Work status among patients with ankylosing spondylitis in Argentina.
To evaluate work status and its determinants among ankylosing spondylitis (AS) patients in our country. We carried out a case-control study, including AS patients older than 16-year-old. Demographic, socioeconomic, and employment data were collected. Individuals from the general population matched by age, sex, and socioeconomic level served as the control group. Functional capacity was evaluated by bath ankylosing spondylitis functional index (BASFI) and health assessment questionnaire (HAQ-S) and disease activity by bath ankylosing spondylitis disease activity index (BASDAI). All patients completed quality of life (ASQol), depression (CES-D), and fatigue (FSS)-validated questionnaires. Sixty-four patients with AS (57 men) and 93 controls (83 men) were included. The frequency of retirement due to age was comparable in both groups, however, a significantly larger number of patients with AS were retired due to disability: 6 (9.4%) versus 0 (P = 0.004). Patients with AS had a significantly greater number of comorbidities than controls (78.7% vs. 31.5%, P = 1 x 10(-8)). Sixteen patients (26.2%) were unemployed compared with 4 controls (4.5%) (P = 0.001). Permanence at work was significantly lower in patients (median age 58, SD 54-61 years) versus controls (median age 66, SD 63-68 years) (log Rank P = 0.001). There were less full-time workers (71% vs. 87%, P = 0.03) and higher number of sick leave days (6.56 +/- 13 vs. 2.13 +/- 4.5, P = 0.01) in AS patients than controls. Unemployed patients had significantly worst quality of life, disease activity, and depression scores than employed patients. In the multivariate analysis, the primary variable associated to unemployment was depression [Odds Ratio (OR): 20, 95% confidence interval (CI), 1.69-258, P = 0.001] followed by disease activity (OR: 1.05, 95% CI, 1-1.1, P = 0.04) and age (OR: 1.1, 95% CI, 1.02-1.21, P = 0.01) as secondary variables. The frequency of work disability among our patients with AS was significantly higher than in age, sex, and socioeconomic matched population. The main variable associated with work disability and unemployment was depression. Whether this factor is contributing to or is a result of disability is not known.


Long-term follow-up of didanosine administered orally twice daily to patients with advanced human immunodeficiency virus infection and hematologic intolerance of zidovudine.
This phase 1 trial was conducted to evaluate the safety and tolerance of didanosine (ddI) in subjects with AIDS or AIDS-related complex (ARC) who previously had demonstrated hematologic intolerance of zidovudine. Thirty subjects, 21 with AIDS and nine with ARC, were enrolled. Initially, didanosine was administered orally twice daily for a total daily dose of either 750 mg or 1,500 mg. Subsequently, the dosage for those receiving 1,500 mg/d was reduced to a maximum of 750 mg/d (375 mg twice daily) when data from this and other phase 1 studies showed that the dosage of 1,500 mg/d (750 mg twice daily) was associated with an unacceptable risk of developing neuropathy. The subjects were studied for 46 weeks (mean time; range, 7-122 weeks). The dose-limiting toxic effect observed was peripheral neuropathy, which occurred in eight patients. Other significant toxic effects included pancreatitis in three patients and xerostomia in eleven. In general, didanosine was well tolerated from a hematologic standpoint by the majority of patients during prolonged administration.


A Review on Osteoarthritis Knee Management via Contrast Bath Therapy and Physical Therapy.
One of the body's main weight-bearing joints is the knee joint. For this reason, osteoarthritis typically involves it. Osteoarthritis of the knee joint is the condition in which sub-chondral sclerosis of bone occurs, narrowing of joint space is present, and osteophyte formation is seen at the edges of the bone; because of this, there is pain, reduced knee range of motion, and this leads to functional activity limitations. This prevalence is increasing because of a reduced active lifestyle; this is becoming usual in younger populations. Non-pharmacological management of this condition using contrast bath therapy given by different methods like using hot and cold water, towel compression, and smart knee pad device, causes alternate vasodilatation and vasoconstriction helps to reduce pain symptoms. Physical therapy exercises like stretching, strengthening hip and knee muscles, and balance training showed beneficial effects on a range of motion and activities. Articles using keywords were searched on Google Scholar and PubMed, 70 articles were seen of which eight were reviewed that meet the inclusion criteria. Contrast therapy helps to remove metabolic waste by improving blood flow thus reducing pain. Strengthening the hip and knee muscles helps to stabilize the knee joint, and balance exercises help to improve proprioception. From this review, it is concluded that contrast bath therapy is effective in reducing pain when given with different methods of application as compared to individual hot or cold treatment, and given with the help of a device will be more effective than the traditional method. Along with this strengthening of the knee and hip musculature, stretching and balance exercise helps to improve range and functional activity. Exercise and electrotherapy aid in symptom relief and slow the progression rate of this condition.


Ghrelin secretion stimulated by {beta}1-adrenergic receptors in cultured ghrelinoma cells and in fasted mice.
Ghrelin, an octanoylated peptide hormone produced in the stomach, rises dramatically in mouse plasma during chronic severe calorie deprivation, an event that is essential to maintain life. The mechanism for this increase is not understood. Here, we study the control of ghrelin secretion in tissue culture cells derived from mice bearing ghrelinomas induced by a tissue-specific SV40 T-antigen transgene. We found that the ghrelin-secreting cells express high levels of mRNA encoding beta(1)-adrenergic receptors. Addition of norepinephrine or epinephrine to the culture medium stimulated ghrelin secretion, and this effect was blocked by atenolol, a selective beta(1)-adrenergic antagonist. When WT mice were treated with reserpine to deplete adrenergic neurotransmitters from sympathetic neurons, the fasting-induced increase in plasma ghrelin was blocked. Inhibition was also seen following atenolol administration. We conclude that ghrelin secretion during fasting is induced by adrenergic agents released by sympathetic neurons and acting directly on beta(1) receptors on the ghrelin-secreting cells of the stomach.


Outcome in neurologically impaired patients with craniovertebral junction tuberculosis: results of combined anteroposterior surgery.
The authors studied the immediate and long-term outcome after transoral decompression, occipitocervical fusion, and antituberculous therapy (ATT) in patients who had neurological deficits due to craniovertebral junction (CVJ) tuberculosis. In this retrospective study, the authors reviewed the management and outcome in nine consecutive patients in whom features of spinal cord compression were observed and CVJ tuberculosis was diagnosed between 1993 and 1999. They ranged in age from 9 to 55 years. Onset of symptoms was acute or subacute and rapidly progressive (median 4 months, range 1-12 months). Patients presented with neck pain (89%), progressive limb weakness (89%), sensory symptoms (22%), and urinary dysfunction (33%). The mean preoperative functional grade based on the Nurick Scale was 3.4 (range 1-5). The disease caused reducible atlantoaxial dislocation (AAD) in three patients (33%), irreducible AAD in two (22%), basilar impression (BI) in one (11%), AAD with BI in one (11%), and C-2 vertebral body (VB) destruction without dislocation in two (22%). Surgery was performed in all cases. Five patients (56%) underwent transoral odontoidectomy, two (22%) transoral decompression of retropharyngeal abscess and granulation tissue, and two (22%) transoral decompression of abscess and diseased parts of the C-2 VB. All patients then underwent occipitocervical (occiput-C3) fusion in which a contoured Steinmann pin and iliac bone grafts were used. Postoperatively, A17 was prescribed for 18 months. In the immediate postoperative period, function in these patients improved from a mean Nurick grade of 3.4 to 2.3 (p < 0.01). At long-term follow-up examination (median 18.8 months, range 7-46 months) function improved from a mean Nurick grade of 3.4 to 0.3 (range 0-2) (p < 0.001). Patients with CVJ tuberculosis with features of cervical myelopathy are ideally managed with transoral decompressive procedures followed by occipitocervical fusion because this therapy provides immediate neurological improvement, stability, and allows early mobilization. The long-term prognosis in patients with this disease is excellent provided it is treated with appropriate surgical intervention(s) and with adequate duration of ATT.


Sexual harassment in middle and high school children and effects on physical and mental health.
Sexual harassment can be physical interaction and touching, as well as, psychological, environmental, or via Internet and text messaging. An online survey in an urban clinic asked children, aged 12 to 18 years the following: demographic data, height and weight, chronic medical conditions, healthcare use, questions concerning sexual harassment-witnessed and exposure, and finally questions from the Pediatric Symptom Checklist (PSC-35). Overall, 124 of 210 (59%) of the 12- to 18-year-olds surveyed had experienced sexual harassment, with the predominance being female 69% (80/116) versus 48% (49/92) male. Participants who had experienced sexual harassment were significantly more likely to score positive for psychological impairment than those who had not experienced sexual harassment (chi-square test P < .001; odds ratio: 4.7 (95% confidence interval, 1.9-11.8). There was a borderline significant association between elevated body mass index and having experienced sexual harassment (2-sample t test P = .08). Sexual harassment has a direct correlation to psychological impairment in adolescents, especially females.


Hypnotics and driving safety: meta-analyses of randomized controlled trials applying the on-the-road driving test.
Many people who use hypnotics are outpatients and are likely to drive a car the day after drug intake. The purpose of these meta-analyses was to determine whether or not this is safe. Placebo-controlled, randomized, double-blind trials were selected if using the on-the-road driving test to determine driving ability the day following one or two nights of treatment administration. Primary outcome measure of the driving test was the Standard Deviation of Lateral Position (SDLP); i.e., the weaving of the car. Fixed effects model meta-analyses were performed. Effect size (ES) was computed using mean standardized (weighted) difference scores between treatment and corresponding placebo SDLP values. Ten studies, published from 1984 to 2002 (207 subjects), were included in the meta-analyses. The morning following bedtime administration, i.e. 10-11 hours after dosing, significant driving impairment was found for the recommended dose of various benzodiazepine hypnotics (ES=0.42; 95% Confidence Interval (CI)=0.14 to 0.71). Twice the recommended dose impaired driving both in the morning (ES=0.68; CI=0.39 to 0.97) and afternoon, i.e. 16-17 hours after dosing (ES=0.57; CI=0.26 to 0.88). Zopiclone 7.5 mg also impaired driving in the morning (ES=0.89; CI=0.54 to 1.23). Zaleplon (10 and 20 mg) and zolpidem (10 mg) did not affect driving performance the morning after dosing. Following middle-of-the-night administration, significantly impaired driving performance was found for zopiclone 7.5 mg (ES=1.51, CI=0.85 to 2.17), zolpidem 10 mg (ES=0.66, CI=0.13 to 1.19) and zolpidem 20 mg (ES=1.16, CI=0.60 to 1.72). Zaleplon (10 and 20 mg) did not affect driving performance. The analyses show that driving a car the morning following nocturnal treatment with benzodiazepines and zopiclone is unsafe, whereas the recommended dose of zolpidem (10 mg) and zaleplon (10 mg) do not affect driving ability.


