Effect of sodium on vasoconstriction and angiotensin II type 1 receptor mRNA expression in cold-induced hypertensive rats.
Angiotensin II and sodium play an important pathogenetic role in several models of hypertension. Now, we investigated the effects of sodium on vasoconstriction and angiotensin II type 1 (AT1) and type 2 (AT2) receptor mRNA expression in aortic vessels from cold-induced hypertensive rats. Wistar rats on low sodium and high sodium diet were exposed to cold-stress for 8 weeks. The effects of angiotensin II infusion on mean arterial blood pressure were investigated in these rats. In addition, angiotensin II induced contraction was measured using aortic rings. Expression of AT1 receptor mRNA and AT2 receptor mRNA was assessed in aortic vessels by reverse transcription polymerase chain reaction. After infusion of angiotensin II mean arterial blood pressure in cold-induced hypertensive rats on high sodium diet was significantly higher compared to cold-induced hypertensive rats on low sodium diet (p < 0.05). Angiotensin II-induced contraction of aortic rings was significantly higher in cold-induced hypertensive rats on high sodium diet compared to cold-induced hypertensive rats on low sodium diet (2.39 +/- 0.03 g vs. 2.21 +/- 0.04 g, n = 12, p < 0.01). Angiotensin AT1 receptor mRNA was significantly higher in cold-induced hypertensive rats on high sodium diet compared to cold-induced hypertensive rats on low sodium diet (p < 0.05). It is concluded that in this nongenetic, nonsurgical animal model of cold-induced hypertension increased vasoconstriction and increased AT1 receptor mRNA expression in aortic vessels are dependent on sodium intake.


Understanding Thermodynamic and Spectroscopic Properties of Tetragonal Mn12 Single-Molecule Magnets from Combined Density Functional Theory/Spin-Hamiltonian Calculations.
We apply broken-symmetry density functional theory to determine isotropic exchange-coupling constants and local zero-field splitting (ZFS) tensors for the tetragonal Mn12(t)BuAc single-molecule magnet. The obtained parametrization of the many-spin Hamiltonian (MSH), taking into account all 12 spin centers, is assessed by comparing theoretical predictions for thermodynamic and spectroscopic properties with available experimental data. The magnetic susceptibility (calculated by the finite-temperature Lanczos method) is well approximated, and the intermultiplet excitation spectrum from inelastic neutron scattering (INS) experiments is correctly reproduced. In these respects, the present parametrization of the 12-spin model represents a significant improvement over previous theoretical estimates of exchange-coupling constants in Mn12, and additionally offers a refined interpretation of INS spectra. Treating anisotropic interactions at the third order of perturbation theory, the MSH is mapped onto the giant-spin Hamiltonian describing the S = 10 ground multiplet. Although the agreement with high-field EPR experiments is not perfect, the results clearly point in the right direction and for the first time rationalize the angular dependence of the transverse-field spectra from a fully microscopic viewpoint. Importantly, transverse anisotropy of the effective S = 10 manifold is explicitly shown to arise largely from the ZFS-induced mixing of exchange multiplets. This effect is given a thorough analysis in the approximate D2d spin-permutational symmetry group of the exchange Hamiltonian.


The prevalence of disc degeneration associated with neural arch defects of the lumbar spine assessed by magnetic resonance imaging.
The morphology of the intervertebral discs in 40 patients with spondylolytic and mild spondylolisthetic defects of the lumbar spine were assessed using magnetic resonance imaging. The results were compared with an age- and sex-matched asymptomatic population, and the difference in prevalence of disc degeneration between the two groups was noted. Under the age of 25 years, degeneration was uncommon in both the disc associated with the neural arch defect and the comparable disc in the control population. However, after this age, the prevalence of the disc degeneration rose in both groups, but was more marked in the spondylytic group, and this difference was statistically significant (P = 0.025). The results suggest that a neural arch defect is associated with an increased prevalence of disc degeneration, which is greater than is seen in a normal aging population.


Identification of C. elegans & C. briggsae miRNAs by modified miRsearch.
In this study, a modified miRsearch program was developed in C++ for the detection of miRNAs. All the mature miRNA sequences of Caenorhabditis elegans, Caenorhabditis briggsae, Caenorhabditis remanei, Drosophila melanogaster, Homo sapiens and Rattus norvegicus available in miRbase was searched by this program for homologous sequences with a maximum of 3-mismatches in the chromosomes of C. elegans excluding the miRNAs of C. elegans. The same strategy was repeated for C. briggsae excluding C. briggsae miRNAs. The probable pre-miRNA sequences with stem loop secondary structures were assessed by implementation of longest-common-subsequence (LCS) algorithm with appropriate scoring system. As miRNA genes could be on either strand, each sequence was searched in both forward and reverse strands. The putative miRNAs were viewed through Mapviewer to identify their intronic or intergenic location in C. elegans and C. briggsae genomes. Further, the quality of stem-loop formation of the remaining pre-miRNA sequences was assessed through RNAFOLD. This algorithm will be helpful in detection of potential miRNAs in future sequencing data, making this an invaluable tool for miRNA prediction.


Detection of oncogenic viruses in water environments by a Luminex-based multiplex platform for high throughput screening of infectious agents.
Recent studies documented the detection of viruses strongly associated with human cancer in urban sewages and other water environments worldwide. The aim of this study was to estimate the occurrence of human oncogenic viruses in environmental samples (sewage, river, marine, and pool/spa water) using highly sensitive and specific multiplex bead-based assays (Luminex technology). A total of 33 samples were analysed for 140 oncogenic viral agents, including mucosal and cutaneous human papillomaviruses (HPVs), human polyomaviruses (HPyV), human herpesviruses (HHV) and mouse mammary tumour virus (MMTV). Eighty-eight percent of the samples tested positive for at least one viral pathogen and the simultaneous presence of more than one virus was frequent (mean number of positivities/sample = 3.03). A total of 30 different Alpha, Beta and Gamma HPVs were detected, including mucosal and cutaneous types. The high-risk type HPV16 was the most frequently detected virus, identified in 73% of the samples. Of the 12 HPyVs tested, only two (BKPyV and MCPyV) were detected. At least one of these two was present in 48% of the samples. MMTV was detected in 21% of the samples, while herpesviruses - HHV-6 and HHV-1 - were detected in two samples (6%). The present study is the first to provide a comprehensive picture of the occurrence of oncogenic viruses belonging to different families and species in diverse water environments, and the first to successfully use, in environmental samples, a Luminex-based multiplex platform for high throughput screening of infectious agents. Our findings, showing that oncogenic viruses are ubiquitous in water environments, pave the way for future studies on the fate of these pathogens in water environments as well as on their potential for transmission via the waterborne route.


Cut-down assisted percutaneous gastrostomy tube placement in morbidly obese patient.
Enteral and parenteral nutrition is primarily indicated in patients that lack adequate oral intake to support their metabolic needs. Percutaneous endoscopic gastrostomy (PEG) has become the preferred procedure of choice. With the increasing prevalence of obesity in the USA, there is a need for special interventions for PEG tube placements in overweight and obese patients. Some challenges that frequently arise with obese patients include sub-optimal transillumination, insufficient abdominal landmarks and inability to estimate the abdominal and gastric walls. We present a case of a patient with persistent dysphagia requiring enteral nutrition with an unconventional placement of a PEG tube given patient's large body habitus.


Studies of the toxicological potential of capsinoids: I. Single-dose toxicity study and genotoxicity studies of CH-19 Sweet extract.
A single-dose oral toxicity lethal-dose study was conducted to examine the toxicity of capsinoids contained in CH-19 Sweet extract. CH-19 Sweet extract was administered once by gavage to SPF (Crl:CD(SD)) Sprague-Dawley male and female rats at dose levels of 0 (vehicle), 5, 10, or 20 ml/kg of body weight (BW). The concentration of capsinoids in the CH-19 Sweet extract was 71.25 mg/ml; this resulted in administered dose levels of capsinoids of 356.25, 712.5, and 1425 mg/kg BW, respectively. The toxicity of CH-19 Sweet extract by single oral administration was low; only transient salivation or decreased spontaneous movement was observed on the day of administration at > or =10 ml/kg BW. It was concluded that the lethal dose of CH-19 Sweet extract was estimated to be higher than 20 ml/kg (1425 mg/kg as capsinoids) for both males and females since no deaths were observed at any dose in this study. A bacterial reverse mutation test of CH-19 Sweet extract was performed employing Salmonella typhimurium and Escherichia coli and using the preincubation method. Treatment with CH-19 Sweet extract did not increase the number of revertant colonies compared with negative controls either in the presence (+S9) or absence (-S9) of metabolic activation. An in vitro chromosome aberration test was conducted using Chinese hamster lung cultured cells (CHL/IU). Treatment with CH-19 Sweet extract failed to induce chromosome aberrations in either short-term or continuous treatment scenarios, with or without metabolic activation (-S9, +S9). In an in vivo micronucleus test using BDF(1) male mice, CH-19 Sweet extract failed to increase the incidence of micronucleated polychromatic erythrocytes (MNPCEs) or decrease the ratio of polychromatic erythrocytes (PCEs) in any of the treatment groups. These results suggest the absence of mutagenicity as well as in vitro and in vivo clastogenicity of capsinoids contained in CH-19 Sweet extract.


Comparison of in vitro metabolism of ticlopidine by human cytochrome P450 2B6 and rabbit cytochrome P450 2B4.
A recent X-ray crystal structure of a rabbit cytochrome P450 2B4 (CYP2B4)-ticlopidine complex indicated that the compound could be modeled with either the thiophene or chlorophenyl group oriented toward the heme prosthetic group. Subsequent NMR relaxation and molecular docking studies suggested that orientation with the chlorophenyl ring closer to the heme was the preferred one. To evaluate the predictive value of these findings, the oxidation of ticlopidine by reconstituted CYP2B4 was studied and compared with CYP2B6, in which the thiophene portion of the molecule likely orients toward the heme. In vitro incubation of ticlopidine with both enzymes yielded the same set of metabolites: 7-hydroxyticlopidine (M1), 2-oxoticlopidine (M2), 5-(2-chlorobenzyl)thieno[3,2-c]pyridin-5-ium metabolite (M3), 5-(2-chlorobenzyl)thieno[3,2-c]pyridin-5-ium metabolite (M4), ticlopidine N-oxide (M5), and ticlopidine S-oxide dimer, a dimerization product of ticlopidine S-oxide (M6). The rates of metabolite formation deviated markedly from linearity with time, consistent with the known inactivation of CYP2B6 by ticlopidine. Fitting to a first-order equation yielded similar rate constants (k(obs)) for both enzymes. However, the amplitude (R(max)) of M1 and M6 formation was 4 to 5 times higher for CYP2B6 than CYP2B4, indicating a greater residence time of ticlopidine with its thiophene ring closer to heme in CYP2B6. In contrast, CYP2B4 formed M4 and M5 in more abundance than CYP2B6, indicating an alternate orientation. Overall, the results suggest that the preferential orientation of ticlopidine in the active site of CYP2B4 predicted by X-ray crystallography and NMR studies is unproductive and that ticlopidine likely reorients within CYP2B4 to a more productive mode.


