Autonomic and cardiovascular effects of chronic delta9-tetrahydrocannabinol administration in mongrel dogs.
Chronic administration of delta9-tetrahydrocannabinol (delta9-THC) 1mg/1kg, s.c., twice a day for 7 days failed to produce any major changes in the pulmonary or systemic hemodynamics and in the myocardial contractility of the mongrel dogs. Chronic delta9-THC treatment did not result in any significant alterations either in the transmission in the lumbar sympathetic chain or in the activity of autonomic receptors within the cardiovascular system. Further systemic pressor responses to bilateral carotid occlusion and reflexly mediated alterations in the perfused hindlimb vascular resistance were essentially identical in both the treated and placebo groups. Pressure-flow curves obtained from the perfused hindlimb preparations suggested that in contrast to the acute studies, neurogenic tone to the hindlimb vasculature was unaltered by chronic delta9-THC and intrinsic tone of the vascular smooth muscle was significantly depressed in the treated animals; in addition it appears that the tone due to circulating catecholamines was significantly enhanced in treated animals. The results of this investigation demonstrated that several acute cardiovascular and autonomic effects of delta9-THC may not be evident following chronic THC-treatment, however, prolonged use may demonstrate certain new pharmacological properties and/or mechanism of actions which cannot readily be seen in the acute studies.


Sexual function and affect in parkinsonian men treated with L-dopa.
Using psychiatric interviews, sexual and affect rating scales, hormonal studies, and neurologic assessment, the authors assessed the effect of L-dopa treatment on men with Parkinson's disease. Patients demonstrated variable affect changes. Approximately one-half of the patients reported an increased sexual interest that was not related to improvement in locomotor function. Hormonal factors appeared to be involved. The findings suggest that male parkinsonian patients who possess an intact hypothalamic-pituitary-gonadal axis experience increased sexual function related to L-dopa treatment.


The role of neutrophils in inflammation.
It has long been noted that inflammation underlies asthma. It is now recognized that there is marked heterogeneity in the stimuli that can cause or aggravate this inflammation, the cells that are involved in the response and the consequences in terms of both pathology and symptoms. The prime role of eosinophilic inflammation in the pathogenesis of asthma is acknowledged in this paper, but the potential role of neutrophilic inflammation to underlie symptoms and physiological changes that are characteristic of asthma is highlighted. A minority group of patients appear to have asthma from clinical signs, but their airway secretions do not contain eosinophils. Their response to treatment is unlike that of patients with typical eosinophilic airway inflammation in that they do not respond to steroid therapy. Published data from in vitro and animal work provide a conceptual framework to explain these observations. The refinement of the technique of examining sputum cellular content to assess airway inflammation provides an opportunity to identify and study this subgroup of patients.


[Computer tomographic features of peritoneal carcinosis (author's transl)].
Out of 59 cases of peritoneal carcinosis (PCA) diagnosed by either laparoscopy, laparotomy, or post mortem 50 cases (85%) could be recognised as such retrospectively by computerized tomography (CT). Beside diagnosing direct metastases one was able to show more subtle indirect signs such as alterations at the mesenterial root, greater omentum and in the pelvis. The accuracy of the CT in the diagnosis of PCA is discussed.


Exploratory survey about dietary supplement use: a hazardous and erratic way to improve one's health?
Dietary supplement (DS) use increased rapidly in recent years. However, evidence of benefits of many DSs for healthy users is scarce and may not equate with known risks of overdose, drug interaction and recently discovered negative long-term effects. This exploratory study aimed to investigate the perceptions and motivations of DS users in Lausanne, Switzerland. A convenience sample (n = 147) was recruited at the entrances of local sales points. Data were collected in on-site semistructured interviews that assessed dietary supplementation habits. The majority of DSs were all-in-one products, containing a mixture of minerals and vitamins, or products containing only minerals. Among the 147 users, 72 (49%) used one all-in-one product and 3 (2%) used two all-in-one products. Thirty-one (21%) consumers did not know for at least one product what the purpose of their DS use was. Seventy-five percent of participants thought that DS use presents no risk or nearly no risk. Only 49% of participants stated that their physicians were informed about their consumption. Although men searched more often for potential risks (p <0.001), they turned less frequently to health professionals to get this information (p = 0.007). As in other surveys performed elsewhere, our study shows that, in Lausanne (Switzerland), DSs are commonly used as mixed products. Risk perception seems generally low among DS users. Physicians should be trained to evaluate patients' perceived needs and DS consumption in order to provide good evidence-based information or to propose alternatives to DS use.


Partnership among hospitals to reduce healthcare associated infections: a quasi-experimental study in Brazilian ICUs.
Healthcare-associated infections (HAIs) are relevant in developing countries where frequencies can be at least 3 times higher than in developed countries. The purpose of this research was to describe the intervention implemented in intensive care units (ICUs) to reduce HAIs through collaborative project and analyze the variation over 18 months in the incidence density (ID) of the three main HAIs: ventilator associated pneumonia (VAP), central line-associated bloodstream infections (CLABSIs) and catheter-related urinary tract infections (CAUTIs) and also the length of stay and mortality in these ICUs. A quasi-experimental study in five public adult clinical-surgical ICUs, to reduce HAIs, through interventions using the BTS-IHI "Improvement Model", during 18 months. In the project, promoted by the Ministry of Health, Brazilian philanthropic hospitals certified for excellence (HE), those mostly private, certified as excellence and exempt from security contributions, regularly trained and monitored public hospitals in diagnostics, data collection and in developing cycles to improve quality and to prevent HAIs (bundles). In the analysis regarding the length of stay, mortality, the IDs of VAP, CLABSIs and CAUTIs over time, a Generalized Estimating Equation (GEE) model was applied for continuous variables, using the constant correlation (exchangeable) between assessments over time. The model estimated the average difference (β coefficient of the model) of the measures analyzed during two periods: a period in the year 2017 (prior to implementing the project) and in the years 2018 and 2019 (during the project). A mean monthly reduction of 0.427 in VAP ID (p = 0.002) with 33.8% decrease at the end of the period and 0.351 in CAUTI ID (p = 0.009) with 45% final decrease. The mean monthly reduction of 0.252 for CLABSIs was not significant (p = 0.068). Length of stay and mortality rates had no significant variation. Given the success in reducing VAP and CAUTIs in a few months of interventions, the achievement of the collaborative project is evident. This partnership among public hospitals/HE may be applied to other ICUs including countries with fewer resources.


Comparison of the effects of different percutaneous tracheotomy techniques on acute tracheal trauma.
As it can easily be performed at the bedside with minimal morbidity, percutaneous dilatational tracheotomy (PDT) is preferred over surgical tracheotomy. The aim of this study is to compare the effects of different PDT techniques on posterior tracheal wall injury. The study was conducted at the Gazi University Laparoscopy Training Center after approval was granted by the ethics committee. After sedation with xylazine/ketamine, electrocardiography, peripheral oxygen saturation, and blood pressure were monitored. Propofol was used to achieve the desired level of sedation during the procedure. There were 16 pigs, randomly allocated into 4 groups. Multiple, single, forceps, and twist dilator techniques were performed in groups I, II, III, and IV, respectively. At the end of the course all pigs were sacrificed and tracheas were harvested for macroscopic and histopathological evaluation. Macroscopic evaluation revealed erythematous/hemorrhagic and ulcerative lesions on the posterior wall of all samples. Histopathological injury was observed in all samples and was similar in all groups. Procedural time was significantly longer in group I than in all other groups (P < 0.05). Although the results are conflicting, bronchoscopy-aided PDT is believed to reduce complications. In our study, PDTs were performed without bronchoscopy, and posterior wall injury was observed in all samples. Therefore, we suggest using bronchoscopy to reduce procedure-related complications and improve patient safety during PDT.


Effect of protein concentrate mixtures and dietary addition of exogenous phytase on major milk minerals and proteins, including casein phosphorylation.
Variations in major milk minerals, proteins, and their posttranslational modifications are largely under genetic influence, whereas the effect of nongenetic factors is less studied. Through a controlled feeding experiment (incomplete balanced Latin square design), the effect of concentrate mixtures, based on fava beans, rapeseed meal, or soybean meal as main P and protein sources, on milk composition was examined under typical Danish management conditions. Concentrations of P, Ca, and Mg, together with proteomics for relative quantification of major milk proteins and their isoforms, were analyzed in milk samples from 24 cows sampled in 4 periods. Each cow was fed 1 of the 3 diets in each period with or without addition of exogenous phytase. Cows were blocked by lactation stage into early and mid-lactation (23.3 ± 6.7 and 176 ± 15 d in milk, respectively, at the beginning of the experiment, mean ± standard deviation). Significant effects of feed concentrate mixture were observed for milk protein concentration, milk urea nitrogen, citrate, and the percentage of mixed and preformed fatty acids as well as mineral composition, and their distributions within micellar or serum phases. Furthermore, relative contents of αS1-casein (CN) 9P form and unglycosylated κ-CN and thereby phosphorylation degree of αS1-CN (PD) and the glycosylation degree of κ-CN were found to be significantly affected by these diets. To our knowledge, we are the first to document that feed concentrate mixture can affect the relative concentrations of αS1-CN phosphorylation isoforms in milk, and the results suggested an effect on αS1-CN 9P and PD, but not on αS1-CN 8P. Furthermore, although only significant for αS1-CN 8P, we found a lower relative concentration of αS1-CN 8P and higher αS1-CN 9P (and thus higher PD) in milk from cows in mid compared with early lactation. Also, protein concentration and concentration of Mg in skim milk and serum as well as relative concentration of α-lactalbumin were found to be significantly affected by lactation stage. Addition of dietary exogenous phytase only had a minor effect on milk composition or functionality with significant effect detected for α-lactalbumin and micellar Mg concentration.


Incidence and mortality risk in coronavirus disease 2019 patients complicated by acute cardiac injury: systematic review and meta-analysis.
The prevalence and prognostic implications of acute cardiac injury (ACI), as a complication of coronavirus disease 2019 (COVID-19), remain unclear. We conducted a systematic review and meta-analysis to investigate the relationship between ACI and mortality risk in COVID-19 patients. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed in abstracting data and assessing validity. We searched MEDLINE, Scopus and Web of Science to locate all articles published up to 10 April 2020 reporting data of COVID-19 survivors and nonsurvivors developing ACI as a complication of the infection. Quality assessment was performed using the Newcastle-Ottawa quality assessment scale. Data were pooled using the Mantel-Haenszel random effects models with odds ratio as the effect measure with the related 95% confidence interval. Statistical heterogeneity between groups was measured using the Higgins I statistic. Eight studies, enrolling 1686 patients (mean age 59.5 years), met the inclusion criteria and were included in the final analysis. Data regarding the outcome of patients complicated with ACI were available for 1615 patients. Of these, 387 (23.9%) experienced ACIs as COVID-19 complications during the hospitalization. The incidence of ACI was significantly higher among non survivors when compared with survivors (61.6 vs. 6.7%, P < 0.0001). The pooled analysis confirmed a significantly increased risk of death in COVID-19 patients complicated with ACI during the disease (odds ratio: 21.6, 95% confidence interval: 8.6-54.4, P < 0.0001, I = 82%). Development of ACI during COVID-19 significantly increases the risk of death during the infection.