Phase 1 studies of central memory-derived CD19 CAR T-cell therapy following autologous HSCT in patients with B-cell NHL.
Myeloablative autologous hematopoietic stem cell transplantation (HSCT) is a mainstay of therapy for relapsed intermediate-grade B-cell non-Hodgkin lymphoma (NHL); however, relapse rates are high. In phase 1 studies designed to improve long-term remission rates, we administered adoptive T-cell immunotherapy after HSCT, using ex vivo-expanded autologous central memory-enriched T cells (TCM) transduced with lentivirus expressing CD19-specific chimeric antigen receptors (CARs). We present results from 2 safety/feasibility studies, NHL1 and NHL2, investigating different T-cell populations and CAR constructs. Engineered TCM-derived CD19 CAR T cells were infused 2 days after HSCT at doses of 25 to 200 × 10(6) in a single infusion. In NHL1, 8 patients safely received T-cell products engineered from enriched CD8(+) TCM subsets, expressing a first-generation CD19 CAR containing only the CD3ζ endodomain (CD19R:ζ). Four of 8 patients (50%; 95% confidence interval [CI]: 16-84%) were progression free at both 1 and 2 years. In NHL2, 8 patients safely received T-cell products engineered from enriched CD4(+) and CD8(+) TCM subsets and expressing a second-generation CD19 CAR containing the CD28 and CD3ζ endodomains (CD19R:28ζ). Six of 8 patients (75%; 95% CI: 35-97%) were progression free at 1 year. The CD4(+)/CD8(+) TCM-derived CD19 CAR T cells (NHL2) exhibited improvement in expansion; however, persistence was ≤28 days, similar to that seen by others using CD28 CARs. Neither cytokine release syndrome nor delayed hematopoietic engraftment was observed in either trial. These data demonstrate the safety and feasibility of CD19 CAR TCM therapy after HSCT. Trials were registered at www.clinicaltrials.gov as #NCT01318317 and #NCT01815749.


The Impact of WhatsApp on the Blood Donation Process in Saudi Arabia.
WhatsApp was the most popular messenger app used in Saudi Arabia with 71% of the total population using it in 2020. WhatsApp is increasingly being used as a tool for mobile health (m-health) interventions; however, concerning blood donation, there is a lack of research studies on the topic. This study aims to measure the general awareness levels of the blood donation process and assess blood donation history, the motivators and inhibitors to donating blood, and to assess the impact of WhatsApp on the blood donation process in Saudi Arabia. In this research study, a descriptive quantitative cross-sectional analysis was adopted. A questionnaire survey was designed using Google Forms and distributed online through social media applications to collect data. All citizens aged above 18 years of age were eligible to participate in the survey. There were a total of 150 participants in the study. More than 90% of participants were aware of their blood group, blood donation requirements, and causes to be deferred from the donation. Furthermore, 27% of participants donated blood because their relatives or friends needed blood, 26% donated due to human solidarity, 18% did not donate blood because of their health condition and 14% did not because of the fear of needles. About 33% of participants relied on WhatsApp to search for blood donors, and all the requests were fulfilled with blood donors. In addition, 94% of participants strongly believed that the WhatsApp application had a significant role in bridging the gap for blood banks' need for blood donors. Social media applications such as WhatsApp can bridge the gap between blood banks, blood donors and the patients in need of blood in Saudi Arabia, where there is a shortage of blood donors.


A small chemical library of 2-aminoimidazole derivatives as BACE-1 inhibitors: Structure-based design, synthesis, and biological evaluation.
In this work, we report a rational structure-based approach aimed at the discovery of new 2-aminoimidazoles as β-secretase inhibitors. Taking advantage of a microwave-assisted synthetic protocol, a small library of derivatives was obtained and biologically evaluated. Two compounds showed promising activities in both enzymatic and cellular assays. Moreover, one of them exhibited the capability to cross the blood-brain barrier as assessed by the parallel artificial membrane permeability assay.


Molecular signature and pathway analysis of human primary squamous and adenocarcinoma lung cancers.
Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, with a poor response to chemotherapy and low survival rate. This unfavorable treatment response is likely to derive from both late diagnosis and from complex, incompletely understood biology, and heterogeneity among NSCLC subtypes. To define the relative contributions of major cellular pathways to the biogenesis of NSCLC and highlight major differences between NSCLC subtypes, we studied the molecular signatures of lung adenocarcinoma (ADC) and squamous cell carcinoma (SCC), based on analysis of gene expression and comparison of tumor samples with normal lung tissue. Our results suggest the existence of specific molecular networks and subtype-specific differences between lung ADC and SCC subtypes, mostly found in cell cycle, DNA repair, and metabolic pathways. However, we also observed similarities across major gene interaction networks and pathways in ADC and SCC. These data provide a new insight into the biology of ADC and SCC and can be used to explore novel therapeutic interventions in lung cancer chemoprevention and treatment.


Development and validation of an indirect competitive enzyme linked-immunosorbent assay for the determination of potentially allergenic sesame (Sesamum indicum) in food.
This study was designed to develop an indirect competitive enzyme linked-immunosorbent assay (ELISA) to detect traces of sesame in food. Antibodies against sesame were prepared by immunizing a hen with a protein extract of white, peeled sesame. The ELISA did not show any cross-reactivity with 12 of 13 food ingredients tested, only for chocolate was a low cross-reactivity of 0.7% observed. To eliminate matrix effects, sesame protein standard solutions were prepared by diluting the sesame extract with blank food matrix (1:20 diluted with PBS). Recovery of sesame protein in food samples (crisp toasts, snacks, and rolls) spiked with different sesame protein concentrations ranged from 85% to 120%, with the exception of multigrain crisp toast, resulting in too high recoveries (117%-160%) and whole grain bread, yielding too low recoveries (70%-85%). In crisp bread, cracker, cereals, and snacks the limit of detection (LOD) was found to be 5 microg of sesame protein/g of food, in fresh breads and rolls, the LOD was 11 microg of sesame protein/g of food.


Microtubules regulate pulmonary vascular smooth muscle contraction.
Microtubules are ubiquitous in eukaryotic cells. However, the role of microtubules in the mechanisms of pulmonary vascular smooth contraction has not previously been described. The purpose of this study was to examine the effect of microtubular inhibition (vinblastine) on the following mechanisms of pulmonary vascular smooth muscle contraction in rats using isolated pulmonary artery rings: (1) receptor-independent, calcium-dependent contraction via smooth muscle cell depolarization (response to KCl); (2) receptor-dependent, calcium-dependent contraction via alpha 1-adrenergic receptor stimulation (response to phenylephrine, PE); (3) receptor-dependent, calcium-independent contraction via thromboxane A2 receptor stimulation (response to the thromboxane mimetic, U-46619). Rats were studied 4 days after administration of vinblastine (750 micrograms/kg i.v.). Concentration-response curves were generated for KCl (5 mM to 100 mM) and for PE and U-46619 (10(-9) to 10(-4) M) (n = 8 rings/4 rats per group). Saline injected rats were controls. Pulmonary vascular smooth muscle contraction by calcium-dependent and -independent mechanisms was significantly increased following microtubular inhibition. These findings suggest that microtubules have an important role in the response of pulmonary vascular smooth muscle to vasoconstricting agonists.


An integrated approach based on multiplexed protein array and iTRAQ labeling for in-depth identification of pathways associated to IVF outcome.
The emergence of high-throughput protein quantification methodologies has enabled the comprehensive characterization by longitudinal and cross-sectional studies of biological fluids under physiological and pathological conditions. In particular, the simultaneous investigation of cytokines and growth factors signaling pathways and their associated downstream effectors by integrated multiplexed approaches offers a powerful strategy to gain insights into biological networks and processes in living systems. A growing body of research indicates that bioactive molecules of human reproductive fluids, including human follicular fluid (hFF), may affect oocyte quality, fertilization and embryo development, thus potentially influencing the physiopathology of pregnancy-related conditions. In this work, an iTRAQ labeling strategy has been complemented with a multiplexed protein array approach to analyze hFFs with the aim to investigate biological processes and pathways related to in vitro fertilization (IVF) outcome. The iTRAQ labeling strategy lead to the quantification of 89 proteins, 30 of which were differentially expressed in hFFs with successful compared to unsuccessful IVF outcome. The targeted study, based on multiplexed antibody protein arrays, allowed the simultaneous quantification of 27 low abundance proteins, including growth factors, chemokines and cytokines endowed with pro- and anti-inflammatory activity. A significant number of differentially regulated proteins were involved in biological functions related to blood coagulation, acute phase response signaling and complement system. Overall, the present results provide an integrated overview of protein changes in hFFs associated to IVF outcome, thus improving current knowledge in reproductive medicine and fertility research.


Administration of Protamine Through Radial Arterial Access: A Prospective Observational Study.
Protamine is mainly used to reverse the anticoagulant effect of heparin after cardiopulmonary bypass (CPB). Unfortunately, it is associated with adverse clinical reactions ranging from minor cardiopulmonary instability to fatal cardiovascular collapse. In the present prospective observational study, effects of protamine administration through peripheral intra-arterial route, i.e., radial artery, were investigated.


Lessons for microenterprise programs from a fresh look at the unemployment insurance self-employment demonstration.
Microenterprise programs aim to foster self-employment among the poor, those on welfare, and the unemployed. The only experimental test of their impact is the Unemployment Insurance Self-Employment Demonstration (UISED). UISED did shorten unemployment spells, but most other impacts were small and the most disadvantaged did not choose to participate. Although UISED provides some weak evidence that long-term income support, long-term work-search waivers, and on-call advice may increase total employment (but perhaps not self-employment) more than capital infusions and up-front classes, UISED does not reveal the best design for microenterprise programs or whether such programs are good social investments.


