Natural History of Subclinical Neovascularization in Nonexudative Age-Related Macular Degeneration Using Swept-Source OCT Angiography.
Swept-source (SS) OCT angiography (OCTA) was used to determine the prevalence, incidence, and natural history of subclinical macular neovascularization (MNV) in eyes with nonexudative age-related macular degeneration (AMD). Prospective, observational, consecutive case series. Patients with intermediate AMD (iAMD) or geographic atrophy (GA) secondary to nonexudative AMD in 1 eye and exudative AMD in the fellow eye. All patients were imaged using both the 3×3 mm and 6×6 mm SS OCTA fields of view (PLEX Elite 9000; Carl Zeiss Meditec, Inc, Dublin, CA). The en face slab used to detect the MNV extended from the outer retina to the choriocapillaris, and projection artifacts were removed using a proprietary algorithm. Prevalence of subclinical MNV and time to exudation with Kaplan-Meier cumulative estimates of exudation at 1 year. From August 2014 through March 2017, 160 patients underwent SS OCTA (110 eyes with iAMD and 50 eyes with GA). Swept-source OCTA identified subclinical MNV at the time of first imaging in 23 of 160 eyes, for a prevalence of 14.4%. Six eyes demonstrated subclinical MNV during the follow-up. Of 134 eyes with follow-up visits, a total of 13 eyes demonstrated exudation, and of these 13 eyes, 10 eyes were found to have pre-existing subclinical MNV. By 12 months, the Kaplan-Meier cumulative incidence of exudation for all 134 eyes was 6.8%. For eyes with subclinical MNV at the time of first SS OCTA imaging, the incidence was 21.1%, and for eyes without subclinical MNV, the incidence was 3.6%. There was no difference in the cumulative incidence of exudation from pre-existing MNV in eyes with iAMD or GA (P = 0.847, log-rank test). After the detection of subclinical MNV, the risk of exudation was 15.2 times (95% confidence interval, 4.2-55.4) greater compared with eyes without subclinical MNV. By 12 months, the risk of exudation was greater for eyes with documented subclinical MNV compared with eyes without detectable MNV. For eyes with subclinical MNV, recommendations include more frequent follow-up and home monitoring. Intravitreal therapy is not recommended until prospective studies are performed.


Identification of Stability Constraints in the Particle Engineering of an Inhaled Monoclonal Antibody Dried Powder.
Monoclonal antibody (mAb) based therapies may provide a valuable new treatment modality for acute and chronic lung diseases, including asthma, respiratory infections, and lung cancer. Currently mAbs are delivered via systemic administration routes, but direct delivery to the lungs via the inhaled route could provide higher concentrations at the site of disease and reduced off-target effects. Though lyophilized mAbs may be reconstituted and delivered to the lungs using nebulizers, dry powder inhalers provide a more patient-friendly delivery method based upon their fast administration time and portability. However, particle engineering processes required to prepare respirable dried powders for DPI delivery involve multiple potential stressors for mAbs, which have not been fully explored. In this study, a systematic examination of various aspects of the particle engineering process (atomization, freezing, drying, and storage) was performed to further understand their impact on mAb structure and aggregation. Using anti-streptavidin IgG1 as a model mAb, atomization settings were optimized using a design of experiments approach to elucidate the relationship between feed flow rate, formulation solid content, and atomization airflow rate and protein structural changes and aggregation. The optimized atomization conditions were then applied to spray drying and spray freezing drying particle engineering processes to determine the effects of freezing and drying on IgG1 stability and aerosol performance of the powders. IgG1 was found to be particularly susceptible to degradation induced by the expansive air-ice interface generated by spray freeze drying and this process also produced powders that exhibited decreased storage stability. This study further delineates the design space for manufacturing of respirable biologic therapies and is intended to serve as a roadmap for future development work.


Sex-Related Disparities in Criminal Justice and HIV Treatment Outcomes: A Retrospective Cohort Study of HIV-Infected Inmates.
We evaluated sex-related differences in HIV and criminal justice (CJ) outcomes. We quantified sex-related differences in criminal offenses, incarcerations, and HIV outcomes among all HIV-infected inmates on antiretroviral therapy (ART) in Connecticut (2005-2012). Computed criminogenic risk scores estimated future CJ involvement. Stacked logistic regression models with random effects identified significant correlates of HIV viral suppression on CJ entry, reflecting preceding community-based treatment. Compared with 866 HIV-infected men on ART (1619 incarcerations), 223 women (461 incarcerations) were more likely to be younger, White, and medically insured, with shorter incarceration periods (mean = 196.8 vs 368.1 days), mostly for public disorder offenses. One third of both women and men had viral suppression on CJ entry, correlating positively with older age and having treated comorbidities. Entry viral suppression inversely correlated with incarceration duration for women and with criminogenic risk score for men. In the largest contemporary cohort of HIV-infected inmates on ART, women's higher prevalence of nonviolent offenses and treatable comorbidities supports alternatives to incarceration strategies. Sex-specific interventions for CJ populations with HIV effectively align public health and safety goals.


Hepatosplenic schistosomiasis in Kenya: an assessment of the enzyme-linked immunosorbent assay (ELISA).
Sera from 124 adult Kenyan patients with chronic splenomegaly and from 93 geographically matched controls without splenomegaly were tested for evidence of Schistosoma mansoni infection by enzyme-linked immunosorbent assay (ELISA). Ova of S. mansoni were detected on stool or rectal snip examination in 23.4% of all patients, whereas 57.3% had a positive ELISA. All patients with parasitological or histological evidence of schistosomal infection had a positive ELISA, and a negative test reliably excluded schistosomiasis. On the basis of liver histology, 23 patients (18.5%) were considered to have hepatosplenic schistosomiasis, of whom 17 (73.9%) had a positive stool or snip. The ELISA was positive in 47.5% of cases of non-schistosomal splenomegaly, and in 52.7% of apparently normal controls. This high seropositive rate in the latter two groups emphasizes that schistosomal infection does not signify disease, and limits the diagnostic value of the test in individual cases of splenomegaly. Marked tribal and, therefore geographical, differences were noted in the prevalence of infection.


Effect of the 3'APOB-VNTR polymorphism on the lipid profiles in the Guangxi Hei Yi Zhuang and Han populations.
Apolipoprotein (Apo) B is the major component of low-density lipoprotein (LDL), very low-density lipoprotein (VLDL) and chylomicrons. Many genetic polymorphisms of the Apo B have been described, associated with variation of lipid levels. However, very few studies have evaluated the effect of the variable number of tandem repeats region 3' of the Apo B gene (3'APOB-VNTR) polymorphism on the lipid profiles in the special minority subgroups in China. Thus, the present study was undertaken to study the effect of the 3'APOB-VNTR polymorphism on the serum lipid levels in the Guangxi Hei Yi Zhuang and Han populations. A total of 548 people of Hei Yi Zhuang were surveyed by a stratified randomized cluster sampling. The epidemiological survey was performed using internationally standardized methods. Serum lipid and apolipoprotein levels were measured. The 3'APOB-VNTR alleles were determined by polymerase chain reaction (PCR) followed by electrophoresis in polyacrylamide gels, and classified according to the number of repeats of a 15-bp hypervariable elements (HVE). The sequence of the most common allele was determined using the PCR and direct sequencing. The possible association between alleles of the 3'APOB-VNTR and lipid variables was examined. The results were compared with those in 496 people of Han who also live in that district. Nineteen alleles ranging from 24 to 64 repeats were detected in both Hei Yi Zhuang and Han. HVE56 and HVE58 were not be detected in Hei Yi Zhuang whereas HVE48 and HVE62 were totally absent in Han. The frequencies of HVE26, HVE30, HVE46, heterozygote, and short alleles (< 38 repeats) were higher in Hei Yi Zhuang than in Han. But the frequencies of HVE34, HVE38, HVE40, homozygote, and long alleles (> or = 38 repeats) were lower in Hei Yi Zhuang than in Han (P < 0.05-0.01). The levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and Apo B in Hei Yi Zhuang but not in Han were higher in VNTR-LS (carrier of one long and one short alleles) than in VNTR-LL (the individual carrying two long alleles) genotypes. The levels of TC, triglycerides (TG), LDL cholesterol, and Apo B in Hei Yi Zhuang were higher in both HVE34 and HVE36 alleles than in HVE32 allele. The levels of TC, TG, HDL-C and Apo B in Hei Yi Zhuang were also higher in homozygotes than in heterozygotes. There were no significant differences in the detected lipid parameters between the VNTR-SS (carrier of two short alleles) and VNTR-LS or VNTR-LL genotypes in both ethnic groups. There were significant differences of the 3'APOB-VNTR polymorphism between the Hei Yi Zhuang and Han populations. An association between the 3'APOB-VNTR polymorphism and serum lipid levels was observed in the Hei Yi Zhuang but not in the Han populations.


Perceived medication adverse effects and coping strategies reported by chronic heart failure patients.
Data on medication adverse effects (AEs) in chronic heart failure (CHF) are primarily based on results from clinical trials. Little is known about AEs perceived by CHF patients in daily practice and how patients deal with these subjective AEs. To describe the scope and nature of perceived AEs of CHF patients, their coping strategies and the relationship of perceived AEs to medication, patient characteristics and quality of life. This cross-sectional observational study included a sample of 680 patients previously hospitalised for CHF. Perceived AEs and coping strategies were collected by interviews based on a structured questionnaire. Medication and clinical information were collected by chart review. Of the 670 CHF patients completing the questionnaire, 17% reported at least one AE. In total, 186 AEs were reported of which 15% could not be linked to any medication. Nausea (4%), dizziness (4%), itches (3%) and rash (3%) were the most prevalent. The drug associated with the highest AE rate was pravastatin (27%). On average, more than five different drugs could be related to the AEs headache, dizziness and nausea. Patients reporting AEs had a lower general health perception, younger age and were more often using antiarrhythmic drugs. Of patients experiencing AEs, 69% conferred with their doctor, 24% reported having done nothing in reaction and 2% discontinued their medication without discussing it with the doctor. Adverse effects are frequently perceived by CHF patients, but they are difficult to recognise and manage in daily practice.


