Antioxidant activities of phenolic acids on ultraviolet radiation-induced erythrocyte and low density lipoprotein oxidation.
The exposure of mammalian cells to UV light induces various deleterious responses. Some of the major harmful effects are DNA damage, cell membrane peroxidation, systemic immune suppression, and aging acceleration. Reactive oxygen species and free radicals are believed to be largely responsible for some of the deleterious effects of UV upon cells. Typical administration of antioxidants has recently proved to represent a successful strategy for protecting the cells against UV-mediated oxidative damage. The objective of this study was to investigate the inhibitory effect of phenolic acids (caffeic acid, ferulic acid, gallic acid, and protocatechuic acid) on oxidative damage in human erythrocytes and low-density lipoprotein (LDL) induced by UVB radiation. The results revealed that the thiobarbituric acids reactive substances induced by UVB were decreased from 2.78 to 0.12-0.89 nmol MDA/mg protein in erythrocyte ghost and from 0.72 to 0.14-0.43 nmol MDA/mg protein in LDL by the addition of phenolic acids (100 muM). Caffeic acid, ferulic acid, and gallic acid exhibited over 85 and 60% inhibitory effect toward UVB-induced oxidation in erythrocytes and LDL, respectively. Phenolic acids, especially gallic acid, could maintain the normal glutathione levels and glutathione peroxidase activity in hemolysate from erythrocytes that were exposed to UVB radiation in comparison with untreated control. The results indicate that the antioxidant activities of caffeic acid and ferulic acid play a potential role in protection against UVB oxidative damage to human erythrocytes and LDL.


Environmental transmission of Clostridium difficile: association between hospital room size and C. difficile Infection.
To evaluate the association between hospital room square footage and acquisition of nosocomial Clostridium difficile infection (CDI). A case-control study was conducted at a university hospital during the calendar year of 2011. Case patients were adult inpatients with nosocomial CDI. Control patients were hospitalized patients without CDI and were randomly selected and matched to cases in a 2:1 ratio on the basis of hospital length of stay in 3-day strata. A multivariate model was developed using conditional logistic regression to evaluate risk factors for nosocomial CDI. A total of 75 case patients and 150 control patients were included. On multivariate analyses, greater square footage of the hospital room was associated with a significantly increased risk of acquiring CDI (odds ratio for every 50 ft² increase, 3.00; 95% CI, 1.75-5.16; P<.001). Other factors associated with an increased risk of CDI were location in a single room (odds ratio, 3.43; 95% CI, 1.31-9.05; P=.01), malignant tumor (4.56; 1.82-11.4; P=.001), and receipt of cefepime (2.48; 1.06-5.82; P=.04) or immunosuppressants (6.90; 2.07-23.0; P=.002) within the previous 30 days. Greater room square footage increased the risk of acquisition of CDI in the hospital setting, likely owing to increased environmental contamination and/or difficulty in effective disinfection. Future studies are needed to determine feasible and effective cleaning protocols based on patient and room characteristics.


Large-scale aqueous synthesis of Cu(In,Ga)Se2 nanoparticles for photocatalytic degradation of ciprofloxacin.
Environmentally friendly synthesis of Cu(In,Ga)Se2 (CIGS) nanoparticles (NPs) is pivotal for producing sustainable photocatalytic compounds to be applied in the remediation of contaminants of emerging concern from water. To this end, we herein report an aqueous synthesis of CIGS NPs, followed by annealing, to give access to phase-pure CIGS crystals with chalcopyrite structure and no signs of secondary phases. Morphological and compositional characterization revealed NPs with an average size of 10-35 nm and uniform distribution of Cu, In, Ga, and Se elements. In addition, the first aqueous large-scale synthesis of CIGS NPs is developed by up-scaling the synthesis procedure, resulting in 5 g of highly crystalline nanoparticles exhibiting an ideal optical band gap of 1.14 eV. The as-synthesized NPs proved the ability to remove 71 and 83% of a contaminant of emerging concern, ciprofloxacin (CIP), under ultraviolet (UV) and visible (Vis) radiations, respectively.


Genetic and molecular organization of ribosomal DNA (rDNA) variants in wild and cultivated barley.
Twenty rDNA spacer-length variants (slvs) have been identified in barley. These slvs form a ladder in which each variant (with one exception) differs from its immediate neighbors by a 115-bp subrepeat. The 20 slvs are organized in two families, one forming an eight-step ladder (slvs 100-107) in the nucleolus organizer region (NOR) of chromosome 7 and the other a 12-step ladder (slvs 108a-118) in the NOR of chromosome 6. The eight shorter slvs (100-107) segregate and serve as markers of eight alleles of Mendelian locus Rrn2 and the 12 longer slvs (108a-118) segregate and serve as markers of 12 alleles of Mendelian locus Rrn1. Most barley plants (90%) are homozygous for two alleles, including one from each the 100-107 and the 108a-118 series. Two types of departures from this typical pattern of molecular and genetic organization were identified, one featuring compound alleles marked by two slvs of Rrn1 or of Rrn2, and the other featuring presence in Rrn1 of alleles normally found in Rrn2, and vice versa. The individual and joint effects on adaptedness of the rDNA alleles are discussed. It was concluded that selection acting on specific genotypes plays a major role in molding the strikingly different allelic and genotypic frequency distributions seen in populations of wild and cultivated barley from different ecogeographical regions.


Right insular damage decreases heartbeat awareness and alters cardio-visual effects on bodily self-consciousness.
Recent evidence suggests that multisensory integration of bodily signals involving exteroceptive and interoceptive information modulates bodily aspects of self-consciousness such as self-identification and self-location. In the so-called Full Body Illusion subjects watch a virtual body being stroked while they perceive tactile stimulation on their own body inducing illusory self-identification with the virtual body and a change in self-location towards the virtual body. In a related illusion, it has recently been shown that similar changes in self-identification and self-location can be observed when an interoceptive signal is used in association with visual stimulation of the virtual body (i.e., participants observe a virtual body illuminated in synchrony with their heartbeat). Although brain imaging and neuropsychological evidence suggest that the insular cortex is a core region for interoceptive processing (such as cardiac perception and awareness) as well as for self-consciousness, it is currently not known whether the insula mediates cardio-visual modulation of self-consciousness. Here we tested the involvement of insular cortex in heartbeat awareness and cardio-visual manipulation of bodily self-consciousness in a patient before and after resection of a selective right neoplastic insular lesion. Cardio-visual stimulation induced an abnormally enhanced state of bodily self-consciousness; in addition, cardio-visual manipulation was associated with an experienced loss of the spatial unity of the self (illusory bi-location and duplication of his body), not observed in healthy subjects. Heartbeat awareness was found to decrease after insular resection. Based on these data we propose that the insula mediates interoceptive awareness as well as cardio-visual effects on bodily self-consciousness and that insular processing of interoceptive signals is an important mechanism for the experienced unity of the self.


[Papilloma of the choroid plexus of the lateral ventricle without generalized hydrocephalus].
A benign papilloma of the choroid plexus of the left lateral ventricle is found in a five-month old infant. An important dilatation of the isolated occipital horn is observed, without generalized enlargement of the ventricles. The clinical signs are limited to a moderate macrocephaly with deviation of head and eyes to the left. The absence of global hydrocephalus is rather exceptional in such cases, where overproduction of cerebrospinal fluid, in an amount proportional to the tumoral mass, is generally admitted. Nevertheless, the literature offers no absolute proof of the role of oversecretion alone in the origin of hydrocephalus, whilst an eventual obstruction of the circulatory pathways and resorption areas of the C.S.F. must be kept in mind. The absence of hydrocephalus, in the present case, suggests that the subarachnoid spaces and arachnoid villi remained patent.


Biosynthesis of silver nanoparticles employing Trichoderma harzianum with enzymatic stimulation for the control of Sclerotinia sclerotiorum.
Biogenic synthesis of silver nanoparticles employing fungi offers advantages, including the formation of a capping from fungal biomolecules, which provides stability and can contribute to biological activity. In this work, silver nanoparticles were synthesized using Trichoderma harzianum cultivated with (AgNP-TS) and without enzymatic stimulation (AgNP-T) by the cell wall of Sclerotinia sclerotiorum. The nanoparticles were evaluated for the control of S. sclerotiorum. The specific activity of the T. harzianum hydrolytic enzymes were determined in the filtrates and nanoparticles. Cytotoxicity and genotoxicity were also evaluated. Both the nanoparticles exhibited inhibitory activity towards S. sclerotiorum, with no new sclerotia development, however AgNP-TS was more effective against mycelial growth. Both the filtrates and the nanoparticles showed specific enzymatic activity. Low levels of cytotoxicity and genotoxicity were observed. This study opens perspectives for further exploration of fungal biogenic nanoparticles, indicating their use for the control of S. sclerotiorum and other agricultural pests.


Bark beetles as lidar targets and prospects of photonic surveillance.
Forestry is raising concern about the outbreaks of European spruce bark beetle, Ips typographus, causing extensive damage to the spruce forest and timber values. Precise monitoring of these beetles is a necessary step towards preventing outbreaks. Current commercial monitoring methods are catch-based and lack in both temporal and spatial resolution. In this work, light scattering from beetles is characterized, and the feasibility of entomological lidar as a tool for long-term monitoring of bark beetles is explored. Laboratory optical properties, wing thickness, and wingbeat frequency of bark beetles are reported, and these parameters can infer target identity in lidar data. Lidar results from a Swedish forest with controlled bark beetle release event are presented. The capability of lidar to simultaneously monitor both insects and a pheromone plume mixed with chemical smoke governing the dispersal of many insects is demonstrated. In conclusion, entomological lidar is a promising tool for monitoring bark beetles.