[Distributed lag effects in the relationship between daily mean temperature and mortality in Shanghai].
To study the impact of daily mean temperature on mortality in Shanghai. With data on daily mortality, meteorological and air pollution, we used a distributed lag nonlinear model (DLNM) to assess the effects of daily mean temperature on deaths (caused by non-accidental, cardiovascular and respiratory) adjusted for both secular, seasonal trends and other confounders. A J-shaped relationship was found consistently between daily mean temperature and non-accidental, cardiovascular and respiratory deaths in Shanghai. Cold effects were delayed by 1 day to 4 days and persisted for 14 - 30 days. Hot effects appeared acute and the highest at the first day, but lasted for 2 days and followed by mortality displacement. In Shanghai, both cold and hot temperatures increased the risk of mortality with delayed effects. Cold effects seemed last longer than heat did.


Chronic intermittent hypoxia induces atherosclerosis via activation of adipose angiopoietin-like 4.
Obstructive sleep apnea is a risk factor for dyslipidemia and atherosclerosis, which have been attributed to chronic intermittent hypoxia (CIH). Intermittent hypoxia inhibits a key enzyme of lipoprotein clearance, lipoprotein lipase, and up-regulates a lipoprotein lipase inhibitor, angiopoietin-like 4 (Angptl4), in adipose tissue. The effects and mechanisms of Angptl4 up-regulation in sleep apnea are unknown. To examine whether CIH induces dyslipidemia and atherosclerosis by increasing adipose Angptl4 via hypoxia-inducible factor-1 (HIF-1). ApoE(-/-) mice were exposed to intermittent hypoxia or air for 4 weeks while being treated with Angptl4-neutralizing antibody or vehicle. In vehicle-treated mice, hypoxia increased adipose Angptl4 levels, inhibited adipose lipoprotein lipase, increased fasting levels of plasma triglycerides and very low density lipoprotein cholesterol, and increased the size of atherosclerotic plaques. The effects of CIH were abolished by the antibody. Hypoxia-induced increases in plasma fasting triglycerides and adipose Angptl4 were not observed in mice with germline heterozygosity for a HIF-1α knockout allele. Transgenic overexpression of HIF-1α in adipose tissue led to dyslipidemia and increased levels of adipose Angptl4. In cultured adipocytes, constitutive expression of HIF-1α increased Angptl4 levels, which was abolished by siRNA. Finally, in obese patients undergoing bariatric surgery, the severity of nocturnal hypoxemia predicted Angptl4 levels in subcutaneous adipose tissue. HIF-1-mediated increase in adipose Angptl4 and the ensuing lipoprotein lipase inactivation may contribute to atherosclerosis in patients with sleep apnea.


[The necessity for centralization of pediatric intensive care].
Substantial evidence indicates that outcome of critically ill children, treated in tertiary paediatric intensive care units (PICUs) is superior to that of those treated in other settings. However, a significant number of children who require this level of care are not admitted to such a unit e.g. due to capacity constraints, reluctance of physicians of general hospitals to refer children to a tertiary centre, and transportation problems. Centralization of care, as recently proposed in the UK, is necessary in the Netherlands, as well, to improve the quality of care. This will require a controlled number of PICU beds in a restricted number of centres, adequate transport facilities and step-down or high dependency units in large general hospitals.


Redox regulation of human thioredoxin network.
Oxidative stresses are largely mediated by intracellular protein oxidations by reactive oxygen species (ROS). Host cells are equipped with antioxidants that scavenge ROS. The cellular reduction/oxidation (redox) balance is maintained by ROS and antioxidants. Accumulating evidence suggests that the redox balance plays an important role in cellular signaling through the redox modification of cysteine residues in various important components of the signal transduction pathway. Thioredoxin (TRX) is a small protein playing important roles in cellular responses, including cell growth, cell cycle, gene expression, and apoptosis, to maintain the redox circumstance. Moreover, many recent papers have shown that the redox regulation by TRX is deeply involved in the pathogenesis of various oxidative stress-associated disorders. This review focuses on TRX and its related molecules, and discusses the role of TRX-dependent redox regulation in oxidative stress-induced signal transduction.


Bacterial vaginosis, human papilloma virus and herpes viridae do not predict vaginal HIV RNA shedding in women living with HIV in Denmark.
Bacterial vaginosis (BV) has been found to be associated with HIV acquisition and transmission. This is suggested to be due to higher HIV RNA levels in cervicovaginal fluids in women living with HIV (WLWH) with BV, as bacteria associated with BV may induce viral replication and shedding in the genital tract despite undetectable HIV RNA plasma viral load. We examined the prevalence and diagnostic predictors of BV and HIV-1 RNA vaginal shedding in women living with HIV (WLWH) in Denmark, taking into account the presence of human papillomavirus (HPV) and herpes viridae. WLWH between 18-51 years were recruited from six Departments of Infectious Diseases in Denmark during enrolment in the SHADE cohort; a prospective cohort study of WLWH attending regular outpatient care. BV was diagnosed by microscopy of vaginal swabs and PCR was used for detection of BV-associated bacteria, HPV, herpes viridae, and vaginal HIV viral load. Median age of the 150 included women was 41 years; ethnicity was predominantly White (35%) or Black (47%). The majority (96%) was on ART and had undetectable (85%) plasma HIV RNA (<40 copies/mL). BV was diagnosed in 32%. Overall, 11% had detectable vaginal HIV RNA. Both before and after adjustment for BV, age, ethnicity, plasma HIV RNA, CD4 cell count, herpes viridae and HPV, we found no significant predictors of HIV RNA vaginal shedding. In well-treated WLWH, BV, herpes viridae or HPV do not predict vaginal HIV RNA shedding. This implies that HIV shedding does not seem to be increased by BV.


DOES FATHERS' PRENATAL MENTAL HEALTH BEAR A RELATIONSHIP TO PARENTING STRESS AT 6 MONTHS?
This study aimed to explore fathers' mental health and retrospectively reported adverse childhood experiences during pregnancy, as well as various pathways predicting self-reported stress at 6 months' postpartum as assessed by the Parenting Stress Index (PSI; R.R. Abidin, ). A total of 835 fathers contributed data to the study. Data collection comprised five time points during pregnancy and one at 6 months' postpartum. The main analyses were performed using linear regression and path analyses. First, linear regression analyses showed that paternal anxiety symptoms during pregnancy predicted stress scores in the PSI child domain at 6 months (coefficient = 0.36). Second, path analyses showed that depressive symptoms during pregnancy predicted parenting stress in the child domain, mediated by spousal disharmony at 6 months' postpartum (coefficient = 0.77). Third, adverse childhood experiences scores predicted parenting stress in the child domain by two different pathways: one mediated by anxiety symptoms in pregnancy (coefficient = 0.29) and the other by depressive symptoms in pregnancy and experienced spousal disharmony at 6 months' postpartum (coefficient = 0.77). The findings suggest that fathers' symptoms of anxiety and depression during pregnancy as well as adverse childhood experiences predict paternal stress and a negative perception of their children's behavior at 6 months' postpartum.


Building a Culture of Continuous Improvement and Employee Engagement Using a Daily Management System Part 1: Overview.
A daily management system (DMS) can be used to implement continuous quality improvement and advance employee engagement. It can empower staff to identify problems in the care environment that impact quality or workflow and to address them on a daily basis. Through DMS, improvement becomes the work of everyone, every day. The authors of this 2-part series describe their work to develop a DMS. Part 1 describes the background and organizing framework of the program.


Field physiology in the aquatic realm: ecological energetics and diving behavior provide context for elucidating patterns and deviations.
Comparative physiology has developed a rich understanding of the physiological adaptations of organisms, from microbes to megafauna. Despite extreme differences in size and a diversity of habitats, general patterns are observed in their physiological adaptations. Yet, many organisms deviate from the general patterns, providing an opportunity to understand the importance of ecology in determining the evolution of unusual adaptations. Aquatic air-breathing vertebrates provide unique study systems in which the interplay between ecology, physiology and behavior is most evident. They must perform breath-hold dives to obtain food underwater, which imposes a physiological constraint on their foraging time as they must resurface to breathe. This separation of two critical resources has led researchers to investigate these organisms' physiological adaptations and trade-offs. Addressing such questions on large marine animals is best done in the field, given the difficulty of replicating the environment of these animals in the lab. This Review examines the long history of research on diving physiology and behavior. We show how innovative technology and the careful selection of research animals have provided a holistic understanding of diving mammals' physiology, behavior and ecology. We explore the role of the aerobic diving limit, body size, oxygen stores, prey distribution and metabolism. We then identify gaps in our knowledge and suggest areas for future research, pointing out how this research will help conserve these unique animals.


Inactivation of bacteria by Purogene.
The bacteriocidal efficacy of Purogene, a stabilized aqueous solution of chlorine dioxide (ClO2) was examined using bacteria of concern to public health. The organisms tested were: Escherichia coli, Pseudomonas aeruginosa, Yersinia enterocolitica, Klebsiella pneumoniae, Streptococcus pyogenes Group A, Salmonella typhimurium and Bacillus subtilis. The test organisms responded differently to inactivation by Purogene. At least a 4 log reduction in bacterial counts was noted when Purogene was applied at a concentration of 0.75 mg/l. Since Purogene is a stabilized complex, it was necessary to provide a chemical environment suitable for the release of ClO2 in this solution. This was done by varying the pH of Purogene from 3.5 to 8.6 (pH of Purogene is 8.6) while keeping the pH of the experimental medium constant (pH 7.0). The results showed that Purogene was most efficacious at the lowest pH tested (pH 3.5). This indicates that as chlorine dioxide solutions were reduced to chlorite (which predominates at pH 8.6), their bacteriocidal efficacy was reduced, suggesting free chlorine dioxide as the active disinfecting species.