Evidence of infection by H5N2 highly pathogenic avian influenza viruses in healthy wild waterfowl.
The potential existence of a wild bird reservoir for highly pathogenic avian influenza (HPAI) has been recently questioned by the spread and the persisting circulation of H5N1 HPAI viruses, responsible for concurrent outbreaks in migratory and domestic birds over Asia, Europe, and Africa. During a large-scale surveillance programme over Eastern Europe, the Middle East, and Africa, we detected avian influenza viruses of H5N2 subtype with a highly pathogenic (HP) viral genotype in healthy birds of two wild waterfowl species sampled in Nigeria. We monitored the survival and regional movements of one of the infected birds through satellite telemetry, providing a rare evidence of a non-lethal natural infection by an HP viral genotype in wild birds. Phylogenetic analysis of the H5N2 viruses revealed close genetic relationships with H5 viruses of low pathogenicity circulating in Eurasian wild and domestic ducks. In addition, genetic analysis did not reveal known gallinaceous poultry adaptive mutations, suggesting that the emergence of HP strains could have taken place in either wild or domestic ducks or in non-gallinaceous species. The presence of coexisting but genetically distinguishable avian influenza viruses with an HP viral genotype in two cohabiting species of wild waterfowl, with evidence of non-lethal infection at least in one species and without evidence of prior extensive circulation of the virus in domestic poultry, suggest that some strains with a potential high pathogenicity for poultry could be maintained in a community of wild waterfowl.


The epitope structure in lipopolysaccharide recognized by the serotype 2-specific monoclonal antibody of Actinobacillus pleuropneumoniae.
The polysaccharide structure recognized by a monoclonal antibody specific to serotype 2 lipopolysaccharide of Actinobacillus pleuropneumoniae was investigated using an enzyme-linked immunosorbent assay inhibition test. Lipopolysaccharide obtained from serotype 2, strain SH-15, was hydrolysed with acetic acid to liberate the polysaccharide portion, and the polysaccharide mixture was fractionated by gel filtration. The longer polysaccharide, composed of O-antigenic polysaccharide and core, fully inhibited the binding of monoclonal antibodies to a whole cell antigen of strain SH-15, whereas the core oligosaccharide without O-polysaccharide did not. No inhibition was observed with the monosaccharides which were the components of serotype 2 LPS. Enzyme-linked immunosorbent assay inhibition ability of O-polysaccharide was completely lost only by O-deacetylation. These results demonstrate that the epitope of the serotype-specific monoclonal antibody resided in O-polysaccharide of LPS and that the O-acetyl group was essential for the epitope structure.


Exopolysaccharides Produced by Phytopathogenic Pseudomonas syringae Pathovars in Infected Leaves of Susceptible Hosts.
Bacterial exopolysaccharide (EPS) was extracted from infected leaves of several host plants inoculated with phytopathogenic strains of Pseudomonas syringae pathovars. Extraction was by a facilitated diffusion procedure or by collection of intercellular fluid using a centrifugation method. The extracted EPS was purified and characterized. All bacterial pathogens which induced watersoaked lesions on their host leaves, a characteristic of most members of this bacterial group, were found to produce alginic acid (a polymer consisting of varying ratios of mannuronic and guluronic acids). Only trace amounts of bacterial EPS could be isolated from leaves inoculated with a pathovar (pv. syringae) which does not induce the formation of lesions with a watersoaked appearance. Guluronic acid was either present in very low amounts or absent in the alginic acid preparations. All bacterial alginates were acetylated (7-11%). Levan (a fructan) was apparently not produced as an EPS in vivo by any of the pathogens tested.


Auditory brainstem potentials in sons of alcoholic fathers.
With the use of event-related brain potentials we have observed sensory as well as cognitive deficits in abstinent alcoholics. By recording auditory brainstem potentials (BSP) from abstinent alcoholics we demonstrated significant delays in brainstem transmission time. We have also reported that P3 amplitudes are significantly reduced in abstinent alcoholics compared to control subjects. Although the neurophysiological deficits observed in abstinent alcoholics are presumed to be alcohol-related effects, it is possible that some of these deficits may exist prior to alcohol exposure, and may be present in subjects at high risk for alcoholism. We have recently observed significantly reduced P3 components in young sons of alcoholics similar to those observed in abstinent alcoholics. In the present study, we examined auditory BSPs in young boys at high risk for alcoholism and matched controls. We found no statistically significant difference in brainstem transmission time between high risk individuals and matched control subjects. These findings suggest that while some brain deficits observed in abstinent alcoholics may antecede the development of alcoholism (P3) and may represent a predisposing factor, other deficits (BSP) appear to be the consequence of alcohol and/or nutritional-related effects.


RNA helicases at work: binding and rearranging.
RNA helicases are ubiquitous, highly conserved enzymes that participate in nearly all aspects of RNA metabolism. These proteins bind or remodel RNA or RNA-protein complexes in an ATP-dependent fashion. How RNA helicases physically perform their cellular tasks has been a longstanding question, but in recent years, intriguing models have started to link structure, mechanism and biological function for some RNA helicases. This review outlines our current view on major structural and mechanistic themes of RNA helicase function, and on emerging physical models for cellular roles of these enzymes.


Family Environment and Childhood Obesity: A New Framework with Structural Equation Modeling.
The main purpose of the current article is to introduce a framework of the complexity of childhood obesity based on the family environment. A conceptual model that quantifies the relationships and interactions among parental socioeconomic status, family food security level, child's food intake and certain aspects of parental feeding behaviour is presented using the structural equation modeling (SEM) concept. Structural models are analysed in terms of the direct and indirect connections among latent and measurement variables that lead to the child weight indicator. To illustrate the accuracy, fit, reliability and validity of the introduced framework, real data collected from 630 families from Urumqi (Xinjiang, China) were considered. The framework includes two categories of data comprising the normal body mass index (BMI) range and obesity data. The comparison analysis between two models provides some evidence that in obesity modeling, obesity data must be extracted from the dataset and analysis must be done separately from the normal BMI range. This study may be helpful for researchers interested in childhood obesity modeling based on family environment.


Depressive, anxiety, and somatoform disorders in primary care: prevalence and recognition.
Recent studies emphasize the negative impact of comorbidity on the course of depression. If undiagnosed, depression and comorbidity contribute to high medical utilization. We aimed to assess (1) prevalences of depression alone and with comorbidity (anxiety/somatoform disorders) in primary care, (2) coexistence of anxiety/somatoform disorders in depressive patients, and (3) diagnostic validity of two screeners regarding depression with versus without comorbidity. We examined 394 primary care outpatients using the Composite International Diagnostic Interview (CIDI), the General Health Questionnaire (GHQ-12), and the Well-Being Index (WHO-5). We conducted configurational frequency analyses to identify nonrandom configurations of the disorders and receiver operating characteristic (ROC)-analyses to assess diagnostic validity of the screeners. Point prevalence of any depressive disorder was 22.8%; with at least one comorbid disorder, 15%; and with two comorbid conditions, 6.1%, which significantly exceeded expected percentage (0.9%, P< or =.0001). Depression without comorbidity occurred significantly less often than expected by chance (P< or =.0007). Comorbidity of depressive and anxiety or somatoform disorders was associated with a high odds ratio (6.25). The screeners were comparable regarding their diagnostic validity for depression with [GHQ-12: area under the curve (AUC)=0.86; WHO-5: AUC=0.88] and without comorbidity (GHQ-12: AUC=0.84; WHO-5: AUC=0.86). It can be concluded that comorbidity between depression and anxiety/somatoform disorders in primary care may occur much more frequently than expected. These results confirm assumptions that the current division between depression and anxiety might be debatable. Validity of screeners tested in our study was not affected by comorbid conditions (e.g., anxiety or somatoform disorders).


Modeling [18 F]MPPF positron emission tomography kinetics for the determination of 5-hydroxytryptamine(1A) receptor concentration with multiinjection.
The selectivity of [18F]MPPF (fluorine-18-labeled 4-(2;-methoxyphenyl)-1-[2;-(N-2"-pirydynyl)-p-fluorobenzamido]ethylpiperazine) for serotonergic 5-hydroxytryptamine(1A) (5-HT1A) receptors has been established in animals and humans. The authors quantified the parameters of ligand-receptor exchanges using a double-injection protocol. After injection of a tracer and a coinjection dose of [18F]MPPF, dynamic positron emission tomography (PET) data were acquired during a 160-minute session in five healthy males. These PET and magnetic resonance imaging data were coregistered for anatomical identification. A three-compartment model was used to determine six parameters: Fv (vascular fraction), K1, k2 (plasma/free compartment exchange rate), koff, kon/Vr (association and dissociation rate), Bmax (receptor concentration), and to deduce Kd (apparent equilibrium dissociation rate). The model was fitted with regional PET kinetics and arterial input function corrected for metabolites. Analytical distribution volume and binding potential were compared with indices generated by Logan-Patlak graphical analysis. The 5HT1A specificity for MPPF was evidenced. A Bmax of 2.9 pmol/mL and a Kd of 2.8 nmol/L were found in hippocampal regions, Kd and distribution volume in the free compartment were regionally stable, and the Logan binding potential was linearly correlated to Bmax. This study confirms the value of MPPF in the investigation of normal and pathologic systems involving the limbic network and 5-HT1A receptors. Standard values can be used for the simulation of simplified protocols.


Regulation of isocitrate lyase gene expression in sunflower.
A cDNA sequence that encodes a portion of sunflower (Helianthus annuus L.) seedling isocitrate lyase was selected from a lambda gt11 cDNA library derived from sunflower seedling cotyledon poly(A)(+) messenger RNA. The library was screened for bacteriophage recombinants that expressed antigens which reacted with antisera directed against cotton seed isocitrate lyase. The isolated cDNA hybridized with a 2 kilobase RNA species that was first detectable in maturing sunflower embryos 19 days after flowering and remained at a constant low level through seed desiccation. The prevalence of this transcript in sunflower cotyledons increased by about 10-fold within 2 days after inhibition in darkness, and transcript levels began to decrease by 5 days after imbibtion. During the first 2 days of germination and growth of sunflower seedlings in light, the rate of isocitrate lyase mRNA accumulation was greater than the rate observed during this period in dark-grown seedlings, giving peak levels about 2-fold higher than corresponding levels in dark-grown seedlings. Illumination of seedlings also promoted an earlier, and more rapid decline of isocitrate lyase transcripts. Peak levels of isocitrate lyase mRNA preceded a corresponding peak in immunologically detectable isocitrate lyase polypeptides by about 24 hours. Isocitrate lyase expression in sunflower cotyledons is developmentally regulated and is modulated, in seedlings, by exposure to light. Mechanisms that control these processes appear to function primarily at the level of mRNA accumulation and are likely to involve changes in transcription rates and/or mRNA stability.


