH were female (61%), Black/African American (67%), and non-Hispanic (78%). Most PWH (61%) and all providers had used telehealth for HIV care. Most PWH and all providers reported being willing to use or (re-)consider telehealth HIV care services in the future. Providers suggested that telehealth is most suitable for routine HIV care encounters and for established, clinically stable, generally healthy PWH. Attitudes toward telehealth were heterogeneous, with most interviewees valuing telehealth similarly or superior to in-person care, yet >20% perceiving it less valuable. Recommendations to improve telehealth included multilevel strategies to address challenges across four domains: technology, the virtual nature of telehealth, administrative processes, and the sociodemographic profile of PWH. Telehealth in HIV care is here to stay; however, it may not yet be suitable for all PWH and all care encounters. Decision processes related to telehealth versus in-person care need to involve providers and PWH. Existing telehealth options require multilevel adjustments addressing persistent challenges.


Defective RNA splicing resulting from a mutation in the cyclic guanosine monophosphate-phosphodiesterase beta-subunit gene.
The authors have previously reported a 3' splice site mutation in intron 2 of the rod cyclic guanosine monophosphate-phosphodiesterase (cGMP) beta-subunit (beta-PDE) gene in a patient with compound heterozygous autosomal recessive retinitis pigmentosa. The purpose of this study is to determine whether this mutation interferes with RNA splicing, what products it generates, and whether the resultant mRNA is able to support the synthesis of the native protein. Two expression constructs were prepared by subcloning genomic DNA fragments (one from the control subject DNA and the other from the patient's DNA) to the pCIS2 expression vector. Recombinant plasmid DNA was introduced into 293 human embryonic kidney cells using the calcium phosphate-mediated transfection procedure. Northern blot hybridization, reverse transcription-polymerase chain reaction, and sequencing were used for RNA analysis. Four major products were present in the RNA pool isolated from cells transfected with the expression construct containing the splice site mutation. One of the transcripts resulted from the activation of a cryptic 3' splice site located in exon 3, 12 nucleotides downstream of the mutated site. The second fragment was longer than the correctly spliced mRNA by approximately 1 kb and contained unspliced intron 2. Two other high molecular weight products corresponded to intermediate lariats. An acceptor splice site mutation in intron 2 of the beta-PDE gene leads to the accumulation of pre-mRNA and intermediate lariats and a 12-nucleotide shorter beta-PDE transcript produced by the use of a cryptic splice site located in exon 3. In the normal beta-PDE mRNA, these 12 nucleotides code for ValPheLeuLys. These amino acids are highly conserved in the putative noncatalytic cGMP-binding domain I of beta-PDE from several species and, probably, are important for the correct folding and function of the protein.


The structure of multi-neuron firing patterns in primate retina.
Current understanding of many neural circuits is limited by our ability to explore the vast number of potential interactions between different cells. We present a new approach that dramatically reduces the complexity of this problem. Large-scale multi-electrode recordings were used to measure electrical activity in nearly complete, regularly spaced mosaics of several hundred ON and OFF parasol retinal ganglion cells in macaque monkey retina. Parasol cells exhibited substantial pairwise correlations, as has been observed in other species, indicating functional connectivity. However, pairwise measurements alone are insufficient to determine the prevalence of multi-neuron firing patterns, which would be predicted from widely diverging common inputs and have been hypothesized to convey distinct visual messages to the brain. The number of possible multi-neuron firing patterns is far too large to study exhaustively, but this problem may be circumvented if two simple rules of connectivity can be established: (1) multi-cell firing patterns arise from multiple pairwise interactions, and (2) interactions are limited to adjacent cells in the mosaic. Using maximum entropy methods from statistical mechanics, we show that pairwise and adjacent interactions accurately accounted for the structure and prevalence of multi-neuron firing patterns, explaining approximately 98% of the departures from statistical independence in parasol cells and approximately 99% of the departures that were reproducible in repeated measurements. This approach provides a way to define limits on the complexity of network interactions and thus may be relevant for probing the function of many neural circuits.


[Mediofacial degloving in extramedullary plasmacytoma with orbital invasion].
Extramedullary solitary plasmacytoma is a rare plasmatic cell tumor occurring in the head and neck. We report the case of a patient with a mass that arose from the sphenoidal base, extended toward the right paranasal sinuses, and invaded the orbit. The clinical characteristics, diagnostic criteria, and therapeutic problems are discussed and reviewed in the literature, with special attention to an alternative therapeutic approach, midfacial degloving.


Variation in antigenic determinants specific to the infective stage of Trypanosoma cruzi.
Monoclonal antibodies reactive with the surface antigens of the Peru strain of Trypanosoma cruzi were analyzed by Western blots and immunofluorescence assays to determine their reactivity with three life cycle stages and five strain isolates of T. cruzi. One monoclonal antibody, 7.6, recognized a 68-kilodalton (kDa) polypeptide in Western blots of Peru strain trypomastigotes, epimastigotes, and amastigotes. A 68-kDa polypeptide was also detected by monoclonal antibody 7.6 in trypomastigotes of the CL and Y strains and in the clonal isolates Esmeraldo clone 3 and Silvio X10 clone 1. Positive immunofluorescence results were obtained for all life cycle stages of the five strains that were reacted with monoclonal antibody 7.6, thus indicating that the antigen recognized by monoclonal antibody 7.6 is universally present in all T. cruzi strains tested. In contrast, monoclonal antibody 4.2 reacted with a polypeptide doublet of 90 and 105 kDa in Western blots of Peru strain trypomastigotes, but it did not detect these antigens in epimastigotes or amastigotes. The same polypeptide doublet of 90 and 105 kDa was also detected in Western blots of Y strain trypomastigotes; however, no bands were detected in blots of strain CL or isolate Silvio X10 clone 1 trypomastigotes. In blots of Esmeraldo clone 3 trypomastigotes, a single band of 130 kDa was detected by monoclonal antibody 4.2. In immunofluorescence assays of monoclonal antibody 4.2, positive reactions were obtained only with trypomastigotes of Peru, Y, and Esmeraldo clone 3 strains. Thus, monoclonal antibody 4.2 recognizes a trypomastigote-specific antigen which is not universally present on all strains of T. cruzi.