Clinical Outcome and Prognostic Factors of Malignant Spinal Dumbbell Tumors.
To investigate the clinical outcome and prognostic factors of malignant spinal dumbbell tumors (m-SDTs). We retrospectively reviewed the clinical outcome of 22 consecutive cases of m-SDTs and analyzed the prognostic factors associated with worse outcome. Nineteen of the 22 cases were managed with surgery (86%), and gross total resection (GTR) was achieved in four cases (21%). The duration of overall survival (OS) ranged from 3 to 140 months, with a median survival time of 15.3 months. The 5 year OS rate was 55.6%. In multivariate analysis, histological subtype (high-grade malignant peripheral nerve sheath tumor) (hazard ratio [HR] 14.9, p = 0.0191), GTR (HR 0.07, p = 0.0343), and presence of local recurrences (HR 11.2, p = 0.0479) were significant and independent predictors of OS. On the basis of clinical data, we propose that GTR and prevention of local recurrence may improve the clinical outcome of m-SDTs.


Polynucleotides. XXIV. Synthesis and properties of a dinucleoside monophosphate derived from uridine 6,2-cyclonucleoside.
A dinucleoside monophosphate, 6,2'-anhydro-6-oxy-1-beta-D-arabinofuranosyluracil-phosphoryl- (3'-5')-6,2'-anhydro-6-oxy-1-beta-D-arabinofuranosyluracil (I) was synthesized by the condensation reaction using DCC from 5'-monomethoxytrityl derivative(VII) and 3'-acetyl-5'-phosphate(X) of the monomer units. Yield was ca. 70%. UV of compound I showed no hypochromicity and its CD spectrum showed only a trough at 252 nm. No temperature dependency of epsilon and [Q] values was observed. These results suggested an unstacked random conformation for I. Complex formation of I with cycloadenosine oligomer could not be detected under the experimental condition.


The effect of Mn on the electrical and mechanical activities in the guinea-pig stomach.
The effects of Mn on electrical and mechanical activities in the circular muscle of the guinea-pig stomach were investigated. A low concentration of Mn (0.1 mM) in Krebs solution caused a prolongation of the first component, resulting in an increase in frequency of the second component. However, a high concentration of Mn (more than 1 mM) had a similar effect on the electrical activities in the early period, but subsequently inhibited them. The membrane was depolarized by Mn from 69 (S.D., +/- 6) to 63 (S.D., +/- 6) mV at 0.1 mM and to 42 (S.D., +/- 5) mV at 2 mM in the Krebs solution. The membrane resistance slightly decreased with 0.1 mM Mn, but slightly increased with 2 mM Mn. A low concentration of Mn (0.1 mM) also increased resting tone and phasic contraction. These contractile responses were completely inhibited when Ca was removed from the bathing solution. The enhanced, later phasic contraction was reduced by verapamil. All these electrical and mechanical responses for Mn were not related to the nervous system. Excess Ca (15 mM) inhibited the actions of Mn on the spontaneous slow waves, the resting potential, and the duration of the second component. Thus, it is concluded that Mn displaces or releases Ca from its stored sites, which are loosely-bound pools, and then induces membrane depolarization, resulting in subsequent stimulation of the Ca-channel, which is blocked by a high concentration of Mn.


Disability and participation in breast and bowel cancer screening in England: a large prospective study.
There is limited information about participation in organised population-wide screening programmes by people with disabilities. Data from the National Health Service routine screening programmes in England were linked to information on disability reported by the Million Women Study cohort participants. Of the 473 185 women offered routine breast or bowel cancer screening, 23% reported some disability. Women with disabilities were less likely than other women to participate in breast cancer screening (RR=0.64, 95% CI: 0.62-0.65) and in bowel cancer screening (RR=0.75, 0.73-0.76). Difficulties with self-care or vision were associated with the greatest reduction in screening participation. Participation in routine cancer screening programmes in England is reduced in people with disabilities and participation varies by type of disability.


Infant feeding in Sweden: socio-demographic determinants and associations with adiposity in childhood and adolescence.
Recent reviews and meta-analyses conclude that breastfeeding constitutes a small but consistent protective effect against obesity or higher values of body mass index (BMI) in children, though in some studies this effect was weakened after adjustment for potential confounders. The aim of this study was to explore the socio-demographic determinants of the duration of breastfeeding in Sweden and the associations between breastfeeding duration and adiposity in childhood and adolescence. This was a cross-sectional study of Swedish children. Height, weight and waist circumference were measured and the sum of five skin fold measurements were obtained in 1137 9- and 15-year old children. Breastfeeding data were retrospectively obtained from the medical records for 812 (71.4%) children. Multiple ordinal logistic regression was applied to study individual effects of the maternal characteristics on the duration of breastfeeding. The relationship between children's anthropometric characteristics and duration of breastfeeding was studied by multiple linear regression. Associations between the odds of being overweight or obese and the duration of breastfeeding were studied by multiple logistic regression. Both linear and logistic models were adjusted for children's age, gender, birth weight, maternal education and parental BMI in 1998 as well as maternal age and smoking status at childbirth. Maternal education was positively associated with the duration of breastfeeding in both 1983 and 1989. Non-smoking mothers were more likely to breastfeed longer than smokers in 1989 (OR = 1.9, 95%CI: 1.3, 3.0). Fifteen-year old children breastfed for shorter than 2 months had 1.2 kg/m(2) (95%CI: 0.1, 2.4) higher BMI, 3.2 cm (95%CI: 0.2, 6.2) higher waist circumference and 10.6 mm (95%CI: 1.7, 19.6) higher sum of five skin fold measurements compared to those breastfed for 6 months or longer when adjusted for children's characteristics and maternal characteristics in 1998. Adjustment for maternal age and smoking status at childbirth weakened these associations to non-significant levels (0.9 kg/m(2), 95%CI: -0.4, 2.1; 1.4 cm, 95%CI: -1.5, 4.4 and 5.1 mm, 95%CI: -4.0, 14.2, respectively). In the 9-year olds, the associations were less pronounced, but in the same direction. No trends between duration of breastfeeding and children's anthropometric characteristics were observed in any of the age groups. Maternal education and smoking were significant predictors of breastfeeding duration in Sweden in the 1980s. Associations with measures of adiposity were observed only in 15-year old children between the children with shortest and longest breastfeeding duration, which were weakened after adjustment for maternal characteristics at childbirth.


Interactions among Glyphosate and Phosphate in Soils: Laboratory Retention and Transport Studies.
The purpose of this study was to determine the effect of PO on the sorption and transport of glyphosate [-(phosphonomethyl) glycine, GPS] in soils. The results of batch experiments indicated significant competition between PO and GPS in two different soils, with PO being preferentially sorbed. The 24-h Freundlich partitioning coefficients for GPS sorption were decreased by 50 to 60% with PO in solution. High sorptive capacities exhibited by soils in the presence of PO suggest the existence of both competitive and ion specific sites in either soil. Miscible displacement transport studies indicated limited effects of competition when GPS was applied in conjunction with or subsequent to pulses of PO. However, when a PO pulse was applied after the application of a GPS pulse, a secondary GPS breakthrough was observed where an additional 4% of the applied herbicide mass was recovered in the effluent solution. This is likely attributed to the PO-mediated displacement of GPS bound to competitive sites. These results are further emphasized by the distribution of residual herbicide in this column, with enrichment of mass at lower depths in the column and a corresponding decrease in GPS mass closer to the column surface. These results indicate that the timing of inorganic P fertilizers relative to GPS applications has a significant impact on the fate of the herbicide in soils. In particular, these findings suggest that GPS may be more liable to leaching in scenarios in which P fertilizers are applied after the application of GPS-based herbicidal formulations.


Proposal of a diagnostic algorithm for radiation-induced dropped head syndrome in long-term childhood cancer survivors based on a prospective study in a specialized clinical setting and a review of the literature.
To prospectively assess the incidence of Dropped Head Syndrome (DHS) in childhood cancer survivors (CCS) and to develop and evaluate a diagnostic algorithm for DHS. A systematic literature search for DHS in combination with neck radiotherapy (RT) exposure was performed. Analyses and a combination of the most common examination methods were integrated into a diagnostic algorithm. Almost all CCSs visiting the local late effects clinic between May 2020 and April 2022 were included in the study. CCS exposed to neck RT with doses ≥ 19 Gy received standardized clinical and neurological assessment and, in case of abnormal results, an MRI scan to confirm muscle atrophy. Two hundred and five CCS were included of whom 41 received RT to the neck with ≥ 19 Gy. In the entire cohort and in the subgroup receiving RT, 2.4% and 12% of CCS were affected by DHS, respectively. Results of clinical and neurological assessment correlated well with MRI results. Neck circumference and neck/thigh ratio were lower after neck RT. Over 50% of CCS experienced neck disability and pain. A relevant proportion of CCS exposed to neck RT is affected by DHS. High concordance of MRI results with the neurological examination supports the clinical value of the diagnostic algorithm. Measurement of neck circumference might be an easy tool for assessment of neck muscle atrophy in survivors at risk. Integration of a diagnostic algorithm for DHS in standard long-term follow-up care facilitates diagnosis as well as initiation of early treatment and obviates the need for invasive examinations.


Triplet CFTR modulators: future prospects for treatment of cystic fibrosis.
Cystic fibrosis (CF) is an autosomal recessive genetic disease characterized by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR). CFTR is a chloride channel responsible for ion flow across epithelial surfaces of lung, sinuses, pancreas, intestine, and liver. Researchers have grouped CFTR genetic mutations into various protein defects: reduced protein synthesis (class 1 mutations), abnormal protein folding and maturation (class 2 mutation), and abnormal gating (class 3 mutation). These mutations usually present as severe forms of CF due to complete absence of CFTR at cell surfaces. Milder forms (eg, protein maturation and conductance defects, classes 4-6) present as less severe forms of CF related to the presence of CFTR at the cell surface. Differences in severity are directly due to CFTR function which is based on the severity of CFTR mutation. This knowledge has proven useful for designing therapy for individual mutations and mutation classes. The discovery and US Food and Drug Administration approval of Kalydeco® (ivacaftor) in early 2011 marked the beginning of a new era of therapies that are focused on improving defective CFTR protein function. However, due to its specificity for the G551D mutation, ivacaftor only benefitŝ5% of CF patients. Approximately 50% of CF patients have two copies of the F508Del mutation, while other CF patients carry only one copy of this gene. More recently, Orkambi®, a two compound medication composed of lumacaftor and ivacaftor, has provided the foundation necessary to further build on molecular concepts of: correction of trafficking, potentiation, and amplification of defective CFTR. These new concepts will form the basis of future CF therapies and extend CFTR treatment to almost 50% of CF patients. Evolving knowledge of the molecular mechanisms responsible for defective CFTR has prompted new research focused on "repair" of each phase of CFTR expression and function, thus creating a new class of combination "CFTR correctors" referred to as "triplet CFTR compounds." This article will review how patients can be selected and treated with these newer agents that are based on specific mutations. In the future, many CF practitioners have expectations that initiation of treatment for CF patients will occur simply by use of biomarkers of CFTR expression (eg, sweat chloride, nasal potential difference, rectal organoids) rather than testing for specific mutations. As continued research identifies biomarkers with greater specificity and which predict clinical response, therapies can potentially be tailored to individual responses.