[Aggressions towards nurses in emergency departments: an international literature review].
Workplace violence is a widespread phenomenon in every kind of settings. Among these ones there are emergency departments (ED), that have distinctive features as like the large daily number of patients' presentations, and high emotional content or stressing situations related to the management of diagnostic-therapeutic priorities. We reviewed the medical and nursing literature to quantify the international widespread of aggressions towards nurses working in EDs, distinguish the typologies and the perpetrators, and identify the consequences on victims and healthcare organizations. Original papers were searched using Medline, CINHAL, and Medscape databases. 35 research articles met the inclusion criteria, but 6 were not retrieved. The rate of verbal abuses reported by ED nurses varies from 50% to 100% of those who were surveyed, while physical violence ranges between 16.7% and 72%. Patients and relatives are the main perpetrators, followed by doctors, and, only in lower percentages, by nurses colleagues. Alcohol, drugs abuse, and overcrowding in EDs are acknowledged as motivating factors for violent events. Under-reporting of aggressions is frequent up to the 80% of victims, and some papers report that nurses consider assaults as a normal part of their work. There is a direct relation between aggressions and symptoms of post-traumatic stress disturb syndrome. Moreover there is a sense of continuous fear in nurses, causing the likelihood of workplace leaving. Special educational courses seem to be effective in diminishing the number of aggressions and to adopt adequate adaptive behaviors.


Early mobilisation of Colles' fractures. A prospective trial.
The results of a prospective controlled trial of early mobilisation of Colles' fractures in the elderly are presented. Early mobilisation produced less pain and a stronger grip. It did not lead to any greater loss of reduction of the fracture. However, there was no significant improvement in the final range of movement of the wrist. Immobilisation of the wrist for six weeks in plaster is extremely inconvenient for the elderly living alone and the patients greatly appreciated the reduction of this period of time to a minimum.


[A combined surgical-orthodontic approach of a class II/1 malocclusion. A case report].
This case report highlights the possibility of a non extraction orthodontic treatment, surgically assisted, in a Class II Division 1 malocclusions in order to reduce maxillary protrusion prior to the surgical advancement of the mandible for the correction of the skeletal deficiency. The combined orthodontic-surgical approach optimizes the profile while allowing the settling of a Angle Class I occlusion at the end of the entire treatment sequence.


Skeletal Muscle Fatigue State Evaluation with Ultrasound Image Entropy.
Muscle fatigue often occurs over a long period of exercise, and it can increase the risk of muscle injury. Evaluating the state of muscle fatigue can avoid unnecessary overtraining and injury of the muscle. Ultrasound imaging can non-invasively visualize muscle tissue in real-time. Image entropy is commonly used to characterize the texture of an image. In this study, we evaluated changes in the ultrasound image entropy (USIE) during the fatigue process. Twelve volunteers performed static sustained contractions of biceps brachii at four different intensities (20%, 30%, 40%, and 50% of maximal voluntary contraction torque). The ultrasound images and surface electromyography (sEMG) signals were acquired during exercise to fatigue. We found that (1) the root-mean-square of the sEMG signal increased, the USIE decreased significantly with time during the sustained contractions; (2) the maximum endurance time (MET) and the decline percentage of USIE were significantly different (p < .05) among the four contraction intensities; (3) the decline slope of USIE of the same volunteer was basically the same at different contraction intensities. The USIE could be a new method for the evaluation of skeletal muscle fatigue state.


Gastric mucosal blood flow and acid secretory changes in man with impromidine: a new specific histamine-H2-receptor agonist.
The effect of impromidine, a new histamine-H2-receptor agonist, on gastric mucosal blood flow (neutral red clearance) and acid secretion was studied in nine volunteers. Impromidine stimulated a dose-dependent increase in neutral red clearance and acid secretion. Simultaneous cimetidine in three doses caused a parallel shift to the right for both acid output and clearance with unchanged maxima compatible with simple surmountable antagonism. There were small cardiovascular changes: an increased heart rate with a decreased diastolic pressure during infusion of impromidine. These changes were antagonised by cimetidine.


Protease Activated Receptor 1 and Its Ligands as Main Regulators of the Regeneration of Peripheral Nerves.
In contrast with the brain and spinal cord, peripheral nerves possess a striking ability to regenerate after damage. This characteristic of the peripheral nervous system is mainly due to a specific population of glial cells, the Schwann cells. Schwann cells promptly activate after nerve injury, dedifferentiate assuming a repair phenotype, and assist axon regrowth. In general, tissue injury determines the release of a variety of proteases which, in parallel with the degradation of their specific targets, also activate plasma membrane receptors known as protease-activated receptors (PARs). PAR1, the prototypical member of the PAR family, is also known as thrombin receptor and is present at the Schwann cell plasma membrane. This receptor is emerging as a possible regulator of the pro-regenerative capacity of Schwann cells. Here, we summarize the most recent literature data describing the possible contribution of PAR1 and PAR1-activating proteases in regulating the regeneration of peripheral nerves.


Outcomes From Whole-Brain Reirradiation Using Pulsed Reduced Dose Rate Radiation Therapy.
Recurrent intracranial metastases after whole-brain irradiation pose a clinical challenge owing to the escalating morbidity associated with their treatment. Although stereotactic radiosurgery is increasingly being used, there are still situations in which whole-brain reirradiation (ReRT) continues to be appropriate. Here, we report our experience using whole-brain pulsed reduced dose rate radiation therapy (PRDR), a method that delivers radiation at a slower rate of 0.067 Gy/min to potentially increase sublethal damage repair and decrease toxicity. Patients undergoing whole-brain ReRT with PRDR from January 1, 2001 to March 2019 were analyzed. The median PRDR ReRT dose was 26 Gy in 2 Gy fractions, resulting in a median total whole-brain dose of 59.5 Gy. Cox regression analysis was used for multivariate analysis. The Kaplan-Meier method was used for overall survival, progression free survival, and to evaluate the ReRT score. Binary logistic regression was employed to evaluate variables associated with rapid death. Seventy-five patients were treated with whole-brain PRDR radiation therapy. The median age was 54 (range, 26-72), the median Karnofsky performance status (KPS) was 80, and 86.7% had recursive partitioning analysis scores of 2. Thirty-two patients had over 10 metastases and 11 had leptomeningeal disease. The median overall survival was 4.1 months (range, 0.29-59.5 months) with a 1 year overall survival of 10.4%. Age, KPS, dexamethasone usage, and intracranial disease volume were significantly correlated with overall survival on multivariate analysis. A KPS ≤70 was associated with rapid death after radiation. The prognostic value of the ReRT score was validated. The most common acute toxicities were fatigue (23.1%) and headache (16.9%). In this large cohort of patients with advanced intracranial metastases, PRDR achieves acceptable survival and may decrease toxicity associated with ReRT. PRDR is an easily implemented technique and is a viable treatment option for ReRT of brain metastases.


Does bone morphogenetic protein 6 (BMP6) affect female fertility in the mouse?
Bone morphogenetic protein 6 (BMP6) is a transforming growth factor beta superfamily member produced by mammalian oocytes as well as other cell types. Despite well-characterized effects of recombinant BMP6 on granulosa cells in vitro, the function of BMP6 in vivo has been ill-defined. Therefore, the effects of genetic deletion of the Bmp6 gene on female mouse fertility were assessed. The mean litter size of Bmp6(-/-) females was reduced by 22% (P < 0.05) compared to Bmp6(+/+) controls. Not only did Bmp6(-/-) females naturally ovulate 24% fewer eggs, but competence of in vitro-matured oocytes to complete preimplantation development after fertilization in vitro was decreased by 50%. No apparent effect of Bmp6 deletion on either the morphology or the dynamics of follicular development was apparent. Nevertheless, levels of luteinizing hormone (LH)/human chorionic gonadotropin (hCG)-induced transcripts, which encode proteins required for cumulus expansion (HAS2, PTGS2, PTX3, and TNFAIP6), and of epidermal growth factor-like peptides (AREG, BTC, and EREG) were lower in Bmp6(-/-) mice than in controls after administration of a reduced dose of hCG (1 IU) in vivo. LH receptor (Lhcgr) transcript levels were not significantly lower in Bmp6(-/-) granulosa cells, suggesting that BMP6 is required for processes downstream of LH receptors. To assess whether another oocyte-derived BMP, BMP15, could have BMP6-redundant functions in vivo, the fertility of Bmp15/Bmp6 double mutants was assessed. Fertility was not significantly reduced in double-homozygous mutants compared with that in double-heterozygous controls. Therefore, BMP6 promotes normal fertility in female mice, at least in part, by enabling appropriate responses to LH and normal oocyte quality. Thus, Bmp6 probably is part of the complex genetic network that determines female fertility.


A Practical Deep Learning Model in Differentiating Pneumonia-Type Lung Carcinoma from Pneumonia on CT Images: ResNet Added with Attention Mechanism.
We aim to develop a deep neural network model to differentiate pneumonia-type lung carcinoma from pneumonia based on chest CT scanning and evaluate its performance. We retrospectively analyzed 131 patients diagnosed with pneumonia-type lung carcinoma and 171 patients with pneumonia treated in Beijing Hospital from October 2019 to February 2021. The average age was 68 (±15) years old, and the proportion of men (162/302) was slightly more than that of women (140/302). In this study, a deep learning based model UNet was applied to extract lesion areas from chest CT images. Lesion areas were extracted and classified by a designed spatial attention mechanism network. The model AUC and diagnostic accuracy were analyzed based on the results of the model. We analyzed the accuracy rate, sensitivity, and specificity and compared the results of the model to the junior and senior radiologists and radiologists based on the model. The model has a good efficiency in detecting pneumonia-like lesions (6.31 seconds/case). The model accuracy rate, sensitivity, and specificity were 74.20%, 60.37%, and 89.36%, respectively. The junior radiologist's accuracy rate, sensitivity, and specificity were 61.00%, 48.08%, and 75.00%, respectively. The senior radiologist's accuracy rate, sensitivity, and specificity were 65.00%, 51.92%, and 79.17%, respectively. The results of junior radiologists based on the model were improved (76.00% for accuracy rate, 62.75% for sensitivity, and 89.80% for specificity). The results of senior radiologists based on the model were also improved (78.00% for accuracy rate, 64.71% for sensitivity, and 91.84% for specificity) and the diagnostic accuracy of which was statistically higher than other groups (P < 0.05). Based on the lesion texture diversity and the lesion boundary ambiguity, the algorithm produced false-positive samples (13.51%). This deep learning model could detect pneumonia-type lung carcinoma and differentiate it from pneumonia accurately and efficiently.