Lipophilicity of the nitrophenols
The lipophilicity of the nitrophenols, expressed as a water-solvent partition coefficient, P, has been investigated using the solvation equation, log P = c + eE + sS + aA + bB + vV. It is shown that this equation accounts quantitatively for lipophilicity in a selection of water-solvent systems, viz: octanol, 1,2-dichloroethane, and cyclohexane. In the latter two systems, the major factor in the increased lipophilicity of 2-nitrophenol over 3- and 4-nitrophenol is the lack of hydrogen bond acidity of 2-nitrophenol. The water-octanol system differs in that the a coefficient is effectively zero, so that hydrogen bond acidity of solutes plays no part, and the three mononitrophenols then have similar lipophilicities. The dinitrophenols and picric acid are similarly discussed. The hydrogen bond acidity of 2,3-dinitrophenol (0.67) is very much larger than that of 2,4- or 2,5-dinitrophenol (0.09 and 0. 11), indicating a very much reduced internal hydrogen bonding. A similar but much smaller effect occurs with 2,6-dinitrophenol (A = 0. 17). Picric acid has a moderate hydrogen bond acidity (0.46) so that the phenolic OH is still available for external hydrogen bonding. These results are confirmed by ab initio calculations which show that 2,3- and 2,6-dinitrophenol and picric acid are significantly distorted away from planarity, which apparently disrupts their internal hydrogen bonding.


Sarsaparilla (Smilax Glabra Rhizome) extract inhibits migration and invasion of cancer cells by suppressing TGF-β1 pathway.
Sarsaparilla, also known as Smilax Glabra Rhizome (SGR), was shown to modulate immunity, protect against liver injury, lower blood glucose and suppress cancer. However, its effects on cancer cell adhesion, migration and invasion were unclear. In the present study, we found that the supernatant of water-soluble extract from SGR (SW) could promote adhesion, inhibit migration and invasion of HepG2, MDA-MB-231 and T24 cells in vitro, as well as suppress metastasis of MDA-MB-231 cells in vivo. Results of F-actin and vinculin dual staining showed the enhanced focal adhesion in SW-treated cells. Microarray analysis indicated a repression of TGF-β1 signaling by SW treatment, which was verified by real-time RT-PCR of TGF-β1-related genes and immunoblotting of TGFBR1 protein. SW was also shown to antagonize TGF-β1-promoted cell migration. Collectively, our study revealed a new antitumor function of Sarsaparilla in counteracting invasiveness of a subset of cancer cells by inhibiting TGF-β1 signaling.


Detection of homogentisic acid by electrospray ionization mass spectrometry.
Homogentisic acid (HGA) is excreted in excessive amounts in the urine of patients with alkaptonuria, which is a hereditary metabolic disorder of phenylalanine and tyrosine. Therefore, the detection of HGA in urine is useful for the diagnosis of alkaptonuria. To evaluate the detection of HGA, we confirmed the color shift of HGA solutions and analyzed them by electrospray ionization mass spectrometry (ESI-MS). We observed the color change of the HGA solutions under different pH conditions (pH 6.0, 7.0, and 8.0) and examined the influences of adding potassium hydroxide (KOH) and ascorbic acid (AA) to the HGA solutions. Then, we analyzed the chemical reaction in HGA solutions using ESI-MS. The HGA solution at pH 8.0 became brown after incubation at room temperature for 24 h and became darker brown with the addition of KOH; however, HGA solutions at pH 6.0 and 7.0 showed no color changes. The brown color change of the HGA solution at pH 8.0 was also inhibited by AA. Moreover, all HGA sample solutions showed the deprotonated molecular ion peak at m/z 167.035 in the negative ion mode after incubation at room temperature for 24 h and with the addition of KOH and AA. We identified the molecular ion of HGA in all sample solutions by ESI-MS, regardless of different pH conditions, color changes, or the presence of AA. These results suggest that spectral analysis by ESI-MS is suitable for the detection of HGA and the diagnosis of alkaptonuria.


Conformational change due to intramolecular hydrophobic interaction leads to large blue-shifted emission from single molecular cage solutions.
We demonstrate a unique negative solvatochromic emission (NSE) process from a conformational change of a coordination cage in response to solvent composition. The cationic cage contains two tetra-(4-pyridylphenyl)ethylene (TPPE) luminogens on two opposite faces, linked by Pt(PEt3)2 and isophthalate. When the solvent changes from acetone/acetonitrile/methanol to water, the emission of single cages gradually shifts to short wavelength (NSE) with a drastic value of ∼60 nm. Small angle X-ray scattering (SAXS) measurements indicate a molecular conformational change during the process and intramolecular π-π stacking and hydrophobic interaction between the TPPE planes could be the driving forces. As a comparison, a cage with a longer inter-fluorophore distance does not have such strong intramolecular interactions and only shows regular positive solvatochromic emission (PSE) under the same conditions.