Analgesic efficacy of median nerve stimulation in mice with chemotherapy-induced peripheral neuropathymodulation of brain-derived neurotrophic factor expression.
Chemotherapeutic agents such as docetaxel (DTX) can trigger chemotherapy-induced peripheral neuropathy (CIPN), which is characterized by unbearable pain. This study was designed to investigate the analgesic effect and related neuronal mechanism of low-frequency median nerve stimulation (LFMNS) on DTX-induced tactile hypersensitivity in mice. To produce CIPN, DTX was administered intraperitoneally 4 times, once every 2 d, to male ICR mice. LFMNS was performed on the wrist area, and the pain response was measured using von Frey filaments on both hind paws. Western blot and immunofluorescence staining were performed using dorsal root ganglion and spinal cord samples to measure the expression of brain-derived neurotrophic factor (BDNF). Repeated LFMNS significantly attenuated the DTX-induced abnormal sensory response and suppressed the enhanced expression of BDNF in the DRG neurons and spinal dorsal area. LFMNS might be an effective non-pharmaceutical option for treating patients suffering from CIPN regulating the expression of peripheral and central BDNF.


Low bone mineral density in patients with well-suppressed HIV infection: association with body weight, smoking, and prior advanced HIV disease.
Human immunodeficiency virus (HIV) and combination antiretroviral therapy (cART) may both contribute to the higher prevalence of osteoporosis and osteopenia in HIV-infected individuals. Using dual-energy X-ray absorptiometry, we compared lumbar spine, total hip, and femoral neck bone mineral density (BMD) in 581 HIV-positive (94.7% receiving cART) and 520 HIV-negative participants of the AGEhIV Cohort Study, aged ≥45 years. We used multivariable linear regression to investigate independent associations between HIV, HIV disease characteristics, ART, and BMD. The study population largely consisted of men who have sex with men (MSM). Osteoporosis was significantly more prevalent in those with HIV infection (13.3% vs 6.7%; P<.001). After adjustment for body weight and smoking, being HIV-positive was no longer independently associated with BMD. Low body weight was more strongly negatively associated with BMD in HIV-positive persons with a history of a Centers for Disease Control and Prevention class B or C event. Interestingly, regardless of HIV status, younger MSM had significantly lower BMD than older MSM, heterosexual men, and women. The observed lower BMD in treated HIV-positive individuals was largely explained by both lower body weight and more smoking. Having experienced symptomatic HIV disease, often associated with weight loss, was another risk factor. The low BMD observed in younger MSM remains unexplained and needs further study.


Mechanism of acute mechanical benefit from VDD pacing in hypertrophied heart: similarity of responses in hypertrophic cardiomyopathy and hypertensive heart disease.
Dual-chamber pacing can improve symptoms in hypertrophic cardiomyopathy (HCM), but the mechanism remains unclear. We hypothesized that pacing generates discoordinate contraction and a rightward shift of the end-systolic pressure-volume relation (ESPVR) and that benefits from this mechanism do not depend on the presence of resting outflow pressure gradients or obstruction. Eleven patients with NYHA class III symptoms, 5 with HCM, and 6 with hypertensive hypertrophy and cavity obliteration, were studied by invasive conductance catheter methods. No patient had coronary artery or primary valvular disease. Pressure-volume relations were recorded before and during VDD pacing by use of a short (75-millisecond) PR interval to achieve preexcitation. Left ventricular cavity pressure was simultaneously recorded at basal and apical sites, with pressure at the basal site used to generate the ESPVRs. VDD pacing shifted the ESPVR rightward, increasing end-systolic volume by 45% (range, 17% to 151%; P=0.002). Resting and provokable gradients declined by 20% (range, -56% to +3%) and 30% (range, -65% to -12%), respectively (P<0.05). Preload declined by 3% to 10% because of the short PR interval. Preload-corrected contractility indexes and myocardial workload declined by approximately 10% (P<0.001). Diastolic compliance and relaxation time were unchanged. Pacing made apical pressure-volume loops discoordinate, limiting cavity obliteration and reducing distal systolic pressures. Results in both patient groups were similar. VDD pacing shifts the ESPVR rightward in HCM patients with cavity obliteration with or without obstruction, increasing end-systolic volumes and reducing apical cavity compression and cardiac work. These effects likely contribute to reduced metabolic demand and improved symptoms.


p210 bcr-abl confers overexpression of inosine monophosphate dehydrogenase: an intrinsic pathway to drug resistance mediated by oncogene.
The p210 bcr-abl fusion protein tyrosine kinase oncogene has been implicated in the pathogenesis of chronic granulocytic leukemia (CGL). Specific intracellular functions performed by p210 bcr-abl have recently been delineated. We considered the possibility that p210 bcr-abl may also regulate the abundance of inosine 5'-monophosphate dehydrogenase (IMPDH) which is a rate-limiting enzyme for de novo guanylate synthesis. We performed studies of the inhibition of IMPDH by tiazofurin, which acts as a competitive inhibitor through its active species that mimics nicotinamide adenine dinucleotide (NAD), i.e. thiazole-4-carboxamide adenine dinucleotide (TAD). The mean inhibitory concentration (IC50) of tiazofurin for cellular proliferation inhibition was 2.3-2.8-fold greater in cells expressing p210 bcr-abl than in their corresponding parent cells proliferating under the influence of growth factors or in growth factor-independent derivative cells not expressing detectable p210 bcr-abl. IMPDH activity was 1.5-2.3-fold greater within cells expressing p210 bcr-abl than in their parent cells. This increase in enzyme activity was a result of 2-fold increased IMPDH protein as determined by immunoblotting. In addition, an increase in the Km value for NAD utilization by IMPDH was observed in p210 bcr-abl transformed cells, but this increase was within the range of resident NAD concentrations observed in the cells. Increased IMPDH protein in p210 bcr-abl transformed cells was traced to an increased level of IMP dehydrogenase II messenger RNA. Thus, regulation of IMPDH gene expression is mediated at least in part by the bcr-abl gene product and may therefore be indicative of a specific mechanism of intrinsic resistance to tiazofurin.


Mutations in pts cause catabolite-resistant sporulation and altered regulation of spo0H in Bacillus subtilis.
A mutation in Bacillus subtilis, ggr-31, that relieves glucose-glutamine-dependent control of a spoVG-lacZ translational fusion was isolated and was subsequently found to confer a pleiotropic phenotype. Mutants cultured in glucose- and glutamine-rich media exhibited a Crs- (catabolite-resistant sporulation) phenotype; enhanced expression of the spo0H gene, encoding sigma H, as evidenced by immunoblot analysis with anti-sigma H antiserum; and derepression of srfA, an operon involved in surfactin biosynthesis and competence development. In addition, ggr-31 mutants exhibited a significant increase in generation time when they were cultured in minimal glucose medium. The mutant phenotype was restored to the wild type by Campbell integration of a plasmid containing part of the ptsG (encoding the enzyme II/III glucose permease) gene, indicating that the mutation probably resides within ptsG and adversely affects glucose uptake. A deletion mutation within ptsI exhibited a phenotype similar to that of ggr-31.


[Population health in programs of medical ecological screening].
Socio-hygienic analysis of population health in Ryazan Province, specifically, in the Pronya River basin, revealed a number of local features: reduced birth rate, aging of the population, high incidence of acute enteric and other infections, tuberculosis, malignant tumors, diseases of the blood and hemopoietic organs in children, frequent complications of pregnancy and labor in children which are explained to a great measure by socioeconomic and socio-hygienic condition, as well as the status of the environment, of water among other things. Correlation coefficients were derived reflecting relationships between morbidity levels and the quality of potable water and foodstuffs, availability of centralized water supply and sewer system, as well as atmospheric air pollution. The data help better validate concrete measures in the program of sanitization of the population in these regions.


The Inhibitory Effect of Capparis Ovata Polysaccharides on Cultured Pterygium Fibroblasts.
Pterygium recurrence after removal surgery is an important problem. Polysaccharides obtained from Capparis species have been shown to possess various biological properties, including anti-tumor activity. This study was an investigation of the effect of Capparis ovata polysaccharides on cultured pterygium fibroblasts and a comparison with the effects of mitomycin C (MMC). Pterygium tissue samples were obtained during excision surgery from 3 patients with primary pterygium, and fibroblasts were isolated. Pterygium fibroblast cultures and L929 cell cultures were treated with different concentrations of MMC and Capparis ovata polysaccharides. Cell proliferation and migration were evaluated. An MTT assay revealed that cell viability decreased with increasing concentrations of Capparis ovata polysaccharides in both cell types. MMC also inhibited the proliferation of both cell types. A scratch-wound assay indicated that both Capparis ovata polysaccharides and MMC molecules reduced proliferation and migration in the pterygium fibroblasts and L929 cells. The in vitro Capparis ovata polysaccharide inhibition of proliferation and migration of pterygium fibroblasts was similar to that of MMC. The results of this study suggested that Capparis ovata polysaccharides may be a valuable candidate drug to treat pterygium.


Bilevel disulfide group reduction in the activation of c(4) leaf nicotinamide adenine dinucleotide phosphate-malate dehydrogenase.
The time course of thioredoxin-mediated reductive activation of isolated Zea mays nicotinamide adenine dinucleotide phosphatemalate dehydrogenase is highly sigmoidal in nature. We examined the factors affecting these kinetics, including the thiol-disulfide status of unactivated and activated forms of the enzyme. The maximum steady rate of activation was increased, and the length of the lag in activation decreased, as the concentrations of thioredoxin-m, dithiothreitol, and KCl were increased. The lag in activation (sigmoidicity) was eliminated by preincubating the unactivated enzyme with 100 mm 2-mercaptoethanol; this pretreatment did not activate the enzyme. Unactivated nicotinamide adenine dinucleotide phosphate-malate dehydrogenase was found to contain approximately two SH groups per subunit, increasing to about four SH per subunit after pretreatment with 2-mercaptoethanol and six SH per subunit after activation by incubating the enzyme with dithiothreitol. We suggest that reduction of one particular higher redox potential disulfide group in unactivated nicotinamide adenine dinucleotide phosphate-malate dehydrogenase facilitates the subsequent reduction of the critical S-S group (regulatory S-S) necessary to generate the active form of the enzyme.