Nosocomial spondylodiscitis after intradiscal electrothermal therapy: Case series.
Intradiscal electrothermal therapy (IDET) is a method applied for treatment of pain caused by the disc and involves reaching spinal disc through a catheter under fluoroscopy and solidifying disc interior by heating. We retrospectively evaluated ten patients treated and followed up with diagnosis of nosocomial spondylodiscitis after IDET. Ten patients, to whom IDET was applied for low back pain treatment in a tertiary healthcare organization, came with complaints of fever and low back pain during postoperative process. Appropriate antibiotics treatment was commenced after the reproduction of Pseudomonas aeruoginosa in abscess culture.Even though spondylodiscitis developing after IDET is a rare complication, it is also a clinical condition that needs to be thought in the patients whose complaints increase and clinically do not recover after the procedure. Adherence to rules of the asepsis will reduce the frequency of infection as in all nosocomial infections.


The Timing of Liver Transplantation Following Downstaging: Wait of Not to Wait?
HCC is a complex disease that is diagnosed in advanced stage and on the background of cirrhosis. Locoregional therapies provide sufficient downstaging to enable patients suitable for radical procedures such liver transplantation. However, the interval between locoregional therapies and definitive therapy is still controversial. We performed a review of literature to evaluate the role of waiting period between locoregional therapies and liver transplantation or resection from the perspective of cure and recurrence rates. Thorough literature search was performed to evaluate the role of locoregional therapy and the interval to definitive therapies for the treatment of hepatocellular cancer. Usually, small tumors with lower tumor burden, in other words, tumors within Milan criteria, can be transplanted with an acceptable overall and disease-free survival. However, treating patients with locally advanced tumors is currently a matter of extensive research. Currently, locoregional therapies are applied to downstage the patients. However, the duration of waiting is a crucial point that needs further research. There is a consensus that the waiting interval between down-staging and transplantation should be no less than 3 months. This is important for selection of favorable tumor biology as well as from the point of antitumor immune response. Currently, there are no surrogate markers for surveillance of response to locoregional therapies as well as the antitumor immune response that develops as a result of down-staging.


End-of-life care education in internal medicine residency programs: an interinstitutional study.
Integrating end-of-life care (EOL) education into medical residency programs requires knowledge of what programs currently teach and what residents learn. Evaluate EOL teaching content and practices in internal medicine residency programs and the EOL knowledge of their faculty and residents. An interinstitutional pilot study. We examined patterns of EOL education, discerned from program directors' responses to structured surveys of institutional teaching and evaluation practices, and EOL knowledge, derived from the performance of faculty and residents on a 36-item knowledge examination. Program directors, faculty, and residents at 32 accredited U.S. internal medicine residency programs. Although all programs cited inclusion of some EOL education, expected EOL domains were not systematically taught or assessed. Pain assessment and treatment training was required in only 60% of programs. Even fewer programs required instruction on nonpain symptoms (<30%) or hospice and nonhospital care settings (22%). EOL assessment depends primarily on faculty's general ratings of residents' global competency; few programs use knowledge examinations or structured skill assessments. Directors identified barriers and support for improving education. On the knowledge examination, the mean score of residents increased across training levels (F = 21.7, p < .001), and the mean score of faculty was higher than residents' (57.6%: 48.9%, t = 51.6, p < .001). Existing internal medicine residency education lacks training in critical EOL care domains. Residency programs need additional training for residents and teaching faculty in EOL content and skills, with assessment practices that demonstrate competencies have been acquired. Program directors perceive institutional support for making these changes.


US detection of renal and ureteral calculi in patients with suspected renal colic.
The purpose of this study was to determine whether the color Doppler twinkling sign could be considered as an additional diagnostic feature of small renal lithiasis (_5mm). 181 patients underwent CT scans performed for other pathologies; the images were also analyzed by a radiologists to identify the incidental presence of renal lithiasis equal to or smaller than 5 mm.These patients underwent an abdominal ultrasound examination, including grayscale analysis of the kidneys and color Doppler. Lithiasis were divided into three groups, on the basis of the diagnostic agreement provided by CT and gray scale results. Then, the twinkling sign sensitivity was assessed in the three groups. The twinkling sign was positive in 177 out of 206 lithiasis (86 %) visible on CT, while the grayscale was absolutely positive in 98 out of 206 lithiasis (47.6%) and doubtful positive in 71 out of 206 lithiasis (31%).The twinkling sign was positive in 100% of absolutely positive and doubtful positive lithiasis on bmode, and in 8 out of 31 lithiasis not visible on b-mode. In the diagnosis of small renal lithiasis, integrating gray-scale with color Doppler may be the most suitable procedure, because the color-Doppler twinkling sign is able to confirm the doubtful diagnosis of renal lithiasis and to detect some lithiasis that are not visible on b-mode.


Retinoids in cancer chemoprevention.
Naturally occurring and synthetic vitamin A metabolites and analogs (retinoids) inhibit tumor development in a variety of cellular, animal, and patient studies. They suppress transformation of cells in vitro and inhibit carcinogenesis in various organs in animal models. In a mouse skin carcinogenesis model, topical retinoids exhibit suppressive effects on tumor promotion, but have no effect on tumor initiation. In other models, retinoids administered in the diet suppress tumor development even in an adjuvant setting after excision of the first tumor. Retinoids suppress carcinogenesis in individuals with premalignant lesions and a high risk to develop cancer of the aerodigestive tract. Likewise, retinoids prevent the development of second primary cancers in head/neck and lung cancer patients who had been treated for the first primary. The mechanisms underlying the anticarcinogenic activity of retinoids appear to be associated with the ability of retinoids to modulate the growth, differentiation, and apoptosis of normal, premalignant, and malignant cells in vitro and in vivo. Most of these effects are mediated by nuclear retinoid receptors, but other mechanisms may also be involved. These studies indicate that retinoids are potentially useful agent for cancer chemoprevention.


Intraoperative imaging to detect coronary stenosis in no-angiography patients.
Sometimes, patients scheduled for cardiac operations other than coronary artery bypass may be unsuitable for preoperative coronary angiography. We routinely use intraoperative high-resolution epicardial ultrasound to select the proper target for the graft and to check graft anastomosis integrity. We describe 3 patients who could not undergo preoperative coronary angiography for different reasons. In all cases, we discovered significant stenosis in the left anterior descending coronary artery, which required bypass grafting. Intraoperative verification by transit-time flow measurements confirmed the significant stenosis detected by imaging.


Impact of linker strain and flexibility in the design of a fragment-based inhibitor.
The linking together of molecular fragments that bind to adjacent sites on an enzyme can lead to high-affinity inhibitors. Ideally, this strategy would use linkers that do not perturb the optimal binding geometries of the fragments and do not have excessive conformational flexibility that would increase the entropic penalty of binding. In reality, these aims are seldom realized owing to limitations in linker chemistry. Here we systematically explore the energetic and structural effects of rigid and flexible linkers on the binding of a fragment-based inhibitor of human uracil DNA glycosylase. Analysis of the free energies of binding in combination with cocrystal structures shows that the flexibility and strain of a given linker can have a substantial impact on binding affinity even when the binding fragments are optimally positioned. Such effects are not apparent from inspection of structures and underscore the importance of linker optimization in fragment-based drug discovery efforts.


Analysis of food samples made easy by microextraction technologies directly coupled to mass spectrometry.
Because of the complexity and diversity of food matrices, their chemical analysis often entails several analytical challenges to attain accurate and reliable results, especially for multiresidue analysis and ultratrace quantification. Nonetheless, microextraction technology, such as solid-phase microextraction (SPME), has revolutionized the concept of sample preparation for complex matrices because of its nonexhaustive, yet quantitative extraction approach and its amenability to coupling to multiple analytical platforms. In recent years, microextraction devices directly interfaced with mass spectrometry (MS) have redefined the analytical workflow by providing faster screening and quantitative methods for complex matrices. This review will discuss the latest developments in the field of food analysis by means of microextraction approaches directly coupled to MS. One key feature that differentiates SPME-MS approaches from other ambient MS techniques is the use of matrix compatible extraction phases that prevent biofouling, which could drastically affect the ionization process and are still capable of selective extraction of the targeted analytes from the food matrix. Furthermore, the review examines the most significant applications of SPME-MS for various ionization techniques such as direct analysis in real time, dielectric barrier desorption ionization, and some unique SPME geometries, for example, transmission mode SPME and coated blade spray, that facilitate the interface to MS instrumentation.


Renin-angiotensin-aldosterone system peptide profiles in patients with COVID-19.
While evidence on the interface between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the renin-angiotensin-aldosterone-system (RAAS) is accumulating, clinical data on RAAS peptide alteration among coronavirus disease-19 (COVID-19) patients is missing. In this exploratory study, we prospectively included adult patients (aged ≥ 18 years) admitted between February 26 and April 30, 2020 to a tertiary care hospital in Switzerland. We assessed the association of an underlying SARS-CoV-2 infection and equilibrium serum levels of RAAS peptides in hospitalized COVID-19 patients 1:1 propensity-score matched with patients suffering from SARS-CoV-2-negative respiratory infections. Subgroup analyses involved stratification for taking RAAS inhibitors. COVID-19 patients had about 50% lower equilibrium serum RAAS peptide levels as compared with matched controls (angiotensin I: 31.6 vs 66.8 pmol/L, -52.7% (95%CI: -68.5% to -36.9%); angiotensin II: 37.7 vs 92.5 pmol/L, -59.2% (95%CI: -72.1% to -46.3%); angiotensin (1-5): 3.3 vs 6.6 pmol/L, -49.7% (95%CI: -59.2% to -40.2%); angiotensin (1-7): 4.8 vs 7.6 pmol/L, -64.9% (95%CI: -84.5% to -45.3%)). While the plasma renin activity was lower in COVID-19 patients (88.6 vs 207.9 pmol/L, -58.5% (95%CI: -71.4% to -45.6%)), there was no difference of angiotensin-converting enzyme (ACE) and ACE2 plasma activity between the groups. Subgroup analyses revealed a pronounced RAAS peptide profile depression in COVID-19 patients among those not on RAAS inhibitors. As compared with SARS-CoV-2-negative patients, we found a downregulated RAAS in presence of a SARS-CoV-2 infection. Whether the lower levels of the protective angiotensin (1-5) and (1-7) are linked to adverse outcomes in COVID-19 warrants further investigation.