Biochemical characterization of Porphyromonas (Bacteroides) gingivalis collagenase.
A protease was purified from Porphyromonas gingivalis 1101, a clinical isolate, by sequential sodium dodecyl sulfate-polyacrylamide gel electrophoresis, substrate diffusion gel electrophoresis, and electroelution. The enzyme cleaved radiolabeled human basement membrane type IV collagen and the synthetic collagen peptide substrate for eukaryotic collagenases. It was inactivated by the thiol protease inhibitor N-ethylmaleimide but not by EDTA or EGTA [ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid] and activated by reducing agents such as beta-mercaptoethanol. The enzyme exists as an active precursor protein of molecular mass 94 kDa and undergoes proteolytic cleavage to 75-, 56-, and 19-kDa forms. Biotin-labeled collagen bound specifically to the 94-kDa form of the protein and to its cleavage products in ligand blots, suggesting a role for this enzyme not only in collagen degradation but also in adhesion to collagenous substrata.


Pre-eclampsia and nasal CPAP: part 1. Early intervention with nasal CPAP in pregnant women with risk-factors for pre-eclampsia: preliminary findings.
Pre-eclampsia is a leading cause of maternal-fetal morbidity and mortality. Significant overlap exists between the risk factors for pre-eclampsia and sleep-disordered breathing. Nasal continuous positive airway pressure (CPAP) has been proposed as therapy for pre-eclampsia. This prospective, longitudinal study was designed to characterize sleep-related breathing patterns in pregnant women with pre-eclampsia risk factors, and to describe the effects of early nasal CPAP therapy in these patients. Twelve pregnant women with pre-eclampsia risk factors underwent polysomnography to characterize sleep-related breathing abnormalities and baseline blood pressure determination. Patients with airflow-limitation underwent nasal CPAP titration and were treated with optimal pressures. Periodic assessments of CPAP compliance and tolerance, sleep quality, and blood pressure control were performed until delivery or pre-eclampsia onset. CPAP retitration was performed between weeks 20 and 22 of pregnancy. Mean respiratory disturbance index was 8.5+/-2.6 events/h of sleep, and initial nasal CPAP pressures were 5-6 cm H(2)O with an increase to 6-9 cm H2O after recalibration. All subjects with chronic hypertension maintained blood pressures below 140/90 with a mean diurnal blood pressure of 122+/-2.5 mmHg over 83+/-1.5 mmHg. Patient characteristics of obesity and prior pre-eclampsia were associated with pregnancies complicated by spontaneous abortion, premature delivery, or pre-eclampsia. Early application of nasal CPAP in pregnant women alleviated sleep-related breathing disturbances but was not sufficient to prevent negative pregnancy outcomes. Obesity and prior pre-eclampsia appeared to be important factors and were associated with the worst complications. However, nasal positive pressure may still be beneficial to decrease severity of outcomes, particularly if individualized to patient risk factors, more particularly hypertension at pregnancy onset.


The DNA sequence and analysis of human chromosome 6.
Chromosome 6 is a metacentric chromosome that constitutes about 6% of the human genome. The finished sequence comprises 166,880,988 base pairs, representing the largest chromosome sequenced so far. The entire sequence has been subjected to high-quality manual annotation, resulting in the evidence-supported identification of 1,557 genes and 633 pseudogenes. Here we report that at least 96% of the protein-coding genes have been identified, as assessed by multi-species comparative sequence analysis, and provide evidence for the presence of further, otherwise unsupported exons/genes. Among these are genes directly implicated in cancer, schizophrenia, autoimmunity and many other diseases. Chromosome 6 harbours the largest transfer RNA gene cluster in the genome; we show that this cluster co-localizes with a region of high transcriptional activity. Within the essential immune loci of the major histocompatibility complex, we find HLA-B to be the most polymorphic gene on chromosome 6 and in the human genome.


Numerical Solution of Inverse Problem in Functional Near Infrared Spectroscopy using L1-Norm Method.
It has been more than three decades since researchers began investigating functional near-infrared spectroscopy (fNIRs) and its applications with near-infrared light for use in both clinical and pre-clinical settings. In order to increase the accuracy of fNIRs of complex tissue structures, it is necessary to create more advanced image reconstruction methods. Real fNIRs data have been used to develop an implementation of the L1-Norm approach for tackling the inverse problem in this work. The Monte Carlo (MC) simulation is used to construct the sensitivity matrix for this research. Finally, a numerical algorithm for the L1-Norm approach of image reconstruction is developed and implemented in MATLAB to aid in the process. The results showed good agreement with the actual fNIRs data.


Cardiac defects, morbidity and mortality in patients affected by RASopathies. CARNET study results.
RASopathies are developmental disease caused by mutations in genes encoding for signal transducers of the RAS-MAPK cascade. The aim of the present study was to provide a comprehensive description of morbidity and mortality in patients with molecularly confirmed RASopathy. A multicentric, observational, retrospective study was conducted in seven European cardiac centres participating to the CArdiac Rasopathy NETwork (CARNET). Clinical records of 371 patients with confirmed molecular diagnosis of RASopathy were reviewed. Mortality was described as crude mortality, cumulative survival and restricted estimated mean survival. Multivariable regression analysis was used to assess the impact of mutated genes on number of interventions and overall prognosis. Cardiac defects occurred in 80.3% of cases, almost half of them underwent at least one intervention. Overall, crude mortality was 0.29/100 patients-year. Cumulative survival was 98.8%, 98.2%, 97.7%, 94.3%, at 1, 5, 10, and 20years, respectively. Restricted estimated mean survival at 20years follow-up was 19.6years. Ten patients died (2.7% of the entire cohort; 3.4% of patients with cardiac defect). Patients with hypertrophic cardiomyopathy (HCM) and age <2years or young adults, as well as subjects with biventricular obstruction and PTPN11 mutations had a higher risk of cardiac death. The risk of intervention was higher in individuals with Noonan syndrome and pulmonary stenosis carrying PTPN11 mutations. Overall, mortality was relatively low, even though the specific association between HCM, biventricular outflow tract obstructions and PTPN11 mutations appeared to be associated with early mortality, including immediate post-operative events and sudden death.


Investigation of the Relationship Between H2O2 and HClO in Living Cells by a Bifunctional, Dual-ratiometric Responsive Fluorescent Probe.
As two important reactive oxygen species, hydrogen peroxide (H2O2) and hypochlorous acid (HClO) play vital roles in many physiological and pathological processes. However, the relationship between these two species is seldom investigated, in part, because of the lack of robust molecular tools that can simultaneously visualize HClO and H2O2 in biosystems. In this work, we present a design strategy to construct a single fluorescent probe that can detect H2O2 and HClO by simultaneously monitoring two distinct detection channels. In the design, one phenothiazine-based coumarin serves as a chromophore and sensor for HClO, while a second coumarin precursor containing a boronate ester acts as a sensor for H2O2. After a head-to-head screening of three candidates differing in their coumarin precursor moieties, probe CSU1 was found to have the optimal characteristics. As shown experimentally, it is able to detect them selectively and sensitively to generate distinct fluorescence signals and patterns in living cells. Furthermore, the endogenous generation of HClO from H2O2 and Cl- catalyzed by myeloperoxidase enzyme in living cells can be clearly monitored by the probe. These studies demonstrate the potential of the probe as a powerful tool to investigate the interplay of HClO and H2O2 in oxidative stress.


Laboratory support during and after the Ebola virus endgame: towards a sustained laboratory infrastructure.
The Ebola virus epidemic in West Africa is on the brink of entering a second phase in which the (inter)national efforts to slow down virus transmission will be engaged to end the epidemic. The response community must consider the longevity of their current laboratory support, as it is essential that diagnostic capacity in the affected countries be supported beyond the end of the epidemic. The emergency laboratory response should be used to support building structural diagnostic and outbreak surveillance capacity.


On domain differences in categorization and context variety.
Membership in many natural categories is considered all-or-none, while membership in most artifact categories is found to be graded. We introduce an alternative for the prevailing view that this domain difference in categorization results from representational differences. The context variety account posits that an item's gradedness reflects the variety of contexts it appears in. Items that feature in a variety of contexts are assumed to be more likely to elicit a graded categorization response, since the suggested target category only provides one of many solutions to the question of the item's identity. We review earlier work that suggested a domain difference in context variety, with artifactual items appearing in a greater variety of contexts than natural ones. The context variety domain difference is established in two separate experiments but is shown not to explain the domain difference in categorization. A selection of artifactual and natural items, for which the domain difference in context variety is reversed, is presented for categorization in a third experiment. This selection, too, fails to provide evidence for the context variety account of categorization differences. The domain difference in categorization is shown to be robust against this manipulation. Context variety appears to have no bearing on categorization, so the context variety account is not a sustainable alternative to accounts that posit representational differences between natural and artifact categories.


Influence of fatigue on construction workers' physical and cognitive function.
Despite scientific evidence linking workers' fatigue to occupational safety (due to impaired physical or cognitive function), little is known about this relationship in construction workers. To assess the association between construction workers' reported fatigue and their perceived difficulties with physical and cognitive functions. Using data from a convenience sample of US construction workers participating in the 2010-11 National Health Interview Survey two multivariate weighted logistic regression models were built to predict difficulty with physical and with cognitive functions associated with workers' reported fatigue, while controlling for age, smoking status, alcohol consumption status, sleep hygiene, psychological distress and arthritis status. Of 606 construction workers surveyed, 49% reported being 'tired some days' in the past 3 months and 10% reported 'tired most days or every day'. Compared with those feeling 'never tired', workers who felt 'tired some days' were significantly more likely to report difficulty with physical function (adjusted odds ratio [AOR] = 2.03; 95% confidence interval [CI] 1.17-3.51) and cognitive function (AOR = 2.27; 95% CI 1.06-4.88) after controlling for potential confounders. Our results suggest an association between reported fatigue and experiencing difficulties with physical and cognitive functions in construction workers.