Generation of human melanocytes from induced pluripotent stem cells.
The discovery of human induced pluripotent stem cells (iPSCs) has provided a model system for studying early events during human development. Developmentally melanocytes originate from migratory neural crest cells that emerge from the neural plate during embryogenesis after a complex process of differentiation, proliferation, and migration out of the neural tube along defined pathways. In the adult, human melanocytes are located in the basal layer of the epidermis, hair follicles, uvea, inner ear, and meninges. In the epidermis, melanocytes produce melanin pigment that gives color to the skin as well as providing protection from ultraviolet light damage. In addition, melanocytes transfer melanin pigment to hair matrix keratinocytes during each hair cycle to maintain hair pigmentation. Characterization of mouse melanocyte stem cells (MELSCs) is more complete than for humans. MELSCs are located in the bulge region of hair follicles, where hair follicle stem cells (HFSCs) also reside. Recently, it has been demonstrated that HFSCs provide a functional nice for MELSCs. According to current cancer stem cell theory, melanomas are considered to evolve from MELSCs, although the exact mechanism remains to be elucidated fully. In humans, importantly, the lack of more specific markers of MELSCs, current understanding of the molecular regulations of melanocyte development remains incomplete. Recently, the generation of melanocytes from iPSCs has lead to some clarification of human melanocyte development in vitro. Utilization of iPSC-derived melanocytes may prove invaluable in further study of human melanocytic development and novel therapies for patients suffering with pigmentation disorders and melanoma.


Measurements of hybrid fertility and a test of mate preference for two house mouse races with massive chromosomal divergence.
Western house mice Mus musculus domesticus are among the most important mammalian model species for chromosomal speciation. Hybrids between chromosomal races of M. m. domesticus suffer various degrees of fertility reduction between full fertility and complete sterility, depending on the complexity of the chromosomal differences between the races. This complexity presents itself in hybrids as meiotic configurations of chromosome chains and rings, with longer configurations having a stronger impact on fertility. While hybrids with short configurations have been intensively studied, less work has been done on hybrids with very long configurations. In this study, we investigated laboratory-reared wild mice from two chromosomally very different races in Switzerland found in close proximity. Hybrids between these races form a meiotic chain of fifteen chromosomes. We performed a detailed analysis of male and female hybrid fertility, including three generations of female backcrosses to one of the parental races. We also tested for possible divergence of mate preference in females. While all male F1 hybrids were sterile with sperm counts of zero, 48% of female F1 hybrids produced offspring. Their litter sizes ranged from one to three which is significantly lower than the litter size of parental race females. When hybrid females were backcrossed to a parental race, half of the offspring resembled the parental race in karyotype and fertility, while the other half resembled the F1 hybrids. In the preference test, females of both races indicated a lack of a preference for males of their own karyotype. Although the fertility of the F1 hybrids was extremely low because of the complexity of the chromosomal differences between the races, reproductive isolation was not complete. As we did not find assortative female preferences, we expect that contact between these races would lead to the production of hybrids and that gene flow would occur eventually, as fertility can be restored fully after one backcross generation.


[How do I treat seborrheic eczema?].
Essentials of the author's own way of therapeutical proceeding are: in cases of low inflammatory seborrheic dermatitis, ointments containing salicylic acid and sulfur; in children, zinc oil and zinc paste with bismuth; in cases of acute seborrheic dermatitis, ointments with glucocorticoids; in seborrheic erythroderma, systemic glucocorticoids.


Specificity protein 1 (sp1) oscillation is involved in copper homeostasis maintenance by regulating human high-affinity copper transporter 1 expression.
Copper is an essential micronutrient for cell growth but is toxic in excess. Copper transporter (Ctr1) plays an important role in regulating adequate copper levels in mammalian cells. We have shown previously that expression of the human high-affinity copper transporter (hCtr1) was transcriptionally up-regulated under copper-depleted conditions and down-regulated under replete conditions; moreover, elevated hCtr1 levels suppress hCtr1 expression. Specificity protein 1 (Sp1) regulates expression of hCtr1 under copper-stressed conditions. In this study, we made the following important observations: 1) Sp1 expression is down-regulated under copper-replete conditions but up-regulated under copper-depleted conditions. These up- and down-regulations of Sp1 in turn regulate hCtr1 expression to control copper homeostasis. 2) Copper-regulated Sp1 expression involved Sp1 binding to its own promoter as demonstrated by the chromatin immunoprecipitation assay; therefore, Sp1 is also transcriptionally self-regulated via hCtr1/copper intermediation. 3) Both zinc finger and glutamine-rich transactivation domains of Sp1 are involved in the Sp1-mediated hCtr1 and Sp1 regulation by copper stresses. 4) Although Sp3 expression is also regulated by copper availability, Sp3 does not regulate hCtr1 homeostasis. Collectively, our results demonstrated that mammalian cells use Sp1 oscillation in response to copper availability to regulate copper homeostasis through hCtr1 expression in a tripartite inter-regulatory relationship. These findings have important implications in mammalian copper physiology regulation.