Reticulohistiocytosis: different dermatoscopic faces and a good response to methotrexate treatment.
The reticulohistiocytoses are a rare group of non-Langerhans cell histiocytic disorders. Recently, dermatoscopic features have been reported for some of the xanthomatous disorders. We report a case of diffuse cutaneous reticulohistiocytosis with 29 reticulohistiocytomas. On dermatoscopy of these lesions, we saw three typical features: a homogeneous pattern with various shades of yellow (defined previously as a 'setting-sun' pattern), brown reticular structures, and central white scar-like patches and streaks. The setting-sun pattern was most commonly seen in combination with brown reticular structures. In four lesions, brown reticular structures surrounded a central white scar-like patch resembling that of a dermatofibroma. However, the presence of the setting-sun pattern in the background gave a different hue to that of the peripheral network seen in a dermatofibroma. A marked clinical improvement was associated with 6 months of systemic methotrexate treatment. Dermatoscopy may aid in the diagnosis of xanthomatous diseases. For this patient, methotrexate was beneficial.


Antioxidant capacity of some plant foods and beverages consumed in the Eastern Region of Nigeria.
Today plant foods and beverages are receiving more scientific attention because of their potential to curb the effect of free radicals in the human system. The present study reports on the antioxidant potentials of some plants foods and beverages consumed in the Eastern Region of Nigeria. The study made use of the ferric reducing antioxidant power, phenolic and the flavonoid contents assays to assess the quality of the antioxidant potentials of the plant foods and beverages. Of the different classes of foods analyzed the following showed high antioxidant potentials: coffee for beverages, star apple for fruits, thyme for vegetable and spices, and raices for alcoholic beverages. Generally the vegetables and spices registered the highest antioxidant properties. The results obtained in this study could help consumers' choice based on the antioxidant capacity of the samples analyzed.


House dust mite sensitivity: interaction of genetics and allergen dosage.
Pairwise analysis of siblings from 21 families showed that house dust mite (HDM) sensitive children were exposed to higher concentrations of Der p I allergen in their mattress (P = 0.005) and bedding (P = 0.04), but not bedroom floor (P = 0.33), than their atopic sibling who was not sensitive to HDM antigens. There was no difference in the exposure to HDM numbers/100 mg of dust in the mattress (P = 0.61) or bedroom floors (P = 0.09). In contrast, pairwise analysis of siblings from 15 families showed that HDM sensitive children were not exposed to significantly different concentrations of Der p I in the mattress (P = 0.96), bedding (P = 0.11) or bedroom floor (P = 0.70) nor HDM numbers/100 mg of dust in the mattress (P = 0.12) and bedroom floor (P = 0.98) than their non-atopic siblings. These findings were identical when absolute allergen load was compared in these pairs. Genetic linkage studies in these families suggest the tendency to atopic IgE responses is conferred by a putative atopy locus on chromosome 11q. These results together suggest that differences in allergen levels in beds, among siblings with a comparable genetic tendency to atopy, play a significant role in determining the development of HDM allergy.


Assessing the benefits of participatory research: a rationale for a realist review.
Participatory research (PR) experts believe that increased community and stakeholder participation in research augments program pertinence, quality, outcome, sustainability, uptake, and transferability. There is, however, a dearth of assessments and measurement tools to demonstrate the contribution of participation in health research and interventions. One systematic review of PR, conducted for the Agency for Health Research and Quality (AHRQ), provided no conclusive evidence concerning the benefits of community participation to enhance research and health outcomes. To overcome methodological gaps and barriers of the AHRQ review, we propose to conduct a systematic realist review, which can be understood as a theory-driven qualitative review capable of capturing the often complex, diffuse and obtuse evidence concerning participation. Reviewing how PR mechanisms and contextual factors mediate and moderate outcomes, the review will generate and test hypotheses (middle-range theories) conceptualizing the benefits of participation and will portray the manner and circumstances in which participation influences outcomes.


Optical properties and antiangiogenic activity of a chalcone derivate.
Chalcones and their derivatives exhibit numerous pharmacological activities such as antibacterial, antifungal, cytotoxic, antinociceptive and anti-inflammatory. Recently, they have been assessed aiming for novel application in nonlinear optics and in the treatment of immune diseases and cancers. In this study, we investigate the optical properties of synthetic chalcona 1E,4E-1-(4-chlorophenyl)-5-(2,6,6-trimethylcyclohexen-1-yl)penta-1,4-dien-3-one (CAB7β) and its antiangiogenic potential using the chorioallantoic membrane (CAM) with the S180 sarcoma cell line. Experimental and theoretical results show intense absorption in the UVA-UVC region, which is associated with a π → π* transition with intramolecular charge transfer from the trimethyl-cyclohexen-1-yl ring to the chlorophenyl ring. Quantum chemical calculations of the first hyperpolarizability, accounting for both solvent and frequency dispersion effects, are in very good concordance with hyper-Rayleigh scattering measurements. In addition, two-photon absorption allowed band centered at 650 nm was observed. Concerning antiangiogenic activity, CAB7β causes a significant reduction in the total number, junctions, length and caliber of blood vessels stimulated by S180 cells reducing the presence of blood vessels, inflammatory cells and others elements related to angiogenic process. It is found that CAB7β is a versatile compound and a promising candidate for linear and nonlinear optical applications, in therapy against sarcoma and phototherapy.


Intimate partner violence among adolescents in Cape Town, South Africa.
This study aimed to describe potentially preventable factors in intimate partner violence (IPV) perpetration and victimization among South African 8th grade students. Data were collected during a pilot evaluation of a classroom 8th grade curriculum on gender-based violence prevention in nine public schools in Cape Town through self-completed interviews with 549 8th grade students, 238 boys and 311 girls. Structural equation models (SEM) predicting IPV were constructed with variables a priori hypothesized to be associated. The majority of students (78.5 %) had had a partner in the past 3 months, and they reported high rates of IPV during that period (e.g., over 10 % of boys reported forcing a partner to have sex, and 39 % of girls reported physical IPV victimization). A trimmed version of the hypothesized SEM (CFI = .966; RMSEA = .051) indicated that disagreement with the ideology of male superiority and violence predicted lower risk of IPV (p < .001), whereas the frequency of using negative conflict resolution styles (e.g., walking off angrily, sending angry text messages, or refusing to talk to them) predicted high IPV risk (p < .001) and mediated the impact of heavy alcohol drinking on IPV (Sobel test, z = 3.16; p < .001). The model fit both girls and boys, but heavy drinking influenced negative styles of resolving conflict more strongly among girls than boys. Findings suggest that interventions to reduce IPV among South African adolescents should challenge attitudes supportive of male superiority and violence; encourage use of positive conflict resolution styles; and discourage heavy alcohol use among both boys and girls.


Paediatric trauma aetiology, severity and outcome.
Paediatric injuries are a major cause of mortality and disability worldwide and account for a significant burden on countries like India with limited resources. There are very few studies from developing nations describing the outcome of paediatric trauma. This retrospective study was done to assess the pattern and outcome of unintentional paediatric trauma in the paediatric population. The patients were categorised into four age groups of <1 year, 1-5 years, 6-10 years and 11-15 years. The data were compared regarding the mode of trauma, new injury severity score (NISS), type of injury and place of injury among different age groups. A total of 1587 paediatric patients below 15 years of age presenting in the Emergency Department of CMC, Vellore were studied over a period of 1 year. Two-thirds were boys (1039: 66.6%). Fall on level ground (28.2%) and road traffic accidents (RTA) (26.5%) were the two most common modes of injury. A gradual change in the place of incident from home to the road with advancing age was noticed. The upper limb (30.8%) and the face (26.2%) were the most common parts of the body to be injured. One-third (35.8%) of the sustained serious injuries was a fracture or a dislocation. RTA (OR: 1.56; 95%CI: 1.08-2.26) and age ≥5 years (OR: 1.17; 95%CI: 1.08-1.26) were found to be independent predictors of severe injury (NISS >8). Only 15% required hospital admission. Fall on level ground and RTAs are the most common modes of injury in the paediatric population. The place of injury shows a gradual change from the confines of home to the open dangerous roads and playgrounds with increasing age with RTA and age ≥5 years being independent predictors of severe injury.


Indirect neonatal hyperbilirubinemia in hospitalized neonates on the Thai-Myanmar border: a review of neonatal medical records from 2009 to 2014.
Indirect neonatal hyperbilirubinemia (INH) is a common neonatal disorder worldwide which can remain benign if prompt management is available. However there is a higher morbidity and mortality risk in settings with limited access to diagnosis and care. The manuscript describes the characteristics of neonates with INH, the burden of severe INH and identifies factors associated with severity in a resource-constrained setting. We conducted a retrospective evaluation of anonymized records of neonates hospitalized on the Thai-Myanmar border. INH was defined according to the National Institute for Health and Care Excellence guidelines as 'moderate' if at least one serum bilirubin (SBR) value exceeded the phototherapy threshold and as 'severe' if above the exchange transfusion threshold. Out of 2980 records reviewed, 1580 (53%) had INH within the first 14 days of life. INH was moderate in 87% (1368/1580) and severe in 13% (212/1580). From 2009 to 2011, the proportion of severe INH decreased from 37 to 15% and the mortality dropped from 10% (8/82) to 2% (7/449) coinciding with the implementation of standardized guidelines and light-emitting diode (LED) phototherapy. Severe INH was associated with: prematurity (< 32 weeks, Adjusted Odds Ratio (AOR) 3.3; 95% CI 1.6-6.6 and 32 to 37 weeks, AOR 2.2; 95% CI 1.6-3.1), Glucose-6-phosphate dehydrogenase deficiency (G6PD) (AOR 2.3; 95% CI 1.6-3.3), potential ABO incompatibility (AOR 1.5; 95% CI 1.0-2.2) and late presentation (AOR 1.8; 95% CI 1.3-2.6). The risk of developing severe INH and INH-related mortality significantly increased with each additional risk factor. INH is an important cause of neonatal hospitalization on the Thai-Myanmar border. Risk factors for severity were similar to previous reports from Asia. Implementing standardized guidelines and appropriate treatment was successful in reducing mortality and severity. Accessing to basic neonatal care including SBR testing, LED phototherapy and G6PD screening can contribute to improve neonatal outcomes.