High failure rate of cementless threaded acetabular cups: a radiographic and histologic study in the goat.
We studied the fixation of the Mecron cementless titanium screw cup radiographically and histologically in 20 dwarf-goats after periods of 0, 6, 26 and 52 weeks. In only 3 goats did histology show good bone-implant contact, whereas in the other 17 goats a fibrous membrane interface was seen. This high failure rate is caused by the poor primary fixation and should be a warning against the use of this implant.


Exceeding WHO Framework Convention on Tobacco Control (FCTC) Obligations: Nepal Overcoming Tobacco Industry Interference to Enact a Comprehensive Tobacco Control Policy.
The tobacco industry works to block, delay, and weaken national tobacco control legislation to implement the WHO Framework Convention on Tobacco Control (FCTC). This article reviews how Nepal overcame industry opposition and to a comprehensive tobacco control law implementing the FCTC. We triangulated newspaper articles and policy documents with key informant interviews. With the support of international health groups, local tobacco control advocates worked with policymakers in Nepal to pass a comprehensive tobacco control law that exceeded FCTC obligations. The tobacco industry exploited a time of political transition to block consideration by Parliament, arranged and sponsored foreign tours for legislators, made death threats to tobacco control advocates and their families, and argued for the economic importance of tobacco farms. Despite strong interference from Health, and Law and Justice ministers, a 2009 Supreme Court ruling helped tobacco control advocates secure a comprehensive tobacco control law in 2011 that included rotating pictorial health warning labels covering 75% of both sides of cigarette packages, 100% smoke free public places and workplaces, private homes and vehicles, and a tobacco advertising, promotion, and sponsorship ban. Advocates in developing countries should utilize Nepal's experience to reject tobacco industry offers of compromise and continue educating politicians and legislators to generate political support to pass a comprehensive tobacco control law. Technical and financial support from international agencies, and effective collaboration and coordination of civil societies, and utilization of domestic litigation are helpful in LMICs where governance is weak (the abstract in Nepali is available as a Supplementary Material). The tobacco industry exploited a time of political transition in Nepal in its effort to block comprehensive tobacco control policy in Parliament by sponsoring foreign tours of legislatures, making death threats to tobacco control advocates and their families, and arguing for the economic importance of tobacco farms. Tobacco control advocates used litigation to raise awareness and educate legislators and promote strong legislation with the involvement of international health groups. Technical and financial support from international agencies, and effective collaboration and coordination of civil societies, and utilization of domestic litigation are helpful in LMICs where governance is weak.


The need for special interventions for multiple hospital admission patients.
Although a high proportion of Medicare hospital admissions and expenditures are accounted for by a small proportion of the elderly who experience chronic patterns of acute hospital use, little emphasis has been placed on reducing hospitalization among these high users. Five interventions that have succeeded in substantially reducing the number of hospital days among high users living at home are discussed in this article, as are several interventions that have reduced hospital use by nursing home residents. With the passage of the Medicare Catastrophic Coverage Act of 1988, research and demonstration activities for high users of hospital care will, for the first time, have a Federal focus.


HIV/AIDS, reproductive and sexual health, and the law.
The law is a frequently overlooked tool for addressing the complex practical and ethical issues that arise from the HIV/AIDS pandemic. The law intersects with reproductive and sexual health issues and HIV/AIDS in many ways. Well-written and rigorously applied laws could benefit persons living with (or at risk of contracting) HIV/AIDS, particularly concerning their reproductive and sexual health. Access to reproductive health services should be a legal right, and discrimination based on HIV status, which undermines access, should be prohibited. Laws against sexual violence and exploitation, which perpetuate the spread of HIV and its negative effects, should be enforced. Finally, a human rights framework should inform the drafting of laws to more effectively protect health.


Rapid and noninvasive diagnostics of Huanglongbing and nutrient deficits on citrus trees with a handheld Raman spectrometer.
Huanglongbing (HLB) or citrus greening is a devastating disease of citrus trees that is caused by the gram-negative Candidatus Liberibacter spp. bacteria. The bacteria are phloem limited and transmitted by the Asian citrus psyllid, Diaphorina citri, and the African citrus psyllid, Trioza erytreae, which allows for a wider dissemination of HLB. Infected trees exhibit yellowing of leaves, premature leaf and fruit drop, and ultimately the death of the entire plant. Polymerase chain reaction (PCR) and antibody-based assays (ELISA and/or immunoblot) are commonly used methods for HLB diagnostics. However, they are costly, time-consuming, and destructive to the sample and often not sensitive enough to detect the pathogen very early in the infection stage. Raman spectroscopy (RS) is a noninvasive, nondestructive, analytical technique which provides insight into the chemical structures of a specimen. In this study, by using a handheld Raman system in combination with chemometric analyses, we can readily distinguish between healthy and HLB (early and late stage)-infected citrus trees, as well as plants suffering from nutrient deficits. The detection rate of Raman-based diagnostics of healthy vs HLB infected vs nutrient deficit is ~ 98% for grapefruit and ~ 87% for orange trees, whereas the accuracy of early- vs late-stage HLB infected is 100% for grapefruits and ~94% for oranges. This analysis is portable and sample agnostic, suggesting that it could be utilized for other crops and conducted autonomously. Graphical abstract.


Essential role of TRPC1 channels in cardiomyoblasts hypertrophy mediated by 5-HT2A serotonin receptors.
Serotonin (5-HT) participates in the development of cardiac hypertrophy through 5-HT(2A) serotonin receptors. The hypertrophic growth of cardiomyoblasts induced by 5-HT(2A) receptors involves the activation of the Ca(2+) responsive calcineurin/NFAT pathway. However, the mechanism whereby NFAT is activated by 5-HT(2A) receptors remains indeterminate. In this study, we examined whether transient receptor potential canonical (TRPC) channels participate in NFAT activation and hypertrophic response triggered by 5-HT. We demonstrate that TRPC1 expression is upregulated in 5-HT-treated rat cardiomyoblasts whereas TRPC6 is induced in a mouse model of heart hypertrophy. Moreover, TRPC1 knockdown by small interfering RNA inhibits NFAT activation and hypertrophic response mediated by 5-HT(2A) receptors. These findings provide new insights about a mechanistic basis for the activation of the calcineurin/NFAT pathway by 5-HT(2A) receptors and highlight the critical role of TRPC1 in the development of cardiac hypertrophy.


The efficacy of granisetron for cancer patients undergoing platinum-based chemotherapy: comparison of 1 miligram versus 3 miligram doses in preventing nausea and vomiting.
To compare the efficacy of anti-emetic and prophylactic effects of 1 milligram (mg) versus 3 mg granisetron in cancer patients. In this double blind, randomized, parallel study, 2-dose regimens of intra venous (IV) granisetron were evaluated in 39 cancer patients who were treated with platinum-based chemotherapy. Patients who met the inclusion criteria were randomized to receive granisetron 1 mg IV plus dexamethasone 20 mg (group A) or granisetron 3 mg iv plus dexamethasone 20 mg (group B). A questionnaire was used to evaluate the anti-emetic effects of granisetron. Subjects consisted of 31 men and 8 women. In group A (19 patients) 57.9% showed complete response from vomiting, 10.5% of major response, and 31.6% of failure to anti-emetic therapy. There were 47.4% of patients free from nausea and 52.6% complained of nausea (mild, moderate, and severe nausea). Among group B (20 patients), 90% showed complete response from vomiting, 5% of major response, and 5% of failure to anti-emetic therapy. Eighty percent of patients were free from nausea, while 15% complained of mild nausea and 5% of moderate nausea. The differences were statistically significant for vomiting (p = 0.02) as well as for nausea (p = 0.03). Intravenous granisetron 3 mg has better efficacy than granisetron 1 mg in preventing cisplatin- induced acute emesis.


Proteomic analyses reveal a role of cytoplasmic droplets as an energy source during epididymal sperm maturation.
A small portion of cytoplasm is generally retained as the cytoplasmic droplet (CD) on the flagellum of spermatozoa after spermiation in mice. CDs are believed to play a role in osmoadaptation by allowing water entrance or exit. However, many lines of evidence suggest that CDs may have roles beyond osmoregulation. To gain more insights, we purified CDs from murine epididymal spermatozoa and conducted proteomic analyses on proteins highly enriched in CDs. Among 105 proteins identified, 71 (68%) were enzymes involved in energy metabolism. We also found that sperm mitochondria underwent a reactivation process and glycolytic enzymes were further distributed and incorporated into different regions of the flagellum during epididymal sperm maturation. Both processes appeared to require CDs. Our data suggest that the CD represents a transient organelle that serves as an energy source essential for epididymal sperm maturation.


Hemoglobin adducts as biomarkers of 1,3-butadiene in occupationally low exposed Italian workers and a few diesel-exposed miners.
Hemoglobin adducts were determined as biomarkers of 1,3-butadiene (BD) in 30 workers and 10 controls from an Italian BD plant and in 14 diesel-exposed miners. N-(2,3,4-trihydroxybutyl)valine (THBVal), an N-terminal valine globin adduct of reactive butadiene metabolites, was analyzed by gas chromatography/high resolution mass spectrometry after a modified Edman degradation and further acetylation. The BD exposure for the plant workers was 31 microg/m(3) (personal sampling). Whereas there was no detectable difference in hemoglobin adduct levels (range 17.7-61.4 pmol/g globin) between the total group of exposed and controls, slight but significant differences could be found between two subgroups of workers from different production units as well as one subgroup and controls (P<0.05), between smoking (n=13) and non-smoking exposed workers (n=17; P=0.066) as well as between smoking exposed workers and controls (P=0.055). Adduct levels of the miners (all non-smokers) were in the same range as those of the Italian BD-workers and controls. The internal exposure and strain measured by THBVal levels resulting from a very low occupational BD exposure was in the range of the contribution of moderate smoking.


Social influences on the development of foraging behavior in free-living common marmosets (Callithrix jacchus).
In this study we investigated the extent and pattern of social influences (i.e., the use of a conspecific as a model) on the foraging behavior of immature, wild common marmosets (Callithrix jacchus) as a function of the age of individuals. We compared the foraging activities and interactions with subadult and adult group members (older than 15 months) of young infants (1-2 months old), older infants (3-4 months old), and juveniles (5-10 months old). In addition to measuring the intensities of model-independent foraging (MIF) and merely paying attention to the model's foraging activities, we examined the frequencies of three types of model-dependent foraging (MDF): "follow the model", "manipulate the same object", and "forage together". We found that older infants were the most attentive and most socially-influenced foragers among the three age categories in absolute terms, but were not more attentive than young infants given their low foraging activity. Juveniles, in contrast, tended to have reduced overall foraging intensity compared to infants, but showed relatively more MDF in cases in which they observed subadult or adult models. Female models appeared to be more attractive than male models. These findings suggest that infants are generally more attentive to the foraging behavior of subadults and adults than juveniles, with the latter being more influenced when they had observed a model before. These subtle age-dependent effects of social foraging not only extend the assumption that young primates seek information from adults, they also suggest a complex interplay among physical and cognitive maturation, independence, and social dynamics.