Arterial Stiffness and Incidence of Diabetes: A Population-Based Cohort Study.
Diabetes is known to be associated with increased arterial stiffness. However, the temporal association between increased carotid-femoral pulse wave velocity (c-f PWV) and diabetes is unclear. The aim of this study is to explore the relationship between arterial stiffness, as determined by c-f PWV, and incidence of diabetes. The study population included participants from the Malmö Diet and Cancer cardiovascular cohort, using measurements from the 2007-2012 reexamination as baseline. Arterial stiffness was evaluated by measuring c-f PWV (SphygmoCor). After excluding participants with prevalent diabetes (according to measurements of fasting glucose, oral glucose tolerance tests, and physician's diagnoses), the final study population consisted of 2,450 individuals (mean age = 71.9 ± 5.6 years). Incidence of diabetes was followed by linkage to local and national diabetes registers. Cox proportional hazards regression was used to assess the incidence of diabetes in relation to the tertiles of c-f PWV, adjusted for potential confounders. During a mean follow-up of 4.43 ± 1.40 years, 68 (2.8%) participants developed diabetes. Crude incidence of diabetes (per 1,000 person-years) was 3.5, 5.7, and 9.5, respectively, for subjects in the first, second, and third tertiles of c-f PWV. After adjustment for potential confounders, the hazard ratio of diabetes was 1.00 (reference), 1.83 (95% CI 0.88-3.8), and 3.24 (95% CI 1.51-6.97), respectively, for the tertiles of c-f PWV (P for trend = 0.002). Increased c-f PWV is associated with increased incidence of diabetes, independent of other risk factors. These results suggest that increased arterial stiffness is an early risk marker for developing diabetes.


Direct activation of G-protein-gated inward rectifying K+ channels promotes nonrapid eye movement sleep.
A major challenge in treating insomnia is to find effective medicines with fewer side effects. Activation of G-protein-gated inward rectifying K+ channels (GIRKs) by GABAB agonists baclofen or γ-hydroxybutyric acid (GHB) promotes nonrapid eye movement (NREM) sleep and consolidates sleep. However, baclofen has poor brain penetration, GHB possesses abuse liability, and in rodents both drugs cause spike-wave discharges (SWDs), an absence seizure activity. We tested the hypothesis that direct GIRK activation promotes sleep without inducing SWD using ML297, a potent and selective GIRK activator. Whole-cell patch-clamp recordings from hypocretin/orexin or hippocampal neurons in mouse brain slices were made to study neuronal excitability and synaptic activity; spontaneous activity, locomotion, contextual and tone-conditioned memory, and novel object recognition were assessed. Electroencephalogram/electromyogram (EEG/EMG) recordings were used to study GIRK modulation of sleep. ML297, like baclofen, caused membrane hyperpolarization, decreased input resistance, and blockade of spontaneous action potentials. Unlike baclofen, ML297 (5-10 µM) did not cause significant depression of postsynaptic excitatory and inhibitory currents (EPSCs-IPSCs), indicating preferential postsynaptic inhibition. ML297 (30 mg/kg, i.p.) inhibited wake activity and locomotion, and preferentially increased NREM sleep without altering EEG delta power, REM sleep, inducing SWDs, or impairing conditioned memory and novel object recognition. This study finds that direct activation of neuronal GIRK channels modulates postsynaptic membrane excitability and prolongs NREM sleep without changing sleep intensity, inducing SWDs, or impairing memory in rodents. These results suggest that direct GIRK activation with a selective compound may present an innovative approach for the treatment of chronic insomnia.


[Use of propolis in the treatment of local suppurative infection].
Experience with the treatment of 460 patients with panaritium, abscesses, phlegmons, infectious wounds have shown that propolis is an expedient remedy (in additional to the the routine treatment). They have shown the stimulating, antiinflammatory and anti-microbial action of propolis.


[Earthquakes--a historical review, environmental and health effects, and health care measures].
Earthquakes are natural disasters that can occur at any time, regardless of the location. Their frequency is higher in the Circum-Pacific and Mediterranean/Trans-Asian seismic belt. A number of sophisticated methods define their magnitude using the Richter scale and intensity using the Mercani-Cancani-Sieberg scale. Recorded data show a number of devastating earthquakes that have killed many people and changed the environment dramatically. Croatia is located in a seismically active area, which has endured a series of historical earthquakes, among which several occurred in the Zagreb area. The consequences of an earthquake depend mostly on the population density and seismic resistance of buildings in the affected area. Environmental consequences often include air, water, and soil pollution. The effects of this kind of pollution can have long-term health effects. The most dramatic health consequences result from the demolition of buildings. Therefore, quick and efficient aid depends on well-organized health professionals as well as on the readiness of the civil defence, fire department, and Mountain Rescue Service members. Good coordination among these services can save many lives Public health interventions must include effective control measures in the environment as secondary prevention methods for health problems caused by unfavourable environmental factors. The identification and control of long-term hazards can reduce chronic health effects. The reduction of earthquake-induced damages includes setting priorities in building seismically safe buildings.