Efficient fabrication of a high-aspect-ratio AFM tip by one-step exposure of a long focal depth holographic femtosecond axilens beam.
In this Letter, we demonstrate a laser fabrication strategy that uses the long focal depth femtosecond axilens laser beam to manufacture the high-aspect-ratio (HAR) micropillars and atomic force microscopy (AFM) probes by one-step exposure. The long depth of focus is generated by modulating laser beam focused at different positions. By adjusting the exposure height, the morphology of HAR micropillars can be tuned flexibly, and the micropillar with an ultra-high aspect ratio (diameter of 1.5 µm, height of 102 µm, ${\rm AR}={70}$AR=70) can be fabricated within 10 ms which is a great challenge for other processing methods to obtain such a HAR microstructure in such a short time. In addition, the HAR micropillar is fabricated onto a cantilever to form the AFM probe. The homemade probe shows fine imaging quality. This method greatly improves the processing efficiency while ensuring the fabrication resolution which provides a powerful method for processing HAR microstructures.


Evaluation of tabletop materials for autocontouring in CT treatment planning.
Computerized tomography (CT) treatment planning has been proven to be essential in precision radiotherapy. Typically CT planning requires a large number of CT scans (between 3 and 50 slices) to be entered into the treatment planning system. A significant amount of time in the planning process is devoted to outlining internal structures, organs, and the external patient contour in each CT slice. In principle, external contours could be generated easily using autocontouring routines; however, in reality it does not always provide a satisfactory contour due to the limitations of the CT tabletop having nearly the same CT number as that of the body structure. A solution to this problem is to create a large CT number gradient interface between the patient and CT tabletop by inserting a thin sheet of low CT number material. The optimum material for a tabletop was investigated from a range of low-density and low atomic number media. Various materials were studied by placing them underneath an unsliced humanoid phantom. A portion of the phantom abdomen was imaged and analyzed on a Picker Premier IQ CT scanner. Results indicate that the tabletop should be made of the material that has a CT number at least 10 times lower than the tissue in contact with the table. A simple and cost-effective method of avoiding failures in autocontouring is to place a thin sheet of low-density material such as cardboard or foam board on the tabletop. Such an insert creates a large CT gradient resulting in a significant improvement in the accuracy of the edge detection algorithm used for autocontouring. Detailed analysis is presented.


Effect of rinse time on microleakage between composite and etched enamel.
This study compared microleakage of composite bonded to etched flattened enamel in seven groups of five extracted maxillary molars. The facial enamel of the molars was ground flat and etched for 20 seconds with 37% phosphoric acid gel. In one group, etching gel was not rinsed but dried only. In four groups, gel was rinsed with an air/water spray for varying amounts of time. In the other two groups, gel was rinsed with water only for two different amounts of time. Etched surfaces were dried, and a liquid resin was applied and polymerized; a button of composite resin was polymerized to the flattened surface. Specimens were thermocycled, stained, then sectioned longitudinally. Microleakage was measured at the occlusal and gingival enamel margins and expressed as a percentage of the total length of interface. A mean (SD) percentage microleakage was determined at the occlusal and at the gingival margins for each group as follows: no rinse--89.60 (14.34); one second--water 0 (0), air/water 0 (0); three seconds--water 0.98 (1.34), air/water 0 (0); five seconds--air/water 0 (0); 20 seconds--air/water 0 (0). Because of abnormal distribution, data were analyzed using Wilcoxon two-sample tests. The no-rinse group had significantly more microleakage than any of the other groups (P = 0.0067), which were not significantly different from each other (P = 0.18). A one-second rinse with either water or air/water spray was as effective as a 20-second rinse with air/water spray in preventing microleakage at the resin-enamel interface.


A radioimmunoassay for serum ferritin.
We describe the development and evaluation of a serum ferritin radioimmunoassay, in which 125l-labeled ferritin and rabbit anti-ferritin antibody are used. Goat anti-rabbit gamma-globulin antibody, together with polyethylene glycol, is used as the separating reagent. The assay has a working range up to 500 mug of ferritin per litre, and a sample requirement of 75 mul of serum for assay at two dilutions. The assay requires 24 h. it has a sensitivity of 1.5 mug of ferritin per litre and a long-term precision (CV) of 13%. Reference intervals for a population of men were 18-330 mug/litre, with no marked age dependence, while those for a population of women older than 50 years were 18-200 mug/litre. Many apparently healthy women in the 20-50 year age group have much lower concentrations. Serum ferritin concentrations of less than 18 mug/litre are indicative of iron deficiency, defined as the absence of stainable iron in an aspirate of bone marrow.


In situ removal of the pipeline embolization device: the 'corking' and 'pseudo-corking' techniques.
The pipeline embolization device (PED) is a revolutionary tool for the endovascular treatment of intracranial aneurysms by flow diversion. Treatment using the PED often requires considerable manipulation and customization by the neurointerventionalist at the time of deployment. Proper use of the PED involves a novel set of techniques and associated jargon, which must be learned by all neurointerventionalists, fellows and residents for safe treatment of patients with this device. In this report, the PED removal techniques referred to as 'corking' and 'pseudo-corking' are described. Corking is used for the removal of a partially deployed in situ PED when the pusher wire is intact whereas 'pseudo-corking' is used if the pusher wire is fractured or disconnected. Knowledge of both techniques is necessary for withdrawing the PED in situations of malposition or failed expansion.


Predicting binding within disordered protein regions to structurally characterised peptide-binding domains.
Disordered regions of proteins often bind to structured domains, mediating interactions within and between proteins. However, it is difficult to identify a priori the short disordered regions involved in binding. We set out to determine if docking such peptide regions to peptide binding domains would assist in these predictions.We assembled a redundancy reduced dataset of SLiM (Short Linear Motif) containing proteins from the ELM database. We selected 84 sequences which had an associated PDB structures showing the SLiM bound to a protein receptor, where the SLiM was found within a 50 residue region of the protein sequence which was predicted to be disordered. First, we investigated the Vina docking scores of overlapping tripeptides from the 50 residue SLiM containing disordered regions of the protein sequence to the corresponding PDB domain. We found only weak discrimination of docking scores between peptides involved in binding and adjacent non-binding peptides in this context (AUC 0.58).Next, we trained a bidirectional recurrent neural network (BRNN) using as input the protein sequence, predicted secondary structure, Vina docking score and predicted disorder score. The results were very promising (AUC 0.72) showing that multiple sources of information can be combined to produce results which are clearly superior to any single source.We conclude that the Vina docking score alone has only modest power to define the location of a peptide within a larger protein region known to contain it. However, combining this information with other knowledge (using machine learning methods) clearly improves the identification of peptide binding regions within a protein sequence. This approach combining docking with machine learning is primarily a predictor of binding to peptide-binding sites, and is not intended as a predictor of specificity of binding to particular receptors.


Enhanced transport into and out of dead-end pores.
Dead-end micro- and nanoscale channels are ubiquitous in nature and are found in geological and biological systems subject to frequent disruptions. Achieving fluid flows in them is not possible through conventional pressure-driven mechanisms. Here we show that chemically driven convective flows leading to transport in and out of dead-end pores can occur by the phenomenon of "transient diffusioosmosis". The advective velocity depends on the presence of an in situ-generated transient ion gradient and the intrinsic charge on the pore wall. The flows can reach speeds of 50 μm/s and cause extraction of otherwise-trapped materials. Our results illustrate that chemical energy, in the form of a transient salt gradient, can be transduced into mechanical motion with the pore wall acting as the pump. As discussed, the phenomena may underlie observed transport in many geological and biological systems involving tight or dead-end micro- and nanochannels.


Paclitaxel-Eluting Stents for Chronically Occluded Saphenous Vein Grafts (EOS) Study.
Objectives:The aim of this study was to report the feasibility, short- and medium-term results of percutaneous coronary intervention (PCI) on saphenous vein graft (SVG) chronic total occlusions (CTO) using paclitaxel-eluting stents (PES). Background:In postbypass patients, PCI on SVG CTO, rather than native vessel CTO, is another treatment option. However, the acute procedural and medium-term outcomes are unknown. Methods:Twenty-two consecutive, symptomatic postbypass patients underwent PCI on SVG CTO; angiographic success was seen in 16 patients (73%). The successful cases were evaluated at 1 year; restudy angiography was performed at 11 +/- 5 months in 15 patients (94%). Results:The patients had a mean age of 73 years with predominance of male (68%); the mean SVG age was 14 years. On average, patients received 3.4 PESs per lesion; the stent size was 3.5 +/- 0.4 mm with a total stent length of 98 +/- 34 mm. The use of embolic protection devices and glycoprotein IIb/ IIIa inhibitors was observed in 6 (38%) and 5 (31%) patients, respectively. The in-hospital major adverse cardiac event (MACE) was 13%, accountable by 2 patients with postprocedure myocardial infarction. At follow-up, 6 patients had angiographic restenosis (40%); there was 1 noncardiac death and 3 target vessel revascularizations. The 1-year MACE was 25%; the graft survival free of occlusion and revascularization was 56%. Conclusions:PCI on SVG CTO is a feasible approach with a fairly high success and low in-hospital complication. However, it is associated with a relatively high angiographic restenosis and MACE at 1 year. (J Interven Cardiol 2010;**:1-6).


On the dimerization of chlorophyll in photosystem II.
In photosystem II, absorbed light energy is transferred to a reaction centre consisting of chlorophyll units. Release of an electron from the reaction centre is the starting point for the charge separation and electron transport chain in PSII. Crystal structures of the reaction centre have identified two chlorophyll monomers forming a dimer with a partial structural overlap, thus being stabilized by van der Waals interactions. However, the magnitude of this interaction is not accurately known. In this work, the structure of the chlorophyll dimer has been optimized for the first time using dispersion-corrected density functional theory (B3LYP-DCP) revealing the magnitude of dimerization to be approximately -17 kcal mol(-1). The dispersion interaction is shown to be of great significance for the chlorophyll dimer stabilization. In addition, the redox potential of the chlorophyll dimer is calculated to be 1283 mV in good agreement with recent experimental data.