Malignant neoplasms of digestive organs (C15-C26) in the Osijek-Baranja County, Croatia.
The Institute of Public Health for the Osjek-Baranja County (OBC) has processed the data on cancer patients that were collected from mandatory county hospitals data reports, county bureaus of statistics and the County Register of Deaths. The cancers were defined according to the International Statistical Classification of Diseases and Related Health Problems, 10th Revision (ICD-10), codes of malignant neoplasms of digestive organs (C15-C26). The aim of this article is to show the size of the problem and the burden of the health care system caused by cancers of the digestive system (C15-C26) in the OBC in the period 2001-2006. This article deals with cancer incidence and mortality data, appertaining age distribution, cancer survival, median age at diagnosis and at death and length of stay in hospitals. The overall incidence and mortality rate from cancer group C15-C26 (101.1 and 80/100,000, respectively, EU standard population) declined in all age groups, comparing the data originating from the 2001-2003 period to the data referring to the 2004-2006 period. The median age at diagnosis of cancer was 67.8 years with a shift of 0.91 year up in second period (the median age in the first period was 67.3 years and in the second one 68.2 years). The median age at diagnosis of cancer in females was 69.7 years while in males was 66.3 years, which represents a difference of 2.9 years in favour of females. The overall relative survival rate of all ages was 23.6%. This figure was slightly bigger for females (24.3%) than for males (23.1%). Concerning all age groups, the number of hospital admissions of males increased during the observation period while the number of hospital admissions of women decreased at the same time. The average length of stay over the six years did not changed significantly. Group of cancer C15-C26 was the most common group of cancers regarding both genders. The five-year relative survival as one of the reliable benchmarks of the quality of the health care system needs to be raised to a great extent in order to come nearer to the EU average within a short period of time.


Cerebrospinal fluid APOE levels: an endophenotype for genetic studies for Alzheimer's disease.
The apolipoprotein E (APOE) genotype is the major genetic risk factor for Alzheimer's disease (AD). We have access to cerebrospinal fluid (CSF) and plasma APOE protein levels from 641 individuals and genome-wide genotyped data from 570 of these samples. The aim of this study was to test whether CSF or plasma APOE levels could be a useful endophenotype for AD and to identify genetic variants associated with APOE levels. We found that CSF (P = 8.15 × 10(-4)) but not plasma (P = 0.071) APOE protein levels are significantly associated with CSF Aβ(42) levels. We used Mendelian randomization and genetic variants as instrumental variables to confirm that the association of CSF APOE with CSF Aβ(42) levels and clinical dementia rating (CDR) is not because of a reverse causation or confounding effect. In addition the association of CSF APOE with Aβ(42) levels was independent of the APOE ε4 genotype, suggesting that APOE levels in CSF may be a useful endophenotype for AD. We performed a genome-wide association study to identify genetic variants associated with CSF APOE levels: the APOE ε4 genotype was the strongest single-genetic factor associated with CSF APOE protein levels (P = 6.9 × 10(-13)). In aggregate, the Illumina chip single nucleotide polymorphisms explain 72% of the variability in CSF APOE protein levels, whereas the APOE ε4 genotype alone explains 8% of the variability. No other genetic variant reached the genome-wide significance threshold, but nine additional variants exhibited a P-value <10(-6). Pathway mining analysis indicated that these nine additional loci are involved in lipid metabolism (P = 4.49 × 10(-9)).


Identification of coccidioidomycosis of the lung by fine needle aspiration biopsy.
A solitary coin lesion in the lung is a frequent presentation of coccidioidomycosis; these lesions may be radiologically indistinguishable from cancer. In a series of 112 fine needle aspiration (FNA) biopsies performed in the San Joaquin Valley on solitary pulmonary nodules, 8 cases were identified as coccidioidomycosis by the presence of spherules in the aspirated material. The immature sporangia ranged in size from 4 micron to 40 micron. The smaller spherules did not show endospores and could have been confused with red blood cells. A methenamine silver or periodic acid-Schiff stain was helpful in identifying the spherules following decolorization of Papanicolaou-stained material; this was especially important when the background material was bloody. Older nonviable spherules showed a folded collapsed cell membrane, which may be associated with long-standing cavitary disease. A complement fixation titer was frequently not elevated. This study demonstrates the utility of FNA biopsy in the identification of cocci granulomas in the lung.


A Review of Incident Prediction, Resource Allocation, and Dispatch Models for Emergency Management.
In the last fifty years, researchers have developed statistical, data-driven, analytical, and algorithmic approaches for designing and improving emergency response management (ERM) systems. The problem has been noted as inherently difficult and constitutes spatio-temporal decision making under uncertainty, which has been addressed in the literature with varying assumptions and approaches. This survey provides a detailed review of these approaches, focusing on the key challenges and issues regarding four sub-processes: (a) incident prediction, (b) incident detection, (c) resource allocation, and (c) computer-aided dispatch for emergency response. We highlight the strengths and weaknesses of prior work in this domain and explore the similarities and differences between different modeling paradigms. We conclude by illustrating open challenges and opportunities for future research in this complex domain.


Long-term effectiveness of interventions promoting physical activity: a systematic review.
This systematic review aims to evaluate the long-term effectiveness of physical activity interventions targeted at healthy adults and to identify effective intervention components. The systematic search in Pubmed, Embase, the Cochrane Library and Psycinfo identified literature published in English and German between January 2001 and June 2007. We included randomised controlled trials investigating physical activity interventions for healthy adults with a minimum study duration of 12 months. Two researchers independently assessed publications according to pre-defined inclusion criteria and methodological quality was rated according to the SIGN criteria. Study characteristics and outcome measures were extracted, and pooled effect estimates with 95% confidence intervals calculated. Of 5508 identified publications 25 studies met the inclusion criteria. There was substantial heterogeneity in study quality, intervention strategies and intervention effects. Compared to no-intervention and minimal-intervention control, gains in weekly energy expenditure and physical fitness of up to 975 kcal and 11% were achieved, respectively. Booster interventions were used in 16 studies. There is evidence for long-term increases in physical activity behaviour and physical fitness. To improve uptake of physical activity additional tailored exercise prescription strategies seem promising. Booster interventions such as phone, mail or internet can help to facilitate long-term effectiveness.


Eyewitness identification performance is not affected by time-of-day optimality.
The circadian rhythm regulates arousal levels throughout the day and determines optimal periods for engaging in mental activities. Individuals differ in the time of day at which they reach their peak: Morning-type individuals are at their best in the morning and evening types perform better in the evening. Performance in recall and recognition of non-facial stimuli is generally superior at an individual's circadian peak. In two studies (Ns = 103 and 324), we tested the effect of time-of-testing optimality on eyewitness identification performance. Morning- and evening-type participants viewed stimulus films depicting staged crimes and made identification decisions from target-present and target-absent lineups either at their optimal or non-optimal time-of-day. We expected that participants would make more accurate identification decisions and that the confidence-accuracy and decision time-accuracy relationships would be stronger at optimal compared to non-optimal time of day. In Experiment 1, identification accuracy was unexpectedly superior at non-optimal compared to optimal time of day in target-present lineups. In Experiment 2, identification accuracy did not differ between the optimal and non-optimal time of day. Contrary to our expectations, confidence-accuracy relationship was generally stronger at non-optimal compared to optimal time of day. In line with our predictions, non-optimal testing eliminated decision-time-accuracy relationship in Experiment 1.


Correlating Quantitative Para-Aortic Lymph Node Computed Tomography Parameters With Fluorodeoxyglucose Positron Emission Tomography for Cervical Cancer Staging: Possible Solution for Resource Constrained Countries.
The aim of the study was to determine the most accurate quantitative morphological parameters on computed tomography (CT) that correlate with fluorodeoxyglucose (FDG)-avid para-aortic nodes (PANs) in patients with cervical cancer. A single-institution retrospective evaluation was performed of women with cervical cancer who underwent pretreatment positron emission tomography (PET)/CT and radiotherapy therapy planning CT between 2009 and 2020. A node-by-node correlation between pretreatment CT and PET/CT was performed for the reference standard of FDG avidity for short- and long-axis diameters, volume, and long-/short-axis ratio (L/S). The FDG-avid PANs were defined as PET-positive and non-FDG-avid PANs from patients without PET-determined PAN metastasis were defined as PET negative. Area under the receiver operator curve was calculated to access diagnostic accuracy of the different quantitative parameters. A total of 94 women (mean age ± standard deviation, 52 ± 13 years) with cervical cancer were included. Forty-seven patients had PET-positive PANs (181 PET-positive PANs) and 47 patients had no PET-positive PANs (141 PET-negative PANs). The area under the receiver operator curve for volume (0.945) was greater ( P < 0.001) than that of short axis (0.895), long axis (0.885), and L/S (0.583). At a specificity set point of 0.90 (127/141 PANs), the cutoff for volume was 0.443 cm 3 or greater (0.85 sensitivity [154/181 PANs]; 95% confidence interval, 0.83-0.93) and for short-axis diameter was 5.9 mm or greater (0.75 sensitivity [135/181 PANs]; 95% confidence interval, 0.68-0.81). Para-aortic lymph node volume demonstrated that improved node-by-node correlation between CT and PET/CT compared with short-axis diameter, long-axis diameter, and L/S and is an alternative to improve detection of PAN suspicious of metastatic diseases in locations without access to PET/CT.


Classic or Bayesian research design and analysis. Does it make a difference?
The role of classical and Bayesian statistical approaches remains in dispute in health services research and policy. The goal of this study was to determine if results differ when both analytic techniques are used with the same data set. We searched MEDLINE and related databases for English-language articles published January 1, 1978 through August 31, 1999. We combined Bayesian and classical statistics search terms and their variants with randomized control trials (RCTs) and meta-analyses. Searches found 18 studies in 14 publications that met all review criteria--nine RCTs, eight meta-analyses, and one epidemiologic estimate. Statistical analyses using both methods agreed in five RCTs, four meta-analyses, and for the epidemiologic estimates. For four RCTs where results disagreed, classical analysis found the experimental intervention was efficacious compared with the control, and Bayesian reanalysis concluded the intervention was not proven efficacious. Classical meta-analyses of the four studies where results disagreed concluded the experimental intervention was not better than the control; Bayesian reanalysis concluded it was efficacious. Classical and Bayesian methods in this review exhibited important divergence of results. Disagreement on many fundamental beliefs between classical and Bayesian statistics means continuing debate. One way to resolve this debate is for proponents of each technique to decide together the circumstances for use of each method and analytic framework. If the experts do not agree on the methodologic requirements, other decision makers likely will force their own views.