Tumor necrosis factor and CD11/CD18 (beta 2) integrins act synergistically to lower cAMP in human neutrophils.
The ability of neutrophils (PMN) to undergo a prolonged respiratory burst in response to cytokines such as tumor necrosis factor-alpha (TNF) depends on expression of CD11/CD18 (beta 2) integrins and interaction with matrix protein-coated surfaces (Nathan, C., S. Srimal, C. Farber, E. Sanchez, L. Kabbash, A. Asch, J. Gailit, and S. D. Wright. 1989. J. Cell Biol. 109:1341-1349). We tested the hypothesis that changes in cAMP mediate the joint action of cytokines and integrins. When plated on FBS- or fibrinogen-coated surfaces, PMN responded to TNF with a sustained fall in intracellular cAMP. This did not occur without TNF; in suspended PMN; in PMN treated with anti-CD18 mAb; or in PMN genetically deficient in beta 2 integrins. A preceding fall in cAMP appeared essential for TNF to induce a respiratory burst, because drugs that elevate cAMP blocked the burst if added any time before, but not after, its onset. Adenosine analogues and cytochalasins also block the TNF-induced respiratory burst if added before, but not after, its onset. Both also blocked the TNF-induced fall in cAMP. The effect of cytochalasins led us to examine the relationship between cAMP and actin reorganization. The same conditions that led to a sustained fall in cAMP led at the same time to cell spreading and the assembly of actin filaments. As with the respiratory burst, cAMP-elevating agents inhibited TNF-induced cell spreading and actin filament assembly if added before, but not after, spreading began. Thus, occupation of TNF receptors and engagement of CD18 integrins interact synergistically in PMN to promote a fall in cAMP. The fall in cAMP is closely related to cell spreading and actin reorganization. These changes are necessary for TNF to induce a prolonged respiratory burst. We conclude that integrins can act jointly with cytokines to affect cell shape and function through alterations in the level of a second messenger, cAMP.


Association Between Age and Outcomes of Catheter Ablation Versus Medical Therapy for Atrial Fibrillation: Results From the CABANA Trial.
Observational data suggest that catheter ablation may be safe and effective to treat younger and older patients with atrial fibrillation. No large, randomized trial has examined this issue. This report describes outcomes according to age at entry in the CABANA trial (Catheter Ablation versus Antiarrhythmic Drug Therapy for Atrial Fibrillation). Patients with atrial fibrillation ≥65 years of age, or <65 with ≥1 risk factor for stroke, were randomly assigned to catheter ablation versus drug therapy. The primary outcome was a composite of death, disabling stroke, serious bleeding, or cardiac arrest. Secondary outcomes included all-cause mortality, the composite of mortality or cardiovascular hospitalization, and recurrence of atrial fibrillation. Treatment effect estimates were adjusted for baseline covariables using proportional hazards regression models. Of 2204 patients randomly assigned in CABANA, 766 (34.8%) were <65 years of age, 1130 (51.3%) were 65 to 74 years of age, and 308 (14.0%) were ≥75 years of age. Catheter ablation was associated with a 43% reduction in the primary outcome for patients <65 years of age (adjusted hazard ratio [aHR], 0.57 [95% CI, 0.30-1.09]), a 21% reduction for 65 to 74 years of age (aHR, 0.79 [95% CI, 0.54-1.16]), and an indeterminate effect for age ≥75 years of age (aHR, 1.39 [95% CI, 0.75-2.58]). Four-year event rates for ablation versus drug therapy across age groups, respectively, were 3.2% versus 7.8%, 7.8% versus 9.6%, and 14.8% versus 9.0%. For every 10-year increase in age, the primary outcome aHR increased (ie, less favorable to ablation) an average of 27% (interaction P value=0.215). A similar pattern was seen with all-cause mortality: for every 10-year increase in age, the aHR increased an average of 46% (interaction P value=0.111). Atrial fibrillation recurrence rates were lower with ablation than with drug therapy across age subgroups (aHR 0.47, 0.58, and 0.49, respectively). Treatment-related complications were infrequent for both arms (<3%) regardless of age. We found age-based variations in clinical outcomes for catheter ablation compared with drug therapy, with the largest relative and absolute benefits of catheter ablation in younger patients. No prognostic benefits for ablation were seen in the oldest patients. No differences were found by age in treatment-related complications or in the relative effectiveness of catheter ablation in preventing recurrent atrial arrhythmias. URL: https://www. gov; Unique identifier: NCT00911508.


Prostate cancer localization using multiparametric MR imaging: comparison of Prostate Imaging Reporting and Data System (PI-RADS) and Likert scales.
To compare the recently proposed Prostate Imaging Reporting and Data System (PI-RADS) scale that incorporates fixed criteria and a standard Likert scale based on overall impression in prostate cancer localization using multiparametric magnetic resonance (MR) imaging. This retrospective study was HIPAA compliant and institutional review board approved. Seventy patients who underwent 3-T pelvic MR imaging, including T2-weighted imaging, diffusion-weighted imaging, and dynamic contrast material-enhanced imaging, with a pelvic phased-array coil before radical prostatectomy were included. Three radiologists, each with 6 years of experience, independently scored 18 regions (12 peripheral zone [PZ], six transition zone [TZ]) using PI-RADS (range, scores 3-15) and Likert (range, scores 1-5) scales. Logistic regression for correlated data was used to compare scales for detection of tumors larger than 3 mm in maximal diameter at prostatectomy. Maximal accuracy was achieved with score thresholds of 8 and higher and of 3 and higher for PI-RADS and Likert scales, respectively. At these thresholds, in the PZ, similar accuracy was achieved with the PI-RADS scale and the Likert scale for radiologist 1 (89.0% vs 88.2%, P = .223) and radiologist 3 (88.5% vs 88.2%, P = .739) and greater accuracy was achieved with the PI-RADS scale than the Likert scale for radiologist 2 (89.6% vs 87.1%, P = .008). In the TZ, accuracy was lower with the PI-RADS scale than with the Likert scale for radiologist 1 (70.0% vs 87.1%, P < .001), radiologist 2 (87.6% vs 92.6%, P = .002), and radiologist 3 (82.9% vs 91.2%, P < .001). For tumors with Gleason score of at least 7, sensitivity was higher with the PI-RADS scale than with the Likert scale for radiologist 1 (88.6% vs 82.6%, P = .032), and sensitivity was similar for radiologist 2 (78.0% vs 76.5, P = .467) and radiologist 3 (77.3% vs 81.1%, P = .125). Radiologists performed well with both PI-RADS and Likert scales for tumor localization, although, in the TZ, performance was better with the Likert scale than the PI-RADS scale. http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.13122233/-/DC1.