[Major surgical complications after 73 consecutive liver transplantations].
In order to evaluate the incidence of postoperative surgical complications requiring additional surgery, we report 73 consecutive liver orthotopic transplantations performed in 60 patients from June 1983 through June 1989. Transplantations were performed in 54 adults and 6 children for the following reasons: postnecrotic cirrhosis in 31, biliary diseases in 16, hepatobiliary malignancy in 7; Wilson's diseases in 3 and fulminant hepatitis in 3. Surgical complications requiring additional surgery occurred in 35 (58%) patients with 53 operations. Twenty-two patients (36%) had postoperative bleeding complications, 5 (8%) biliary complications, one had a late artery thrombosis and 16 (26%) had miscellaneous complications. The latter group included 6 abdominal hernias, 3 bowel perforations, 2 bowel obstructions, 2 cases of pneumothorax, 2 cases of chylous ascitis, one liver necrosis, one hepatic artery kinking, one peritonitis and one cardiac tamponade. The incidence of surgical complications was not significantly different in patients who underwent retransplantation as compared to those who had a single transplantation. We did not find a significant difference in surgical complication rate according to the preoperative liver disease. In comparison with the literature, in our series, we had a higher rate of abdominal hernia but a lower rate of biliary complications.


Effectiveness of Fosfomycin for the Treatment of Multidrug-Resistant Escherichia coli Bacteremic Urinary Tract Infections: A Randomized Clinical Trial.
The consumption of broad-spectrum drugs has increased as a consequence of the spread of multidrug-resistant (MDR) Escherichia coli. Finding alternatives for these infections is critical, for which some neglected drugs may be an option. To determine whether fosfomycin is noninferior to ceftriaxone or meropenem in the targeted treatment of bacteremic urinary tract infections (bUTIs) due to MDR E coli. This multicenter, randomized, pragmatic, open clinical trial was conducted at 22 Spanish hospitals from June 2014 to December 2018. Eligible participants were adult patients with bacteremic urinary tract infections due to MDR E coli; 161 of 1578 screened patients were randomized and followed up for 60 days. Data were analyzed in May 2021. Patients were randomized 1 to 1 to receive intravenous fosfomycin disodium at 4 g every 6 hours (70 participants) or a comparator (ceftriaxone or meropenem if resistant; 73 participants) with the option to switch to oral fosfomycin trometamol for the fosfomycin group or an active oral drug or parenteral ertapenem for the comparator group after 4 days. The primary outcome was clinical and microbiological cure (CMC) 5 to 7 days after finalization of treatment; a noninferiority margin of 7% was considered. Among 143 patients in the modified intention-to-treat population (median [IQR] age, 72 [62-81] years; 73 [51.0%] women), 48 of 70 patients (68.6%) treated with fosfomycin and 57 of 73 patients (78.1%) treated with comparators reached CMC (risk difference, -9.4 percentage points; 1-sided 95% CI, -21.5 to ∞ percentage points; P = .10). While clinical or microbiological failure occurred among 10 patients (14.3%) treated with fosfomycin and 14 patients (19.7%) treated with comparators (risk difference, -5.4 percentage points; 1-sided 95% CI, -∞ to 4.9; percentage points; P = .19), an increased rate of adverse event-related discontinuations occurred with fosfomycin vs comparators (6 discontinuations [8.5%] vs 0 discontinuations; P = .006). In an exploratory analysis among a subset of 38 patients who underwent rectal colonization studies, patients treated with fosfomycin acquired a new ceftriaxone-resistant or meropenem-resistant gram-negative bacteria at a decreased rate compared with patients treated with comparators (0 of 21 patients vs 4 of 17 patients [23.5%]; 1-sided P = .01). This study found that fosfomycin did not demonstrate noninferiority to comparators as targeted treatment of bUTI from MDR E coli; this was due to an increased rate of adverse event-related discontinuations. This finding suggests that fosfomycin may be considered for selected patients with these infections. ClinicalTrials.gov Identifier: NCT02142751.


Knowledge and actions for the control of the vector Aedes aegypti in a municipality in the Legal Amazon.
Infections caused by arboviruses that have mostly impacted the Brazilian morbidity and mortality are caused by the same vector, Aedes aegypti. Preventive actions related to the vector are the most effective strategies in the prevention and control of these diseases. This study aimed to associate the knowledge on the vector that transmits dengue, Zika and chikungunya with the sociodemographic and behavioral preventive practices towards Aedes aegypti in the municipality of Tangara da Serra, Mato Grosso State, in the Brazilian Legal Amazon. A probabilistic urban population sampling was obtained by clusters: census sectors and households. The sample size calculation considered 10% of loss and a 1.5 design effect. This is a cross-sectional research carried out through a household survey in February and March 2018. There were 583 participants. The study variables were knowledge on the vector, sociodemographic characteristics and preventive practices related to the vector. The statistical analysis was based on a bivariate analysis and Poisson multiple regressions. Inadequate or insufficient knowledge on the vector Aedes aegypti remained associated with education in the categories illiterate (p<0.001) and 8 years of study or less (p<0.001), in addition to not adopting practices of capping and cleaning the water tank (p=0.002) and not using insecticides at home (p=0.007). It is concluded that there is a need for health communication actions that consider characteristics the population, especially the level of education and previous knowledge on the vector, allowing a dialogical approach and enabling the community participation in preventive practices and control of the vector Aedes aegypti .


Rationale and design of the validation of bladder health instrument for evaluation in women (VIEW) protocol.
Bladder health is an understudied state and difficult to measure due to lack of valid and reliable instruments. While condition specific questionnaires assess presence, severity and degree of bother from lower urinary tract symptoms, the absence of symptoms is insufficient to assume bladder health. This study describes the methodology used to validate a novel bladder health instrument to measure the spectrum of bladder health from very healthy to very unhealthy in population based and clinical research. Three samples of women are being recruited: a sample from a nationally representative general population and two locally recruited clinical center samples-women with a targeted range of symptom severity and type, and a postpartum group. The general population sample includes 694 women, 18 years or older, randomly selected from a US Postal delivery sequence file. Participants are randomly assigned to electronic or paper versions of the bladder health instrument along with a battery of criterion questionnaires and a demographic survey; followed by a retest or a two-day voiding symptom diary. A total of 354 women around 7 clinical centers are being recruited across a spectrum of self-reported symptoms and randomized to mode of completion. They complete the two-day voiding symptom diary as well as a one-day frequency volume diary prior to an in-person evaluation with a standardized cough stress test, non-invasive urine flowmetry, chemical urine analysis and post void residual measurement. Independent judge ratings of bladder health are obtained by interview with a qualified health care provider. A total of 154 postpartum women recruited around 6 of the centers are completing similar assessments within 6-12 weeks postpartum. Dimensional validity will be evaluated using factor analysis and principal components analysis with varimax rotation, and internal consistency with Cronbach's alpha. Criterion validity will be assessed using multitrait-multimethod matrix including correlations across multiple data sources and multiple types of measures. We aim to validate a bladder health instrument to measure the degree of bladder health within the general population and among women (including postpartum) recruited from local clinical centers. Trial registration NCT04016298 Posted July 11, 2019 ( https://www.clinicaltrials.gov/ct2/show/NCT04016298?cond=bladder+health&draw=2&rank=1 ).


Effect of atorvastatin on vascular endothelial function in moderately nicotine-dependent smokers.
We investigated the effect of atorvastatin on vascular endothelial function in moderately nicotine-dependent smokers. One hundred and sixty moderately nicotine-dependent smokers were randomly divided into the atorvastatin group (N = 80) and the control group (N = 80). Total cholesterol (TC), triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol (LDL-C), fasting plasma glucose levels, aspartate aminotransferase, total bilirubin, creatine phosphokinase, and brachial artery flow-mediated vasodilation function (FMD) were measured before and 12 months after atorvastatin treatment. After a 12-month atorvastatin therapy, the TC and LDL-C levels of patients were decreased significantly (P < 0.05) and the FMD of patients were improved significantly (P < 0.05). Compared with the control group, TC and LDL-C of the patients were significantly decreased (P < 0.05) and the FMD of the patients were significantly improved (P < 0.05). Atorvastatin may significantly improve endothelial function in moderately nicotine-dependent smokers.


Genetic factors determine the contribution of leukotrienes to acute inflammatory responses.
Leukotrienes (LT) are potent lipid mediators synthesized by the 5-lipoxygenase pathway of arachidonic acid (AA) metabolism. LT have been implicated in a broad spectrum of inflammatory processes. To investigate the influence of genetic factors on the contribution of LT to acute inflammation, we generated congenic 5-lipoxygenase-deficient 129, C57BL/6 (B6), and DBA/1Lac (DBA) mouse lines. Topical application of AA evoked a vigorous inflammatory response in 129 and DBA mice, whereas only a modest response was seen in B6 animals. The response to AA in 129 and DBA strains is LT dependent. In contrast, LT make little contribution to this response in B6 mice. AA-induced inflammation in B6 mice is prostanoid dependent, since this response was substantially reduced by treating B6 mice with a cyclooxygenase inhibitor. These data suggest that prostanoids are essential for AA-induced cutaneous inflammation in B6 mice, whereas LT are the major mediators of this response in 129 and DBA strains. In contrast, the response to AA in the peritoneal cavity is robust in the 129 and B6 strains, but was significantly blunted in DBA mice, showing that strain differences in the response to AA are tissue specific. Variations in these and other experimental models of inflammation appear to correlate directly with the ability of a particular mouse strain and a specific tissue to respond to LT, specifically LTC4. Taken together, these findings indicate that the relative contribution of prostanoids and LT to inflammatory responses is variable not only between strains but also between different tissues within these inbred mouse lines.


[Effect of antibodies to S-100 group proteins on the electrical activity and chemical sensitivity of the cerebral cortical neurons].
The influence of antibodies to proteins S-100 group on electrical activity and chemical sensitivity of rabbit cortical neurons has been investigated by means of extracellular recording and microiontophoresis. It has been found that anti-S-100 increase as a rule spontaneous discharge rate of the neurons, decrease, blockade or invert the neuronal responses to acetylcholine, noradrenaline and glutamate action. It is supposed that proteins S-100 group take part in regulation of eleitrogenic and postsynaptic (primarily glutamate- and GABA-ergic) processes of neural and glial cells in the brain.