Diffuse cutaneous metastases as the only sign of extranodal tumor spread in a patient with adenocarcinoma of the colon.
Cutaneous metastases from large bowel cancer are uncommon and are usually associated with organ involvement. Localization of lesions to the skin is mainly attributed to vascular and anatomical relationship, since most of them are seen in the abdominal wall or in a surgical scar. We report a 73-year-old woman in whom metastatic nodules from a poorly differentiated adenocarcinoma of the right colon developed throughout the skin (buttock, trunk, chest wall, arms, and neck) and remained the only sign of extranodal tumor spread until patient's death, seven months later. This unusual behaviour suggests that localization of neoplastic cells to the skin may be a site-specific process, determined by adhesion molecules and/or by growth factors found at that site.


Simultaneous GC-EI-MS determination of Delta9-tetrahydrocannabinol, 11-hydroxy-Delta9-tetrahydrocannabinol, and 11-nor-9-carboxy-Delta9-tetrahydrocannabinol in human urine following tandem enzyme-alkaline hydrolysis.
A sensitive and specific method for extraction and quantification of Delta(9)-tetrahydrocannabinol (THC), 11-hydroxy-Delta(9)-tetrahydrocannabinol (11-OH-THC), and 11-nor-9-carboxy-Delta(9)-tetrahydrocannabinol (THCCOOH) in human urine was developed and fully validated. To ensure complete hydrolysis of conjugates and capture of total analyte content, urine samples were hydrolyzed by two methods in series. Initial hydrolysis was with Escherichia coli beta-glucuronidase (Type IX-A) followed by a second hydrolysis utilizing 10N NaOH. Specimens were adjusted to pH 5-6.5, treated with acetonitrile to precipitate protein, and centrifuged, and the supernatants were subjected to solid-phase extraction. Extracted analytes were derivatized with BSTFA and quantified by gas chromatography-mass spectrometry with electron impact ionization. Standard curves were linear from 2.5 to 300 ng/mL. Extraction efficiencies were 57.0-59.3% for THC, 68.3-75.5% for 11-OH-THC, and 71.5-79.7% for THCCOOH. Intra- and interassay precision across the linear range of the assay ranged from 0.1 to 4.3% and 2.6 to 7.4%, respectively. Accuracy was within 15% of target concentrations. This method was applied to the analysis of urine specimens collected from individuals participating in controlled administration cannabis studies, and it may be a useful analytical procedure for determining recency of cannabis use in forensic toxicology applications.


Nonanticoagulant heparin prevents histone-mediated cytotoxicity in vitro and improves survival in sepsis.
Extracellular histones are considered to be major mediators of death in sepsis. Although sepsis is a condition that may benefit from low-dose heparin administration, medical doctors need to take into consideration the potential bleeding risk in sepsis patients who are already at increased risk of bleeding due to a consumption coagulopathy. Here, we show that mechanisms that are independent of the anticoagulant properties of heparin may contribute to the observed beneficial effects of heparin in the treatment of sepsis patients. We show that nonanticoagulant heparin, purified from clinical grade heparin, binds histones and prevents histone-mediated cytotoxicity in vitro and reduces mortality from sterile inflammation and sepsis in mouse models without increasing the risk of bleeding. Our results demonstrate that administration of nonanticoagulant heparin is a novel and promising approach that may be further developed to treat patients suffering from sepsis.


A mathematical model of the inner medullary collecting duct of the rat: pathways for Na and K transport.
A mathematical model of the inner medullary collecting duct (IMCD) of the rat has been developed representing Na+, K+, Cl-, HCO3-, CO2, H2CO3, phosphate, ammonia, and urea. Novel model features include: finite rates of hydration of CO2, a kinetic representation of the H-K-ATPase within the luminal cell membrane, cellular osmolytes that are regulated in defense of cell volume, and the repeated coalescing of IMCD tubule segments to yield the ducts of Bellini. Model transport is such that when entering Na+ is 4% of filtered Na+, approximately 75% of this load is reabsorbed. This requirement renders the area-specific transport rate for Na+ comparable to that for proximal tubule. With respect to the luminal membrane, there is experimental evidence for both NaCl cotransport and an Na+ channel in parallel. The experimental constraints that transepithelial potential difference is small and that the fractional apical resistance is greater than 85% mandate that more than 75% of luminal Na+ entry be electrically silent. When Na+ delivery is limited, an NaCl cotransporter can be effective at reducing luminal Na+ concentration to the observed low urinary values. Given the rate of transcellular Na+ reabsorption, there is necessarily a high rate of peritubular K+ recycling; also, given the lower bound on luminal membrane Cl- reabsorption, substantial peritubular Cl- flux must be present. Thus, if realistic limits on cell membrane electrical resistance are observed, then this model predicts a requirement for peritubular electroneutral KCl exit.


Interviral Recombination between Plant, Insect, and Fungal RNA Viruses: Role of the Intracellular Ca2+/Mn2+ Pump.
Recombination is one of the driving forces of viral evolution. RNA recombination events among similar RNA viruses are frequent, although RNA recombination could also take place among unrelated viruses. In this paper, we have established efficient interviral recombination systems based on yeast and plants. We show that diverse RNA viruses, including the plant viruses tomato bushy stunt virus, carnation Italian ringspot virus, and turnip crinkle virus-associated RNA; the insect plus-strand RNA [(+)RNA] viruses Flock House virus and Nodamura virus; and the double-stranded L-A virus of yeast, are involved in interviral recombination events. Most interviral recombinants are minus-strand recombinant RNAs, and the junction sites are not randomly distributed, but there are certain hot spot regions. Formation of interviral recombinants in yeast and plants is accelerated by depletion of the cellular SERCA-like Pmr1 ATPase-driven Ca2+/Mn2+ pump, regulating intracellular Ca2+ and Mn2+ influx into the Golgi apparatus from the cytosol. The interviral recombinants are generated by a template-switching mechanism during RNA replication by the viral replicase. Replication studies revealed that a group of interviral recombinants is replication competent in cell-free extracts, in yeast, and in the plant Nicotiana benthamiana We propose that there are major differences among the viral replicases to generate and maintain interviral recombinants. Altogether, the obtained data promote the model that host factors greatly contribute to the formation of recombinants among related and unrelated viruses. This is the first time that a host factor's role in affecting interviral recombination is established.IMPORTANCE Viruses with RNA genomes are abundant, and their genomic sequences show astonishing variation. Genetic recombination in RNA viruses is a major force behind their rapid evolution, enhanced pathogenesis, and adaptation to their hosts. We utilized a previously identified intracellular Ca2+/Mn2+ pump-deficient yeast to search for interviral recombinants. Noninfectious viral replication systems were used to avoid generating unwanted infectious interviral recombinants. Altogether, interviral RNA recombinants were observed between plant and insect viruses, and between a fungal double-stranded RNA (dsRNA) virus and an insect virus, in the yeast host. In addition, interviral recombinants between two plant virus replicon RNAs were identified in N. benthamiana plants, in which the intracellular Ca2+/Mn2+ pump was depleted. These findings underline the crucial role of the host in promoting RNA recombination among unrelated viruses.


A Randomized Controlled Trial on the Efficacy of a Psychosocial Behavioral Intervention to Improve the Lifestyle of Patients With Severe Mental Disorders: Study Protocol.
Patients with severe mental disorders die on average 20 years prior to the general population. This mortality gap is mainly due to the higher prevalence of physical diseases and the adoption of unhealthy lifestyle behaviors.The LIFESTYLE trial aims to evaluate the efficacy of a new psychosocial group intervention (including psychoeducational, motivational, and problem-solving techniques) focused on healthy lifestyle behavior compared to a brief educational group intervention in a community sample of patients with severe mental disorders. The trial is a national-funded, multicentric, randomized controlled trial with blinded outcome assessments, which is carried out in six outpatient units of the Universities of Campania "Luigi Vanvitelli" in Naples, Bari, Genova, L'Aquila, Pisa, and Rome-Tor Vergata. All patients are assessed at the following time points: baseline (T0); 2 months post-randomization (T1); 4 months post-randomization (T2); 6 months post-randomization (T3); 12 months post-randomization (T4); and 24 months post-randomization (T5). T1 and T2 assessments include only anthropometric tests. The BMI, a reliable and feasible anthropometric parameter, has been selected as primary outcome. In particular, the mean value of BMI at 6 months from baseline (T3) will be evaluated through a Generalized Estimated Equation model. The work hypothesis is that the LIFESTYLE psychosocial group intervention will be more effective than the brief educational group intervention in reducing the BMI. We expect a mean difference between the two groups of at least one point (and standard deviation of two points) at BMI. Secondary outcomes are: the improvement in dietary patterns, in smoking habits, in sleeping habits, physical activity, personal and social functioning, severity of physical comorbidities, and adherence to medications. The expected sample size consists of 420 patients (70 patients for each of the six participating centers), and they are allocated with a 1:1 ratio randomization, stratified according to center, age, gender, and educational level. Heavy smoking, sedentary behavior, and unhealthy diet pattern are very frequent and are associated with a reduced life expectancy and higher levels of physical comorbidities in people with severe mental disorders. New interventions are needed and we hope that the LIFESTYLE protocol will help to fill this gap. 2015C7374S.


Meeting after meeting: 20 years of discoveries by the members of the Exocytosis-Endocytosis Club.
Twenty years ago, a group of French cell biologists merged two scientific clubs with the aim of bringing together researchers in the fields of Endocytosis and Exocytosis. Founded in 1997, the first annual meeting of the Exocytosis Club was held in 1998. The Endocytosis Club held quarterly meetings from its founding in 1999. The first joint annual meeting of the Exocytosis-Endocytosis Club took place in Paris in April, 2001. What started as a modest gathering of enthusiastic scientists working in the field of cell trafficking has gone from strength to strength, rapidly becoming an unmissable yearly meeting, vividly demonstrating the high quality of science performed in our community and beyond. On the occasion of the 20th meeting of our club, we want to provide historic insight into the fields of exocytosis and endocytosis, and by extension, to subcellular trafficking, highlighting how French scientists have contributed to major advances in these fields. Today, the Exocytosis-Endocytosis Club represents a vibrant and friendly community that will hold its 20th meeting at the Presqu'Ile de Giens, near Toulon in the South of France, on May 11-13, 2017.