Sensitivity of pyruvate dehydrogenase phosphate phosphatase to magnesium ions. Similar effects of spermine and insulin.
The effects of Mg2+ on the activity of pyruvate dehydrogenase phosphate phosphatase within intact mitochondria prepared from control and insulin-treated rat epididymal adipose tissue was explored by incubating the mitochondria in medium containing the ionophore A23187. The apparent Ka for Mg2+ was approximately halved in the mitochondria derived from insulin-treated tissue in both the absence and the presence of Ca2+. In this system, the major effect of Ca2+ was also to decrease the apparent Ka for Mg2+, rather than to change the Vmax. of the phosphatase. Damuni, Humphreys & Reed [(1984) Biochem. Biophys. Res. Commun. 124, 95-99] have reported that spermine activates ox kidney pyruvate dehydrogenase phosphate phosphatase. Studies were carried out on phosphatase from pig heart and rat epididymal adipose tissue which confirm and extend this observation. The major effect of spermine is shown to be a decrease in the Ka for Mg2+, which is apparent in both the presence and the absence of Ca2+. Spermine did not affect the sensitivity of the phosphatase to Ca2+ at saturating concentrations of Mg2+. Other polyamines tested were not as effective as spermine. No alteration in the maximum activity or Mg2+-sensitivity of pyruvate dehydrogenase phosphate phosphatase was apparent in extracts of mitochondria from insulin-treated tissue. The close similarity of the effects of spermine and the changes in kinetic properties of pyruvate dehydrogenase phosphate phosphatase within mitochondria from insulin-treated adipose tissue suggests that insulin may activate pyruvate dehydrogenase by increasing the concentration of spermine within the mitochondria. However, it is concluded that insulin is more likely to alter the interaction of the pyruvate dehydrogenase system with some other polybasic intramitochondrial component whose action can be mimicked by spermine.


A follow-up examination of intestinal parasitic infections of the Army soldiers in Whachon-gun, Korea.
A follow-up stool examination was done to know the status of intestinal parasitic infections in Army soldiers who were stationing in Whachon-gun, Kangwon-do, Korea in 1993. Of 233 examined soldiers, Infections with Clonorchis sinensis (0.4%), Metagonimus spp. (0.9%), Echinostoma hortense (0.4%), Neodiplostomum seoulensis (0.4) and Giardia lamblia (3/233) were found. E. hortense and N. seoulensis infections were each 75th, and 27th cases in Korea. Regular control program of intestinal parasitic infections might be able to contribute to diminish the prevalence rate in young Army soldiers in Korea.


Funding and college-provided nutritional resources on diet quality among female athletes.
ObjectiveTo examine funding and college-provided nutritional resources and to assess whether these are associated with diet quality and subsequent dietitian referral among female collegiate athletes of different sports levels. Participants: Female athletes (N = 120) from NCAA, NJCAA, and Club sports. Methods: Differences in questionnaire-based demographics, diet quality, and dietitian referrals were analyzed using Kruskal-Wallis and Chi-Square tests, with p < 0.05. Factors associated with diet quality and dietitian referral were examined using regression. Results: NCAA reported more funding than Club and NJCAA (p < 0.05). NJCAA expressed insufficient funds for purchasing food and reported fewer college-provided nutritional resources (p < 0.05) while showing lower diet quality scores and higher subsequent dietitian referrals than NCAA and Club. No significant associations for dietary quality and dietitian referrals were found. Conclusions: Athletes across all sports levels reported insufficient funds for purchasing food and low diet quality, with NJCAA, showing the least funding and fewest nutritional resources.


Hippocampus segmentation on epilepsy and Alzheimer's disease studies with multiple convolutional neural networks.
Background: Hippocampus segmentation on magnetic resonance imaging is of key importance for the diagnosis, treatment decision and investigation of neuropsychiatric disorders. Automatic segmentation is an active research field, with many recent models using deep learning. Most current state-of-the art hippocampus segmentation methods train their methods on healthy or Alzheimer's disease patients from public datasets. This raises the question whether these methods are capable of recognizing the hippocampus on a different domain, that of epilepsy patients with hippocampus resection. New Method: In this paper we present a state-of-the-art, open source, ready-to-use, deep learning based hippocampus segmentation method. It uses an extended 2D multi-orientation approach, with automatic pre-processing and orientation alignment. The methodology was developed and validated using HarP, a public Alzheimer's disease hippocampus segmentation dataset. Results and Comparisons: We test this methodology alongside other recent deep learning methods, in two domains: The HarP test set and an in-house epilepsy dataset, containing hippocampus resections, named HCUnicamp. We show that our method, while trained only in HarP, surpasses others from the literature in both the HarP test set and HCUnicamp in Dice. Additionally, Results from training and testing in HCUnicamp volumes are also reported separately, alongside comparisons between training and testing in epilepsy and Alzheimer's data and vice versa. Conclusion: Although current state-of-the-art methods, including our own, achieve upwards of 0.9 Dice in HarP, all tested methods, including our own, produced false positives in HCUnicamp resection regions, showing that there is still room for improvement for hippocampus segmentation methods when resection is involved.


Sickle cell anemia.
Sickle cell anemia (SCA) is a disease caused by production of abnormal hemoglobin, which binds with other abnormal hemoglobin molecules within the red blood cell to cause rigid deformation of the cell. This deformation impairs the ability of the cell to pass through small vascular channels; sludging and congestion of vascular beds may result, followed by tissue ischemia and infarction. Infarction is common throughout the body in the patient with SCA, and it is responsible for the earliest clinical manifestation, the acute pain crisis, which is thought to result from marrow infarction. Over time, such insults result in medullary bone infarcts and epiphyseal osteonecrosis. In the brain, white matter and gray matter infarcts are seen, causing cognitive impairment and functional neurologic deficits. The lungs are also commonly affected, with infarcts, emboli (from marrow infarcts and fat necrosis), and a markedly increased propensity for pneumonia. The liver, spleen, and kidney may experience infarction as well. An unusual but life-threatening complication of SCA is sequestration syndrome, wherein a considerable amount of the intravascular volume is sequestered in an organ (usually the spleen), causing vascular collapse; its pathogenesis is unknown. Finally, because the red blood cells are abnormal, they are removed from the circulation, resulting in a hemolytic anemia. For the patient with SCA, however, the ischemic complications of the disease far outweigh the anemia in clinical importance.


Effects of whole body vibration on spinal proprioception in healthy individuals.
Low back pain (LBP) is a common health problem with high reoccurrence rate. As patients with LBP are often found to be proprioception impaired, new proprioception exercises should be explored. Whole body vibration (WBV) has been proven to improve muscle function and proprioception. The aim of this study was to determine the effects of WBV on spinal proprioception when WBV was administered in standing and seated postures. Twenty healthy male individuals (mean age: 23.2±1.2 years) were recruited and randomly assigned to two WBV groups: WBV in standing or WBV in seated posture. Their body posture, lumbar repositioning ability, maximum reaching distance and lumbopelvic coordination during dynamic motion in flexion and extension were assessed before, immediately after, 30 minutes after and 1 hour after 5 minutes of WBV (18 Hz, 6 mm amplitude) exposure. A Mixed ANOVA was used to analyze the effects of group and time factors on these four outcome measures. There were no significant interaction (group and time) and group effects on all outcome measures. Participants were found to have significant different time effect on body posture, lumbar repositioning ability, maximum reaching distance and lumbopelvic coordination. WBV could significantly improve spinal proprioception including body posture, lumbar repositioning ability, maximum reaching distance and lumbopelvic coordination in healthy individuals. WBV protocol is recommended to confirm its clinical application for improving spinal proprioception and its effects on patients with LBP is warranted.


Decreased tobacco-specific nitrosamines by microbial treatment with Bacillus amyloliquefaciens DA9 during the air-curing process of burley tobacco.
Tobacco specific nitrosamines (TSNA) mainly consisting of N-nitrosonornicotine (NNN), N-nitrosoanatabine (NAT), N-nitrosoanabasine (NAB), and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) are a group of toxic components threatening human health. To inhibit TSNA formation in tobacco leaves, a high nitrite reductive strain with low nitrate reduction ability was isolated and applied to tobacco leaves in an attempt to lower the nitrite precursor of TSNA. By morphology, physiology, biochemistry, and 16S rDNA sequence analysis, the strain DA9 was identified as Bacillus amyloliquefaciens. Under the optimized fermentation parameters (glucose 40 g/L, NH4Cl 4 g/L, corn steep liquor 8 g/L, MnSO4 0.01 g/L, KH2PO4 1.0 g/L, MgSO4 0.3 g/L, initial pH 7.0, inoculum age 6 h, inoculum size 3%, temperature 37 °C), the maximum cell dentisity of 1.2 × 10(9) CFU/mL was obtained at 36 h. The DA9 cell suspensions were applied in the air-curing process of the Burley tobacco (Eyan 6) leaves. The treatment by DA9 cells lowered 32% of the nitrite content and 47% of total TSNA content in the tobacco leaves, and the concentrations of the NNN, NNK, and NAT were decreased by 48%, 12%, and 35%, respectively. Collectively, this study provides a promising strain and a novel strategy for decreasing TSNA during the air-curing process.


Evaluation of the effect of age of the younger mice on the rejuvenation of the older mice by heterochronic parabiosis.
Heterochronic parabiosis is used to study the systemic effects of aging and involves surgically connecting two animals of different ages such that they have common blood circulation. Although this technique has been prevalent for a long time, there is no scientific consensus on the age of the animals that should be used. We hypothesized that the younger the animal, the greater would be its rejuvenating effect. Hence, to test this hypothesis, we created parabiosis of 67-week-old mice with younger mice of different ages (4-week-old and 8-week-old). We evaluated the changes in appearance and the expression IL-1A, IL-6, and Cdkn2a (p16) in the liver, kidney, brain, and skin. These cytokines belong to the senescence-associated secretory phenotype (SASP) factors, and are indicators of aging. Although we did not find any significant changes in the appearance of the mice, we found statistically significant differences in some SASP factors between the liver of the 4-week-old and 8-week-old pairs. However, overall, compared to the 8-week-old mice, the 4-week-old does not exert a significantly higher rejuvenation effect on the older mice. Hence, we concluded that the rejuvenation of older mice during heterochronic parabiosis might not be affected by the exact age of the younger mice.


Effect of Nirmatrelvir/Ritonavir (Paxlovid) on Hospitalization among Adults with COVID-19: an EHR-based Target Trial Emulation from N3C.
This study leverages electronic health record data in the National COVID Cohort Collaborative's (N3C) repository to investigate disparities in Paxlovid treatment and to emulate a target trial assessing its effectiveness in reducing COVID-19 hospitalization rates. From an eligible population of 632,822 COVID-19 patients seen at 33 clinical sites across the United States between December 23, 2021 and December 31, 2022, patients were matched across observed treatment groups, yielding an analytical sample of 410,642 patients. We estimate a 65% reduced odds of hospitalization among Paxlovid-treated patients within a 28-day follow-up period, and this effect did not vary by patient vaccination status. Notably, we observe disparities in Paxlovid treatment, with lower rates among Black and Hispanic or Latino patients, and within socially vulnerable communities. Ours is the largest study of Paxlovid's real-world effectiveness to date, and our primary findings are consistent with previous randomized control trials and real-world studies.