Examining substrate uptake patterns of Rhodocyclus-related PAO in full-scale EBPR plants by using the MAR-FISH technique.
While recognised as the important population responsible for enhanced biological phosphorus removal (EBPR), detailed knowledge on the physiology of Rhodocyclus-related polyphosphate accumulating organisms (PAO) has yet to be grasped. The objective of this study was to examine the in situ substrate uptake patterns of Rhodocyclus-related PAO present in full-scale EBPR plants by the combined technique of microautoradiography-fluorescent in situ hybridization (MAR-FISH). The presence of these PAO in the four investigated plants was confirmed by FISH and they constituted 17%, 9%, 8%, and 7% of the sludge community. By using MAR-FISH technique, Rhodocyclus-related PAO in all the plants demonstrated similar anaerobic substrate uptake patterns. They were capable of assimilating acetate, aspartate and glutamate under anaerobic condition but they showed negative uptake with palmitate. A significant fraction of the MAR-positive cells assimilated acetate, aspartate or glutamate was found to be Rhodocyclus-related PAO. Dual staining with DAPI and FISH showed that these PAO also accumulated polyphosphate aerobically with aspartate and glutamate as carbon source. The ability of assimilating amino acids besides acetate strongly indicates the versatile physiology of Rhodocyclus-related PAO, which could benefit them to achieve predominance in EBPR activated sludge.


What did the laparoscopic Nissen approach of the gastro-oesophageal reflux really change for the patients 8 years later?
Nissen fundoplication (NF) is recognized as the surgical treatment of the gastro-oesophageal reflux disease (GERD). NF can be achieved either by open surgery or by laparoscopic approach. From 1987 to 1997, 210 patients were treated for GERD by NF: 61 by open and 149 by laparoscopic approach. All the patients were followed more than 1 year and were scored by clinical assessment (Visick scale adaptation). In case of Visick score > 1, GI-endoscopy, X-ray series or 24-hour pH-study complete the evaluation. The operative time was comparable between both groups. The postoperative recovery was statistically faster in the laparoscopic group (p = 0.0001). The mean time of follow-up was 6 years after open NF and 4 years after laparoscopic NF. After open NF or laparoscopic NF, 72% and 67% of the patients are respectively scored Visick 1, 13% and 21%--Visick 2, 6.8% and 6%--Visick 3 and 8.2% and 6%--Visick 4 (NS). Patients with recurrence of GERD were scored Visick 4, so failure of the surgical treatment is observed in 5 patients after open NF and 9 patients after laparoscopic NF. The occurrence of incisional hernia was significantly higher in the open group (p = 0.0001). NF remains a safe procedure for surgical treatment of GERD and can be achieved by laparoscopic approach with comparable results to those by open laparotomy. In our experience, the advantages of the laparoscopic approach is a faster postoperative recovery and a lower risk of incisional hernia.


Honey bees are the dominant diurnal pollinator of native milkweed in a large urban park.
In eastern North America, the field milkweed, Asclepias syriaca L. (Asclepiadaceae), is used in planting schemes to promote biodiversity conservation for numerous insects including the endangered monarch butterfly, Danaus plexippus (Linnaeus) (Nymphalidae). Less is known about its pollinators, and especially in urban habitats where it is planted often despite being under increasing pressure from invasive plant species, such as the related milkweed, the dog-strangling vine (DSV), Vincetoxicum rossicum (Kleopow) Barbar. (Asclepiadaceae). During the A. syriaca flowering period in July 2016, we surveyed bees in open habitats along a DSV invasion gradient and inspected 433 individuals of 25 bee species in 12 genera for pollinia: these were affixed to bees that visited A. syriaca for nectar and contain pollen packets that are vectored (e.g., transferred) between flowers. Of all bees sampled, pollinia were found only on the nonindigenous honeybee, Apis mellifera (43% of all bees identified), as well as one individual bumblebee, Bombus impatiens Cresson. Pollinia were recorded from 45.2% of all honeybees collected. We found no relationship between biomass of DSV and biomass of A. syriaca per site. There was a significant positive correlation between A. syriaca biomass and the number of pollinia, and the proportion vectored. No relationship with DSV biomass was detected for the number of pollinia collected by bees but the proportion of vectored pollinia declined with increasing DSV biomass. Although we find no evidence of DSV flowers attracting potential pollinators away from A. syriaca and other flowering plants, the impacts on native plant-pollinator mutualisms relate to its ability to outcompete native plants. As wild bees do not appear to visit DSV flowers, it could be altering the landscape to one which honeybees are more tolerant than native wild bees.


Development of the Comprehensive Cervical Dystonia Rating Scale: Methodology.
We present the methodology utilized for development and clinimetric testing of the Comprehensive Cervical Dystonia (CD) Rating scale, or CCDRS. The CCDRS includes a revision of the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS-2), a newly developed psychiatric screening tool (TWSTRS-PSYCH), and the previously validated Cervical Dystonia Impact Profile (CDIP-58). For the revision of the TWSTRS, the original TWSTRS was examined by a committee of dystonia experts at a dystonia rating scales workshop organized by the Dystonia Medical Research Foundation. During this workshop, deficiencies in the standard TWSTRS were identified and recommendations for revision of the severity and pain subscales were incorporated into the TWSTRS-2. Given that no scale currently evaluates the psychiatric features of cervical dystonia (CD), we used a modified Delphi methodology and a reiterative process of item selection to develop the TWSTRS-PSYCH. We also included the CDIP-58 to capture the impact of CD on quality of life. The three scales (TWSTRS2, TWSTRS-PSYCH, and CDIP-58) were combined to construct the CCDRS. Clinimetric testing of reliability and validity of the CCDRS are described. The CCDRS was designed to be used in a modular fashion that can measure the full spectrum of CD. This scale will provide rigorous assessment for studies of natural history as well as novel symptom-based or disease-modifying therapies.


Aspiration of osteoprogenitor cells for augmenting spinal fusion: comparison of progenitor cell concentrations from the vertebral body and iliac crest.
Successful arthrodesis in challenging clinical scenarios is facilitated when the site is augmented with autograft bone. The iliac crest has long been the preferred source of autograft material, but graft harvest is associated with frequent complications and pain. Connective tissue progenitor cells aspirated from the iliac crest and concentrated with allograft matrix and demineralized bone matrix provide a promising alternative to traditional autograft harvest. The vertebral body, an even larger reservoir of myeloproliferative cells, should provide progenitor cell concentrations similar to those of the iliac crest. Twenty-one adults (eleven men and ten women with a mean age of 59 +/- 14 years) undergoing posterior lumbar arthrodesis and pedicle screw instrumentation underwent transpedicular aspiration of connective tissue progenitor cells. Aspirates were obtained from two depths within the vertebral body and were quantified relative to matched, bilateral aspirates from the iliac crest that were obtained from the same patient at the same time. Histochemical analysis was used to determine the prevalence of vertebral progenitor cells relative to the depth of aspiration, the vertebral level, age, and gender, as compared with the iliac crest standard. The cell count, progenitor cell concentration (cells/cc marrow), and progenitor cell prevalence (cells/million cells) were calculated. Aspirates of vertebral marrow demonstrated comparable or greater concentrations of progenitor cells compared with matched controls from the iliac crest. Progenitor cell concentrations were consistently higher than matched controls from the iliac crest (p = 0.05). The concentration of osteogenic progenitor cells was, on the average, 71% higher in the vertebral aspirates than in the paired iliac crest samples (p = 0.05). With the numbers available, there were no significant differences relative to vertebral body level, the side aspirated, the depth of aspiration, or gender. An age-related decline in cellularity was suggested for the iliac crest aspirates. The vertebral body is a suitable site for aspiration of bone marrow for graft augmentation during spinal arthrodesis.


Myosin VI: an innovative motor that challenged the swinging lever arm hypothesis.
The swinging crossbridge hypothesis states that energy from ATP hydrolysis is transduced to mechanical movement of the myosin head while bound to actin. The light chain-binding region of myosin is thought to act as a lever arm that amplifies movements near the catalytic site. This model has been challenged by findings that myosin VI takes larger steps along actin filaments than early interpretations of its structure seem to allow. We now know that myosin VI does indeed operate by an unusual approximately 180 degrees lever arm swing and achieves its large step size using special structural features in its tail domain.


The Effect of Cognition on the Aided Benefit in Terms of Speech Understanding and Listening Effort Obtained With Digital Hearing Aids: A Systematic Review.
Purpose Hearing aids are the primary rehabilitation devices used to compensate for presbycusis, though large intersubject variability in hearing aid benefit has been reported. This systematic review aimed to investigate how intersubject differences in cognition could influence the aided benefit for speech understanding and listening effort with bilateral digital hearing aids. Method Articles were selected through systematic searches in MEDLINE, Embase, Central, and reference lists. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. Results The initial search resulted in 1,092 unique hits, of which 16 were included. The effect of cognition on the aided benefit in terms of speech understanding and listening effort was examined in 12 and four studies, respectively. The aided speech and listening effort benefit obtained from hearing aid use in general or from a specific digital feature (i.e., microphone directionality, noise reduction, amplitude compression, and frequency compression) was associated with four cognitive functions (i.e., working memory, processing speed, selective attention, and executive functions). Conclusions Hearing aid users with poorer cognitive functioning derived more aided benefit in terms of speech understanding from hearing aid settings facilitating the matching process between the incoming auditory signal and representations stored in long-term memory. However, since the number of included studies was limited, this trend should be interpreted with caution. Supplemental Material https://doi.org/10.23641/asha.13626509.


Hepatic hemangioendothelioma associated with production of humoral thyrotropin-like factor.
We report on 7 patients referred for treatment of hepatic hemangioendothelioma with increased thyrotropin levels. The serum thyroxine level was decreased in 4 and increased in 2. Immunohistochemistry showed positive staining of tumor, but not of normal liver tissue, for thyrotropin. We propose secretion by the tumor of a thyrotropin-like factor.