Quantified electrostatic preorganization in enzymes using the geometry of the electron charge density.
Electrostatic preorganization is thought to be a principle factor responsible for the impressive catalytic capabilities of enzymes. The full protein structure is believed to facilitate catalysis by exerting a highly specific electrostatic field on the active site. Computationally determining the extent of electrostatic preorganization is a challenging process. We propose using the topology and geometry of the electron charge density in the enzyme's active site to asses the effects of electrostatic preorganization. In support of this approach we study the convergence of features of the charge density as the size of the active site model increases in Histone Deacetylase 8. The magnitude of charge density at critical points and most Bader atomic charges are found to converge quickly as more of the protein is included in the simulation. The exact position of critical points however, is found to converge more slowly and be strongly influenced by the protein residues that are further away from the active site. We conjecture that the positions of critical points are affected through perturbations to the wavefunctions in the active site caused by dipole moments from amino acid residues throughout the protein. We further hypothesize that electrostatic preorganization, from the point of view of charge density, can not be easily understood through the charges on atoms or the nature of the bonding interactions, but through the relative positions of critical points that are known to correlate with reactivity and reaction barriers.


PCSK6 regulated by LH inhibits the apoptosis of human granulosa cells via activin A and TGFβ2.
Mammalian proprotein convertases (PCs) play an important role in folliculogenesis, as they proteolytically activate a variety of substrates such as the transforming growth factor beta (TGFβ) superfamily. PC subtilism/kexin 6 (PCSK6) is a member of the PC family and is ubiquitously expressed and implicated in many physiological and pathological processes. However, in human granulosa cells, the expression of the PC family members, their hormonal regulation, and the function of PCs are not clear. In this study, we found that PCSK6 is the most highly expressed PC family member in granulosa cells. LH increased PCSK6 mRNA level and PCSK6 played an anti-apoptosis function in KGN cells. Knockdown of PCSK6 not only increased the secretion of activin A and TGFβ2 but also decreased the secretion of follistatin, estrogen, and the mRNA levels of FSH receptor (FSHR) and P450AROM (CYP19A1). We also found that, in the KGN human granulosa cell line, TGFβ2 and activin A could promote the apoptosis of KGN cells and LH could regulate the follistatin level. These data indicate that PCSK6, which is regulated by LH, is highly expressed in human primary granulosa cells of pre-ovulatory follicles and plays important roles in regulating a series of downstream molecules and apoptosis of KGN cells.


Substituting Sodium Hydrosulfite with Sodium Metabisulfite Improves Long-Term Stability of a Distributable Paper-Based Test Kit for Point-of-Care Screening for Sickle Cell Anemia.
Sickle cell anemia (SCA) is a genetic blood disorder that is particularly lethal in early childhood. Universal newborn screening programs and subsequent early treatment are known to drastically reduce under-five SCA mortality. However, in resource-limited settings, cost and infrastructure constraints limit the effectiveness of laboratory-based SCA screening programs. To address this limitation our laboratory previously developed a low-cost, equipment-free, point-of-care, paper-based SCA test. Here, we improved the stability and performance of the test by replacing sodium hydrosulfite (HS), a key reducing agent in the hemoglobin solubility buffer which is not stable in aqueous solutions, with sodium metabisulfite (MS). The MS formulation of the test was compared to the HS formulation in a laboratory setting by inexperienced users (n = 3), to determine visual limit of detection (LOD), readout time, diagnostic accuracy, intra- and inter-observer agreement, and shelf life. The MS test was found to have a 10% sickle hemoglobin LOD, 21-min readout time, 97.3% sensitivity and 99.5% specificity for SCA, almost perfect intra- and inter-observer agreement, at least 24 weeks of shelf stability at room temperature, and could be packaged into a self-contained, distributable test kits comprised of off-the-shelf disposable components and food-grade reagents with a total cost of only $0.21 (USD).


Molecular basis for allelic polymorphism of the maize Globulin-1 gene.
An abundant protein in maize (Zea mays L.) embryos is a storage globulin encoded by the polymorphic Glb1 gene. Several Glb1 protein size alleles and a null allele have been described. Here we report the isolation and nucleotide sequence analysis of genomic clones corresponding to two Glb1 size alleles (Glb1-L and Glb1-S) and to the Glb1-0 null allele. The Glb1-L and Glb1-0 alleles differ from Glb1-S by the presence of small nucleotide insertions which are imperfect or perfect duplications, respectively, of adjacent sequences. In the case of Glb1-L, the insertion is in-frame and results in a protein larger than that encoded by Glb1-S, whereas in Glb1-0 the insertion causes a translational frameshift which introduces a premature termination codon. Although steady-state levels of Glb1-0 transcripts are extremely low in Glb1-0/0 embryos, nuclear transcription assays indicate that the Glb1-0 gene is transcribed at a level comparable to that of Glb1-L. This suggests that the low amounts of Glb1-0 transcripts in the cytoplasm may be due to mRNA instability.


Critical incidents of nonadherence with standard precautions guidelines among community hospital-based health care workers.
To identify, categorize, and assess critical incidents of nonadherence to standard precautions. Qualitative and quantitative analysis of a written, mail-out survey. Community hospitals. Statewide stratified random sample of community hospital-based health care workers at risk for blood exposure. MAIN VARIABLE: Responses to the question: "Think of an incident during the past year when you didn't adhere to universal precautions. Please describe the situation and why you didn't adhere." Reasons given for not using precautions included: belief that stopping to use standard precautions would have put the patient at risk (22%); using precautions would have interfered with patient care (20%); precautions were not warranted in a specific situation (14%); did not anticipate the potential for exposure (14%); and high job demands that had caused respondent to be in a hurry (11%). Less often, equipment was not available (7%), respondent forgot (6%), respondent thought that the patient did not pose a risk (4%), or the available equipment was not effective (3%). In terms of overall exposure rates, 34% of those who described an incident had experienced a sharps injury during the previous 3 months and 42% had experienced a mucocutaneous exposure. In terms of overall nonadherence, 44% wore gloves less than 100% of the time, while 61% washed their hands less than 100% of the time. Needlestick injuries were lowest among those who had forgotten to use precautions, while mucocutaneous exposures were highest among those who had not anticipated potential exposure while performing the task. Failure to wear gloves routinely was highest among those who said that following precautions interfered with their ability to provide care and among those who believed a particular patient to be low risk; failure to wash hands routinely was also highest among the latter group and lowest among those who said necessary equipment was not available. Using specific information about local incidents of nonadherence to standard precautions may enhance training, especially if the program identifies incidents of unanticipated exposure and helps workers plan for them in the future. Closer examination of job demands and responsibilities that interfere with standard precautions may increase the likelihood of adherence.


Prediction of the Maximum Number of Repetitions and Repetitions in Reserve From Barbell Velocity.
To provide 2 general equations to estimate the maximum possible number of repetitions (XRM) from the mean velocity (MV) of the barbell and the MV associated with a given number of repetitions in reserve, as well as to determine the between-sessions reliability of the MV associated with each XRM. After determination of the bench-press 1-repetition maximum (1RM; 1.15 ± 0.21 kg/kg body mass), 21 men (age 23.0 ± 2.7 y, body mass 72.7 ± 8.3 kg, body height 1.77 ± 0.07 m) completed 4 sets of as many repetitions as possible against relative loads of 60%1RM, 70%1RM, 80%1RM, and 90%1RM over 2 separate sessions. The different loads were tested in a randomized order with 10 min of rest between them. All repetitions were performed at the maximum intended velocity. Both the general equation to predict the XRM from the fastest MV of the set (CV = 15.8-18.5%) and the general equation to predict MV associated with a given number of repetitions in reserve (CV = 14.6-28.8%) failed to provide data with acceptable between-subjects variability. However, a strong relationship (median r2 = .984) and acceptable reliability (CV < 10% and ICC > .85) were observed between the fastest MV of the set and the XRM when considering individual data. These results indicate that generalized group equations are not acceptable methods for estimating the XRM-MV relationship or the number of repetitions in reserve. When attempting to estimate the XRM-MV relationship, one must use individualized relationships to objectively estimate the exact number of repetitions that can be performed in a training set.


[Modern therapy for dementia].
The most frequently diagnosed dementia diseases include Alzheimer disease (AD), vascular dementia (VD) and dementia with Lewy bodies. Cholinesterase (ChE) inhibitors and the NMDA receptor antagonist memantine are currently recommended as first line drugs for the treatment of AD. These anti-dementia drugs have not yet been approved for the treatment of VD and DLB although the results of controlled clinical studies support the effectiveness of the ChE inhibitors for both diseases. The treatment of the primary disease and the secondary prevention of cerebrovascular accidents constitute the primary objectives of VD therapy. Although single or multiple domain cognitive deficits are the clinical key symptoms of dementia, noncognitive psychopathological symptoms (so-called behavioral disorders) are particularly common and may even dominate the clinical course in the moderate to severe stages. Therefore, it is important to recognize, diagnose and specifically treat these additional symptoms. During the last decade, the classic neuroleptics and benzodiazepine have been largely replaced by modern antidepressants, atypical antipsychotics and benzodiazepine analogues.


The Chp1-Tas3 core is a multifunctional platform critical for gene silencing by RITS.
RNA interference (RNAi) is critical for the assembly of heterochromatin at Schizosaccharomyces pombe centromeres. Central to this process is the RNA-induced initiation of transcriptional gene silencing (RITS) complex, which physically anchors small noncoding RNAs to chromatin. RITS includes Ago1, the chromodomain protein Chp1, and Tas3, which forms a bridge between Chp1 and Ago1. Chp1 is a large protein with no recognizable domains, apart from its chromodomain. Here we describe how the structured C-terminal half of Chp1 binds the Tas3 N-terminal domain, revealing the tight association of Chp1 and Tas3. The structure also shows a PIN domain at the C-terminal tip of Chp1 that controls subtelomeric transcripts through a post-transcriptional mechanism. We suggest that the Chp1-Tas3 complex provides a solid and versatile platform to recruit both RNAi-dependent and RNAi-independent gene-silencing pathways for locus-specific regulation of heterochromatin.