Fine mapping for Weaver syndrome in Brown Swiss cattle and the identification of 41 concordant mutations across NRCAM, PNPLA8 and CTTNBP2.
Bovine Progressive Degenerative Myeloencephalopathy (Weaver Syndrome) is a recessive neurological disease that has been observed in the Brown Swiss cattle breed since the 1970's in North America and Europe. Bilateral hind leg weakness and ataxia appear in afflicted animals at 6 to 18 months of age, and slowly progresses to total loss of hind limb control by 3 to 4 years of age. While Weaver has previously been mapped to Bos taurus autosome (BTA) 4∶46-56 Mb and a diagnostic test based on the 6 microsatellite (MS) markers is commercially available, neither the causative gene nor mutation has been identified; therefore misdiagnosis can occur due to recombination between the diagnostic MS markers and the causative mutation. Analysis of 34,980 BTA 4 SNPs genotypes derived from the Illumina BovineHD assay for 20 Brown Swiss Weaver carriers and 49 homozygous normal bulls refined the Weaver locus to 48-53 Mb. Genotyping of 153 SNPs, identified from whole genome sequencing of 10 normal and 10 carrier animals, across a validation set of 841 animals resulted in the identification of 41 diagnostic SNPs that were concordant with the disease. Except for one intergenic SNP all are associated with genes expressed in nervous tissues: 37 distal to NRCAM, one non-synonymous (serine to asparagine) in PNPLA8, one synonymous and one non-synonymous (lysine to glutamic acid) in CTTNBP2. Haplotype and imputation analyses of 7,458 Brown Swiss animals with Illumina BovineSNP50 data and the 41 diagnostic SNPs resulted in the identification of only one haplotype concordant with the Weaver phenotype. Use of this haplotype and the diagnostic SNPs more accurately identifies Weaver carriers in both Brown Swiss purebred and influenced herds.


The Cdkn1aSUPER Mouse as a Tool to Study p53-Mediated Tumor Suppression.
Cdkn1a, which encodes p21, functions as a major route for p53-mediated cell-cycle arrest. However, the consequence of Cdkn1a gene dosage on tumor suppression has not been systematically investigated. Here, we employed BAC transgenesis to generate a Cdkn1aSUPER mouse, which harbors an additional Cdkn1a allele within its natural genomic context. We show that these mice display enhanced cell-cycle arrest and reduced apoptosis in response to genotoxic stress. Furthermore, using a chemically induced skin cancer model and an autochthonous Kras-driven lung adenocarcinoma model, we show that Cdkn1aSUPER mice display a cancer protection phenotype that is indistinguishable from that observed in Tp53SUPER animals. Moreover, we demonstrate that Tp53 and Cdkn1a cooperate in mediating cancer resistance, using a chemically induced fibrosarcoma model. Overall, our Cdkn1aSUPER allele enabled us to assess the contribution of Cdkn1a to Tp53-mediated tumor suppression.


Injury history as a risk factor for incident injury in youth soccer.
To determine if athletes with a self reported history of previous injury have a higher incident injury rate than athletes without a self reported injury history. A prospective cohort study of Classic League soccer players playing at the level under 12 through under 18. Injury history forms were mailed to all registering Classic League soccer players in the North Carolina Youth Soccer Association during 1997-2000 (n = 7000); 1483 (19%) returned the baseline questionnaire and were followed up for injuries. There were 5139 player-seasons of follow up and an estimated 171 957 athlete-exposures. More than half self reported an injury history (59.7%). Overall, the unadjusted incidence rate was 4.6 (95% confidence interval (CI) 4.3 to 4.9) incident injuries per 1000 athlete-exposures. Multivariate generalised Poisson regression modelling indicated that players with one previous injury had a twofold greater risk of incident injury (IRR = 2.6; 95% CI 2.0 to 3.3), and those with two or more previous injuries had a threefold greater risk of incident injury (IRR = 3.0; 95% CI 2.3 to 3.8) compared with athletes with no previous injuries. Injury history was associated with an increased injury rate. This suggests that, even in these youth soccer players, those with an injury history may be at higher risk.


Introduction.
Discreteness provides unique opportunities for controlling the flow of light. As in solidstate physics, optical discrete or lattice configurations are known to exhibit a succession of allowed Floquet-Bloch bands and forbidden bandgaps. In weakly coupled systems, the Floquet-Bloch states can be accurately described by local modes, and thus the tight-binding approximation or coupled-mode theory is applicable. As a result, the field dynamics become effectively discretized. In optics, arrays of evanescently coupled waveguides, photonic crystal fibers, chains of coupled microresonators, and photonic crystals are prime examples of such structures where discrete wave dynamics can be experimentally investigated. Perhaps the most exciting outcome of the interplay between discreteness and optica nonlinearity is the existence of self-localized entities better known as discrete solitons. This class of optical solitons were first suggested in the late 1980s and successfully observed in AlGaAs waveguide arrays a decade later. Since then, discrete optical solitons have been observed in many other material systems such as in optically induced lattices, in quadratic waveguide arrays, and in liquid-crystal cells. This experimental work has not only resulted in a deeper understanding of nonlinear processes in periodic environments, but it has also helped to assess the potential of these self-trapped states toward future applications. Nowadays, the field of discrete optical dynamics in nonlinear lattices is at an exciting stage of development. Even though some of the basic concepts in this area have been around for a while, much remains to be explored and discovered.


Sucrose for analgesia in newborn infants undergoing painful procedures.
Administration of oral sucrose with and without non-nutritive sucking is frequently used as a non-pharmacological intervention for procedural pain relief in neonates. To determine the efficacy, effect of dose and safety of oral sucrose for relieving procedural pain in neonates. The standard methods of the Cochrane Neonatal Collaborative Review Group were used. Randomized controlled trials in which term and/or preterm neonates (postnatal age maximum of 28 days corrected for postmenstrual age) received sucrose for procedural pain. Control conditions included water, pacifier, positioning/containing or breastfeeding. The main outcome measures were physiological and/or behavioural pain indicators and/or composite pain scores. A weighted mean difference (WMD) with 95% confidence intervals (CI) using the fixed effects model was reported for continuous outcome measures. Forty-four studies enrolling 3,496 infants were included. Results from only a few studies could be combined in meta-analyses. Sucrose significantly reduced duration of total crying time (seconds) [WMD -39.26 (95% CI -44.29, -34.24), 88 neonates], but did not reduce duration of first cry (seconds) during heel lance [WMD -8.99 (95% CI -20.07, 2.10), 192 neonates]. No significant differences were found for percent change in heart rate from baseline at one minute [WMD 0.90 (95% CI -5.81, 7.61), 86 neonates] and three minutes [WMD -6.20 (95% CI -15.27, 2.88), 86 neonates] post-heel lance, or for mean heart rate at three minutes post-heel lance [WMD -0.98 (95% CI -8.29, 6.32), 154 neonates]. Oxygen saturation (%) was significantly lower in infants given sucrose during ROP examination compared to controls [WMD -2.58 (95% CI -4.94, - 0.23), 62 neonates]. Infants given sucrose post-heel lance had significantly lower PIPP scores at 30 seconds [WMD -1.64 (95% CI -2.47, - 0.81), 220 neonates] and 60 seconds [WMD -2.05 (95% CI -3.08, -1.02), 195 neonates]. For ROP exams, sucrose did not significantly reduce PIPP scores [WMD -0.65 (95% CI -1.88, 0.59), 82 neonates]. There were no differences in adverse effects between sucrose and control groups. Sucrose is safe and effective for reducing procedural pain from single events. An optimal dose could not be identified due to inconsistency in effective sucrose dosage among studies.Further investigation on repeated administration of sucrose in neonates and the use of sucrose in combination with other non-pharmacological (e.g. behavioural, physical) and pharmacologic interventions is needed. Sucrose use in extremely low birth-weight and unstable and/or ventilated neonates needs to be addressed.


Tissue oximetry during cardiac surgery and in the cardiac intensive care unit: A prospective observational trial.
Cerebral oximetry using near-infrared spectroscopy (NIRS) has well-documented benefits during cardiac surgery. The authors tested the hypothesis that NIRS technology can be used at other sites as a tissue oximeter during cardiac surgery and in the Intensive Care Unit (ICU). To establish feasibility of monitoring tissue oximetry during and after cardiac surgery, to examine the correlations between tissue oximetry values and cerebral oximetry values, and to examine correlations between oximetry values and mean arterial pressure (MAP) in order to test whether cerebral oximetry can be used as an index organ. A large, single-center tertiary care university hospital prospective observational trial of 31 patients undergoing cardiac surgery with cardiopulmonary bypass was conducted. Oximetry stickers were applied to both sides of the forehead, the nonarterial line forearm, and the skin above one paraspinal muscle. Data were collected from before anesthesia induction until extubation or for at least 24 h in patients who remained intubated. Categorical variables were evaluated with Chi-square or Fisher's exact tests, while Wilcoxon rank-sum tests or student's t-tests were used for continuous variables. The correlation between cerebral oximetry values and back oximetry values ranged from r = 0.37 to 0.40. The correlation between cerebral oximetry values and forearm oximetry values ranged from r = 0.11 to 0.13. None of the sites correlated with MAP. Tissue oximetry at the paraspinal muscle correlates with cerebral oximetry values while at the arm does not. Further research is needed to evaluate the role of tissue oximetry on outcomes such as acute renal failure, prolonged need for mechanical ventilation, stroke, vascular ischemic complications, prolonged ICU and hospital length of stay, and mortality in cardiac surgery.


Ecotoxicological responses of three ornamental herb species to cadmium.
Cadmium is one of the most toxic elements. The ideal vegetal cover should be ensured by the selection of appropriate plant species for successful phytoremediation. In the present study, the ecotoxicological effects of Cd on the following 3 ornamental herbs were investigated: Italian ryegrass (Lolium multiflorum Lam.), white clover (Trifolium repens L.), and alfalfa (Medicago sativa L.). Based on the inhibition rate of seed germination, root and shoot elongation, early seedling growth, median inhibition concentration (IC50) values, and index of tolerance (IT) values, ecotoxicological indicators were determined. The results showed that 10 μM to 50 μM Cd had little effect on seed germination or root and shoot elongation of the 3 ornamental herbs (p > 0.01). With an increase in Cd concentrations, alfalfa (M. sativa) was the most sensitive to Cd toxicity in terms of seed germination and root elongation. Based on the IC50 of root elongation, Italian ryegrass (L. multiflorum) was the least sensitive to Cd. Based on the IC50 of seed germination and shoot elongation, white clover had the least sensitivity to Cd. Among the 3 ornamental herbs, based on the IC50 of seed germination and root and shoot elongation, alfalfa (M. sativa) was all the most sensitive plant. According to the index of tolerance, Italian ryegrass (L. multiflorum) was the most tolerant plant.