Coexisting psoriasis,psoriatic arthritis, gout and Dupuytren's contracture.
The authors describe the case of a 60-year-old Caucasian man with psoriasis who subsequently developed psoriatic arthritis, gout and Dupuytren's contracture. This is the first report documenting the simultaneous occurrence of psoriasis, psoriatic arthritis, gout and Dupuytren's contracture in a single patient. The etiopathology underlying the concurrent presence of these diseases is discussed.


Ion-pumping microbial rhodopsins.
Rhodopsins are light-sensing proteins used in optogenetics. The word "rhodopsin" originates from the Greek words "rhodo" and "opsis," indicating rose and sight, respectively. Although the classical meaning of rhodopsin is the red-colored pigment in our eyes, the modern meaning of rhodopsin encompasses photoactive proteins containing a retinal chromophore in animals and microbes. Animal and microbial rhodopsins possess 11-cis and all-trans retinal, respectively, to capture light in seven transmembrane α-helices, and photoisomerizations into all-trans and 13-cis forms, respectively, initiate each function. Ion-transporting proteins can be found in microbial rhodopsins, such as light-gated channels and light-driven pumps, which are the main tools in optogenetics. Light-driven pumps, such as archaeal H(+) pump bacteriorhodopsin (BR) and Cl(-) pump halorhodopsin (HR), were discovered in the 1970s, and their mechanism has been extensively studied. On the other hand, different kinds of H(+) and Cl(-) pumps have been found in marine bacteria, such as proteorhodopsin (PR) and Fulvimarina pelagi rhodopsin (FR), respectively. In addition, a light-driven Na(+) pump was found, Krokinobacter eikastus rhodopsin 2 (KR2). These light-driven ion-pumping microbial rhodopsins are classified as DTD, TSA, DTE, NTQ, and NDQ rhodopsins for BR, HR, PR, FR, and KR2, respectively. Recent understanding of ion-pumping microbial rhodopsins is reviewed in this paper.


Effects of minocycline and tetracycline on the vaginal yeast flora.
Two groups of women with non-specific genital infection were treated for two weeks with tetracycline 250 mg six-hourly and minocycline 100 mg twice daily respectively. Cultures for yeasts were performed before treatment and at the end of the first and second weeks. Before treatment yeasts, mostly Candida albicans, were recovered from 13% of the women. After one and two weeks' treatment yeasts were isolated from 22 and 29% of women treated with tetracycline, and from 19 and 29% of women treated with minocycline. It is concluded that despite inhibition of the growth of yeasts shown by minocycline in vitro, there is no evidence of any significant difference between the actions of tetracycline and minocycline on the vaginal yeast flora.


Mental Health, Social Support, and Death Anxiety in Patients With Chronic Kidney Failure.
Purpose: This study aimed to investigate the relationship between mental health, perceived social support, and death anxiety, and the predictive roles of mental health and perceived social support in the explanation of death anxiety in a sample of adults with chronic kidney disease. Methods: A demographic questionnaire, the Symptom Check List-25, the Social Support Survey Scale, and the Death Anxiety Scale (DAS) were used in the present study. The sample consisted of 58 adult patients with chronic kidney failure. Results: Findings showed that mental health had significantly positive relationships to the total score of the death anxiety and the fear of death, the fear of pain and disease, and the death thoughts subscales of the DAS. Social support had a significant negative relationship to the total score of the death anxiety and the fear of pain and disease, the death thoughts, and the transient time and the short life subscales of the DAS. Mental health and combined mental health and social support explained 14% and 21% of death anxiety variation in patients with chronic kidney failure, respectively. Conclusion: Mental health and social support constructs can relatively predict the variations of death anxiety in patients with chronic kidney failure.


Future trends in the treatment of urinary incontinence.
Anticholinergic drugs act on efferent nerves to counteract overactive bladder (OAB) after it occurs. To prevent the occurrence of OAB, therapies should be directed at blocking the afferent nerves that control the bladder. Tachykinin-receptor antagonists hold great promise in this regard, since they can be administered orally and do not increase the risk of urinary retention that occurs with anticholinergics. Advanced drug delivery systems, such as controlled-release oral oxybutynin (oxybutynin-XL) can reduce the incidence of anticholinergic side effects. In a similar manner intravesical therapy for OAB is site specific, and thus also reduces the occurrence of adverse events. Moreover, the difficulties of intravesical therapy may now be overcome with advanced delivery techniques such as an implantable, long-acting drug-delivery pump. Another intravesical therapy that has met with great acceptance and success is the administration of chili pepper extracts, especially resiniferitoxin, which may be effective for up to 3 months with one application. Finally, gene therapy holds great promise for OAB, because it is possible to access all of the genitourinary organs via endoscopy and other minimally invasive techniques that are ideally suited for gene therapy.


Effect of Combined Antihypertensive and Lipid-Lowering Therapies on Cognitive Function: A New Treatment Strategy?
Risk factors for cardiovascular disease such as hypertension and hyperlipidemia are associated with cognitive decline. However, there is still no clear evidence that the use of antihypertensive or lipid-lowering therapy can prevent or delay cognitive decline or development of dementia. To provide a reference for clinical treatment, we analyzed the potential mechanisms of cognitive dysfunction induced by hypertension and hyperlipidemia, the clinical research and controversy of antihypertensive and lipid-lowering therapies on cognitive function, and the clinical value of combined antihypertensive and lipid-lowering therapy. It is currently believed that hypertension and elevated blood cholesterol levels in middle-aged people may be related to cognitive impairment or dementia in the elderly. Some studies suggest that intensive antihypertensive or lipid-lowering therapies are better than standard antihypertensive or lipid-lowering therapy, yet further tests are needed to confirm their effects on cognitive function. Actively controlling potential risk factors from middle age may be important for Alzheimer's disease (AD) prevention.


Loperamide plus azithromycin more effectively treats travelers' diarrhea in Mexico than azithromycin alone.
Because the combination of loperamide and some antimicrobials has proven to be more efficacious than the antimicrobial agent alone in the treatment of travelers' diarrhea, we set out to prove loperamide plus azithromycin was more efficacious than azithromycin alone. During the summers of 2002 to 2003, 176 US adults recently arrived in Guadalajara, Mexico were enrolled in a prospective, double-blinded, randomized trial of the treatment of acute diarrhea. Subjects received single doses (1,000 or 500 mg) of azithromycin or a single 500 mg dose of azithromycin plus loperamide. Subjects gave a pre- and post-treatment stool sample for analysis and maintained daily diaries of symptoms and passage of stools. The duration of diarrhea was significantly (p=0.0002) shorter following treatment with azithromycin plus loperamide (11 h) than with either dose of azithromycin alone (34 h). In the first 24 hours, the average number of unformed stools passed was 3.4 (azithromycin alone) and 1.2 (combination) for a significant (p<0.0001) difference of 2.2 unformed stools. This difference equated with 20% of azithromycin-treated subjects continuing to pass six or more unformed stools in the first 24 hours post-treatment compared with only 1.7% of combination-treated subjects. For the treatment of travelers' diarrhea in an Escherichia coli predominant region of the world, a single 500 mg dose of azithromycin appeared as effective as a 1,000 mg dose. Loperamide plus 500 mg of azithromycin was safe and more effective than either dose of azithromycin. To realize the substantial clinical benefit that accrues to a subset of subjects, we feel loperamide should routinely be used in combination with an antimicrobial agent to treat travelers' diarrhea.


[Analysis on current status and influential factors of occupational stress among couriers].
Objective: To investigate the current status and influencing factors of occupational stress among couriers. Methods: Couriers (n=925) were selected on this study used cluster sampling method from January to March 2018. They were from SF and Zhongtong Express Co., Ltd., on the Wechat platform, and surveyed by a job stress questionnaire based on a job demand-control model.Valid questionnaires(n=617) were obtained. Results: A total of 418 workers were occupational stress positive (67.7%). The results of Chi-square analysis showed that there were significant differences in occupational stress among workers categorized by job position, working years, mealtime, sleeping time, and weekly work time (P<0.05). The multivariate logistic analysis indicated that non-regular meals, short-term sleep and less than 0.5 working years were risk factors for occupational stress(P<0.05). Conclusion: Couriers generally have occupational stress. The main influencing factors are job position, working years mealtime, sleeping time, and weekly work time. It is necessary to guide healthy lifestyle, rationally organize labor and assign tasks, and improve working environment to relieve their occupational stress.


Host-plant genotypic diversity mediates the distribution of an ecosystem engineer.
Ecosystem engineers affect ecological communities by physically modifying the environment. Understanding the factors determining the distribution of engineers offers a powerful predictive tool for community ecology. In this study, we examine whether the goldenrod bunch gall midge (Rhopalomyia solidaginis) functions as an ecosystem engineer in an old-field ecosystem by altering the composition of arthropod species associated with a dominant host plant, Solidago altissima. We also examine the suite of factors that could affect the distribution and abundance of this ecosystem engineer. The presence of bunch galls increased species richness and altered the structure of associated arthropod communities. The best predictors of gall abundance were host-plant genotype and plot-level genotypic diversity. We found positive, nonadditive effects of genotypic diversity on gall abundance. Our results indicate that incorporating a genetic component in studies of ecosystem engineers can help predict their distribution and abundance, and ultimately their effects on biodiversity.


Surface analysis of a nano-sized oxide formed on alloy 600 in a high temperature/pressure aqueous solution.
Even though nickel based Alloy 600 (Ni 75 wt%, Cr 15 wt% and Fe 10 wt%) shows superior corrosion and mechanical properties, numerous corrosion problems, caused by a long time exposure of more than 30 years under a high temperature and high pressure water chemical environment have occurred. Especially, a lead induced stress corrosion cracking (SCC) has been a very important issue. A SCC is deeply related to a nano-sized oxide properties, formed on an Alloy 600 surface, because a crack initiates and propagates through a breakdown and modification of a thin surface oxide formed naturally on Alloy 600 in an aqueous solution. Therefore an investigation of an oxide properties would provide key information to elucidate the mechanism of a SCC and to establish a countermeasure. In the present work, a surface oxide film formed on Alloy 600 in an aqueous solution at 315 degrees C without/with a lead oxide and nickel boride as a SCC accelerator and an inhibitor, respectively, was analyzed by using a transmission electron microscopy, equipped with an energy dispersive X-ray spectroscopy and an X-ray photoelectron spectroscopy, equipped with an ion sputter for a depth profiling. In both the ammonia solutions without/with NiB, a duplex oxide layer was formed, i.e., a porous outer oxide mainly composed of NiO and Ni(OH)2 and a relatively dense inner Cr2O3 layer. Lead was incorporated into the oxide layer leading to a Cr depletion in the oxide layer and a passivity degradation. The passivity of the surface oxide was increased when NiB was added into a solution with PbO, which was in accordance with the increase of the SCC resistance. Passivity degradation by lead and the inhibitive mechanism of nickel boride were explained by a defect chemistry in an oxide semiconductor and an adhesion preference as a function of the wetting angle, respectively.