Brain reactivity to visual food stimuli after moderate-intensity exercise in children.
Exercise may play a role in moderating eating behaviors. The purpose of this study was to examine the effect of an acute bout of exercise on neural responses to visual food stimuli in children ages 8-11 years. We hypothesized that acute exercise would result in reduced activity in reward areas of the brain. Using a randomized cross-over design, 26 healthy weight children completed two separate laboratory conditions (exercise; sedentary). During the exercise condition, each participant completed a 30-min bout of exercise at moderate-intensity (~ 67% HR maximum) on a motor-driven treadmill. During the sedentary session, participants sat continuously for 30 min. Neural responses to high- and low-calorie pictures of food were determined immediately following each condition using functional magnetic resonance imaging. There was a significant exercise condition*stimulus-type (high- vs. low-calorie pictures) interaction in the left hippocampus and right medial temporal lobe (p < 0.05). Main effects of exercise condition were observed in the left posterior central gyrus (reduced activation after exercise) (p < 0.05) and the right anterior insula (greater activation after exercise) (p < 0.05). The left hippocampus, right medial temporal lobe, left posterior central gyrus, and right anterior insula appear to be activated by visual food stimuli differently following an acute bout of exercise compared to a non-exercise sedentary session in 8-11 year-old children. Specifically, an acute bout of exercise results in greater activation to high-calorie and reduced activation to low-calorie pictures of food in both the left hippocampus and right medial temporal lobe. This study shows that response to external food cues can be altered by exercise and understanding this mechanism will inform the development of future interventions aimed at altering energy intake in children.


Reducing falls in the inpatient hospital setting.
This quality improvement project's objective was to introduce and assess a process change to potentially reduce fall rates on an inpatient medical-surgical unit. The Iowa Model of Evidence-Based Practice was used to guide the implementation of this project. This project was piloted over a 3-month period from October to December 2016 on a 38-bed medical-surgical unit at a community-based hospital in the southeastern United States. Prior to the implementation of this quality improvement project, staff received falls education using a modified pre-existing falls prevention protocol, with a focus on increasing the consistency of bed/chair alarm use for patients identified as being at risk for falling. Preintervention and postintervention fall rates were statistically compared to assess for change in practice. The average monthly preintervention fall rate was 8.67 falls/1000 patient days, as compared with 5.07 falls postintervention, which resulted in an overall decrease of 44.5% in the average number of falls per month. This project illustrated that education and a consistent risk stratification for bed/chair alarm use may be an important component of an effective evidence-based falls prevention program.


Undried cellulose gel film-- a high permeability dialysis membrane.
Undried cellulose gel film manufactured by British Cellophane Ltd (BCL) has been evaluated in vivo and in vitro. Results obtained indicate that undried cellulose gel film is superior in terms of ultrafiltration and middle molecular clearance to the widely used Cuprophan membrane and comparable with the Rhône Poulenc AN69 Acrylopolynitrile membrane for middle molecular clearance. The gel film is suitable for use with conventional dialysis equipment and in terms of residual blood volume, leak rate and pyrogenicity is indistinguishable from cuprophan.


[Electromyographic signal processing and analysis methods].
Clinical electromyography is a methodology for recording and analysing the bioelectrical activity of the skeletal muscle tissue in order to diagnose neuromuscular pathology. The possibilities of application and the diagnostic performance of electromyography have evolved parallel to a growing understanding of the properties of electricity and the development of electrical and electronic technology. The first commercially available electromyography equipment for medical use was introduced in the middle of the 20th century. It was based on analog electronic circuits. The subsequent development of digital technology made available more powerful and accurate systems, controlled by microprocessors, for recording, displaying, storing, analysing, and classifying the myoelectric signals. In the near future, it is likely that advances in the new information and communication technologies could result in the application of artificial intelligence systems to the automatic classification of signals as well as expert systems for electromyographic diagnosis support.


New directions in natural killer cell-based immunotherapy of human cancer.
Efforts at harnessing the antitumour activity of natural killer (NK) cells have been investigated for the immunotherapy of human cancer for over two decades. Initial trials, focusing on the use of ex vivo-generated lymphokine activated killer (LAK) cells or activated NK cells, or in vivo cytokine therapy to expand and activate NK cells against autologous tumours, have yielded only modest success. Recent understanding of the means by which NK cells kill target cells through a complex set of activating and inhibitory receptors recognising corresponding ligands on tumour cells has paved the way for the design of improved strategies for NK cell-based immunotherapy. The net balance of activating and inhibitory signals through NK cell receptors determines whether an NK cell becomes activated or not. Successful therapeutic strategies should now focus on manipulating the balance in favour of activating receptor signalling. In the case of autologous cancers, such strategies may include the use of monoclonal antibodies with cytokines to better direct NK cells to their tumour targets through the process of antibody-dependent cellular cytotoxicity (ADCC) or the in vivo blocking of inhibitory interactions between NK receptors (NKRs) and ligands on tumour cells. Alternatively, allogeneic NK cells can be used whenever there is mismatching of inhibitory NK cell receptors and ligands. Finally, methods to modulate expression of NK cell receptors and their ligands on tumour cells by cytokines and other agents should be explored. In this review, the impact of NKR biology on the development of novel strategies for the use of NK cells in the treatment of human cancer is discussed.


The landscape of cancer research and cancer care in China.
The rising cancer incidence rate in China poses a substantial public health concern, although there have been remarkable improvements in the country's cancer mortality and survival rates. In this Review, we outline the current landscape and future directions of cancer care and research in China. We discuss national screening programs and strategies for cancer detection and delve into the evolving landscape of cancer care, emphasizing the adoption of multidisciplinary, comprehensive treatment and precision oncology. Additionally, we examine changes in drug research and development policies that have enabled approval of new drugs. Finally, we look to the future, highlighting key priorities and identifying gaps. Effectively addressing challenges and seizing opportunities associated with cancer research in China will enable the development of targeted approaches to alleviate the global burden of cancer.


Communicating Risks and Benefits in Informed Consent for Research: A Qualitative Study.
Multiple studies have documented major limitations in the informed consent process for the recruitment of clinical research participants. One challenging aspect of this process is successful communication of risks and benefits to potential research participants. This study explored the opinions and attitudes of informed consent experts about conveying risks and benefits to inform the development of a survey about the perspectives of research nurses who are responsible for obtaining informed consent for clinical trials. The major themes identified were strategies for risks and benefits communication, ensuring comprehension, and preparation for the role of the consent administrator. From the experts' perspective, inadequate education and training of the research staff responsible for informed consent process contribute to deficiencies in the informed consent process and risks and benefits communication. Inconsistencies in experts' opinions and critique of certain widely used communication practices require further consideration and additional research.


Host specialization in ticks and transmission of tick-borne diseases: a review.
Determining patterns of host use, and the frequency at which these patterns change, are of key importance if we are to understand tick population dynamics, the evolution of tick biodiversity, and the circulation and evolution of associated pathogens. The question of whether ticks are typically host specialists or host generalists has been subject to much debate over the last half-century. Indeed, early research proposed that morphological diversity in ticks was linked to host specific adaptations and that most ticks were specialists. Later work disputed this idea and suggested that ticks are largely limited by biogeographic conditions and tend to use all locally available host species. The work presented in this review suggests that the actual answer likely lies somewhere between these two extremes. Although recent observational studies support the view that phylogenetically diverse host species share ticks when found on similar ecological ranges, theory on host range evolution predicts that host specialization should evolve in ticks given their life history characteristics. Contemporary work employing population genetic tools to examine host-associated population structure in several tick systems support this prediction and show that simple species records are not enough to determine whether a parasite is a true host generalist; host specialization does evolve in ticks at local scales, but may not always lead to speciation. Ticks therefore seem to follow a pattern of being global generalists, local specialists. Given this, the notion of host range needs to be modified from an evolutionary perspective, where one simply counts the number of hosts used across the geographic distribution, to a more ecological view, where one considers host use at a local scale, if we are to better understand the circulation of tick-borne pathogens and exposure risks for humans and livestock.


Race/ethnicity, nativity, and lifetime risk of mental disorders in US adults.
There has been no comprehensive examination of how race/ethnicity and nativity intersect in explaining differences in lifetime prevalence of mental disorders among Asian, Black, Latino, and White adults. This study aims to estimate racial/ethnic differences in lifetime risk of mental disorders and examine how group differences vary by nativity. Survival models were used to estimate racial/ethnic and nativity differences in lifetime risk of DSM-IV anxiety, mood, and substance use disorders in a nationally representative sample of over 20,000 respondents to four US surveys. Asians had the lowest lifetime prevalence of mental disorders (23.5%), followed by Blacks (37.0%), Latinos (38.8%), and Whites (45.6%). Asians and Blacks had lower lifetime risk than Whites for all disorders even after adjusting for nativity; Latinos and Whites had similar risk after adjusting for nativity. Risk of disorder onset was lowest for foreign-born respondents in years before migration. There were significant race/ethnicity and nativity interactions for mood and substance use disorders. Odds of mood disorder onset were higher for Whites with at least one US-born parent. Odds of substance use disorder onset among Asians were higher for US-born respondents; for Latinos, they were higher for those with at least one US-born parent. Parental foreign-born nativity is associated with a low risk of mental disorders, but not uniformly across racial/ethnic groups or disorders. Exposure to the US context may be associated with greater mental disorder risk for Latinos and Whites particularly. Investigations of cultural processes, including among Whites, are needed to understand group differences.


Something from "nothing"--eight weak estrogenic chemicals combined at concentrations below NOECs produce significant mixture effects.
We tested whether multicomponent mixtures of xenoestrogens would produce significant effects when each component was combined at concentrations below its individual NOEC or EC01 level. The estrogenic effects of eight chemicals of environmental relevance, including hydroxylated PCBs, benzophenones, parabenes, bisphenol A, and genistein, were recorded using a recombinant yeast estrogen screen (YES). To ensure that no chemical contributed disproportionately to the overall combination effect, a mixture was prepared at a mixture ratio proportional to the potency of each individual component. The performance of four approaches for the calculation of additive combination effects (concentration addition, toxicity equivalency factors, effect summation, and independent action) was compared. Experimental testing of the predictions revealed that concentration addition and its application, the toxicity equivalency factor approach, were valid methods for the calculation of additive mixture effects. There was excellent agreement between prediction and observation. In contrast, independent action and effect summation led to clear underestimations of the experimentally observed responses. Crucially, there were substantial mixture effects even though each chemical was present at levels well below its NOEC and EC01. We conclude that estrogenic agents are able to act together to produce significant effects when combined at concentrations below their NOECs. Our results highlight the limitations of the traditional focus on the effects of single agents. Hazard assessments that ignore the possibility of joint action of estrogenic chemicals will almost certainly lead to significant underestimations of risk.