[When should cholecystectomy be practiced? Not always an easy decision].
Gallstone disease is a frequent medical problem. Cholelithiasis affects 10% of the population and 30% of patients with gallstones will undergo surgery. The treatment of choice for symptomatic gallstones remains cholecystectomy. A prophylactic cholecystectomy is indicated for asymptomatic patients in the presence of polyps, porcelain gallbladder or during bariatric surgery. The management of the complications of gallstone disease is discussed. At present, common bile duct stones, even if discovered preoperatively, should be managed by a multidisciplinary team including surgeons trained in laparoscopic techniques and gastroenterologists. This review is complemented by the information from a prospective database generated by a program called "DODIG" on 1099 cholecystectomies performed in our institution.


Chromosome-specific DNA repeats: rapid identification in silico and validation using fluorescence in situ hybridization.
Chromosome enumeration in interphase and metaphase cells using fluorescence in situ hybridization (FISH) is an established procedure for the rapid and accurate cytogenetic analysis of cell nuclei and polar bodies, the unambiguous gender determination, as well as the definition of tumor-specific signatures. Present bottlenecks in the procedure are a limited number of commercial, non-isotopically labeled probes that can be combined in multiplex FISH assays and the relatively high price and effort to develop additional probes. We describe a streamlined approach for rapid probe definition, synthesis and validation, which is based on the analysis of publicly available DNA sequence information, also known as "database mining". Examples of probe preparation for the human gonosomes and chromosome 16 as a selected autosome outline the probe selection strategy, define a timeline for expedited probe production and compare this novel selection strategy to more conventional probe cloning protocols.


Selective pharmacologic inhibition of a PASTA kinase increases Listeria monocytogenes susceptibility to β-lactam antibiotics.
While β-lactam antibiotics are a critical part of the antimicrobial arsenal, they are frequently compromised by various resistance mechanisms, including changes in penicillin binding proteins of the bacterial cell wall. Genetic deletion of the penicillin binding protein and serine/threonine kinase-associated protein (PASTA) kinase in methicillin-resistant Staphylococcus aureus (MRSA) has been shown to restore β-lactam susceptibility. However, the mechanism remains unclear, and whether pharmacologic inhibition would have the same effect is unknown. In this study, we found that deletion or pharmacologic inhibition of the PASTA kinase in Listeria monocytogenes by the nonselective kinase inhibitor staurosporine results in enhanced susceptibility to both aminopenicillin and cephalosporin antibiotics. Resistance to vancomycin, another class of cell wall synthesis inhibitors, or antibiotics that inhibit protein synthesis was unaffected by staurosporine treatment. Phosphorylation assays with purified kinases revealed that staurosporine selectively inhibited the PASTA kinase of L. monocytogenes (PrkA). Importantly, staurosporine did not inhibit a L. monocytogenes kinase without a PASTA domain (Lmo0618) or the PASTA kinase from MRSA (Stk1). Finally, inhibition of PrkA with a more selective kinase inhibitor, AZD5438, similarly led to sensitization of L. monocytogenes to β-lactam antibiotics. Overall, these results suggest that pharmacologic targeting of PASTA kinases can increase the efficacy of β-lactam antibiotics.


[Perceived stress and its influence on the eating behaviours of students at the University of Moncton, Moncton Campus].
Measure and analyze the link between perceived stress and eating behaviours of first (St1) and fourth-year students (St4) at the University of Moncton at the beginning (T1) and end (T2) of an academic trimester. Ninety-four subjects from various university programs participated in the study. The Perceived Stress scale was used to measure perceived stress. A three-day food record and a food frequency questionnaire were used to measure food consumption and its frequency. At T1, both first and fourth-year students show low levels of perceived stress. At T2, the perceived stress levels of St4 increase significantly (22,3 +/- 1,4; p =0,005) As stress increases, dietary profiles of students, measured according to the level of conformity to the Canada's Food Guide for Healthy Eating, show an increased consumption of milk and milk products for St1, T1 (p=0,05) and of breads and cereals for St4, T2 (p=0,02). Significant negative correlations were found among St4 between perceived stress and thiamine(r= -0,48; p=0,006) and zinc (r= -0,42; p=0,02). ingestion. No other correlations with perceived stress were found with either energy or other nutrient intakes. These results demonstrate the importance of intervening within the university student population and implementing information sessions on stress management and healthy eating behaviours among university students.


Parent perceptions of minimally invasive dental treatment of Australian Aboriginal pre-school children in rural and remote communities.
Aboriginal* children in rural and remote communities in Australia have a higher burden of dental decay and poorer access to dental services than their non-Aboriginal counterparts. In the Kimberley region of Western Australia (WA), Aboriginal children experience six times the rate of untreated dental decay of non-Aboriginal children. Access to dental care is challenged by the availability and appropriate delivery of services in remote locations. This study elicited the experiences and perceptions of parents and carers who participated in a project that tested the minimally invasive atraumatic restorative treatment and the Hall technique approaches (ART-HT) to manage early childhood dental caries among Australian Aboriginal preschool children. The core study design was a stepped-wedge, cluster-community-randomised controlled trial. Consenting communities in the Kimberley region of WA were randomised into early and delayed intervention groups. Children were clinically examined at study commencement; the early intervention group was offered dental treatment using the ART-HT approach, and the delayed group was advised to seek dental care from their usual service provider. At the 12-month follow-up, children in both groups were re-examined and offered care using the minimally invasive model of care, and parents and carers were invited to take part in focus group or one-to-one interviews. Semistructured interviews, guided by the yarning approach, were conducted with consenting parents and carers in community locations of convenience to participants. The same open-ended questions were asked of all participants, and the interviews were audio-recorded with permission and transcribed by an independent agency. Thematic analysis was undertaken, the transcripts were coded by NVivo software, and emergent themes were identified and developed. One-to-one interviews were conducted with 29 parents and carers (10 from five test communities; 19 from eight control communities). Interview participants consisted of 3 males and 26 females. Following thematic analysis, three main themes (and subthemes) were identified: (1) access to care (barriers, service availability, impact on family due to lack of access); (2) experience of care (cultural safety, child-centred care, comprehensiveness of care); (3) community engagement (service information, engagement, oral health education). Structural and system factors as well as geography were identified as barriers by parents and carers in accessing timely and affordable dental care in culturally safe environments; parents and carers also identified the impacts from lack of access to care. They valued comprehensive care delivered within community, underpinned by child- and family-centred care. Of equal importance was the holistic approach adopted through the building of community engagement and trusting relationships. A high level of satisfaction was reported by parents and carers with their experience of dental care for their children with the minimally invasive approach. Satisfaction was expressed around ease of accessing services delivered in a child- and family-centred manner, and that were well supported by appropriate engagement between service providers, communities and families. The findings from this study suggest a minimally invasive dental care model can be considered effective and culturally acceptable and should be considered in delivering oral health services for young children in rural and remote locations. * The term Aboriginal is inclusive of Aboriginal and Torres Strait Islander peoples.


Structural and chemical characterization of isolated centrosomes.
A procedure adapted from that described by Mitchison and Kirschner [Nature 312:232-237, 1984] was used to isolate centrosomes from human lymphoid cells. High yields of homogeneous centrosomes (60% of the theoretical total, assuming one centrosome per cell) were obtained. Centrosomes were isolated as pairs of centrioles, plus their associated pericentriolar material. Ultrastructural investigation revealed: 1) a link between both centrioles in a centrosome formed by the gathering in of a unique bundle of thin filaments surrounding each centriole; 2) a stereotypic organization of the pericentriolar material, including a rim of constant width at the proximal end of each centriole and a disc of nine satellite arms organized according to a ninefold symmetry at the distal end and; 3) an axial hub in the lumen of each centriole at the distal end surrounded by some ill-defined material. The total protein content was 2 to 3 X 10(-2) pg per isolated centrosome, a figure that suggests that the preparations were close to homogeneity. The protein composition was complex but specific, showing proteins ranging from 180 to 300 kD, one prominent band at 130 kD, and a group of proteins between 50 and 65 kD. Actin was also present in centrosome preparations. Functional studies demonstrated that the isolated centrosomes were competent to nucleate microtubules in vitro from purified tubulin in conditions in which spontaneous assembly could not occur. They were also very effective at inducing cleavage when microinjected into unfertilized Xenopus eggs.


Reflexivity over and above convention: the new orthodoxy in the sociology of personal life, formerly sociology of the family.
There is a new orthodoxy in the field that was once understood as the sociology of the family, and is increasingly understood as the sociology of 'personal life', 'intimacy', 'relationships' and 'families'. The orthodoxy highlights the open-endedness of intimate relations at the expense of the family as an institution; that is, reflexivity over and above convention. This article argues that the new orthodoxy not only overstates reflexivity at the expense of convention, but abdicates understanding to frameworks grounded in biologistic and economistic understandings of human behaviour. The article makes its point through attention to three areas of research at odds with the new orthodoxy: paternity uncertainty, inheritance and family business. It then proposes that conceptualization of the family as an institutional regime gives due weight to the reflexive reconfiguration of family relationships and practices on the one hand, and their institutional embeddedness on the other.


[Therapies for the Improvement of Stroke Recovery - Assessment of Clinical Trial Results].
Recovery processes after stroke include restoration or compensation of function initially lost or newly acquired after injury. Therapeutic interventions can either directly improve these processes and/or inhibit processes that impede regeneration. Numerous experimental studies suggested a great opportunity for such treatments, but the results from recent large clinical trials with neuromodulators such as dopamine and fluoxetine have been rather disappointing. The reasons for this are manifold and involve the extrapolation of results from animal models to humans. Given the differences between animals and humans in genetic and epigenetic background, brain size and anatomy, cerebral vascular anatomy, immune system, as well as clinical function, and behavior, direct extrapolation is unlikely to work. Backward blockades include the incompatible adaption of clinical trial objectives and outcomes in clinical trials with regard to previous preclinical findings. For example, the clinical recovery trial design widely varies and has been characterized by the selection of different clinical endpoints, the inclusion a wide spectrum of stroke subtypes and clinical syndromes, and different time windows for treatment initiation after onset of infarction. This review will discuss these aspects based on the results of the recent stroke recovery trials with the aim to contributing to the development of a therapy that improves the functional outcome of a chronic stroke patient.