Directed Evolution as a Probe of Rate Promoting Vibrations Introduced via Mutational Change.
In this article, we study with transition path sampling and reaction coordinate analysis how directed evolution in the Kemp eliminase family of artificial enzymes makes differential use of rapid rate promoting vibrations as a component of their chemical mechanism. Even though this family was initially created by placing the expected active site in a fixed protein matrix, we find a shift from largely static to more dynamic active sites that make use of donor-acceptor compression as the evolutionary process proceeds. We see that this introduction of dynamics significantly shifts the order of processes in the reaction. We also suggest that the lack of "design for dynamics" may help explain the relatively low proficiency of such designed enzymes.


Intra-abdominal bleeding during treprostinil infusion in a patient with pulmonary arterial hypertension.
Medical treatment of pulmonary arterial hypertension (PAH) is increasingly common. Prostacyclins were introduced in the early 90s, and treprostinil is one of the most frequently used drugs of this class today, owing to its long half-life and to the possibility to administer the molecule through several routes. Treprostinil is considered a safe drug and is associated with a significant improvement of exercise capacity, especially in patients with idiopathic PAH (iPAH). Systemic sclerosis-associated PAH (sc-PAH) correlates to a worse prognosis compared with that of iPAH. Despite these considerations, safety data on treprostinil are still limited and mainly derived from randomised controlled trials and retrospective studies with relatively small and heterogeneous cohorts of patients with PAH. We report the occurrence of a severe intra-abdominal bleeding during treprostinil infusion in a patient with sc-PAH.


ADP-ribosyl transferase and NAD glycohydrolase activities in rat liver mitochondria.
ADP-ribosyl transferase and NAD glycohydrolase activities have been estimated in mitochondria in mitoplasts as well as in other submitochondrial fractions. A high activity of these two enzymes was present in mitoplasts as compared to the outer membrane preparation or intermembrane compartment. Inhibitor studies provide strong evidence for the involvement of ADP-ribosyl transferase in the process of ADP-ribosylation of mitochondrial proteins. When NAD glycohydrolase was blocked by nicotinamide or 3-aminobenzamide, the incorporation of ADP-ribose into mitochondrial proteins still occurs. ADP-ribosyl transferase activity could also be detected when NAD glycohydrolase was separated by hydroxylapatite chromatography. The protein-linked ADP-ribose moiety appears to be an oligomer in mitochondria.


Complications in surgical patients.
Complications are common in hospitalized surgical patients. Provider error contributes to a significant proportion of these complications. Surgical patients were concurrently observed for the development of explicit complications. All complications were reviewed by the attending surgeon and other members of the service and evaluated for the severity of sequelae (major or minor) and for whether the complication resulted from medical error (avoidable) or not. University teaching hospital with a level I trauma designation. All inpatients (operative or nonoperative) from 4 different surgical services: general surgery, combined general surgery and trauma, vascular surgery, and cardiothoracic surgery. Total complication rate (number of complications divided by the number of patients) and the number of patients with complications. Complications were separated into those with major or minor sequelae and the proportion of each type that were due to medical error (avoidable). Rates of complications in a recent Institute of Medicine report were used as a criterion standard. The data for the respective groups (general surgery, vascular surgery, combined general surgery and trauma, and cardiothoracic surgery) are as follows. The number of patients was 1363, 978, 914, and 1403; number of complications, 413, 409, 295, and 378; total complication rate, 30.3%, 42.4%, 32.3%, and 26.9%; minor complication rate, 13.3%, 19.9%, 13.5%, and 13.0% (percentage of minor complications that were avoidable, 37.4%, 59.0%, 51.2%, and 49.5%); major complication rate, 16.2%, 21.1%, 18.1%, and 12.9% (percentage of major complications that were avoidable, 53.4%, 60.7%, 38.8%, and 38.7%); and mortality rate, 1.83%, 3.33%, 2.28%, and 3.34% (percentage of mortality that was avoidable, 28.0%, 44.1%, 19.0%, and 25.0%). Despite mortality rates that compare favorably with national benchmarks, a prospective examination of surgical patients reveals complication rates that are 2 to 4 times higher than those identified in an Institute of Medicine report. Almost half of these adverse events were judged contemporaneously by peers to be due to provider error (avoidable). Errors in care contributed to 38 (30%) of 128 deaths. Recognition that provider error contributes significantly to adverse events presents significant opportunities for improving patient outcomes.


Anti-IL-17 antibody improves hepatic steatosis by suppressing interleukin-17-related fatty acid synthesis and metabolism.
To investigate the relationship between interleukin-17 and proteins involved in fatty acid metabolism with respect to alcoholic liver disease, male ICR mice were randomized into five groups: control, alcoholic liver disease (ALD) at 4 weeks, 8 weeks, and 12 weeks, and anti-IL-17 antibody treated ALD. A proteomic approach was adopted to investigate changes in liver proteins between control and ALD groups. The proteomic analysis was performed by two-dimensional difference gel electrophoresis. Spots of interest were subsequently subjected to nanospray ionization tandem mass spectrometry (MS/MS) for protein identification. Additionally, expression levels of selected proteins were confirmed by western blot. Transcriptional levels of some selected proteins were determined by RT-PCR. Expression levels of 95 protein spots changed significantly (ratio >1.5, P < 0.05) during the development of ALD. Sterol regulatory element-binding protein-lc (SREBP-1c), carbohydrate response element binding protein (ChREBP), enoyl-coenzyme A hydratase (ECHS1), and peroxisome proliferator-activated receptor alpha (PPAR-α) were identified by MS/MS among the proteins shown to vary the most; increased IL-17 elevated the transcription of SREBP-1c and ChREBP but suppressed ECHS1 and PPAR-α. The interleukin-17 signaling pathway is involved in ALD development; anti-IL-17 antibody improved hepatic steatosis by suppressing interleukin-17-related fatty acid metabolism.


A measure of cortico-cortical potentials evoked by 10 Hz direct electrical stimulation of the brain and by means of a differential recording mode of electrocorticographic signals.
Direct electrical stimulation (DES) at 60 Hz is used to perform real-time functional mapping of the brain during wide-awake neurosurgery. The electrophysiological effects of DES are largely unknown, locally and at a more remote distance. Here, by lowering the DES frequency to 10 Hz and by using a differential recording mode of electro-corticographic (ECoG) signals to improve the focality, we were able to record cortico-cortical evoked potentials easily with standard current amplitude of stimulation (2 mA). DES applied at 10 Hz and differential recording of ECoG could be used to map on-line the connectivity between different sub-cortical and cortical areas with a higher spatial accuracy.


Osteomyelitis of the skull vault from a human bite.
We report a case of extensive osteomyelitis of the skull vault from a human bite. The presentation and surgical management of this unusual condition is described. The microbiological findings are comparable to known patterns of infection after human bites. Surgical management and prophylaxis after this injury are discussed.


[Data reduction, smoothing and base line correction preceding an automatic evaluation of ECG signals (author's transl)].
In storing electronically digital data of signals, too many items are used. Especially the great number of data produced in the analogue-digital-conversion of the ECG leads to serious problems in long distance transmission and storage. It is proposed to described such ECG signals through polynominal fragments, to which such a position across the noise-level distorted data is given that at the same time the data are levelled in a flexible manner. Based on these calculated reduced data, shape recognition problems can be solved more easily. As an example, a suggestion is given to construct the isoelectric segment of an ECG.


Interleukin-2 induced mitogenesis of human peripheral blood T-lymphocytes: role of accessory cells.
We and others have shown that interleukin-2 (IL-2) is mitogenic to a subset of unstimulated T lymphocytes in human peripheral blood (1-7). We extend our work here in showing that prolonged continuous exposure of human peripheral blood lymphocytes to exogenous IL-2 throughout the 7-8 day culture is not necessary since mitogenesis occurs reproducibly after short term (2-3 hr) pulse exposure. The mitogenic effect of pulse exposure to IL-2 is not significantly reduced by inclusion of anti-Tac monoclonal antibody in the pulsing medium. However, anti-Tac monoclonal antibody markedly inhibits the response if present continuously throughout the 7 day culture. The mitogenic effect of IL-2 is dependent on the presence of accessory cells (monocytes) but the accessory cell requirement can be replaced by the phorbol ester TPA (10(-8 to 10(-11) M). Purified monocytes subjected to short term pulse exposure to IL-2 can cause proliferative response in unprimed autologous lymphocytes in co-cultures. The mitogenic effect of IL-2 pulsed monocytes can not be suppressed by inclusion of anti-Tac antibody in the pulsing medium although the same concentration of the antibody suppresses the effect if present throughout culture. The response of lymphocytes to IL-2 pulsed monocytes is not inhibitable by the continuous presence of a monoclonal antibody to human HLA-DR antigens (OK-Ia1) in culture.


The rete mirabile of the maxillary artery in the lion (Panthera leo).
The afferent and efferent arterial branches of the maxillary rete were investigated in 4 lion (Panthera s. Felis leo) heads preserved in the author's department. The heads were injected with acryl plastic via the common carotid arteries to make corrosion casts of the carotid system, and examined from the standpoint of comparative anatomy. The following afferent arterial branches were observed. Medial retial branches from the maxillary artery, anterior retial branches from the anterior deep temporal artery and intraretial branches of the maxillary artery passing in the rete. The rete was constructed from the following arterial resources: Most of the lateral and inferior surfaces of the rete and deep part of the maxillary nerve tunnel from the intraretial branches; the posterior surface and posterior part of the lateral surface from the medial retial branches, and the anterosuperior part of the lateral surface from the anterior retial branches. Eight efferent arterial branches were observed. The external ethmoidal, lacrimal, interretial and anastomotic arteries, the extraocular muscular, meningeal and temporal muscular branches and the communicating branch with the external ethmoidal artery. The anastomotic artery was always well developed and played the role of the main supply route to the brain instead of the obliterated internal carotid artery as observed in the cat. Unlike that of the cat, however, the maxillary artery of the lion always passed lateral to the pterygoideus lateralis muscle, and the lateral part of the rete was not constructed because there were no lateral retial branches such as those observed in the cat.