Role of viruses in uveitis.
The viruses and related organisms, which have been either demonstrated or suspected as the origin of various forms of uveitis, cause mostly morphologically non-specific disease. On the other hand, unidentified viruses have been supposed to play a role in the pathogenesis of well-defined systemic diseases complicated by uveitis. The syndromes in which the uveitis has a specific clinical appearance are briefly presented, including the available laboratory techniques, and their diagnostic value is discussed. In most cases, however, the determination of the responsible virus remains very difficult.


The clonal root system of balsam poplar in upland sites of Quebec and Alberta.
Balsam poplar seeds are short-lived and require moist seedbeds soon after they are released to germinate. In addition to sexual reproduction, balsam poplar stands can regenerate clonally by root suckering. The origin of stands will in turn affect their genetic structure and root system architecture, which are poorly understood for upland forest stands. Three stands were hydraulically excavated in Quebec (moist) and Alberta (dry) to determine the origin of trees and to characterize root systems with respect to presence of parental roots and root grafts connections. Clones were identified using single-nucleotide polymorphism (SNPs), and all stems, roots and root grafts were aged using dendrochronology techniques. All 82 excavated trees were of sucker origin, and four of the six stands contained a single clone. Parental root connections were found between 22% and 25% of excavated trees, and 53% and 48% of trees were linked with a root graft between the same or different clones, in Alberta and Quebec, respectively. Mean distance between trees connected by parental root was significantly lower than the distance between unconnected trees (0.47 ± 0.25 m vs. 3.14 ± 0.15 m and 1.55 ± 0.27 m vs. 4.25 ± 0.13 m) in Alberta and in Quebec, respectively. The excavations also revealed many dead stumps with live roots, maintained through root connections with live trees. This research highlights that balsam poplar growing in upland stands is a clonal species that can maintain relatively high genotypic diversity, with frequent root connections between trees at maturity. Maintaining an extensive root system through root connections increases the chances of a clone surviving when the above ground tree is dead and may also enhance the resilience of balsam poplar stands after disturbance.


Spinocerebellar ataxia type 6: evidence for a strong founder effect among German families.
The authors found a strong geographic cluster of spinocerebellar ataxia type 6 (SCA6) families in the Northrhine-Westfalia area, suggesting a founder effect in the German SCA6 population. Genotyping with DNA markers linked to the CACNL1A4 gene on chromosome 19p13 revealed a common haplotype and shared allelic characteristics in the majority of German families. The observed founder effect may be related to the relative meiotic stability of CAG repeats in this type of autosomal dominant cerebellar ataxia.


Varicose eczema.
The term "varicose eczema", although made acceptable by its use, is ambiguous and misleading. It would prompt us to believe that varicose eczema is different from common dermatological eczema. There is no such difference, and it would be more correct to speak of eczema of the varicose patient. The development of eczema in the case of a varicose patient may: --either develop in the case of a varicose patient who does not normally suffer from eczematous dermatosis; in this case static dermatitis represents a point of local reference for an eczematous crisis triggered off by a general factor and finding there a zone of reduced resistance; --or develop in the case of a known habitual eczematic. In this case, venous stasis increases and maintains the eczema. In both cases no local dermatological treatment will be able to cure the eczema, which will develop into a critical condition often provoking the development of a leg ulcer, and will necessitate the suppression of the venous counter-current. To try and understand the pathological mechanism of "varicose eczema", we have to remember the rudiments of the physiology of the cutaneous barrier, familiar to dermatologists but less so to phlebologists, and also some elements of the physiopathology of venous insufficiency, and in particular the tissular elements following the pattern explained by Comel's Italian school, by the term "histo-angiological decompensation". The circulatory unit "arteries-capillaries-veins-lymphatic-vessels-tissues" form an ensemble which has to be taken into account, as any disorders in any one of these elements reacts on all the others. These elementary rudiments lead us to understand the importance of an integral aetiopathogenic picture of varicose eczema, and the importance of the multidisciplinary collaboration between phlebologists and dermatologists in order to treat this affection, the border-line of our two specialties.