Impact of Changing Surgical Strategies on Clinical Outcomes in Patients with Parotid Carcinoma: A 53-Year Single-Institution Experience.
Background and Objectives: We investigated the clinical outcomes of patients who underwent surgery for parotid carcinoma in a single institution during a 53-year period. This study aimed to estimate the impact of changing the surgical approach to parotid carcinoma on clinical outcomes including the incidence rate of the facial nerve palsy. Materials and Methods: Sixty-seven patients with parotid carcinoma who underwent surgery between 1966 and 2018 were retrospectively reviewed. Group A consisted of 29 patients who underwent surgery from 1966 to 2002, and Group B consisted of 38 patients from 2002 to 2018. Treatment outcomes were estimated. Additionally, candidate prognostic factors of Group B, the current surgical approach group, were evaluated. Results: Partial parotidectomy and total parotidectomy were performed in 35 and 32 patients, respectively. Partial parotidectomy was performed in 4 patients in Group A and 31 patients in Group B, with a predominant increase in Group B. The facial nerve was preserved in 43 patients, among whom 8 in Group A (8/17; 47.1%) and 7 in Group B (7/26; 26.9%) had temporary postoperative facial nerve palsy. Postoperative radiotherapy was performed on 35 patients. The 5-year OS, DSS, and DFS rates for Group A were 77.1%, 79.9%, and 71.5%, respectively. The 5-year OS, DSS, and DFS rates for Group B were 77.1%, 77.1%, and 72.4%, respectively. Clinical T4 stage, clinical N+ stage, stage IV disease, and tumor invasion of the facial nerve were independent prognostic factors in Group B. Conclusions: The incidence of facial nerve palsy in the current surgical approach group decreased compared with that in the previous surgical approach group. The current surgical management and treatment policies for parotid carcinoma have led to improved outcomes.


Supporting fingerprint identification assessments using a skin stretch model - A preliminary study.
To support fingerprint expert opinion, this research proposes an approach that combines subjective human analysis (as currently applied by fingerprint practitioners) with a statistical test of the result. This approach relies on the hypothesis that there are limits to the distortion caused by skin stretch. Such limits can be modelled by applying a multivariate normal probability density function to the distances and angle formed by a marked ridge characteristic and the two closest neighbouring minutiae. This study presents a model tested on 5 donors in total. The "expected range" of distortion in a within-source comparison using 10 minutiae was determined and compared to between-source comparisons. The expected range of log probability densities for within-source comparisons marked with 10 minutiae was determined to be from -33.4 to -60.0, with all between-source data falling outside this range, between -83 and -305. These results suggest that the proposed generated metric could be a powerful tool for the assessment of fingerprint expert opinion in operational casework.


Extensive Nicolau Syndrome Following Intramuscular Injection of Paracetamol in a Patient Who Is HIV Positive.
Nicolau syndrome (NS) is a type of adverse skin reaction occurring after parenteral drug injection. In certain conditions, it can cause ischemic necrosis of the skin and the underlying adipose tissue. The actual cause of NS is not clear though inflammation, vasospasm, and thromboembolic occlusion of blood vessels have been proposed. In this case presentation, we report an interesting case of a 30-year-old man who turned out be human immunodeficiency virus (HIV) positive on investigations, developed extensive purpuric lesions of his skin on left buttock and then spread to the trunk and shoulders after receiving intramuscular injection of paracetamol. With a suggestive history and further supported by clinical examination, a diagnosis of NS following injection of paracetamol was made. Though NS is considered to be rare, at times it can be devastating. Being a common procedure in the life of a health-care professional, the awareness regarding this entity is very essential. Despite intense medical literature search in, we could not find a single report of NS after intramuscular injection of paracetamol in a patient who is HIV positive, thus obliging this communication.


[Results of the first dermatomycoses quality control study in Germany].
For the first time in the history of German mycology, a multicenter study for identification of dermatophytes, yeasts and molds was conducted under the auspices of the German Speaking Mycological Society and the German Dermatological Society. A total of 1,008 dermatological offices and dermatology hospitals as well as 106 institutes of microbiology participated in this voluntary quality control trial. They were requested to identify four pathogens: Trichophyton tonsurans, Trichophyton mentagrophytes, Aspergillus niger, and Candida glabrata. T. tonsurans was correctly determined by 749 participants (67.2%), T. mentagrophytes by 974 (87.4%), A. niger by 922 (82.8%) and C. glabrata by 973 (87.3%). Four pathogens were identified at the species level by 591 investigators (53.1%). Three species were correctly identified by 310 investigators (27.8%), two by 143 (12.8%) and 0-1 by 70 (6.3%). The first dermatomycological quality control study in Germany may therefore be considered a success. Further trials will be carried out, initially at intervals of one year.


Age and Perceived Employability as Moderators of Job Insecurity and Job Satisfaction: A Moderated Moderation Model.
Workforce ageing and the need to work longer implies several challenges worldwide. Due to the potential for career prolongation, one such implication is to understand how age and perceived employability buffers relationship effects between job insecurity and job satisfaction. Therefore, this research aims to investigate the moderating roles of perceived employability and age on the relationship between job insecurity and job satisfaction. Hypotheses were tested using a three-way interaction model based on a cross-sectional design with a representative sample of 1,116 Chilean workers. Results show that age plays an important role in employees with high perceived employability; however, it has no effect on employees with low perceived employability. Younger workers with high perceived employability suffer less than do older employees with high perceived employability in terms of intrinsic job satisfaction. From a theoretical point of view, perceived employability in older workers does not reduce the unfavorable consequences of job insecurity. Regarding practical implications, organizations should manage and develop older workers by focusing on intrinsic aspects of their careers and on retirement preparation, as this will improve control and other positive resources in this population.


Depth dependent dynamics in the hydration shell of a protein.
We study the dynamics of hydration water/protein association in folded proteins using lysozyme and myoglobin as examples. Extensive molecular dynamics simulations are performed to identify underlying mechanisms of the dynamical transition that corresponds to the onset of amplified atomic fluctuations in proteins. The results indicate that the number of water molecules within a cutoff distance of each residue scales linearly with protein depth index and is not affected by the local dynamics of the backbone. Keeping track of the water molecules within the cutoff sphere, we observe an effective residence time, scaling inversely with depth index at physiological temperatures while the diffusive escape is highly reduced below the transition. A depth independent orientational memory loss is obtained for the average dipole vector of the water molecules within the sphere when the protein is functional. While below the transition temperature, the solvent is in a glassy state, acting as a solid crust around the protein, inhibiting any large scale conformational fluctuations. At the transition, most of the hydration shell unfreezes and water molecules collectively make the protein more flexible.


Learning With E-books and Project-based Strategy in a Community Health Nursing Course.
With advances in information technology, "information-assisted instruction" has been gradually introduced to nursing education curricula. Specifically, the integration of an e-book system can effectively enhance nursing students' attention and interest. Most studies on nursing education that incorporated e-books have focused on the advantages of convenience and assistance provided by e-books. Few studies have addressed community health nursing and off-campus practice activities in relation to suitable teaching strategies for learning activities. This study involved designing and planning a multimedia e-book learning system with a project-based learning activity that conforms to the curriculum and practical requirements of a community health nursing course. The purpose was to reduce the gap between theory and practice and realize an effective learning process. For learning evaluations, a final examination analysis with an independent sample t test; a scoring scheme with intrateam, interteam, and expert ratings; and Bloom's taxonomy-based analysis were conducted. The evaluation results indicated that the comprehension and learning abilities of the experimental group using the e-book system with a mobile device were effectively improved. In addition, the exploratory process involved in project-based learning can develop multiple cognitive skills and problem-solving ability, thereby realizing effective learning.


Arteriography with simultaneous gastric distention to detect insulin-secreting tumors of the pancreas.
Gaseous distention of the stomach at the time of arteriography enhances the contrast of densities within the pancreatic parenchyma, resulting in excellent visualization and therefore precise preoperative localization of insulin-secreting tumors of the pancreas. This relatively simple modification of selective arteriography was used in the last three consecutive patients we have seen with insulinomas. Apparently, the presence of air in the stomach makes the "tumor blush" that results from the uptake of the contrast dye by the vessels within the insulinoma and is clearer than in selective arteriography alone. The stomach was distended at the time of selective arteriography with carbonated soft drinks in two cases and by gas-producing pills in one. In all three cases, the location of the tumor shown by arteriography coincided exactly with the operative findings. Distal pancreatectomy was required in two; enucleation of the insulinoma was possible in one. All three patients recovered from operation uneventfully and were completely relieved of symptoms.


Suspended sediment prolongs larval development in a coral reef fish.
Increasing sediment input into coastal environments is having a profound influence on shallow marine habitats and associated species. Coral reef ecosystems appear to be particularly sensitive, with increased sediment deposition and re-suspension being associated with declines in the abundance and diversity of coral reef fishes. While recent research has demonstrated that suspended sediment can have negative impacts on post-settlement coral reef fishes, its effect on larval development has not been investigated. In this study, we tested the effects of different levels of suspended sediment on larval growth and development time in Amphiprion percula, a coral reef damselfish. Larvae were subjected to four experimental concentrations of suspended sediment spanning the range found around coastal coral reefs (0-45 mg l(-1)). Larval duration was significantly longer in all sediment treatments (12 days) compared with the average larval duration in the control treatment (11 days). Approximately 75% of the fish in the control had settled by day 11, compared with only 40-46% among the sediment treatments. In the highest sediment treatment, some individuals had a larval duration twice that of the median duration in the control treatment. Unexpectedly, in the low sediment treatment, fish at settlement were significantly longer and heavier compared with fish in the other treatments, suggesting delayed development was independent of individual condition. A sediment-induced extension of the pelagic larval stage could significantly reduce numbers of larvae competent to settle and, in turn, have major effects on adult population dynamics.