First Report of Late Blight Caused by Phytophthora infestans Clonal Lineage US-23 on Tomato and Potato in Atlantic Canada.
Phytophthora infestans (Mont.) de Bary has produced significant losses in potato and tomato yield and quality during recent late blight epidemics in North America. During the 1990s, more aggressive and genetically diverse P. infestans genotypes migrated to Canada and the United States (2). For example, US-8 became predominant and was found to be more aggressive in potato than previous clonal lineages of P. infestans. Recent P. infestans genotypes in potato and tomato plants from the United States and Canada include US-22, US-23, and US-24 representing clonal lineages with unique epidemiological characteristics (2,3,4). Characteristic phenotypic traits have been described for P. infestans clonal lineages US-8, US-22, US-23, and US-24 based on the mating type, mefenoxam sensitivity, pathogenicity, and rate of germination suggesting an association between phenotypic variations and the genotype (1,4). Analysis of P. infestans isolates collected in Canada during 2010 revealed the presence of the US-23 clonal lineage in four different areas of western Canada but not in eastern Canada (4). Isolates of P. infestans collected from eastern Canada for several years prior to 2011 were all US-8 A2 mating type. Isolation and analysis of 98 P. infestans isolates in 2011 from New Brunswick and Prince Edward Island followed standard procedures (2,3,4). Results confirmed the presence of the US-23 clonal lineage in Atlantic Canada on potato and tomato leaves with late blight symptoms, increasing the genetic complexity of P. infestans in eastern Canada. Allozyme banding patterns at the glucose-6-phosphate isomerase (Gpi) locus showed a 100/100 profile in 10 P. infestans isolates, consistent with the US-23 clonal lineage (2,3,4). Furthermore, in vitro mefenoxam sensitivity was observed in all 10 P. infestans US-23 isolates from New Brunswick and Prince Edward Island. Mating type assays confirmed the isolates were of the A1 mating type. RFLP analysis of EcoR1-digested genomic DNA using the multilocus RG57 sequence as a probe produced the DNA pattern 1, 2, 5, 6, 10, 13, 14, 17, 20, 21, 24, 24a, 25, indicative of US-23 (2,4). Microsatellite analysis using polymorphic markers on New Brunswick and Prince Edward Island P. infestans isolates produced the Pi4B 213/217 bp, D13 134 bp, and PiG11 140/155 bp profile of P. infestans US-23 (1). These results show the presence of the P. infestans A1 and A2 mating types in New Brunswick and Prince Edward Island, which increases the probability of sexual recombination. To our knowledge, this is the first report of P. infestans clonal lineage US-23 causing late blight in New Brunswick and Prince Edward Island, increasing the genetic diversity from previous years in eastern Canada and underscoring the annual fluctuation occurring in the population composition. References: (1) G. Danies et al. Plant Dis. 97:873, 2013. (2) S. B. Goodwin et al. Phytopathology 84:553, 1994. (3) C. H. Hu et al. Plant Dis. 96:1323, 2012. (4) M. L. Kalischuk et al. Plant Dis. 96:1729, 2012.


Identification of a new human immunodeficiency virus type 1 distinct from group M and group O.
A highly divergent HIV-1 isolate, designated YBF 30, was obtained in 1995 from a 40-year-old Cameroonian woman with AIDS. Depending on the genes studied, phylogenetic analysis showed that YBF30 branched either with SIVcpz-gab or between SIVcpz-gab and HIV-1 group M. The structural genes and tat, vpr, and nef of YBF30 are approximately equidistant from those of HIV-1 group M and SIVcpz-gab. In contrast, vif and rev are closer to HIV-1 group M, and vpu is highly divergent. Using a YBF30 V3 loop peptide enzyme immunoassay, we screened 700 HIV-1-positive sera collected in Cameroon; three reacted strongly with the YBF30 peptides and one was confirmed as being related to YBF30 by genetic analysis of a pol fragment. YBF30 is as distinct from SIVcpz-gab as it is from HIV-1 group M and can thus be considered as the prototype strain of a new human immunodeficiency virus group.


A Redox Homeostasis Modulatory Hydrogel with GLRX3+ Extracellular Vesicles Attenuates Disc Degeneration by Suppressing Nucleus Pulposus Cell Senescence.
Characterized by nucleus pulposus (NP) cell senescence and extracellular matrix (ECM) degradation, disc degeneration is a common pathology for various degenerative spinal disorders. To date, effective treatments for disc degeneration are absent. Here, we found that Glutaredoxin3 (GLRX3) is an important redox-regulating molecule associated with NP cell senescence and disc degeneration. Using a hypoxic preconditioning method, we developed GLRX3+ mesenchymal stem cell-derived extracellular vehicles (EVs-GLRX3), which enhanced the cellular antioxidant defense, thus preventing reactive oxygen species (ROS) accumulation and senescence cascade expansion in vitro. Further, a disc tissue-like biopolymer-based supramolecular hydrogel, which was injectable, degradable, and ROS-responsive, was proposed to deliver EVs-GLRX3 for treating disc degeneration. Using a rat model of disc degeneration, we demonstrated that the EVs-GLRX3-loaded hydrogel attenuated mitochondrial damage, alleviated the NP senescence state, and restored ECM deposition by modulating the redox homeostasis. Our findings suggested that modulation of redox homeostasis in the disc can rejuvenate NP cell senescence and thus attenuate disc degeneration.


[Identification of novel compound heterozygous mutations in the ANTXR2 gene in a Chinese patient with juvenile hyaline fibromatosis].
To identify pathogenic mutations of ANTXR2 gene in a patient with juvenile hyaline fibromatosis. Genomic DNA was extracted from peripheral venous blood sample from the patient. All coding exons (exons 1-17) and splicing sites of the ANTXR2 gene were amplified with PCR. Potential mutations were detected with direct sequencing of the PCR products. 100 unrelated healthy subjects were used as the controls. CLUSTALX (1.81) was employed to analyze cross-species conservation of the mutant amino acid. Impact of the mutations was analyzed with software including SIFT, PolyPhen-2 and MutationTaster. A compound heterozygous mutation c.1074delT/c.1153G>C, was identified, among which c.1153G>C has not been reported previously and was predicted to be probably damaging. Both mutations were not found among the 100 healthy controls. The patient's condition may be attributed to the compound heterozygous mutations of c.1074delT and c.1153G>C of the ANTXR2 gene. Above results has facilitated molecular diagnosis for this patient.


Cluster perturbation theory. III. Perturbation series for coupled cluster singles and doubles excitation energies.
The cluster perturbation series, CPS(D), for coupled cluster singles and doubles excitation energies is considered. It is demonstrated that the second-order model CPS(D-2) is identical to the configuration interaction singles with perturbative doubles, CIS(D) model. The third-order model, CPS(D-3), provides excitation energies of coupled cluster singles and doubles (CCSD) quality in the sense that the difference between CPS(D-3) and CCSD excitation energies is of the same size or smaller than the effect of adding triples corrections to CCSD excitation energies. We further show that the third-order corrections can be efficiently implemented, in particular, when the resolution of the identity approximation is used for integrals. We also show that the CPS(D-3) excitation energies can be determined for system sizes that are far beyond what can be considered in conventional CCSD excitation energy calculations.


[Hospital mortality in myocardial infarction].
The author considers the results of conservative treatment of 9709 patients who received continuous intravenous drip nitroglycerin as a component of the basic therapy. For these patients hospital lethality amounted to 17.5%. The lethality in shown to vary with sex, age, infarction extent, primary or repeated occurrence. The results obtained were compared to those from other institutions. It is believed that hospital lethality standards should not be inappropriately overstated.


12-Lipoxygenase promotes epithelial-mesenchymal transition via the Wnt/β-catenin signaling pathway in gastric cancer cells.
12-Lipoxygenase (12-LOX) plays a major role in the progression and metastasis of various types of cancer. In gastric cancer (GC), the expression level of 12-LOX is significantly up-regulated; however, its function, and underlying mechanism of action remain unclear. The mRNA and protein expression levels of 12-LOX were assessed using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot analyses, respectively, in GC cell lines. 12-LOX expression was stably up-regulated using lentiviral vector in BGC823 and MGC803 cells, and cell-counting kit-8 (CCK8), colony formation, and invasion assays were performed to verify the function of 12-LOX in proliferation and metastasis. In addition, the expression levels of epithelial-mesenchymal transition (EMT) differentiation markers and downstream targets of the Wnt/β-catenin signaling pathway were examined by Western blotting. A nude mouse model of tumor growth and metastasis was established to investigate the role of 12-LOX in vivo. Our findings demonstrate that 12-LOX mRNA and protein were highly expressed in GC cell lines. 12-LOX overexpression promoted GC cell proliferation, migration, and invasion both in vitro and in vivo. In addition, up-regulation of 12-LOX promoted the EMT in GC cells, as reflected by a decrease in E-cadherin expression and an increase in N-cadherin and Snail expression. 12-LOX overexpression in GC cells also increased the expression of multiple downstream targets of the Wnt/β-catenin signaling pathway. These findings revealed that 12-LOX functions as an oncogene in promoting GC cell proliferation and metastasis in vitro and in vivo. In addition, 12-LOX might regulate the EMT via the Wnt/β-catenin signaling pathway, indicating a potential role for 12-LOX as a target in GC treatment.


Focus on nursing point-of-care tools: application of a new evaluation rubric.
Point-of-care tools (PoCTs) provide evidence-based information on patient care and procedures at the time of need. Registered nurses have unique practice needs, and many PoCTs are marketed to support their practice. However, there is little reported evidence in the literature about evaluating nursing-focused PoCTs. The investigators developed a rubric containing evaluation criteria based on content, coverage of nursing topics, transparency of the evidence, user perception, and customization of PoCTs for supporting nursing practice. The investigators selected five PoCTs cited in the literature and of interest to local nursing leadership: ClinicalKey for Nursing, DynaMed, Lippincott's Advisor and Procedures, Nursing Reference Center Plus, and UpToDate. Application of the rubric found Lippincott had the highest coverage of diagnoses, while ClinicalKey for Nursing had strong content focused on interventions and outcomes. Nursing Reference Center Plus provided the most well-rounded coverage of nursing terminology and topics. DynaMed and UpToDate were more transparent with indicating conflict of interest, but both had lower coverage of nursing terminology, content, and care processes. None of the five PoCTs strongly met all of the evaluated criteria. The rubric developed for this study highlights each PoCT's strengths and weaknesses that can then be used to inform the decision-making process based on priorities and budget. The investigators recommend licensing a nursing PoCT and a PoCT like DynaMed or UpToDate to provide comprehensive, evidence-based, patient care coverage and to meet the diverse information needs of nurses.