The effect of Baduanjin exercise on the physical and mental health of college students: A randomized controlled trial.
Around the world, college students physical and mental health is deteriorating. Finding practical ways to enhance college students health is crucial. One of the traditional Chinese Qigong exercises is Baduanjin, which is possibly one of the most efficient workout techniques out there. However, it is unknown how Baduanjin practice may affect college students health. The purpose of this study was to evaluate the effect of Qigong Baduanjin on the physical and mental health of female college freshmen. A total of 78 female college students were recruited and randomly divided into Baduanjin group or control group. Participants in the control group were told to keep their original habits of life and exercise. The Baduanjin exercise group received 12 weeks of Baduanjin exercise, 3 days a week and 1 hour a day. After the 12 week randomized controlled trial, the physical and mental health indexes of female students in Baduanjin group and control group were evaluated, including physical shape, physical function, physical fitness and scl-90 self-assessment scale. Compared with the control group, at the end of the 12 week intervention, the weight, body mass index, diastolic blood pressure, systolic blood pressure, somatization score, obsessive-compulsive disorder score, interpersonal sensitivity score, depression score, anxiety score and phobic anxiety score of Baduanjin group decreased significantly. Compared with the control group, the vital capacity, vital capacity index, Stand test, Genchi test, Stand on 1 leg with closed eyes, standing bends and squats of the Baduanjin group have been significantly improved. Compared with usual activities, Qigong Baduanjin exercise has advantages in improving female college students body shape (weight and body mass index), cardiovascular and respiratory lung function, flexibility, balance ability, muscle endurance and mental health.


Measuring presence during the navigation in a virtual environment using EEG.
In the Virtual Reality field, presence refers to the sense of "being there" in the virtual world. Our aim in this work is to evaluate the usefulness of the Emotiv EPOC EEG device to measure the brain activations due to the sense of presence during the navigation in a Virtual Environment (VE), using for the analysis the sLORETA tool. We compare between two experimental conditions: free and automatic navigation through a VE. In this preliminary step, we monitored 9 healthy subjects, obtaining significant differences between the free and automatic navigation conditions in the activity of the right insula for the Theta and Alpha bands. The insula activation is related to stimulus attention and selfawareness processes, directly related with the sense of presence.


Essential Role for FtsL in Activation of Septal Peptidoglycan Synthesis.
Spatiotemporal regulation of septal peptidoglycan (PG) synthesis is achieved by coupling assembly and activation of the synthetic enzymes (FtsWI) to the Z ring, a cytoskeletal element that is required for division in most bacteria. In Escherichia coli, the recruitment of the FtsWI complex is dependent upon the cytoplasmic domain of FtsL, a component of the conserved FtsQLB complex. Once assembled, FtsWI is activated by the arrival of FtsN, which acts through FtsQLB and FtsA, which are also essential for their recruitment. However, the mechanism of activation of FtsWI by FtsN is not clear. Here, we identify a region of FtsL that plays a key role in the activation of FtsWI which we designate AWI (activation of FtsWI) and present evidence that FtsL acts through FtsI. Our results suggest that FtsN switches FtsQLB from a recruitment complex to an activator with FtsL interacting with FtsI to activate FtsW. Since FtsQLB and FtsWI are widely conserved in bacteria, this mechanism is likely to be also widely conserved.IMPORTANCE A critical step in bacterial cytokinesis is the activation of septal peptidoglycan synthesis at the Z ring. Although FtsN is the trigger and acts through FtsQLB and FtsA to activate FtsWI the mechanism is unclear. Here, we find an essential role for FtsL in activating septal peptidoglycan (PG) synthesis and find that it acts on FtsI. Our results suggest a model where FtsWI is recruited in an inactive form by FtsQLB, and upon the arrival of FtsN, FtsQLB undergoes a conformational change so that a region of FtsL, which we designate the AWI domain, becomes available to interact with FtsI and activate the FtsWI complex. This mechanism for activation of the divisome has similarities to the activation of the elongasome and is likely to be widely conserved in bacteria.


Bilirubin is inversely related to diabetic peripheral neuropathy assessed by sural nerve conduction study.
Diagnosis of diabetic peripheral neuropathy (DPN) depends on subjective findings, certain investigations for DPN risks have not been performed enough. Bilirubin protects against vascular complications by reducing oxidative stress in diabetes, but is not fully tested for DPN. This study aimed to evaluate sural nerve conduction impairments (SNCI) as an objective DPN marker and the contribution of bilirubin to SNCI. Using DPN-Check® , SNCI was defined as a decline of amplitude potential or conduction velocity below the normal limit in 150 inpatients with diabetes. The correlations between SNCI and conventional DPN diagnosis criteria, the incidence of diabetic retinopathy/nephropathy, biomarkers for atherosclerosis, cardiac function by ultrasonic cardiogram, and bilirubin were statistically tested, followed by the comparison of logistic regression models for SNCI to find confounders with bilirubin. The incidence of SNCI was 72.0%. The sensitivity and specificity of SNCI for DPN prediagnosis by simplified criteria were 54.6 and 90.5%, respectively, and similarly corresponded with diabetic retinopathy and nephropathy (sensitivity 57.4 and 50.0%, respectively). SNCI significantly related to diabetes duration, declined estimated glomerular filtration rate, albuminuria and total bilirubin. SNCI incidence was attenuated in the higher bilirubin tertiles (89.8/65.3/54.8%, P < 0.001). Bilirubin was an independent inverse risk factor for SNCI, even after adjustment by known risk factors for DPN and markers for microvascular complications. SNCI is a comprehensive marker for diabetic complications. We first showed the independent inverse relationship between bilirubin and SNCI through the independent pathway with other complications, provably reducing oxidative stress, as previously reported.


Diel patterning in the bacterial community associated with the sea anemone Nematostella vectensis.
Microbes can play an important role in the physiology of animals by providing essential nutrients, inducing immune pathways, and influencing the specific species that compose the microbiome through competitive or facilitatory interactions. The community of microbes associated with animals can be dynamic depending on the local environment, and factors that influence the composition of the microbiome are essential to our understanding of how microbes may influence the biology of their animal hosts. Regularly repeated changes in the environment, such as diel lighting, can result in two different organismal responses: a direct response to the presence and absence of exogenous light and endogenous rhythms resulting from a molecular circadian clock, both of which can influence the associated microbiota. Here, we report how diel lighting and a potential circadian clock impacts the diversity and relative abundance of bacteria in the model cnidarian Nematostella vectensis using an amplicon-based sequencing approach. Comparisons of bacterial communities associated with anemones cultured in constant darkness and in light:dark conditions revealed that individuals entrained in the dark had a more diverse microbiota. Overall community composition showed little variation over a 24-hr period in either treatment; however, abundances of individual bacterial OTUs showed significant cycling in each treatment. A comparative analysis of genes involved in the innate immune system of cnidarians showed differential expression between lighting conditions in N. vectensis, with significant up-regulation during long-term darkness for a subset of genes. Together, our studies support a hypothesis that the bacterial community associated with this species is relatively stable under diel light conditions when compared with static conditions and that particular bacterial members may have time-dependent abundance that coincides with the diel photoperiod in an otherwise stable community.


A detailed linkage map of rainbow trout produced using doubled haploids.
We report the first detailed genetic linkage map of rainbow trout (Oncorhynchus mykiss). The segregation analysis was performed using 76 doubled haploid rainbow trout produced by androgenesis from a hybrid between the "OSU" and "Arlee" androgenetically derived homozygous lines. Four hundred and seventy-six markers segregated into 31 major linkage groups and 11 small groups (< 5 markers/group). The minimum genome size is estimated to be 2627.5 cM in length. The sex-determining locus segregated to a distal position on one of the linkage groups. We analyzed the chromosomal distribution of three classes of markers: (1) amplified fragment length polymorphisms, (2) variable number of tandem repeats, and (3) markers obtained using probes homologous to the 5' or 3' end of salmonid-specific small interspersed nuclear elements. Many of the first class of markers were clustered in regions that appear to correspond to centromeres. The second class of markers were more telomeric in distribution, and the third class were intermediate. Tetrasomic inheritance, apparently related to the tetraploid ancestry of salmonid fishes, was detected at one simple sequence repeat locus and suggested by the presence of one extremely large linkage group that appeared to consist of two smaller groups linked at their tips. The double haploid rainbow trout lines and linkage map present a foundation for further genomic studies.


Multi-lineage differentiation of human mesenchymal stromal cells on the biophysical microenvironment of cell-derived matrix.
We obtained fibroblast- (FDM) and preosteoblast- (PDM) derived matrices in vitro from their respective cells. Our hypothesis was that these naturally occurring cell-derived matrices (CDMs) would provide a better microenvironment for the multi-lineage differentiation of human mesenchymal stromal cells (hMSCs) than those based on traditional single-protein-based platforms. Cells cultured for 5-6 days were decellularized with detergents and enzymes. The resulting matrices showed a fibrillar surface texture. Under osteogenic conditions, human bone-marrow-derived stromal cells (HS-5) exhibited higher amounts of both mineralized nodule formation and alkaline phosphatase (ALP) expression than those cultured on plastic or gelatin. Osteogenic markers (Col I, osteopontin, and cbfa1) and ALP activity from cells cultured on PDM were notably upregulated at 4 weeks. The use of FDM significantly improved the cellular expression of chondrogenic markers (Sox 9 and Col II), while downregulating that of Col I at 4 weeks. Both CDMs were more effective in inducing cellular synthesis of glycosaminoglycan content than control substrates. We also investigated the effect of matrix surface texture on hMSC (PT-2501) differentiation; soluble matrix (S-matrix)-coated substrates exhibited a localized fibronectin (FN) alignment, whereas natural matrix (N-matrix)-coated substrates preserved the naturally formed FN fibrillar alignment. hMSCs cultured for 4 weeks on N-matrices under osteogenic or chondrogenic conditions deposited a greater amount of calcium and proteoglycan than those cultured on S-matrices as assessed by von Kossa and Safranin O staining. In contrast to the expression levels of lineage-specific markers for cells cultured on gelatin, FN, or S-matrices, those cultured on N-matrices yielded highly upregulated levels. This study demonstrates not only the capacity of CDM for being an effective inductive template for the multi-lineage differentiation of hMSCs, but also the critical biophysical role that the matrix fibrillar texture itself plays on the induction of stem cell differentiation.