Long-distance RNA-RNA interactions between terminal elements and the same subset of internal elements on the potato virus X genome mediate minus- and plus-strand RNA synthesis.
Potexvirus genomes contain conserved terminal elements that are complementary to multiple internal octanucleotide elements. Both local sequences and structures at the 5' terminus and long-distance interactions between this region and internal elements are important for accumulation of potato virus X (PVX) plus-strand RNA in vivo. In this study, the role of the conserved hexanucleotide motif within SL3 of the 3' NTR and internal conserved octanucleotide elements in minus-strand RNA synthesis was analyzed using both a template-dependent, PVX RNA-dependent RNA polymerase (RdRp) extract and a protoplast replication system. Template analyses in vitro indicated that 3' terminal templates of 850 nucleotides (nt), but not 200 nt, supported efficient, minus-strand RNA synthesis. Mutational analyses of the longer templates indicated that optimal transcription requires the hexanucleotide motif in SL3 within the 3' NTR and the complementary CP octanucleotide element 747 nt upstream. Additional experiments to disrupt interactions between one or more internal conserved elements and the 3' hexanucleotide element showed that long-distance interactions were necessary for minus-strand RNA synthesis both in vitro and in vivo. Additionally, multiple internal octanucleotide elements could serve as pairing partners with the hexanucleotide element in vivo. These cis-acting elements and interactions correlate in several ways to those previously observed for plus-strand RNA accumulation in vivo, suggesting that dynamic interactions between elements at both termini and the same subset of internal octanucleotide elements are required for both minus- and plus-strand RNA synthesis and potentially other aspects of PVX replication.


Comparison of electrode sites in electrical stimulation of the cochlea.
There is considerable controversy about the "best" location for single channel cochlear implant electrodes. We measured the electrically induced auditory brain stem response (EABR) in a series of normal to totally denervated cat ears in response to promontory (P), round window (RW) and scala tympani (ST) stimulation. The status of the ganglion cell population was then assessed by light microscopy. In ears with light to medium ganglion cell loss the ST EABR yielded the most definitive input-output functions. RW responses were present at increased thresholds and smaller peak amplitudes. P responses were worse or even missing completely. In severely damaged ears, including some with no detectable ganglion cells, ST and RW EABRs were both markedly reduced with considerable overlap between the two sites. P responses, when present, were almost buried in the electrical noise near threshold. Extrapolating these results to humans suggests that when ganglion cell loss is very severe the RW or ST is an acceptable stimulation site. When ganglion cell loss is moderate or better, ST electrodes are superior.


The r(20) syndrome.
A 21-year-old woman with a ring-20 chromosome is described. The clinical findings, behaviour problems, epilepsy, and low grade mental retardation are the same as in the 3 cases described earlier. It seems to be justified to speak of a specific ring-20 syndrome.


The Impact of COVID-19 on Patient, Family Member, and Stakeholder Research Engagement: Insights from the PREPARE NOW Study.
Little is known about the impact of COVID-19 on patient, family member, and stakeholder patient-centered outcomes research engagement. To answer the research questions: (1) What is the impact of COVID-19 on the lives of patients with kidney disease and their families? (2) What is the impact of COVID-19 on research engagement for patient and family member research team members who are themselves at very high risk for poor COVID-19 outcomes? and (3) How can we help patients, family members, and stakeholder team members engage in research during COVID-19? We conducted virtual semi-structured interviews with patient and family member co-investigators and kidney disease stakeholders from the PREPARE NOW study during November 2020. The interview guide included questions about participants' experiences with the impact of COVID-19 on research engagement. Seven patient and family member co-investigators and eight kidney disease stakeholders involved in a kidney disease patient-centered outcomes research project participated in the interviews, data analysis, and writing this manuscript. We used a content analysis approach and identified the main themes using an inductive process. Respondents reported three main ways that COVID-19 has impacted their lives: emotional impact, changing behaviors, and changes in health care delivery. The majority of respondents reported no negative impact of COVID-19 on their ability to engage in this research project. Suggestions for patient-centered outcomes research during COVID-19 and other emergencies include virtual research activities; active engagement; and promoting trust, honesty, transparency, and authenticity. COVID-19 has had a significant negative impact on patient, family member, and stakeholder research team members; however, this has not resulted in less research engagement. Clinicaltrials.gov NCT02722382.


Pathogenicity of clade 220.127.116.11 H5N1 highly pathogenic avian influenza virus in American kestrel (Falco sparverius).
Birds of prey, including endangered species, have been infected with H5 highly pathogenic avian influenza viruses (HPAIVs) in several countries. In this present study, we assessed the pathogenicity of the clade 184.108.40.206 H5N1 HPAIV in American kestrels (Falco sparverius) with a view to preventing future outbreaks in raptors. The kestrels were intranasally inoculated with the virus or fed the meat of chicks that had died from viral infection. Kestrels in both groups initially had reduced food intake, showed clinical signs such as depression and neurologic manifestations, and succumbed to the infection within 6 days. The kestrels primarily shed the virus orally from 1 day post-inoculation until death, with an average titre of 104.5-5.7 EID50/ml, which is comparable to the inoculum titre. The viruses replicated in almost all tested tissues; notably, the feather calamuses also contained infectious virions and/or viral genes. Pancreatic lesions were present in several infected birds, as shown in previous cases of HPAIV infection in raptors. These results indicate that kestrels are highly susceptible to infection by clade 184.108.40.206 H5 HPAIVs, which readily occurs through the consumption of infected bird carcasses. Early detection and removal of HPAIV infected carcasses in the field is essential for preventing outbreaks in raptors. RESEARCH HIGHLIGHTS Clade 22.214.171.124 H5 HPAIV caused lethal infection in American kestrels. Kestrels with the HPAIV showed neurologic signs and eye disorders. The HPAIV replicated in systemic tissues of kestrels, and was orally shed. The HPAIV was recovered from feather calamus of kestrels.


Impaired germinal center responses and suppression of local IgG production during intracellular bacterial infection.
Germinal centers (GCs) are specialized microenvironments in secondary lymphoid organs that facilitate the development of high-affinity, isotype-switched Abs, and immunological memory; consequently, many infections require GC-derived IgG for pathogen clearance. Although Ehrlichia muris infection elicits a robust expansion of splenic, IgM-secreting plasmablasts, we detected only very low frequencies of isotype-switched IgG-secreting cells in mouse spleens, until at least 3 wk postinfection. Instead, Ag-specific IgG was produced in lymph nodes, where it required CD4 T cell help. Consistent with these findings, organized GCs and phenotypically defined splenic GC B cells were found in lymph nodes, but not spleens. Ehrlichial infection also inhibited spleen IgG responses against a coadministered T cell-dependent Ag, hapten 4-hydroxy-3-nitrophenyl acetyl (NP)-conjugated chicken gamma globulin in alum. NP-specific B cells failed to undergo expansion and differentiation into GC B cells in the spleen, Ab titers were reduced, and splenic IgG production was inhibited nearly 10-fold when the Ag was administered during infection. Our data provide a mechanism whereby an intracellular bacterial infection can compromise local immunity to coinfecting pathogens or antigenic challenge.


Surface-Driven Keto-Enol Tautomerization: Atomistic Insights into Enol Formation and Stabilization Mechanisms.
Tautomerisation of simple carbonyl compounds to their enol counterparts on metal surfaces is envisaged to enable an easier route for hydrogenation of the C=O bond in heterogeneously catalyzed reactions. To understand the mechanisms of enol formation and stabilization over catalytically active metal surfaces, we performed a mechanistic study on keto-enol tautomerization of a monocarbonyl compound acetophenon over Pt(111) surface. By employing infrared reflection adsorption spectroscopy in combination with scanning tunneling microscopy, we found that enol can be formed by building a ketone-enol dimer, in which one molecule in the enol form is stabilized through hydrogen bonding to the carbonyl group of the second ketone molecule. Based on the investigations of the co-adsorption behavior of acetophenone and hydrogen, we conclude that keto-enol tautomerization occurs in the intramolecular process and does not involve hydrogen transfer through the surface hypothesized previously.


Numerical modeling of atoll island hydrogeology.
We implemented Ayers and Vachers' (1986) inclusive conceptual model for atoll island aquifers in a comprehensive numerical modeling study to evaluate the response of the fresh water lens to selected controlling climatic and geologic variables. Climatic factors include both constant and time-varying recharge rates, with particular attention paid to the effects of El Niño and the associated drought it brings to the western Pacific. Geologic factors include island width; hydraulic conductivity of the uppermost Holocene-age aquifer, which contains the fresh water lens; the depth to the contact with the underlying, and much more conductive, Pleistocene karst aquifer, which transmits tidal signals to the base of the lens; and the presence or absence of a semiconfining reef flat plate on the ocean side. Sensitivity analyses of steady-steady simulations show that lens thickness is most strongly sensitive to the depth to the Holocene-Pleistocene contact and to the hydraulic conductivity of the Holocene aquifer, respectively. Comparisons between modeling results and published observations of atoll island lens thicknesses suggest a hydraulic conductivity of approximately 50 m/d for leeward islands and approximately 400 m/d for windward islands. Results of transient simulations show that lens thickness fluctuations during average seasonal conditions and El Niño events are quite sensitive to island width, recharge rate, and hydraulic conductivity of the Holocene aquifer. In general, the depletion of the lens during drought conditions is most drastic for small, windward islands. Simulation results suggest that recovery from a 6-month drought requires about 1.5 years.


Comparison Of Dietary Practices And Body Mass Index Among Educated Housewives And Working Women In Karachi.
Body Mass Index (BMI) is considered as a major determinant of health. The objective of study was to find out differences between dietary practices, as well as BMI in educated housewives and working woman. It is supposed that both study groups may have difference in work pressures with resultant diverse preferences for food. This can affect health status particularly in relation to obesity in women. Furthermore, we selected participants with 14 years' education expecting basic awareness of healthful diet. This cross-sectional study had a convenient sampling method and sample size of 600 with 300 house wives and 300 working women, aged 35-45 years. Dietary habits were recorded by interview. Body Mass Index was calculated by standard formula, and results obtained by Chi-Square using SPSS-17. Working women had healthier dietary practices. Number of meals, fruits, fish/ poultry and water consumption was better in working mothers with significant p-value <0.00.1. Intake of vegetables and fast food was found similar. BMI comparison showed that majority of housewives were noted as overweight whereas working women showed normal weight (p-value <0.001). Most housewives responded that they have a sedentary life style as opposed to working women p-value <0.001. Self- assessment of diet quality was comparable as it was mentioned moderate by most of the participants, however more working females accepted that they need to improve their diet and would need expert advice. Healthier BMI, active life style and better dietary habits were witnessed in working women as compared to housewives.