Unexpected online gambling disorder in late-life: a case report.
The lifetime prevalence of problem or Gambling disorder (GD) in the elderly (i.e., those over 60 years old) is reported to range from 0.01 to 10.9%. Research has identified several specific risk factors and vulnerabilities in the elderly. Since the late 1990s, an increase in online GD has been observed in the youth population, whereas casinos, slot machines, and bingo seem to be the activities of choice among the elderly. Interestingly, online GD has not been described in the elderly to date. We report an 83-year-old man who started online casino gambling from the age of 80 years, leading to debts that exceeded €30,000. He underwent a full clinical and neuropsychological assessment, without any evidence of cognitive impairment or any associated neurodegenerative disease. However, he had risk factors for GD, including adjustment disorder, stressful life events, previous offline casino GD when 50 years old, and dysfunctional personality traits. The change to online GD may have been due to his isolation, movement difficulties, and his high level of education, which facilitated his access to the Internet. Care management focused on individual cognitive-behavioral therapy. The prevalence of online GD may be underestimated among the elderly, and may increase among isolated old people with movement difficulties and ready access to the Internet. However, late-life GD should be considered a diagnosis of elimination, requiring a full medical, psychiatric (including suicide risk), and cognitive assessment. Specific therapeutic approaches need to be proposed and developed.


A laboratory method for determination of anaerobic energy expenditure during sprinting.
Highly trained sprinters, marathon runners and untrained male control subjects were studied during treadmill sprinting. After confirming a workload which elicited exhaustion in just over a minute (mean time to exh. = 64.6 +/- 2.5 sec.), each subject performed sprints of 15, 30, 45 and 60 seconds duration in order that their energy expenditure could be segmented per 15-sec. of sprinting time. During every sprint, O2 consumption was recorded by closed-circuit spirometry. Following each sprint, serial 30-sec. venous blood samples were drawn in order to determine the peak lactate concentration. Energy expenditure was therefore determined as follows: i) aerobic energy from increments in O2 uptake, expressed in Kcal; ii) lactacid energy from increments in peak lactate, with the difference between peaks utilized to calculate the anaerobic glycolytic contribution to that 15-sec. segment, expressed in Kcal according to Margaria; iii) alactacid energy, expended over the initial 15-sec. segments, from the difference between the total energy requirement per 15-sec. less the measured aerobic plus the lactacid contributions. The sprinters expended the greatest (p less than .05) anaerobic energy (46.2 +/- 5.1 Kcal) when compared to either the marathoners (31.6 +/- 5.7 Kcal) or controls (33.0 +/- 1.6 Kcal). The athletic groups demonstrated superior alactacid energy (sprinters = 21.4 +/- 4.4 Kcal; marathoners = 15.8 +/- 2.3 Kcal), both expending a substantial amount of energy from this source (20%) past 30-sec. In contrast, over the initial 30-sec. of sprinting, the control subjects had depleted their alactacid energy (12.2 +/- 3.3 Kcal). Only minor differences were observed in aerobic energy expenditure between the three subject groups throughout the sprint to exhaustion.


Effect of stanford pouch and ileal conduit urinary diversions on bone mineral density and metabolism.
After urinary-intestinal diversions metabolic complications may occur in long term follow up. We aimed to evaluate bone metabolism changes in urinary diverted patients. Nineteen patients with urinary diversions (11 Stanford pouch and 8 ileal conduit) performed with diagnosis of locally invasive bladder cancer and 19 age-sex matched healthy subjects were enrolled in the study. Bone mineral density (BMD), arterial blood pH, bicarbonate and base excess as well as bone mineralisation parameters at urine and serum were evaluated for all groups. For statistical evaluation, nonparametric comparisons between groups were used. Comparison of ileal conduit and control groups displayed higher alkaline phosphatase and parathormone levels in the patient group though the difference was not significant. The mean BMD values of ileal conduit group were osteopenic, revealing a significant difference with the control group. Statistically significant differences between alkaline phosphatase, parathormone levels of Stanford pouch and control groups were apparent whereas BMD values were not significantly different. When the two patient groups were compared with each other, no difference in BMD or bone metabolism parameter values could be observed. Patients with urinary diversions are under risk of bone demineralisation and must be followed by BMDs, arterial blood analysis and bone mineral metabolism parameters.


Paths to light trapping in thin film GaAs solar cells.
It is now well established that light trapping is an essential element of thin film solar cell design. Numerous light trapping geometries have already been applied to thin film cells, especially to silicon-based devices. Less attention has been paid to light trapping in GaAs thin film cells, mainly because light trapping is considered less attractive due to the material's direct bandgap and the fact that GaAs suffers from strong surface recombination, which particularly affects etched nanostructures. Here, we study light trapping structures that are implemented in a high-bandgap material on the back of the GaAs active layer, thereby not perturbing the integrity of the GaAs active layer. We study photonic crystal and quasi-random nanostructures both by simulation and by experiment and find that the photonic crystal structures are superior because they exhibit fewer but stronger resonances that are better matched to the narrow wavelength range where GaAs benefits from light trapping. In fact, we show that a 1500 nm thick cell with photonic crystals achieves the same short circuit current as an unpatterned 4000 nm thick cell. These findings are significant because they afford a sizeable reduction in active layer thickness, and therefore a reduction in expensive epitaxial growth time and cost, yet without compromising performance.


Religious and secular spirituality: Methodological implications of definitions for health research.
The importance of spirituality as a research topic has been increasingly recognized, which has led to several studies on the topic. Areas including psychology, medicine, and nursing have produced studies on spirituality under a plurality of definitions and methods, which reveals the complexity of the theme. However, this has resulted in a range of potential problems, including: (1) the use of overlapping and contradictory terms between studies, or even within the same study, (2) research methodologies that do not fit the definitions (sometimes unreflectively) assumed by the authors, (3) difficulties, or even the impossibility, of comparing the results of studies, (4) controversies in respect of the inclusion/exclusion of secular groups in research on spirituality, and (5) ambiguous measurements, often being exclusively dependent on each participant's individual interpretation of what spirituality means. This article discusses these problems, recommends theoretical and methodological alternatives and presents taxonomy of definitions of spirituality.