S14G-humanin alleviates acute lung injury by inhibiting the activation of NF-κB.
Acute lung injury (ALI) is characterized by severely damaged alveoli and blood vessels, seriously affecting the health of patients and causing a high mortality rate. The pathogenesis of ALI is complex, with inflammatory reactions and oxidative stress (OS) mainly involved. S14G humanin (HNG) is derived from humanin (HN), which is claimed with promising anti-inflammatory functions. Herein, the protective influence of HNG on ALI will be explored in a mouse model. The ALI model was established in mice via intratracheal instillation of 3 mg/kg LPS, followed by an intraperitoneal injection of 3 and 6 mg/kg HNG, respectively. Thicker alveolar walls, aggravated neutrophil infiltration, and increased wet weight/dry weight (W/D) ratio were observed in ALI mice, accompanied by an aggravated apoptotic state, all of which were notably alleviated by HNG. Furthermore, increased number of total cells and neutrophils in bronchoalveolar lavage fluid (BALF), elevated secretion of inflammatory cytokines, enhanced reactive oxygen species (ROS) and Malondialdehyde (MDA) levels, and declined superoxide dismutase-2 (SOD2) levels were observed in ALI mice, which were markedly ameliorated by HNG. Moreover, the upregulated levels of NOD-like receptor family pyrin domain containing 3 (NLRP3), caspase-1, and caspases cleave gasdermin D N/caspases cleave gasdermin D FL (GSDMD N/GSDMD FL) in ALI mice were signally repressed by HNG. Lastly, the upregulation of Toll-like receptor 4 (TLR4) and p-p65/p65, and downregulation of IκB-α observed in ALI mice were sharply reversed by HNG. Collectively, HNG alleviated the ALI in mice by inhibiting the activation of nuclear factor kappa B (NF-κB) signaling.


Modeling Competing Infectious Pathogens from a Bayesian Perspective: Application to Influenza Studies with Incomplete Laboratory Results.
In seasonal influenza epidemics, pathogens such as respiratory syncytial virus (RSV) often co-circulate with influenza and cause influenza-like illness (ILI) in human hosts. However, it is often impractical to test for each potential pathogen or to collect specimens for each observed ILI episode, making inference about influenza transmission difficult. In the setting of infectious diseases, missing outcomes impose a particular challenge because of the dependence among individuals. We propose a Bayesian competing-risk model for multiple co-circulating pathogens for inference on transmissibility and intervention efficacies under the assumption that missingness in the biological confirmation of the pathogen is ignorable. Simulation studies indicate a reasonable performance of the proposed model even if the number of potential pathogens is misspecified. They also show that a moderate amount of missing laboratory test results has only a small impact on inference about key parameters in the setting of close contact groups. Using the proposed model, we found that a non-pharmaceutical intervention is marginally protective against transmission of influenza A in a study conducted in elementary schools.


Acute mountain sickness in athletes with neurological impairments.
Acute mountain sickness (AMS) is a symptom complex noticed commonly among high altitude travelers. The occurrence of AMS depends on multiple factors that have been studied extensively. However, AMS in individuals with neurological impairments has not been considered in detail. A total of 168 subjects, including active controls, inactive controls, and those with spinal cord injury (SCI), multiple sclerosis, and traumatic brain injury (TBI), were studied at the National Veterans Winter Sports Clinic in Snowmass, Colorado, from 2007 to 2009 for the occurrence of AMS. Lake Louise Score was used to quantify symptoms. A higher than anticipated occurrence of AMS (42.85%) among the study population was noted, with significantly higher Lake Louis Scores among athletes with neurological impairments. Disability group, prior history of AMS, and prior occurrence of headache at high altitude could be used as predictors for the development of AMS symptoms. More research is warranted specifically targeting the interaction between factors affecting AMS and the pathophysiology of neurological impairments like SCI and TBI to further our understanding about prophylactic medications and treatments for AMS, especially because many military personnel with neurological impairments continue on Active Duty.


Immunodetection of Canine Parvovirus (CPV) in clinical samples by polyclonal antisera against CPV-VP2 protein expressed in Esherichia coli as an antigen.
The entire virion protein 2 (VP2) gene of Canine Parvovirus (CPV) was amplified by polymerase chain reaction (PCR) and engineered to be expressed by a bacterial expression vector pET-28a, under the control of the IPTG-inducible T7lac promoter. SDS-PAGE gel revealed that VP2 expressed as a 67kDa, and found mainly in the pellet of the bacterial lysates, suggesting that cytoplasmic expression is not preferred. The recombinant protein VP2 fused with His-tag was purified from Esherichia coli using Ni-NTA resin under denaturing conditions. SDS-PAGE analysis also showed the high expression of several lower molecular weight (LMW) bands. Western blot analysis showed that polyclonal antisera produced by rabbit against E. coli-VP2 protein reacted specifically with the purified VP2 protein as well as two other LMW bands. Some of the resulting LMW products failed to keep their antigenic site in the N-terminal region of the VP2. The degradation of recombinant VP2 protein in E. coli could be due to the action of host proteases. The immunodetection ability of the polyclonal antisera was compared with that of a commercial monoclonal antibody to test numerous clinical specimens by immuno-dot blot assays. There were distinctive differences in the degree of immunodetection ability of polyclonal antisera and monoclonal antibody to react with CPV antigens. The reaction time of polyclonal antisera was much faster in visual color appearance than that of monoclonal antibody during NBT/BCIP staining. The result from diagnostic PCR assay confirmed the presence of CPV in 44 out of 46 specimens collected, consistent with polyclonal antisera-positive result. Therefore, the polyclonal antisera can be used for CPV detection in the faeces of diarrhoeic dogs, which was found to be more rapid, sensitive, broad but less specific than the monoclonal antibody.


Fate and efficacy of polyacrylamide applied in furrow irrigation: full-advance and continuous treatments.
Polyacrylamide (PAM) is applied to 400000 irrigated hectares annually in the USA to control irrigation-induced erosion, yet the fate of dissolved PAM applied in irrigation water is not well documented. We determined the fate of PAM added to furrow streams under two treatments: Initial-10, 10 mg L(-1) PAM product applied only during the initial hours of the irrigation, and Cont-1, 1.0 mg L(-1) PAM product applied continuously during the entire irrigation. The study measured PAM concentrations in 167-m-long PAM-treated furrow streams and along a 530-m tail ditch that received this runoff. Soil was Portneuf silt loam (coarse-silty, mixed, superactive, mesic Durinodic Xeric Haplocalcid) with 1.5% slope. Samples were taken at three times during the irrigations, both during and after PAM application. Polyacrylamide was adsorbed to soil and removed from solution as the streams traversed the soil-lined channels. The removal rate increased with stream sediment concentration. Stream sediment concentrations were higher when PAM concentrations were <2 mg L(-1) a.i., for early irrigations, and when untreated tributary flows combined with the stream. In these cases, PAM concentration decreased to undetectable levels over the flow lengths used in this study. When inflows contained >6 mg L(-1) PAM a.i., stream sediment concentrations were minimal and PAM concentrations did not change down the furrow, though they decreased to undetectable levels within 0.5 h after application ceased. One percent of applied PAM was lost in tail-ditch runoff. This loss could have been eliminated by treating only the furrow advance or not treating the last two irrigations.


Crosslinking-immunoprecipitation (iCLIP) analysis reveals global regulatory roles of hnRNP L.
Heterogeneous nuclear ribonucleoprotein L (hnRNP L) is a multifunctional RNA-binding protein that is involved in many different processes, such as regulation of transcription, translation, and RNA stability. We have previously characterized hnRNP L as a global regulator of alternative splicing, binding to CA-repeat, and CA-rich RNA elements. Interestingly, hnRNP L can both activate and repress splicing of alternative exons, but the precise mechanism of hnRNP L-mediated splicing regulation remained unclear. To analyze activities of hnRNP L on a genome-wide level, we performed individual-nucleotide resolution crosslinking-immunoprecipitation in combination with deep-sequencing (iCLIP-Seq). Sequence analysis of the iCLIP crosslink sites showed significant enrichment of C/A motifs, which perfectly agrees with the in vitro binding consensus obtained earlier by a SELEX approach, indicating that in vivo hnRNP L binding targets are mainly determined by the RNA-binding activity of the protein. Genome-wide mapping of hnRNP L binding revealed that the protein preferably binds to introns and 3' UTR. Additionally, position-dependent splicing regulation by hnRNP L was demonstrated: The protein represses splicing when bound to intronic regions upstream of alternative exons, and in contrast, activates splicing when bound to the downstream intron. These findings shed light on the longstanding question of differential hnRNP L-mediated splicing regulation. Finally, regarding 3' UTR binding, hnRNP L binding preferentially overlaps with predicted microRNA target sites, indicating global competition between hnRNP L and microRNA binding. Translational regulation by hnRNP L was validated for a subset of predicted target 3'UTRs.


Solvation of Large Polycyclic Aromatic Hydrocarbons in Helium: Cationic and Anionic Hexabenzocoronene.
The adsorption of helium on charged hexabenzocoronene (Hbc, C42H18), a planar polycyclic aromatic hydrocarbon (PAH) molecule of D6h symmetry, was investigated by a combination of high-resolution mass spectrometry and classical and quantum computational methods. The ion abundance of HenHbc+ complexes versus size n features prominent local anomalies at n = 14, 38, 68, 82, and a weak one at 26, indicating that for these "magic" sizes, the helium evaporation energies are relatively large. Surprisingly, the mass spectra of anionic HenHbc- complexes feature a different set of anomalies, namely at n = 14, 26, 60, and 62, suggesting that the preferred arrangement of the adsorbate atoms depends on the charge of the substrate. The results of our quantum calculations show that the adsorbate layer grows by successive filling of concentric rings that surround the central benzene ring, which is occupied by one helium atom each on either side of the substrate. The helium atoms are fairly localized in filled rings and they approximately preserve the D6h symmetry of the substrate, but helium atoms in partially filled rings are rather delocalized. The first three rings contain six atoms each; they account for magic numbers at n = 14, 26, and 38. The size of the first ring shrinks as atoms are filled into the second ring, and the position of atoms in the second ring changes from hollow sites to bridge sites as atoms are filled into the third ring. Beyond n = 38, however, the arrangement of helium atoms in the first three rings remains essentially frozen. Presumably, another ring is filled at n = 68 for cations and n = 62 for anions. The calculated structures and energies do not account for the difference between charge states, although they agree with the measurements for the cations and show that the first solvation shell of Hbc± is complete at n = 68. Beyond that size, the adsorbate layer becomes three-dimensional, and the circular arrangement of helium changes to hexagonal.