Occurrence of symptom clusters.
Although concurrent symptoms are frequently reported in clinical practice, symptom management research has not reflected this reality. Concurrent, related symptoms, i.e., symptom clusters, are possibly the next generation of work to be done in the area of symptom management. It has been suggested that certain clusters of symptoms may have a synergistic effect on future patient outcomes, and may predict morbidity. The overall goal of this article is to present initial research in the area, along with strategies for development of the concept of symptom clusters. In addition, a working definition of symptom clusters is offered, as well as current issues with the concept and suggestions for future research.


Reversible complete atrioventricular block in a neonate with maternal anti-Sjögren's syndrome-associated antibody: atypical phenotype of autoimmune congenital heart block.
The fetus of anti-Sjögren's syndrome-associated antibody-positive mother developed complete atrioventricular block at 39 weeks of gestation and required urgent ventricular pacing after birth. Unexpectedly, the patient recovered from the atrioventricular block within a few days. Fraction analysis of maternal anti-Sjögren's syndrome-associated antibody revealed positivity for isolated anti-Ro/SSA 60 kDa antibody, which is abnormal as most patients with complete atrioventricular block present with anti-Ro/SSA 52 kDa positivity, which may indicate a potentially atypical late and reversible manifestation of an autoimmune congenital atrioventricular block in this patient.


Nitric oxide in cerebral vasospasm: theories, measurement, and treatment.
In recent decades, a large body of research has focused on the role of nitric oxide (NO) in the development of cerebral vasospasm (CV) following subarachnoid hemorrhage (SAH). Literature searches were therefore conducted regarding the role of NO in cerebral vasospasm, specifically focusing on NO donors, reactive nitrogen species, and peroxynitrite in manifestation of vasospasm. Based off the assessment of available evidence, two competing theories are reviewed regarding the role of NO in vasospasm. One school of thought describes a deficiency in NO due to scavenging by hemoglobin in the cisternal space, leading to an NO signaling deficit and vasospastic collapse. A second hypothesis focuses on the dysfunction of nitric oxide synthase, an enzyme that synthesizes NO, and subsequent generation of reactive nitrogen species. Both theories have strong experimental evidence behind them and hold promise for translation into clinical practice. Furthermore, NO donors show definitive promise for preventing vasospasm at the angiographic and clinical level. However, NO augmentation may also cause systemic hypotension and worsen vasospasm due to oxidative distress. Recent evidence indicates that targeting NOS dysfunction, for example, through erythropoietin or statin administration, also shows promise at preventing vasospasm and neurotoxicity. Ultimately, the role of NO in neurovascular disease is complex. Neither of these theories is mutually exclusive, and both should be considered for future research directions and treatment strategies.


Treatment issues with chronic hepatitis C: special populations and pharmacy strategies.
Combination therapy with peginterferon alfa and ribavirin now eliminates detectable hepatitis C virus (HCV) from the blood of more than half of patients with long-term infections. However, many of those infected with HCV have low rates of response to therapy and/or are more susceptible to drug side effects that limit adherence to therapy. African Americans with HCV, for example, tend to be more difficult to cure with drug therapy. Individuals coinfected with both human immunodeficiency virus and HCV are also more difficult to treat. As managed care organizations begin offering anti-HCV therapy to a broader range of patients, special strategies for limiting medication side effects and enhancing overall clinical and economic outcomes will become more important. In particular, assessing the early virologic response to therapy at 12 weeks can help clinicians identify patients who are highly likely to be responsive at the end of the full course, while also identifying likely nonresponders--who can be taken off therapy and thereby avoid unnecessary side effects and costs. In all patients remaining on therapy, efforts to boost adherence will also enhance the overall rate of sustained virologic response. Special attention should be paid to managing depression and cytopenias with patient education and either dose reduction or use of hematopoietic growth factors. These 2 basic treatment strategies--of stopping treatment early or, alternatively, of pressing for full patient compliance over the full course of therapy--are flip sides of the same management coin that health plans and clinicians can employ to optimize results and cost effectiveness with the current standard of therapy for chronic HCV infection.


Crystallization and preliminary X-ray analysis of the DNA binding domain of the Hin recombinase with its DNA binding site.
The Hin recombinase catalyzes site-specific inversion of DNA. Chemical and genetic studies on Hin binding to the recombination sites indicates that both major and minor DNA groove interactions are critical. In order to determine the molecular nature of these interactions, we have crystallized a synthetically derived 52 amino acid peptide consisting of the DNA binding domain of Hin with a 14 base-pair oligonucleotide representing a recombination half-site. This communication presents preliminary diffraction and analysis of these cocrystals and a packing model for the complex within the crystal.


Genetic susceptibility--molecular epidemiology of head and neck cancer.
In parts of the developing world (South Central Asia in particular), squamous cell carcinoma of the head and neck (SCCHN) is one of the most common malignancies encountered. Although tobacco and alcohol are clearly defined as etiologic factors in these malignancies, clinical observations have suggested that inherited genetic factors put some individuals at increased risk for SCCHN. Emerging data (both phenotypic and genotypic) support this concept of genetic susceptibility to SCCHN and point to differences in DNA repair ability, carcinogen metabolism, and cell cycle control as the systems important to the risk of tobacco-induced malignancies. The ability to identify such high-risk individuals will have major influences on the practice of cancer prevention in the future.


Pediatric Drug Development: Outlook for Science-Based Innovation.
There has been significant progress in pediatric drug development during the past 15 years. Results from 1,200 pediatric studies have been submitted to the US Food and Drug Administration (FDA). Over 700 drug labels have been revised with information to guide pediatric use. Two international pediatric trial networks have been established.1,2 The failure rate for pediatric efficacy trials has fallen from over 40%3 to about 20%. Taken together, the outlook for pediatric drug development is positive.


Tetanus toxoid-loaded transfersomes for topical immunization.
Topical immunization is a novel immunization strategy by which antigens and adjuvants are applied topically to intact skin to induce potent antibody and cell-mediated responses. Among various approaches for topical immunization, the vesicular approach is gaining wide attention. Proteineous antigen alone or in combination with conventional bioactive carriers could not penetrate through the intact skin. Hence, specially designed, deformable lipid vesicles called transfersomes were used in this study for the non-invasive delivery of tetanus toxoid (TT). Transfersomes were prepared and characterized for shape, size, entrapment efficiency and deformability index. Fluorescence microscopy was used to investigate the mechanism of vesicle penetration through the skin. The immune stimulating activity of these vesicles was studied by measuring the serum anti-tetanus toxoid IgG titre following topical immunization. The immune response was compared with the same dose of alum adsorbed tetanus toxoid (AATT) given intramuscularly, topically administered plain tetanus toxoid solution, and a physical mixture of tetanus toxoid and transfersomes again given topically. The results indicated that the optimal transfersomal formulation had a soya phosphatidylcholine and sodium deoxycholate ratio of 85:15%, w/w. This formulation showed maximum entrapment efficiency (87.34 +/- 3.81%) and deformability index (121.5 +/- 4.21). An in-vivo study revealed that topically administered tetanus toxoid-loaded transfersomes, after secondary immunization, elicited an immune response (anti-TT-IgG) comparable with that produced by intramuscular AATT. Fluorescence microscopy revealed the penetration of transfersomes through the skin to deliver the antigen to the immunocompetent Langerhans cells.


Contrast-enhanced carotid magnetic resonance angiography: comparison of single-dose and double-dose of gadolinium using the randomly segmented central k-space ordering technique.
The aim of this study was to evaluate whether the single dose of gadolinium is sufficient for contrast-enhanced magnetic resonance angiography (MRA) of carotid arteries with the use of newly developed randomly segmented central k-space ordering technique called contrast-enhanced timing-robust angiography (CENTRA). A total of 44 patients underwent carotid MRA in a 1.5T MR scanner using a fluoroscopically monitored, manually triggered, CENTRA pulse sequence. Patients were randomly assigned into two groups according to the dose of contrast medium (gadolinium chelate) administered: group 1 referred to those who received double doses (0.2 mmol/kg) and group 2 received single doses (0.1 mmol/kg). The contrast-to-noise (CNR) ratios of the seven regions of interest were calculated. The delineation of nine vascular regions and the degree of venous overlay were evaluated by two blinded readers on a five-point scale. For quantitative evaluation, the CNRs at the brachiocephalic artery were greater in patients in group 1 than that in group 2 (p = 0.015), while the differences did not differ between the two groups for the remaining regions of interest (p > 0.05). For qualitative evaluation, there were no significant differences between the two groups in delineation of nine vascular regions and venous overlaying (p > 0.05). With the use of the CENTRA technique, carotid MRA may be performed using a single dose of gadolinium and the image quality is comparable to that of the standard double dose protocol.


Gallium-68: chemistry and radiolabeled peptides exploring different oncogenic pathways.
Abstract Early and specific tumor detection and also therapy selection and response evaluation are some challenges of personalized medicine. This calls for high sensitive and specific molecular imaging such as positron emission tomography (PET). The use of peptides for PET molecular imaging has undeniable advantages: possibility of targeting through peptide-receptor interaction, small size and low-molecular weight conferring good penetration in the tissue or at cellular level, low toxicity, no antigenicity, and possibility of wide choice for radiolabeling. Among β(+)-emitter radioelements, Gallium-68 is a very attractive positron-emitter compared with carbon-11 or fluorine-18 taking into account its easy production via a (68)Ge/(68)Ga generator and well established radiochemistry. Gallium-68 chemistry is based on well-defined coordination complexes with macrocycle or chelates having strong binding properties, particularly suitable for linking peptides that allow resistance to in vivo transchelation of the metal ion. Understanding specific and nonspecific molecular mechanisms involved in oncogenesis is one major key to develop new molecular imaging tools. The present review focuses on peptide signaling involved in different oncogenic pathways. This peptide signalization might be common for tumoral and non-tumoral processes or could be specific of an oncological process. This review describes gallium chemistry and different (68)Ga-radiolabeled peptides already in use or under development aiming at developing molecular PET imaging of different oncological processes.