Estimation of annual effective dose due to natural and man-made radionuclides in the metropolitan area of the Bay of Cadiz (SW of Spain).
In order to investigate the radiological hazard of naturally occurring radioactive material (NORM) and man-made (137)Cs radionuclide in the Bay of Cádiz, 149 samples of sediments have been analysed. Activity concentration in all the samples was determined using a HPGe detection system. Activity concentrations values of (226)Ra, (232)Th, (40)K and (137)Cs in the samples were 12.6±2.6 (2.5-40.6), 18.5±4.0 (2.8-73.4), 451±45 (105-1342) and 3.2±1.3 (0.2-16.0) Bq kg(-1), respectively. Outdoor external dose rate due to natural and man-made radionuclides was calculated to be 35.79±1.69 (4.71-119.16) nGy h(-1) and annual effective dose was estimated to be 43.89±2.27 (5.78-146.14) µSv y(-1). Results showed low levels of radioactivity due to NORM and man-made (137)Cs radionuclide in marine sediments recovered from the Bay of Cádiz (Spain), discarding any significant radiological risks related to human activities of the area. Furthermore, the obtained data set could be used as background levels for future research.


Determination of the dipole moments of RNAse SA wild type and a basic mutant.
In this study, we report the effects of acidic to basic residue point mutations (5K) on the dipole moment of RNAse SA at different pHs. Dipole moments were determined by measuring solution capacitance of the wild type (WT) and the 5K mutant with an impedance analyzer. The dipole moments were then (1) compared with theoretically calculated dipole moments, (2) analyzed to determine the effect of the point mutations, and (3) analyzed for their contribution to overall protein-protein interactions (PPI) in solution as quantitated by experimentally derived second virial coefficients. We determined that experimental and calculated dipoles were in reasonable agreement. Differences are likely due to local motions of residue side chains, which are not accounted for by the calculated dipole. We observed that the proteins' dipole moments increase as the pH is shifted further from their isoelectric points and that the wild-type dipole moments were greater than those of the 5K. This is likely due to an increase in the proportion of one charge (either negative or positive) relative to the other. A greater charge disparity corresponded to a larger dipole moment. Finally, the larger dipole moments of the WT resulted in greater attractive overall PPI for that protein as compared to the 5K.


Purification and Characterization of Phenylalanine Ammonia Lyase from Trichosporon cutaneum.
Trichosporon cutaneum phenylalanine ammonia lyase was selected as a model to investigate the dual substrate activity of this family of enzymes. Sequencing of the PAL gene identified an extensive intron region at the N-terminus. Five amino acid residues differing from a prior report were identified. Highest Phe : Tyr activities (1.6 ± 0.3 : 0.4 ± 0.1 μ mol/h g wet weight) were induced by Tyr. The enzyme has a temperature optimum of 32°C and a pH optimum of 8-8.5 and shows no metal cofactor dependence. Michaelis-Menten kinetics (Phe, K m 5.0 ± 1.1 mM) and positive allostery (Tyr, K' 2.4 ± 0.6 mM, Hill coefficient 1.9 ± 0.5) were observed. Anion exchange chromatography gave a purification fold of 50 with 20% yield. The His-Gln motif (substrate selectivity switch region) indicates the enzyme's ability to act on both substrates.


Long-Term Vemurafenib Exposure Induced Alterations of Cell Phenotypes in Melanoma: Increased Cell Migration and Its Association with EGFR Expression.
Acquired resistance during BRAF inhibitor therapy remains a major challenge for melanoma treatment. Accordingly, we evaluated the phenotypical and molecular changes of isogeneic human V600E BRAF-mutant melanoma cell line pairs pre- and post-treatment with vemurafenib. Three treatment naïve lines were subjected to in vitro long-term vemurafenib treatment while three pairs were pre- and post-treatment patient-derived lines. Molecular and phenotypical changes were assessed by Sulforhodamine-B (SRB) assay, quantitative RT-PCR (q-RT-PCR), immunoblot, and time-lapse microscopy. We found that five out of six post-treatment cells had higher migration activity than pretreatment cells. However, no unequivocal correlation between increased migration and classic epithelial-mesenchymal transition (EMT) markers could be identified. In fast migrating cells, the microphthalmia-associated transcription factor (MITF) and epidermal growth factor receptor (EGFR) mRNA levels were considerably lower and significantly higher, respectively. Interestingly, high EGFR expression was associated with elevated migration but not with proliferation. Cells with high EGFR expression showed significantly decreased sensitivity to vemurafenib treatment, and had higher Erk activation and FRA-1 expression. Importantly, melanoma cells with higher EGFR expression were more resistant to the EGFR inhibitor erlotinib treatment than cells with lower expression, with respect to both proliferation and migration inhibition. Finally, EGFR-high melanoma cells were characterized by higher PD-L1 expression, which might in turn indicate that immunotherapy may be an effective approach in these cases.


The essence of humour and its effects and functions: a qualitative study.
Humour is one of the innate abilities that an individual develops whilst growing up and which is affected by his/her experiences in life. The purpose of this study was to describe which categories can be included in the term 'humour' and to describe the effects and functions that humour has on people. The study was exploratory. The data were based on 20 interviews, nine of which were made with women and 11 with men who had no formal connection to health services or nursing. Ages ranged from 17 to 75 years and all the interviewees were from Sweden. The research question was: 'what does humour mean to you?'. The answers given were labelled as: laughter, happiness, unforeseen events/situations, real humour/art form, jokes, plays on words/puns, situation comedy and political satire. The categories were: possibilities/obstacles and weapon/protection. We conclude that the essence of humour can be categorized as possibilities/obstacles and weapon/protection. Humour has effects and functions on individuals. Empathy is a prerequisite for the use of humour in the context of health services and nursing.


The relationship between diabetes and periodontal disease.
There is good evidence to support the claim that periodontitis may be more prevalent among diabetic patients than nondiabetic people. Similarly, studies have shown that periodontal therapy influences glycemic control in people with diabetes mellitus. Given that nearly 10% of Canadians are affected by either type 1 or type 2 diabetes (including those in whom the disease is undiagnosed), all dentists will encounter patients with diabetes. Dental practitioners must be aware of the implications of this relationship and manage their patients' periodontal care accordingly.


More than Meets the Eye: Aspergillus-Related Orbital Apex Syndrome.
The patient is a 67-year-old Caucasian male with a past medical history of diabetes mellitus type 2, coronary artery disease (CAD) status post stent placement, renal cell carcinoma (RCC) status post left nephrectomy and bilateral adrenalectomy secondary to metastatic disease, and aspergillus pneumonia who was transferred from an outside hospital for evaluation of progressively worsening pulsating right temple and retrobulbar headache. Initial studies ruled out glaucoma, giant cell arteritis, and stroke, or aneurysmal pathology. The only positive finding was right sphenoid sinus disease on imaging that had caused bony destruction and infiltration of the right orbital apex. Broad-spectrum antibiotics were started for bacterial versus fungal sinusitis and the patient was admitted to the medical floor with consultations to Neurology, Otolaryngology (ENT), and Ophthalmology. ENT took the patient emergently to the OR. The final diagnosis was chronic aspergillus sinusitis and right-sided orbital apex syndrome (OAS). Antibiotics and antifungals were optimized by the infectious disease team. ENT also ordered steroid washouts post-operatively with budesonide and saline as well as sinus debridements every couple of weeks.


Carbon-14 in patagonian tree rings.
The radiocarbon activity found in tree rings from southern Argentina shows secular fluctuations which are synchronous with and of the same amplitude as those known for the Northern Hemisphere. Comparable measurements indicate that the activity in Patagonian trees is about five per mil lower than in European trees.


Control of several emissions during olive pomace thermal degradation.
Biomass plays an important role as an energy source, being an interesting alternative to fossil fuels due to its environment-friendly and sustainable characteristics. However, due to the exposure of customers to emissions during biomass heating, evolved pollutants should be taken into account and controlled. Changing raw materials or mixing them with another less pollutant biomass could be a suitable step to reduce pollution. This work studied the thermal behaviour of olive pomace, pyrenean oak and their blends under combustion using thermogravimetric analysis. It was possible to monitor the emissions released during the process by coupling mass spectrometry analysis. The experiments were carried out under non-isothermal conditions at the temperature range 25-750 °C and a heating rate of 20 °C·min⁻¹. The following species were analysed: aromatic compounds (benzene and toluene), sulphur emissions (sulphur dioxide), 1,4-dioxin, hydrochloric acid, carbon dioxide and nitrogen oxides. The results indicated that pollutants were mainly evolved in two different stages, which are related to the thermal degradation steps. Thus, depending on the pollutant and raw material composition, different emission profiles were observed. Furthermore, intensity of the emission profiles was related, in some cases, to the composition of the precursor.


Therapeutic effects of 15 Hz pulsed electromagnetic field on diabetic peripheral neuropathy in streptozotocin-treated rats.
Although numerous clinical studies have reported that pulsed electromagnetic fields (PEMF) have a neuroprotective role in patients with diabetic peripheral neuropathy (DPN), the application of PEMF for clinic is still controversial. The present study was designed to investigate whether PEMF has therapeutic potential in relieving peripheral neuropathic symptoms in streptozotocin (STZ)-induced diabetic rats. Adult male Sprague-Dawley rats were randomly divided into three weight-matched groups (eight in each group): the non-diabetic control group (Control), diabetes mellitus with 15 Hz PEMF exposure group (DM+PEMF) which were subjected to daily 8-h PEMF exposure for 7 weeks and diabetes mellitus with sham PEMF exposure group (DM). Signs and symptoms of DPN in STZ-treated rats were investigated by using behavioral assays. Meanwhile, ultrastructural examination and immunohistochemical study for vascular endothelial growth factor (VEGF) of sciatic nerve were also performed. During a 7-week experimental observation, we found that PEMF stimulation did not alter hyperglycemia and weight loss in STZ-treated rats with DPN. However, PEMF stimulation attenuated the development of the abnormalities observed in STZ-treated rats with DPN, which were demonstrated by increased hind paw withdrawal threshold to mechanical and thermal stimuli, slighter demyelination and axon enlargement and less VEGF immunostaining of sciatic nerve compared to those of the DM group. The current study demonstrates that treatment with PEMF might prevent the development of abnormalities observed in animal models for DPN. It is suggested that PEMF might have direct corrective effects on injured nerves and would be a potentially promising non-invasive therapeutic tool for the treatment of DPN.