Palliative Role of Aqueous Ginger Extract on N-Nitroso-N-Methylurea-Induced Gastric Cancer.
Ginger (Zingiber officinale) is a spice and also an herbal medicine used worldwide for managing GI tract disturbances. However, its role in gastric cancer is sparingly known. This study ensures the standardization of gastric cancer by the induction of N-nitroso N-methyl Urea (MNU) and to determine the role of the aqueous extract of ginger (AGE) in MNU-induced gastric cancer in albino Wistar rats. Accordingly, the anticancer potential of AGE and its possible mode of action were assessed on rats exposed to MNU, by various biochemical and molecular assays. As evidenced by the extent of lipid peroxidation, gastrin levels and histopathological sections in MNU-induced cancerous lesions at 8 wk which was stabilized at 16 wk confirming the induction of gastric carcinoma by the chemical carcinogen. Further, results revealed that AGE alleviated the oxidative stress as evidenced by the stomach antioxidant enzymes (SOD, catalase, GPx, and GR), markers of oxidative stress (TRx, GRx) and Gastrin, a specific marker for gastric cancer and a decreased level of pro-inflammatory markers (NF-kB, TNF-α, IL-6, PGE2) which was further confirmed by histopathological analysis. AGE is responsible to mitigate oxidative stress and inflammation related to gastric cancer and could be used as a potential dietary intervention in gastric cancer therapy.


Alteration of aminoacyl-tRNA synthetase activities by phosphorylation with casein kinase I.
The phosphorylation of a highly purified aminoacyl-tRNA synthetase complex from rabbit reticulocytes by the cyclic nucleotide-independent protein kinase, casein kinase I, has been examined, and the effects of phosphorylation on the synthetase activities were determined. The synthetase complex, purified as described (Kellermann, O., Tonetti, H., Brevet, A., Mirande, M., Pailliez, J.-P., and Waller, J.-P. (1982) J. Biol. Chem. 257, 11041-11048), contains seven aminoacyl-tRNA synthetases and four unidentified proteins and is free of endogenous protein kinase activity. Incubation of the complex with casein kinase I in the presence of ATP results in the phosphorylation of four synthetases, namely, glutamyl-, isoleucyl-, methionyl-, and lysyl-tRNA synthetases. Phosphorylation by casein kinase I alters binding of the aminoacyl-tRNA synthetase complex to tRNA-Sepharose. The phosphorylated synthetase complex elutes from tRNA-Sepharose at 190 mM NaCl, while the nonphosphorylated complex elutes at 275 mM NaCl. Phosphorylation by casein kinase I results in a significant inhibition of aminoacylation by the glutamyl-, isoleucyl-, methionyl-, and lysyl-tRNA synthetases; the activities of the nonphosphorylated synthetases remain unchanged. These data indicate that phosphorylation of aminoacyl-tRNA synthetases in the high molecular weight complex alters the activities of these enzymes. One of the unidentified proteins present in the complex (Mr 37,000) is also highly phosphorylated by casein kinase I. From a comparison of the properties and phosphopeptide pattern of this protein with that of casein kinase I, it appears that the Mr 37,000 protein in the synthetase complex is an inactive form of casein kinase I. This observation provides further evidence for a physiological role for casein kinase I in regulating synthetase activities.


Splenectomy in patients with mixed myelodysplastic/myeloproliferative disease.
According to the classification of the World Health Organization, the designation myelodysplastic/myeloproliferative disorder, unclassifiable may be applied to cases that have clinical, laboratory, and morphologic features that support a diagnosis of a myelodysplastic syndrome (MDS) as well as a myeloproliferative disorder (MPD), but that do not meet the criteria for any of the other entities included in the MDS/MPD category [3]. In this paper we report on two Caucasian patients with unclassifiable myelodysplastic syndromes with proliferative characteristics. Both patients were suffering from thrombocytopenia and splenomegaly and underwent splenectomy. The weight of the spleen specimens was more than 2000 g. Histopathology findings revealed a marked infiltration of the spleen with extramedullary hematopoiesis. After surgery, one patient showed a rapid increase of platelets in peripheral blood and developed severe thrombocytosis. In the other case, the patient was suffering from a decrease of platelets and died in hypovolemic shock caused by gastrointestinal bleeding. In summary, these two cases demonstrate the difficulties of prognosis and treatment in patients with mixed myelodysplastic/myeloproliferative disorders. Additionally, we indicate the potential positive outcome of splenectomy as ultima ratio in patients with these hematological features and severe thrombopenia.


A physiotherapy perspective of musculoskeletal imaging in sport.
This paper presents a physiotherapy perspective on the role that imaging is now playing in the diagnosis and management of musculoskeletal and sporting injuries. Although the Royal College of Radiologists and the UK Chartered Society of Physiotherapy were founded in the latter part of the nineteenth century, it is 100 years later that developments in the UK NHS have led to increased roles for non-medical healthcare professionals and allied health professionals, such as physiotherapists, in an extended clinical role. Physiotherapists, perhaps because of their knowledge of clinical and applied anatomy, have keenly taken up the opportunities offered to request and interpret imaging in its various forms; the most commonly available are plain radiography, musculoskeletal ultrasound and MRI. This has meant taking formal courses under the auspices of universities with mentorship and tutoring within the clinical setting, which are part of a continuing professional development. The ability to request several forms of imaging has enhanced physiotherapy practice and has increased the appreciation of the responsibilities which accompany this new role.


Rapid Laser Reactive Sintering for Sustainable and Clean Preparation of Protonic Ceramics.
One of the essential challenges for energy conversion and storage devices based on protonic ceramics is that the high temperature (1600-1700 °C) and long-time firing (>10 h) are inevitably required for the fabrication, which makes the sustainable and clean manufacturing of protonic ceramic devices impractical. This study provided a new rapid laser reactive sintering (RLRS) method for the preparation of nine protonic ceramics [i.e., BaZr0.8Y0.2O3-δ (BZY20), BZY20 + 1 wt % NiO, BaCe0.7Zr0.1Y0.1Yb0.1O3-δ (BCZYYb), BCZYYb + 1 wt % NiO, 40 wt % BCZYYb + 60 wt % NiO, BaCe0.85Fe0.15O3-δ-BaCe0.15Fe0.85O3-δ (BCF), BaCo0.4Fe0.4Zr0.1Y0.1O3-δ (BCFZY0.1), BaCe0.6Zr0.3Y0.1O3-δ (BCZY63), and La0.7Sr0.3CrO3-δ (LSC)] with desired crystal structures and microstructures. Following this, the dual-layer half-cells, comprising the porous electrode and dense electrolyte, were prepared by the developed RLRS technique. After applying the BCFZY0.1 cathode, the protonic ceramic fuel cell (PCFC) single cells were prepared and tested initially. The derived conductivity of the RLRS electrolyte films showed comparable proton conductivity with the electrolyte prepared by conventional furnace sintering. The initial cost estimation based on electricity consumption during the sintering process for the fabrication of PCFC single cells showed that RLRS is more competitive than the conventional furnace sintering. This RLRS can be combined with the rapid additive manufacturing of ceramics for the sustainable and clean manufacturing of protonic ceramic energy devices and the processing of other ceramic devices.


The Relationship between Electronic Cigarette Use with or without Cigarette Smoking and Alcohol Use among Adolescents: Finding from the 11th Korea Youth Risk Behavior Web-based Survey.
Electronic cigarette (EC) consumption ('vaping') is rapidly increasing, not only in adults but also in adolescents. Little is known about the association between vaping and problem behaviors such as drinking. We used data from the 11th Korea Youth Risk Behavior Web-based Survey, which was conducted in 2015 and included 68,043 participants who were Korean middle and high school students. The survey assessed EC, cigarette, and alcohol use. Multiple regression analysis was used to examine risk of current drinking and problem drinking across the following categories of users: never user (never used either product), former user (use of EC or cigarettes in the past, but not currently), vaping only, smoking only, and dual user (current use of both products). EC only users were 1.2% in males, and 0.3% in females. Dual user of both conventional cigarettes and ECs were 5.1% in males, and 1.2% in females. Drinking frequency, drinking quantity per once, and problem drinking were higher among vapers than non-vapers and former-vapers, moreover, were higher among daily vapers than intermittent vapers. Compared to never users, EC only users were higher on risk of current drink and problem drink. The dual users were highest on risk of current drink. Vaping is independently associated with alcohol use problems in Korean students, even those not currently smoking. Moreover, dual use of cigarettes and ECs is strongly associated with alcohol use problems. Therefore, vaping students should be concerned about their hidden alcohol use problems.


Flower opening and closure: a review.
Flower opening and closure are traits of a reproductive syndrome, as it allows pollen removal and/or pollination. Various types of opening can be distinguished such as nocturnal and diurnal and single or repetitive. Opening is generally due to cell expansion. Osmotic solute levels increase by the conversion of polysaccharides (starch or fructan) to monosaccharides, and/or the uptake of sugars from the apoplast. Repeated opening and closure movements are often brought about by differential elongation. In tulip petals, for example, the upper and lower sides of the mesophyll exhibit a 10 degrees C difference in optimum temperature for elongation growth, resulting in opening in the morning and closure in the evening. Opening and closure in several other species is regulated by changes in light intensity and, in some species with nocturnal opening, by an increase in relative humidity. A minimum duration of darkness and light are usually required for opening and closure, respectively, in flowers that open during the day. Both phytochrome and a blue light receptor seem involved in light perception. In some species, opening and closure are regulated by an endogenous rhythm, which, in all cases investigated, can be reset by changes from dark to light and/or light to dark. So far, Arabidopsis mutants have not been used to investigate the timing of flower opening and closure. As its flowers open and close in a circadian fashion, several mutants that are involved in the circadian clock and its light input may help to provide an insight into this type of flower opening. The co-ordination of processes culminating in synchronized flower opening is, in many species, highly intricate. The complex control by endogenous and exogenous factors sets flower opening and closure apart from most other growth processes.