From somatic variants towards precision oncology: Evidence-driven reporting of treatment options in molecular tumor boards.
A comprehensive understanding of cancer has been furthered with technological improvements and decreasing costs of next-generation sequencing (NGS). However, the complexity of interpreting genomic data is hindering the implementation of high-throughput technologies in the clinical context: increasing evidence on gene-drug interactions complicates the task of assigning clinical significance to genomic variants. Here we present a method that automatically matches patient-specific genomic alterations to treatment options. The method relies entirely on public knowledge of somatic variants with predictive evidence on drug response. The output report is aimed at supporting clinicians in the task of finding the clinical meaning of genomic variants. We applied the method to 1) The Cancer Genome Atlas (TCGA) and Genomics Evidence Neoplasia Information Exchange (GENIE) cohorts and 2) 11 patients from the NCT MASTER trial whose treatment discussions included information on their genomic profiles. Our reporting strategy showed a substantial number of patients with actionable variants in the analyses of TCGA and GENIE samples. Notably, it was able to reproduce experts' treatment suggestions in a retrospective study of 11 patients from the NCT MASTER trial. Our results establish a proof of concept for comprehensive, evidence-based reports as a supporting tool for discussing treatment options in tumor boards. We believe that a standardized method to report actionable somatic variants will smooth the incorporation of NGS in the clinical context. We anticipate that tools like the one we present here will become essential in summarizing for clinicians the growing evidence in the field of precision medicine. The R code of the presented method is provided in Additional file 6 and available at https://github.com/jperera-bel/MTB-Report .


Oncostatin M induces RIG-I and MDA5 expression and enhances the double-stranded RNA response in fibroblasts.
Interleukin (IL)-6-type cytokines have no direct antiviral activity; nevertheless, they display immune-modulatory functions. Oncostatin M (OSM), a member of the IL-6 family, has recently been shown to induce a distinct number of classical interferon stimulated genes (ISG). Most of them are involved in antigen processing and presentation. However, induction of retinoic acid-inducible gene (RIG)-I-like receptors (RLR) has not been investigated. Here we report that OSM has the capability to induce the expression of the DExD/H-Box RNA helicases RIG-I and melanoma differentiation antigen 5 (MDA5) as well as of the transcription factors interferon regulatory factor (IRF)1, IRF7 and IRF9 in primary fibroblasts. Induction of the helicases depends on tyrosine as well as serine phosphorylation of STAT1. Moreover, we could show that the OSM-induced STAT1 phosphorylation is predominantly counter-regulated by a strong STAT3-dependent SOCS3 induction, as Stat3 as well as Socs3 knock-down results in an enhanced and prolonged helicase and IRF expression. Other factors involved in regulation of STAT1 or IRF1 activity, like protein tyrosine phosphatase, non-receptor type 2 (PTPN2), promyelocytic leukaemia protein (PML) or small ubiquitin-related modifier 1 (SUMO1), play a minor role in OSM-mediated induction of RLR. Remarkably, OSM and interferon-γ (IFN-γ) synergize to mediate transcription of RLR and pre-treatment of fibroblasts with OSM fosters the type I interferon production in response to a subsequent encounter with double-stranded RNA. Together, these findings suggest that the OSM-induced JAK/STAT1 signalling is implicated in virus protection of non-professional immune cells and may cooperate with interferons to enhance RLR expression in these cells.


A comparison of the safety and efficacy of mibefradil and nifedipine SR in patients with renal disease and hypertension.
The antihypertensive efficacy and safety of mibefradil and nifedipine SR were compared in 143 patients with chronic renal failure and mild-to-moderate hypertension in a multicenter, double-blind, randomized, parallel-design study. At treatment week 12, a significantly greater decrease in sitting diastolic blood pressure (SDBP) was seen with mibefradil than with nifedipine SR (12.8 mmHg vs 8.1 mmHg, respectively; p = 0.014). A significantly greater number of mibefradil-treated patients achieved normalization of SDBP by week 12 (62% vs 37%; p < 0.01). The changes in renal function parameters and the incidence of adverse events were similar in both groups. In this population, 12 weeks of treatment with mibefradil were more effective than nifedipine SR for lowering blood pressure and had similar effects on renal function parameters.


Generation of proton-motive force by an archaeal terminal quinol oxidase from Sulfolobus acidocaldarius.
The terminal quinol oxidase of the cytochrome aa3 type was isolated from the extreme thermoacidophilic archaeon Sulfolobus acidocaldarius. In micellar solution, the enzyme oxidized various quinols and exerted the highest activity with the physiological substrate caldariella quinol. The enzyme was functionally reconstituted into monolayer liposomes composed of archaeal tetraether lipids also derived from S. acidocaldarius. With the electron donor system ascorbate and N,N,N',N'-tetramethyl-p-phenylenediamine, the reconstituted enzyme was more active in the archaeal lipids as compared to lipids derived from Escherichia coli at temperatures above 50 degrees C. Due to the low proton permeability of the tetraether lipids, it was possible to generate a steady-state transmembrane electrical potential (delta psi, interior negative), and transmembrane pH gradient (delta pH, interior alkaline) at temperatures up to 70 degrees C. The successful functional reconstitution of the cytochrome aa3-type quinol oxidase from Sulfolobus identifies it as the key energy converter in the respiratory system of this hyperthermophilic archaeon.


Fine control for the preparation of ceria nanorods (111).
The morphologies and exposed surfaces of ceria nanocrystals are important factors in determining their performance. In order to establish a structure-property relationship for ceria nanomaterials, it is essential to have materials with well-defined morphologies and specific exposed facets. This is also crucial for acquiring high resolution 17O solid-state NMR spectra. In this study, we explore the synthesis conditions for preparing CeO2 nanorods with exposed (111) facets. The effects of alkali concentration, hydrothermal temperature and time, cerium source and oxidation agent are investigated and optimal synthesis conditions are found. The resulting CeO2 nanorods show very narrow 17O NMR peaks for the oxygen ions in the first, second and third layers, providing a foundation for future research on mechanisms involving ceria materials using 17O solid-state NMR spectroscopy.


Evaluation of total adiponectin, adipocyte fatty acid binding protein and fibroblast growth factor 21 levels in individuals with metabolic syndrome.
Although many studies have investigated the relationships of several adipokines to metabolic syndrome (MetS), the interrelationships of adiponectin (ADP), adipocyte fatty acid binding protein (A-FABP) and fibroblast growth factor 21 (FGF 21) have not been described in detail. We examined 209 asymptomatic dyslipidemic patients divided into MetS+ (n=73) and MetS- (n=136) groups. The aim of study was to evaluate the relationships between observed adipokines, to compare the levels of total ADP, A-FABP and FGF 21 in individuals with and without MetS, and to elucidate the relationships of individual adipokines to lipid parameters, markers of insulin resistance and endothelial hemostatic markers in these groups. In MetS+ group, we found the independent positive association ADP with A-FABP (beta=0.4888, p=0.0382), A-FABP with FGF 21 (beta=0.3811, p=0.0002) and von Willebrand factor (beta=0.4502, p=0.0013), and FGF 21 with A-FABP (beta=0.4422, p=0.0002). Our study has confirmed the well-established risk profile of subjects with MetS, although clinically asymptomatic. MetS+ patients had also lower levels of ADP and higher levels of A-FABP and FGF 21. Our study evaluated the interrelationships of ADP, A-FABP and FGF 21 in asymptomatic dyslipidemic subjects with diagnosis of MetS. Especially strong association between A-FABP and FGF 21 needs to be clarified in further studies.


Specific and sensitive immunological diagnosis of Chagas' disease by competitive antibody enzyme immunoassay using a Trypanosoma cruzi-specific monoclonal antibody.
Coexistence of Chagas' disease with leishmaniasis and T. rangeli infection in endemic areas and cross-reactivity between corresponding etiological agents can confuse the immunodiagnosis of Chagas' disease. A discriminative serological test could therefore represent a major advance in specific immunodiagnosis. A competitive antibody enzyme immunoassay against a component 5-enriched preparation, using a T. cruzi species-specific monoclonal antibody has allowed development of a specific serodiagnosis of Chagas' disease with high sensitivity (96.6% in undetermined and chronic phases of infection). This test can differentiate Chagas' disease from other cross-reacting parasitic diseases in areas where concomitant infections are unknown or suspected.


An insertion device for the soft X-ray photochemistry beamline at SPring-8.
A figure-8 undulator is an insertion device (ID) proposed at SPring-8 to reduce the heat-load problems encountered with ordinary linear undulators. This device is useful when the K value is high in order to obtain low-energy photons as the fundamental of the undulator radiation. It has therefore been adopted as the ID for the soft X-ray photochemistry beamline (BL27SU) at SPring-8 because linearly polarized photons between 100 and 2000 eV are necessary for the experiments on this beamline. The figure-8 undulator for BL27SU is now under construction and, in the first phase of operation, is expected to cover the energy range down to 500 eV. In the second and third phases, the lowest energy may be reduced to 170 and 100 eV, respectively.


16S rRNA gene-based analysis of microbial community by whole-genome amplification and minigel-single-strand conformation polymorphism technique.
We have developed an analytical technique for the 16S rRNA gene that comprises whole-genome amplification and the polymerase chain reaction (PCR)-minigel-single-strand conformation polymorphism technique (WGA-SSCP). Under optimal conditions, SSCP bands could be detected when genomic DNA from bacteria of interest comprised 0.5% or more of the specimen. This method will be effective for the identification of nonculturable bacteria in a microbial community.


Prognostic importance of expression of the Wilms' tumor 1 gene in newly diagnosed acute promyelocytic leukemia.
Wilms' tumor 1 gene (WT1) is known to be highly expressed in acute promyelocytic leukemia (APL) but information on its impact on prognosis is lacking. WT1 expression was analyzed in bone marrow samples of 79 patients with APL at initial diagnosis. Patients had a differing outcome according to their level of WT1 expression. In patients who achieved a complete remission (CR), low or high WT1 expression was significantly associated with inferior overall survival (OS) compared to intermediate WT1 expression (49% for WT1high vs. 63% for WT1low vs. 93% for WT1int; p=0.008). Moreover, there were significant differences in relapse-free survival (RFS) between the three expression groups (42% for WT1high vs. 63% for WT1low vs. 83% for WT1int; p=0.047). In multivariable analysis WT1 expression showed an independent prognostic impact on OS of responders to induction therapy. In conclusion, the level of WT1 expression can add prognostic information in APL risk stratification.