Case-control study of smoking and non-melanoma skin cancer.
To investigate the association between cigarette smoking and basal and squamous cell carcinomas (BCC and SCC) of the skin, a clinic-based case-control study was conducted in Tampa, FL. Patients with histologically confirmed BCC/SCC were recruited from a university dermatology clinic (n = 215 BCC, 165 SCC). Controls were comprised of individuals with no history of skin cancer who screened negative for skin cancer upon physical examination at the affiliated cancer screening or primary care clinics (n = 315). Information on smoking and other risk factors was obtained from self-administered questionnaires. After adjustment for age, sex, and other skin cancer-risk factors, ever smoking was not associated with BCC (odds ratio (OR) = 1.26, 95% confidence interval (CI) = 0.83-1.92), but was statistically significantly associated with SCC (OR = 1.97, 95% CI = 1.19-3.26), with significant trends observed for SCC associated with increasing cigarettes per day (p = 0.01) and pack-years smoked (p = 0.01). Among men, smoking ≥20 pack-years was associated with non-significant increased risks of BCC (OR = 1.90, 95% CI = 0.88-4.12) and SCC (OR = 1.97, 95% CI = 0.84-4.66), whereas among women, no association was observed with BCC (OR = 0.98, 95% CI = 0.39-2.46) while a statistically significant three-fold risk was observed with SCC (OR = 3.00, 95% CI = 1.02-8.80). Cigarette smoking is more strongly associated with SCC than BCC, particularly among women.


Symptom Duration and Risk Factors for Delayed Return to Usual Health Among Outpatients with COVID-19 in a Multistate Health Care Systems Network - United States, March-June 2020.
Prolonged symptom duration and disability are common in adults hospitalized with severe coronavirus disease 2019 (COVID-19). Characterizing return to baseline health among outpatients with milder COVID-19 illness is important for understanding the full spectrum of COVID-19-associated illness and tailoring public health messaging, interventions, and policy. During April 15-June 25, 2020, telephone interviews were conducted with a random sample of adults aged ≥18 years who had a first positive reverse transcription-polymerase chain reaction (RT-PCR) test for SARS-CoV-2, the virus that causes COVID-19, at an outpatient visit at one of 14 U.S. academic health care systems in 13 states. Interviews were conducted 14-21 days after the test date. Respondents were asked about demographic characteristics, baseline chronic medical conditions, symptoms present at the time of testing, whether those symptoms had resolved by the interview date, and whether they had returned to their usual state of health at the time of interview. Among 292 respondents, 94% (274) reported experiencing one or more symptoms at the time of testing; 35% of these symptomatic respondents reported not having returned to their usual state of health by the date of the interview (median = 16 days from testing date), including 26% among those aged 18-34 years, 32% among those aged 35-49 years, and 47% among those aged ≥50 years. Among respondents reporting cough, fatigue, or shortness of breath at the time of testing, 43%, 35%, and 29%, respectively, continued to experience these symptoms at the time of the interview. These findings indicate that COVID-19 can result in prolonged illness even among persons with milder outpatient illness, including young adults. Effective public health messaging targeting these groups is warranted. Preventative measures, including social distancing, frequent handwashing, and the consistent and correct use of face coverings in public, should be strongly encouraged to slow the spread of SARS-CoV-2.


The Anesthetic Effects of Lidocaine with Epinephrine in Digital Nerve Blocks: A Systematic Review.
There is a long-standing stigma associated with the use of epinephrine in digital nerve blocks (DNBs) over the concern of digital necrosis. We conducted a systematic review to assess the duration of anesthesia, onset of anesthesia, and complications of lidocaine with epinephrine compared with plain lidocaine for DNBs in adults. We searched Medline via Ovid, Cochrane Library, and ClinicalTrials.gov on January 28, 2020. We included randomized controlled trials that examined lidocaine with epinephrine 1:80,000 to 1:1,000,000 (1-12.5 µg/mL) and plain lidocaine for DNBs of fingers or toes in adults. We completed a blinded review of all unique articles, followed by full-text reviews, data extraction, and quality assessment of all eligible trials. Risk of bias was assessed to inform qualitative data analysis. We identified seven studies with a combined 363 adults and 442 DNBs that met the inclusion criteria. All five studies that reported duration of anesthesia established longer duration in the epinephrine-supplemented lidocaine group, with significant increases in three. Two of the three studies that reported the onset of anesthesia demonstrated significant differences. The two studies that reported complications did not have a single case of digital necrosis. In adults, the use of lidocaine with epinephrine 1:80,000 to 1:1,000,000 (1-12.5 µg/mL) for DNB yields a longer duration of anesthetic effect and seems to be as safe as plain lidocaine in healthy adults. Several studies had some concern for bias, and additional studies are warranted.


Biochemical evaluation of the effects of storage on feline erythrocytes.
To describe the biochemical changes that occur during storage of feline packed red blood cells. Feline packed red blood cells were obtained from the manufacturer via overnight delivery immediately following collection. Bag spikes were placed using aseptic technique and samples were drawn on days 1, 4, 7, 14, 21, 28 and 35. Sodium, potassium, chloride, glucose, lactate, pH and ammonia were measured at each time point. Aerobic and anaerobic bacterial cultures were submitted following collection on day 35. There were statistically significant increases in the median concentrations of lactate and ammonia within the first 2 weeks of storage to a concentration of 12·38 mmol/L and 447·96 µmol/L, respectively. Glucose concentrations decreased significantly by day 28 to a mean of 1·86 mmol/L. Median sodium and chloride concentrations increased throughout the course of storage to a concentration of 158·20 and 131·00 mmol/L, respectively. Mean potassium concentrations decreased to a concentration of 2·40 mmol/L. These results show that biochemical derangements within feline packed red blood cells are progressive, with some alterations, such as lactate and ammonia, occurring early within the storage periods, while others, including glucose and electrolytes, are slower to develop. Additional prospective research evaluating the clinical effects of these biochemical alterations is required.


Survivors versus nonsurvivors postburn: differences in inflammatory and hypermetabolic trajectories.
To evaluate whether a panel of common biomedical markers can be utilized as trajectories to determine survival in pediatric burn patients. Despite major advances in clinical care, of the more than 1 million people burned in the United States each year, more than 4500 die as a result of their burn injuries. The ability to predict patient outcome or anticipate clinical trajectories using plasma protein expression would allow personalization of clinical care to optimize the potential for patient survival. A total of 230 severely burned children with burns exceeding 30% of the total body surface, requiring at least 1 surgical procedure were enrolled in this prospective cohort study. Demographics, clinical outcomes, and inflammatory and acute-phase responses (serum cytokines, hormones, and proteins) were determined at admission and at 11 time points for up to 180 days postburn. Statistical analysis was performed using a 1-way analysis of variance, the Student t test, χ test, and Mann-Whitney test where appropriate. Survivors and nonsurvivors exhibited profound differences in critical markers of inflammation and metabolism at each time point. Nonsurvivors had significantly higher serum levels of interleukin (IL)-6, IL-8, granulocyte colony-stimulating factor, monocyte chemoattractant protein-1, C-reactive protein, glucose, insulin, blood urea nitrogen, creatinine, and bilirubin (P < 0.05). Furthermore, nonsurvivors exhibited a vastly increased hypermetabolic response that was associated with increases in organ dysfunction and sepsis when compared with survivors (P < 0.05). Nonsurvivors have different trajectories in inflammatory, metabolic, and acute phase responses allowing differentiation of nonsurvivors from survivors and now possibly allowing novel predictive models to improve and personalize burn outcomes.


The Bidirectional Associations Between Psychotic Experiences and DSM-IV Mental Disorders.
While it is now recognized that psychotic experiences are associated with an increased risk of later mental disorders, we lack a detailed understanding of the reciprocal time-lagged relationships between first onsets of psychotic experiences and mental disorders. Using data from World Health Organization World Mental Health (WMH) Surveys, the authors assessed the bidirectional temporal associations between psychotic experiences and mental disorders. The WMH Surveys assessed lifetime prevalence and age at onset of psychotic experiences and 21 common DSM-IV mental disorders among 31,261 adult respondents from 18 countries. Discrete-time survival models were used to examine bivariate and multivariate associations between psychotic experiences and mental disorders. Temporally primary psychotic experiences were significantly associated with subsequent first onset of eight of the 21 mental disorders (major depressive disorder, bipolar disorder, generalized anxiety disorder, social phobia, posttraumatic stress disorder, adult separation anxiety disorder, bulimia nervosa, and alcohol abuse), with odds ratios ranging from 1.3 (95% CI=1.2-1.5) for major depressive disorder to 2.0 (95% CI=1.5-2.6) for bipolar disorder. In contrast, 18 of 21 primary mental disorders were significantly associated with subsequent first onset of psychotic experiences, with odds ratios ranging from 1.5 (95% CI=1.0-2.1) for childhood separation anxiety disorder to 2.8 (95% CI=1.0-7.8) for anorexia nervosa. While temporally primary psychotic experiences are associated with an elevated risk of several subsequent mental disorders, these data show that most mental disorders are associated with an elevated risk of subsequent psychotic experiences. Further investigation of the underlying factors accounting for these time-order relationships may shed light on the etiology of psychotic experiences.


The etiological features of anterior uveitis in a Turkish population.
To identify any patterns in the cause of anterior uveitis in a Turkish population and compare them with results from previous studies. The clinical records of 75 patients between January 2009 and January 2010 were retrospectively analyzed and classified as anterior uveitis according to Standardization of Uveitis Nomenclature criteria. Complete blood count, sedimentation rate, chest radiography, purified protein derivative skin test, and venereal disease research laboratory test were done on all patients. Additional serologic and radiographic tests were performed when indicated. Forty-one (54.6%) were male and 34 (45.3%) were female patients. The mean age at presentation was 39.1 ± 12.6 years. Fifty-six (74.6%) had unilateral and 19 (25.3%) had bilateral disease at presentation. A specific diagnosis was able to be established in 54 (72%) patients. The most common diagnoses were anterior uveitis associated with human leukocyte antigen B27 (14.6%) and Fuchs uveitis syndrome (14.6%). The second most common diagnosis was uveitis associated with herpes simplex virus (13.3%), followed by Behcet's uveitis (6.6%). Systemic disease associations were noted in 15 (20%) patients, and the most commonly associated systemic disease was Behcet's disease (6.6%). Fuchs uveitis syndrome and anterior uveitis associated with human leukocyte antigen B27 were the most common form of anterior uveitis in this study. Using a systematic approach, a diagnosis was able to be established in 72% of the anterior uveitis cases.