Late preconditioning with isoflurane in cultured rat cortical neurones.
We tested the hypothesis that isoflurane induces late preconditioning in cultured rat cortical neurones and preconditioning elicits changes in expression of Kir6.2 (the ion-conducting subunit of the metabolically responsive ATP-sensitive potassium (K(ATP)) channel) and EAAC1 (neuronal glutamate transporter). Primary cultures of rat cortical neurones were exposed to non-lethal oxygen-glucose deprivation (OGD), i.e. ischaemic preconditioning, for 30 min, 100 microM of diazoxide, a potent opener of the mitochondrial K(ATP) (mitoK(ATP)) channels, for 60 min or 1.4% isoflurane for 3 h. Lethal OGD was performed for 120 min 24 h after preconditioning stimuli. Neuronal injury was assessed by measurement of lactate dehydrogenase (LDH) efflux into the medium 24 h after lethal OGD, and neural viability was determined by proliferation assay. Gene and protein expression was confirmed by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and western blot analysis 24 h after preconditioning stimuli. All preconditioning stimuli resulted in a significant decrease in LDH activity and maintained neuronal viability. These effects were abolished by 5-hydroxydecanoate, a selective inhibitor of the mitoK(ATP) channel. Quantitative RT-PCR and Western blot analysis demonstrated that there was no significant difference between Kir6.2 mRNA and protein levels. All preconditioning stimuli resulted in > or =2-fold increases in EAAC1 mRNA and protein compared with control. Isoflurane induced late preconditioning in cultured rat cortical neurones. Ischaemic and pharmacological preconditioning with diazoxide and isoflurane induced ischaemic tolerance in the cultured neurones via mitoK(ATP) channels without an increase in Kir6.2 expression, and induced upregulation of EAAC1 expression.


Simultaneous Differential Scanning Calorimetry-Synchrotron X-ray Powder Diffraction: A Powerful Technique for Physical Form Characterization in Pharmaceutical Materials.
We report a powerful new technique: hyphenating synchrotron X-ray powder diffraction (XRD) with differential scanning calorimetry (DSC). This is achieved with a simple modification to a standard laboratory DSC instrument, in contrast to previous reports which have involved extensive and complex modifications to a DSC to mount it in the synchrotron beam. The high-energy X-rays of the synchrotron permit the recording of powder diffraction patterns in as little as 2 s, meaning that thermally induced phase changes can be accurately quantified and additional insight on the nature of phase transitions obtained. Such detailed knowledge cannot be gained from existing laboratory XRD instruments, since much longer collection times are required. We demonstrate the power of our approach with two model systems, glutaric acid and sulfathiazole, both of which show enantiotropic polymorphism. The phase transformations between the low and high temperature polymorphs are revealed to be direct solid-solid processes, and sequential refinement against the diffraction patterns obtained permits phase fractions at each temperature to be calculated and unit cell parameters to be accurately quantified as a function of temperature. The combination of XRD and DSC has further allowed us to identify mixtures of phases which appeared phase-pure by DSC.


Remarkable agrivoltaic influence on soil moisture, micrometeorology and water-use efficiency.
Power demands are set to increase by two-fold within the current century and a high fraction of that demand should be met by carbon free sources. Among the renewable energies, solar energy is among the fastest growing; therefore, a comprehensive and accurate design methodology for solar systems and how they interact with the local environment is vital. This paper addresses the environmental effects of solar panels on an unirrigated pasture that often experiences water stress. Changes to the microclimatology, soil moisture, water usage, and biomass productivity due to the presence of solar panels were quantified. The goal of this study was to show that the impacts of these factors should be considered in designing the solar farms to take advantage of potential net gains in agricultural and power production. Microclimatological stations were placed in the Rabbit Hills agrivoltaic solar arrays, located in Oregon State campus, two years after the solar array was installed. Soil moisture was quantified using neutron probe readings. Significant differences in mean air temperature, relative humidity, wind speed, wind direction, and soil moisture were observed. Areas under PV solar panels maintained higher soil moisture throughout the period of observation. A significant increase in late season biomass was also observed for areas under the PV panels (90% more biomass), and areas under PV panels were significantly more water efficient (328% more efficient).


Does strengths of a positive direct antiglobulin test predicts the need for phototherapy and duration of phototherapy? - a single center, retrospective study.
Use of Direct Antiglobulin test (DAT) in management of neonatal hyperbilirubinemia is conflicting. whether strength of positive DAT predicts the need for phototherapy, duration of phototherapy and need for major interventions. We retrospectively collected data on all DAT positive neonates with birth gestational age ≥32 weeks over six years (2014-2019). Data regarding blood group, DAT and clinical details were obtained from a hospital database. We also collected data on serial hemoglobin and other relevant laboratory parameters. We also collected data on infants receiving major interventions such as exchange transfusion, in-utero transfusion, immunoglobulins, and postnatal transfusion for the duration of the study period. All of these infants were electronically followed up for a period of 6 weeks. This study was approved by institutional audit authority. All the statistics were performed using SPSS software. Out of 1285 DAT tests performed, only 91 infants were positive (7%), and 78 DAT positive infants were available for analysis. There were 54 infants with DAT (1+), 15 infants with DAT (2+), 7 infants with DAT (3+) and 2 infants with DAT (4+). There was no significant statistical difference in terms of need for phototherapy, duration of phototherapy, need for major interventions and hemoglobin levels at different time points between the groups (DAT 1+ Vs DAT ≥2+; DAT ≤2+ Vs DAT >2). A Total of 10 infants received major intervention, with one infant receiving all three interventions (DAT 3+ with significant maternal antibodies), 2 additional infants (both DAT1+) received exchange transfusion, 6 additional infants received immunoglobulin (2 infants: DAT 2+; 4 infants: DAT 1+) and one additional infant (DAT 1+) with significant maternal antibodies received a postnatal transfusion. Strength of a DAT did not predict the need for phototherapy, duration of phototherapy, and the need for major hemolysis related intervention in the first 6 weeks of life.


Salvage photodynamic therapy for persistent esophageal cancer after chemoradiation therapy.
Locally advanced esophageal cancer may not be completely eradicated after chemoradiation therapy (CRT) and further treatment options are limited. Since 1998, we have used porfimer sodium photodynamic therapy (PDT) for inoperable patients with persistent mucosal carcinoma after CRT. Seven patients have undergone PDT after CRT: median age 75 (range 68-85), four patients male, three patients female. After upper endoscopy with biopsies documented neoplasm after CRT, patients were evaluated with contrast-enhanced computed tomography of the chest and abdomen as well as endoscopic ultrasound to confirm persistence/recurrence of only mucosal disease. Two patients had squamous carcinoma while five patients had Barrett's adenocarcinoma (Barrett's median segment length=8cm; range 5-10cm). PDT was performed after infusion of 2mg/kg porfimer sodium using a median light dose of 150J/cm (range 100-200) using the bare fiber method. After PDT, all patients developed strictures requiring dilation (median number of dilations required=5, range 1-18). These patients have subsequently been followed with endoscopy every 3-6 months (mean follow up=30 months, range 12-50 months). After an initial response, the two patients with squamous cell carcinoma have subsequently been found to have recurrent disease and are being treated with erlotinib. The other five patients treated for Barrett's carcinoma have remained disease free although one had died 33 months from metastatic colon cancer. In selected patients, PDT may be useful in the treatment of persistent/recurrent mucosal esophageal cancer after incomplete response to CRT.


[Body dysmorphic disorder: clinical aspects, nosological dimensions and controversies with anorexia nervosa].
There is strong evidence about the co-existence of body dysmorphic disorder (BDD) and eating disorders (ED), particularly with anorexia nervosa (AN). An exhaustive review of the specialised literature regarding these disorders was carried out. The results show that their co-occurrence implies a more complex diagnosis and treatment, a more severe clinical symptomatology and a worse prognosis and outcome. Both disorders display common similarities, differences and comorbidities, which allow authors to classify them in different nosological spectra (somatomorphic, anxious, obsessive-compulsive, affective and psychotic). Their crossover involves higher levels of body dissatisfaction and body image distortion, depression, suicidal tendency, personality disorders, substance use/abuse, obsessive-compulsive disorder, social phobia, alexithymia and childhood abuse or neglect background. Treatment including cognitive-behavioral psychotherapy and selective reuptake serotonin inhibitors are effective for both, BDD and ED; nevertheless, plastic surgery could exacerbate BDD. Clinical traits of BDD must be systematically detected in patients suffering from ED and vice versa.


[Postgraduate education and the board certification system from the standpoint of thoracic surgery as one of subspecialty fields].
The board certification system for thoracic surgeon has been established as one of subsupecialty fields of the same system of surgery and has been managed by the unique system of joint committee of which member was from both The Japanese Association for Chest Surgery and The Japanese Association for Thoracic Surgery. Since then, 5 years have passed and the first renewal of the license was carried out in 2009. Several inconsistencies between the system for surgeon and thoracic surgeon have been corrected and the differences among subspecialty fields were adequately modified during this period. However, further improvement is necessary such as treating the one who cannot renew the license due to inevitable reasons. The program of postgraduate clinical training system in this country also should be reviewed for efficient training for future surgeons, since it contains too much duty for only 2 years. It must be considered that much time is necessary for growing a dependable experienced surgeon whose active working period is shorter compared to other field of medicine.


Distance education as a response to pandemics: Coronavirus and Arab culture.
Some countries have replaced face-to-face education with distance education in response to the coronavirus. This form of distance education differs from conventional distance education: being suddenly, unreadily and forcefully implemented, invading schooling and constituting a globally discussed phenomenon. This article builds a conceptual framework for this education, addressing the question: What are the ramifications of implementing distance education amid coronavirus? It targets Arab culture, although globalisation and the media may have harmonised any substantial cross-cultural variations. Various ramifications have emerged through analysing social-media posts, online classes and interviews. Concerning social and cultural ramifications, some may, for ideological considerations, tolerate, support, reject or subvert this education through campaigning, rumour and humour. Regarding pedagogical and psychological ramifications, unreadiness and incompetence may compromise education. Additionally, staying home may entail problems (pandemic-related stress, anxiety, depression, domestic violence, divorce and pregnancy), preventing students and teachers from learning and teaching. Concerning procedural and logistical ramifications, some Arab contexts may be digitally readier than non-Arab contexts. Additionally, stakeholders may intensify efforts to profit, ethically or unethically, from the over-demand for this education. Distance education is one of several social distancing initiatives, which Arabs have welcomed despite their well-rooted social closeness, bonding to debond, forming unorthodox 'distanceship'.