The identification of an Onchocerca-specific recombinant antigen containing a T cell epitope.
Recombinant Onchocerca volvulus Ag have been derived from expression libraries and examined for their ability to stimulate PBMC from patients infected with O. volvulus. Ten clones producing recombinant Ag were selected and plaque purified; lysogens were produced and found to express beta-galactosidase fusion proteins ranging in molecular mass from 115 to 138 kDa. When ammonium sulfate-precipitated lysates of these recombinant phage clones were examined for their ability to stimulate PBMC from a patient with onchocerciasis, all 10 recombinants produced stimulation above that to nonrecombinant phage. When individual fusion proteins, affinity purified on anti-beta-galactosidase linked to agarose, were used to stimulate PBMC from patients with onchocerciasis, only one of the recombinant Ag induced PBMC proliferation (stimulation index greater than 4) above that to Ag from nonrecombinant phage. Characterization of the DNA coding for this Ag showed it to be 1.2 kb in length with a small (90 bp) open reading frame; furthermore, it appears to be Onchocerca specific (on genomic dot blots) and single copy. Using overlapping peptides encompassing the entire open reading frame, one T cell epitope has been localized.


[The retired person in a socialist society].
There are not possibilities to stop aging. Therefore we should add to years life. To it necessary making the problems of aging to a task for the complete society. In our socialist country pensioners guaranteed on foundation of the constitution, the employment-low-book and the votes of party and government all chances to life carefree and with activities.


Electrical stimulation superimposed on voluntary training can limit sensory integration in neural adaptations.
P. Bezerra, S. Zhou, Z. Crowley, A. Davie, and R. Baglin (2011) suggested that the neural mechanisms responsible for steadiness improvement relate in particular to the discharge behavior of motor units and the practice and learning of skills rather than the strength gain after electromyostimulation superimposed over voluntary training. However, the afferent inputs are determining in control of the force level produced and thus contribute to ensure muscle steadiness. Hence, it is possible that electromyostimulation interferes in neurophysiological afference integration and prevents neural adaptations that enable improvement of the control of force (and then muscle steadiness) to occur. Therefore, the neural adaptations induced by electromyostimulation superimposed onto voluntary training should also be researched in relation to the sensory pathways.


Natural Language Processing Insight into LGBTQ+ Youth Mental Health During the COVID-19 Pandemic: Longitudinal Content Analysis of Anxiety-Provoking Topics and Trends in Emotion in LGBTeens Microcommunity Subreddit.
Widespread fear surrounding COVID-19, coupled with physical and social distancing orders, has caused severe adverse mental health outcomes. Little is known, however, about how the COVID-19 crisis has impacted LGBTQ+ youth, who disproportionately experienced a high rate of adverse mental health outcomes before the COVID-19 pandemic. We aimed to address this knowledge gap by harnessing natural language processing methodologies to investigate the evolution of conversation topics in the most popular subreddit for LGBTQ+ youth. We generated a data set of all r/LGBTeens subreddit posts (n=39,389) between January 1, 2020 and February 1, 2021 and analyzed meaningful trends in anxiety, anger, and sadness in the posts. Because the distribution of anxiety before widespread social distancing orders was meaningfully different from the distribution after (P<.001), we employed latent Dirichlet allocation to examine topics that provoked this shift in anxiety. We did not find any differences in LGBTQ+ youth anger and sadness before and after government-mandated social distancing; however, anxiety increased significantly (P<.001). Further analysis revealed a list of 10 anxiety-provoking topics discussed during the pandemic: attraction to a friend, coming out, coming out to family, discrimination, education, exploring sexuality, gender pronouns, love and relationship advice, starting a new relationship, and struggling with mental health. During the COVID-19 pandemic, LGBTQ+ teens increased their reliance on anonymous discussion forums when discussing anxiety-provoking topics. LGBTQ+ teens likely perceived anonymous forums as safe spaces for discussing lifestyle stressors during COVID-19 disruptions (eg, school closures). The list of prevalent anxiety-provoking topics in LGBTQ+ teens' anonymous discussions can inform future mental health interventions in LGBTQ+ youth.


Transcriptome analysis of the citrus red mite, Panonychus citri, and its gene expression by exposure to insecticide/acaricide.
The citrus red mite, Panonychus citri, is known for its ability rapidly to evolve resistance to insecticides/acaricides and to adapt to hosts that produce toxins. In this study, we constructed an unprecedented four gigabase pair transcriptome of P. citri, which was assembled into 64 149 unique transcripts, the functions of which were annotated by five public databases. A total of 116 unique transcripts were identified as representatives of potential involvement in the detoxification of xenobiotics. Genes recorded to encoding insecticide/acaricide target proteins were also obtained from the P. citri transcriptome. In order to explore novel candidate genes potentially involved in the pesticide detoxification of P. citri, we also constructed digital gene expression libraries of short-term transcriptome responses of P. citri to pesticides, which resulted in the identification of 120 unique transcripts potentially associated with insecticide/acaricide detoxification. Our study will facilitate molecular research on pesticide resistance in citrus red mites, as well as in other phytophagous mites.


Mon1a and FCHO2 are required for maintenance of Golgi architecture.
Mon1a has been shown to function in the endolysosomal pathway functioning in the Mon1-Ccz1 complex and it also acts in the secretory pathway where it interacts with dynein and affects ER to Golgi traffic. Here we show that Mon1a is also required for maintenance of the Golgi apparatus. We identified the F-BAR protein FCHO2 as a Mon1a-interacting protein by both yeast two-hybrid analysis and co-immunoprecipitation. siRNA-dependent reductions in Mon1a or FCHO2 resulted in Golgi fragmentation. Membrane trafficking through the secretory apparatus in FCHO2-depleted cells was unaltered, however, reduction of FCHO2 affected the uniform distribution of Golgi enzymes necessary for carbohydrate modification. Fluorescence recovery after photobleaching analysis showed that the Golgi ministacks in Mon1a- or FCHO2-silenced cells did not exchange resident membrane proteins. The effect of FCHO2 silencing on Golgi structure was partially cell cycle-dependent and required mitosis-dependent Golgi fragmentation, whereas the effect of Mon1a-silencing on Golgi disruption was not cell cycle-dependent. mCherry-FCHO2 transiently colocalized on Golgi structures independent of Mon1a. These findings suggest that Mon1a has functions throughout the secretory pathway including interacting with dynein at the ER-Golgi interface in vesicle formation and then interacting with FCHO2 at the Golgi to generate lateral links between ministacks, thus creating Golgi ribbons.


Planning for rabies control in Ontario.
Ten geographic cells of rabies cases were identified within southern Ontario. Some had regular 3-year peaks, whereas others had weak cycles with mean periods of up to 9 years. Incidence of rabies was related to soil types (highest on sandy and clay loams), land use (abundant where hay and pasture were dominant), and drainage (poor drainage supported only low levels of rabies). A spatial stochastic simulation model is being used to evaluate risks and tactics associated with reduction of rabies by use of vaccine baits. The model indicated that persistence of rabies is unlikely in areas with less than 4,000 km2 of contiguous fox habitat. In sensitivity tests the model was most affected by the values of four input parameters: rate of contact among foxes, incubation period of rabies, fox density, and a density-dependent feedback that reduces fox recruitment when density approaches or exceeds a predetermined "carrying capacity." In a majority of model experiments, a single vaccination of 60% of a fox population eradicated rabies, but only if vaccination took place just after a rabies outbreak, when the number of both foxes and rabid animals was reduced. Rabies control will probably be applied to individual cells or clusters of cells rather than to the entire 98,000 km2 enzootic zone, at least at first. If rabies is eradicated the fox populations may increase, but modestly. Skunks were more important than foxes as vectors of rabies in urban Ontario. Since there is no effective oral rabies vaccine for skunks, skunks were trapped alive and vaccinated by injection.(ABSTRACT TRUNCATED AT 250 WORDS)


Si Donor Incorporation in GaN Nanowires.
With increasing interest in GaN based devices, the control and evaluation of doping are becoming more and more important. We have studied the structural and electrical properties of a series of Si-doped GaN nanowires (NWs) grown by molecular beam epitaxy (MBE) with a typical dimension of 2-3 μm in length and 20-200 nm in radius. In particular, high resolution energy dispersive X-ray spectroscopy (EDX) has illustrated a higher Si incorporation in NWs than that in two-dimensional (2D) layers and Si segregation at the edge of the NW with the highest doping. Moreover, direct transport measurements on single NWs have shown a controlled doping with resistivity from 10(2) to 10(-3) Ω·cm, and a carrier concentration from 10(17) to 10(20) cm(-3). Field effect transistor (FET) measurements combined with finite element simulation by NextNano(3) software have put in evidence the high mobility of carriers in the nonintentionally doped (NID) NWs.


Health-related quality of life and pain interference in two patient cohorts with neuropathic pain: breast cancer survivors and HIV patients.
Persistent pain is common in HIV patients and breast cancer (BC) survivors. The aim of this study was to compare two patient groups with neuropathic pain (NP) regarding several psychological variables and Health-related Quality of Life. Although, treatment of pain is always planned individually, the knowledge of the differences and similarities between the patient groups may help us to understand more precisely the targets of the interventions for pain. Eighty nine BC and 73 HIV patients with symptoms of neuropathic pain (patients with ≥3/7 in the Douleur Neuropathique four interview part (DN4i)) participated in a cross-sectional study. Patients completed questionnaires about mood (HADS), symptoms of insomnia (ISI), pain catastrophizing (PCS), personality (TIPI), Mental and Physical Health-related Quality of Life (M/PHrQoL, RAND/SF-36), and pain intensity and interference (BPI). Analyses were applied by using t-tests and linear regression to assess associations between the studied factors. HIV patients reported higher anxiety (p<0.001), depressive symptoms (p<0.001), pain catastrophizing (p<0.001) and pain interference (p<0.001), poorer sleep (p<0.001), and lower HrQoL in all dimensions compared with BC survivors. There were significant differences in personality traits extraversion, emotional stability, and agreeableness between the two patient groups. In HIV patients, pain interference (β=-0.344, p<0.001) and mood (β=-0.580, p<0.001) and in the BC group, mood (β=-0.591, p<0.001), extraversion (β=0.229, p=0.005) and sleep (β=-0.154, p=0.042) associated with MHrQoL. Pain interference (HIV β=-0.645, p<0.001, BC β=-0.491, p<0.001) and age (HIV β=-0.016, p=0.042 and BC β=-0.018, p=0.019) associated with PHrQoL in both groups, and catastrophizing in the BC group (β=-0.303, p<0.001). HIV patients and BC survivors with neuropathic pain, measured with DN4i, have significant differences in various health-related variables and Health-related Quality of Life with both patient groups reporting low HrQoL. The differences in low HrQoL may reflect the fundamental differences between these diseases, BC survivors in remission and HIV patients living with a chronic disease that is under control. This study brings information about the diversity of different patient populations with symptoms of neuropathic pain, and how neuropathic pain associates with wide range of health-related factors. Interventions to support better coping with the symptoms of neuropathic pain could be tailored more individually if the background disease is taken into account.