Maximum preservation of the media in carotid endarterectomy.
Carotid endarterectomy (CEA) is intended to remove atheromatous plaque by dissecting a plane between the intima and the media (circular medial fibers), but this may not be the optimal dissection plane. The present technique is based on identifying the plane that divides the media from the plaque, so preserving the media on the adventitia as much as possible. This plane is more difficult to find and follow than the easy-to-dissect plane usually located between the media and the adventitia, because the plaque invades the media and so the dividing plane is located within the media. In this prospective observational study, CEA was performed in 22 patients to histologically examine the excised plaques and small samples of the whole arterial wall, and evaluate the clinical outcomes. Plaque had invaded the luminal part of the media in the whole arterial wall sample of 80% of cases. Thin medial layers covering > 80% of the surface of the plaque were found in 16 of 22 plaques (73%). Some atheromatous component was sometimes left in the preserved media, rather than completely removed with the media. No morbidity or mortality had occurred by discharge. Only 1 small ipsilateral infarction (4.5%) and no restenosis of greater than 50% were detected during the mean follow-up period of 7 years. Since the plaque usually invades the media, the optimum dissection plane may be located within the media, dividing it into two layers. The presence of some remnant atheromatous components in the preserved media was not associated with surgical complications or restenosis.


Validation of automatic measurement of QT interval variability.
Increased variability of beat-to-beat QT-interval durations on the electrocardiogram (ECG) has been associated with increased risk for fatal and non-fatal cardiac events. However, techniques for the measurement of QT variability (QTV) have not been validated since a gold standard is not available. In this study, we propose a validation method and illustrate its use for the validation of two automatic QTV measurement techniques. Our method generates artificial standard 12-lead ECGs based on the averaged P-QRS-T complexes from a variety of existing ECG signals, with simulated intrinsic (QT interval) and extrinsic (noise, baseline wander, signal length) variations. We quantified QTV by a commonly used measure, short-term QT variability (STV). Using 28,800 simulated ECGs, we assessed the performance of a conventional QTV measurement algorithm, resembling a manual QTV measurement approach, and a more advanced algorithm based on fiducial segment averaging (FSA). The results for the conventional algorithm show considerable median absolute differences between the simulated and estimated STV. For the highest noise level, median differences were 4-6 ms in the absence of QTV. Increasing signal length generally yields more accurate STV estimates, but the difference in performance between 30 or 60 beats is small. The FSA algorithm proved to be very accurate, with most median absolute differences less than 0.5 ms, even for the highest levels of disturbance. Artificially constructed ECGs with a variety of disturbances allow validation of QTV measurement procedures. The FSA algorithm provides highly accurate STV estimates under varying signal conditions, and performs much better than traditional beat-by-beat analysis. The fully automatic operation of the FSA algorithm enables STV measurement in large sets of ECGs.


Antiplatelet Therapy After Noncardioembolic Stroke.
Background and Purpose- We assessed the efficacy and safety of antiplatelet agents after noncardioembolic stroke or transient ischemic attack and examined how these vary according to patients' demographic and clinical characteristics. Methods- We did a network meta-analysis (NMA) of data from 6 randomized trials of the effects of commonly prescribed antiplatelet agents in the long-term (≥3 months) secondary prevention of noncardioembolic stroke or transient ischemic attack. Individual patient data from 43 112 patients were pooled and reanalyzed. Main outcomes were serious vascular events (nonfatal stroke, nonfatal myocardial infarction, or vascular death), major bleeding, and net clinical benefit (serious vascular event or major bleeding). Subgroup analyses were done according to age, sex, ethnicity, hypertension, qualifying diagnosis, type of vessel involved (large versus small vessel disease), and time from qualifying event to randomization. Results- Aspirin/dipyridamole combination (RRNMA-adj, 0.83; 95% CI, 0.74-0.94) significantly reduced the risk of vascular events compared with aspirin, as did clopidogrel (RRNMA-adj, 0.88; 95% CI, 0.78-0.98), and aspirin/clopidogrel combination (RRNMA-adj, 0.83; 95% CI, 0.71-0.96). Clopidogrel caused significantly less major bleeding and intracranial hemorrhage than aspirin, aspirin/dipyridamole combination, and aspirin/clopidogrel combination. Aspirin/clopidogrel combination caused significantly more major bleeding than aspirin, aspirin/dipyridamole combination, and clopidogrel. Net clinical benefit was similar for clopidogrel and aspirin/dipyridamole combination (RRNMA-adj, 0.99; 95% CI, 0.93-1.05). Subgroup analyses showed no heterogeneity of treatment effectiveness across prespecified subgroups. The excess risk of major bleeding associated with aspirin/clopidogrel combination compared with clopidogrel alone was higher in patients aged <65 years than it was in patients ≥65 years (RRNMA-adj, 3.9 versus 1.7). Conclusions- Results favor clopidogrel and aspirin/dipyridamole combination for long-term secondary prevention after noncardioembolic stroke or transient ischemic attack, regardless of patient characteristics. Aspirin/clopidogrel combination was associated with a significantly higher risk of major bleeding compared with other antiplatelet regimens.