Antigenic variation of human and bovine parainfluenza virus type 3 strains.
Three human and six bovine parainfluenza virus type 3 (PIV3) strains were examined by the use of 60 monoclonal antibodies (MAbs). Fifty-three MAbs to the human C243 strain were directed against six, four, nine and seven epitopes of the haemagglutinin-neuraminidase (HN), fusion (F), nucleocapsid (N) and matrix proteins, respectively. Seven MAbs to the bovine strain were directed against three epitopes of the HN protein and three epitopes of the F protein. Each strain was characterized in ELISA and immunofluorescence tests with all MAbs and in a haemagglutination inhibition assay with the anti-HN MAbs. There were marked differences between human and bovine viruses, primarily in the HN protein where five epitopes differed. One epitope of the F and one of the N protein also differed. Bovine PIV3 was found to be a homogeneous subtype and distinct from human PIV3.


The influence of soil heterogeneity on exploratory tunnelling by the subterranean termite Coptotermes frenchi (Isoptera: Rhinotermitidae).
The exploration of sand-filled arenas by workers of an entire colony of the Australian, subterranean foraging, tree-nesting termite, Coptotermes frenchi Hill was investigated under laboratory conditions. The first experiment tested whether termite exploration of sand was influenced by the presence of gaps or objects in the sand. Gaps and objects were chosen to represent soil heterogeneity in the urban environment: gaps to represent tunnels dug by other animals, perspex strips to represent cables and pipes, and wood strips to represent roots. Termites always chose to explore gaps thoroughly before they began tunnelling in the sand. Significantly more and longer tunnels were excavated from the end of gaps at the far end of the arenas, and relatively little tunnelling occurred around and along objects. Termite density was significantly greater around and along wood compared with perspex blocks. The second experiment tested whether termite exploratory tunnelling was influenced by soil moisture. The termites tunnelled slowly in dry sand, but after discovering a patch of wet sand, increased tunnelling five-fold until it was completely explored, after which activity declined. Energy and water conservation may be behind these patterns of exploratory tunnelling as well as those seen in large field studies, but caution is urged when interpreting small scale laboratory experiments to explain large scale field data.


Internal Medicine Program Directors' Perceptions of the "All In" Match Rule: A Cross-Sectional Survey.
Since 2013, the National Resident Matching Program (NRMP) has asked all programs to declare themselves to be "all in" or "all out" for the NRMP. Before this rule was enacted, program directors who were surveyed expressed concerns about what they anticipated with the change, including resources for increased applications and potential delays with residency start times. This study investigated the positive and negative effects of the rule change on recruiting seen from the perspective of internal medicine (IM) program directors. In this mixed model cross-sectional survey, Accreditation Council for Graduate Medical Education-accredited IM program directors were surveyed regarding their impressions of the impact of the policy change. Data were aggregated using constant comparative analysis. A total of 127 of 396 (32%) IM program directors responded, and 122 of 127 (96%) identified their program as "all in." A total of 110 respondents expressed impressions of the rule change, with 48% (53 of 111) reporting positive responses, 28% (31 of 111) neutral responses, and 24% (27 of 111) negative responses. Programs with higher percentages of visa-holding residents had lower positive responses (37% [22 of 60] versus 61% [31 of 51]). Resident quality was felt to be unchanged or improved by most program directors (93%, 103 of 111), yet 24% (27 of 112) reported increases in delayed start times for visa-holding residents. Qualitative analysis identified increased fairness, at the expense of an increase in program resources as a result of the change. A slight majority of residency programs reported a neutral or negative impression of the rule change. Since the rule change, program directors noted increased application volume and delayed residency starts for visa-holding residents.


Prevention and management of knee osteoarthritis and knee cartilage injury in sports.
Articular cartilage defects in the knee of young or active individuals remain a problem in orthopaedic practice. These defects have limited ability to heal and may progress to osteoarthritis. The prevalence of knee osteoarthritis among athletes is higher than in the non-athletic population. The clinical symptoms of osteoarthritis are joint pain, limitation of range of motion and joint stiffness. The diagnosis of osteoarthritis is confirmed by the symptoms and the radiological findings (narrowing joint space, osteophyte formation and subchondral sclerosis). There is no strong correlation between symptoms and radiographic findings. The aetiology of knee osteoarthritis is multifactorial. Excessive musculoskeletal loading (at work or in sports), high body mass index, previous knee injury, female gender and muscle weakness are well-known risk factors. The high-level athlete with a major knee injury has a high incidence of knee osteoarthritis. Cartilage injuries are frequently observed in young and middle-aged active athletes. Often this injury precedes osteoarthritis. Reducing risk factors can decrease the prevalence of knee osteoarthritis. The prevention of knee injury, especially anterior cruciate ligament and meniscus injury in sports, is important to avoid progression of knee osteoarthritis.


Gene Deletion of VIP Leads to Increased Mortality Associated with Progressive Right Ventricular Hypertrophy.
Vasoactive Intestinal Peptide (VIP) knockout mice exhibit asthma, pulmonary hypertension, and left ventricular wall thinning. Humans with these disorders have premature death. We show here that VIP KO mice have reduced survival (100% mortality at 20 months), vs. 100% survival among WT C57BL/6 mice. Moreover, the ratios of weights of right ventricle divided by left ventricle plus septum were progressively increased in VIP KO mice with age. Core temperatures were lower in VIP KO mice when compared to WT littermates, with an associated pro-inflammatory cytokine milieu. Overall, our results indicate that VIP is important for survival in mice. Its absence leads to increased mortality, with progressive right ventricular hypertrophy as a surrogate of pulmonary hypertension, lower body weight, hypothermia, and pro-inflammatory milieu. These studies support VIP as a novel therapeutic agent in pulmonary hypertension.


The boundary for quantum advantage in Gaussian boson sampling.
Identifying the boundary beyond which quantum machines provide a computational advantage over their classical counterparts is a crucial step in charting their usefulness. Gaussian boson sampling (GBS), in which photons are measured from a highly entangled Gaussian state, is a leading approach in pursuing quantum advantage. State-of-the-art GBS experiments that run in minutes would require 600 million years to simulate using the best preexisting classical algorithms. Here, we present faster classical GBS simulation methods, including speed and accuracy improvements to the calculation of loop hafnians. We test these on a ∼100,000-core supercomputer to emulate GBS experiments with up to 100 modes and up to 92 photons. This reduces the simulation time for state-of-the-art GBS experiments to several months, a nine-orders of magnitude improvement over previous estimates. Last, we introduce a distribution that is efficient to sample from classically and that passes a variety of GBS validation methods.


[Gerstmann's syndrome in a 9 year old boy].
Gerstmann's syndrome encompasses the tetrad of finger agnosia, agraphia, acalculia and right-left confusion and is associated with lesions of the left angular gyrus, situated at the confluence of the temporal, parietal and occipital lobes. The localizing value of this syndrome has been questioned because multiple mechanisms can account for each of the four components of the syndrome. This clinical association is infrequent in children and it is impossible to diagnose in early stages of life because of parietal lobes have a slow functional development during childhood. We present the case of a learning disabled boy, 9 year old and right handed, who developed Gerstmann's syndrome. Acalculia, right-left disorientation, agraphia and finger agnosia were clearly identified by neuropsychological studies at this time, but there was no evidence of this dysfunction when he was first studied being 5 year old. This patient had perinatal asphyxia and suffered from focal clonic seizures in early neonatal period. In this case, a infarcted lesion was found at the confluence of parietal and occipital lobes in cranial CT an MRI scans. We conclude that is very important to identify this syndrome during childhood using a wide range of neuropsychological tests in order to diminish learning disorders with an early psychopedagogic supervision.


Oxidative stress and NF-kappaB activation: correlation in patients following allogeneic bone marrow transplantation.
Although in vitro data has linked reactive oxygen species (ROS) to activation of nuclear factor kappaB (NF-kappaB), little data exist regarding this relationship in human disease. We hypothesized that bone marrow transplantation (BMT) would impart a degree of oxidative stress that might lead to in vivo activation of the redox-sensitive transcription factor NF-kappaB. Because NF-kappaB regulates transcription of many proinflammatory mediators, we reasoned that activation of NF-kappaB might contribute to the development of transplant-related complications. To evaluate NF-kappaB activation in humans, we measured NF-kappaB binding activity in nuclear extracts of bronchoalveolar lavage (BAL) cells obtained before and after allogeneic bone marrow transplantation (BMT) in 7 patients. Changes in BAL cell NF-kappaB binding activity were compared with changes in urinary F2-isoprostane concentration, an indicator of in vivo free radical-catalyzed lipid peroxidation. Although the extent of in vivo lipid peroxidation has substantial interindividual variability over time, we found a strong correlation between the pre/post-BMT ratio of urinary isoprostane concentrations and pre/post-BMT ratio of NF-kappaB binding activity in BAL cells, R = 0.96, p = 0.0005). This correlation is selective, because no relationship was found between the transcription factor CREB and urinary F2-isoprostane excretion. Although limited by the small number of patients studied, our data link oxidant stress to NF-kappaB activation in human alveolar macrophages following BMT. It is possible that such interactions may contribute to the clinical course after BMT by affecting transcription of proinflammatory genes.


Risk factors for reduced salivary flow rate in a Japanese population: the Hisayama Study.
The purpose of this study was to determine distinct risk factors causing reduced salivary flow rate in a community-dwelling population using a prospective cohort study design. This was a 5-year follow-up survey of 1,377 community-dwelling Japanese individuals aged ≥40 years. The salivary flow rate was evaluated at baseline and follow-up by collecting stimulated saliva. Data on demographic characteristics, use of medication, and general and oral health status were obtained at baseline. The relationship between reduced salivary flow rate during the follow-up period and its predictors was evaluated after adjustment for confounding factors. In a multivariate logistic regression model, higher age and plaque score and lower serum albumin levels were significantly associated with greater odds of an obvious reduction in salivary flow rate (age per decade, odds ratio [OR] = 1.25, 95% confidence interval [CI] = 1.03-1.51; serum albumin levels <4 g/dL, OR = 1.60, 95% CI = 1.04-2.46; plaque score ≥1, OR = 1.53, 95% CI = 1.04-2.24). In a multivariate linear regression model, age and plaque score remained independently associated with the increased rate of reduced salivary flow. These results suggest that aging and plaque score are important predictors of reduced salivary flow rate in Japanese adults.