Quality of life in elders living alone in Taiwan.
The aim of this study was to identify and describe predictors of QOL of elders who live alone in Taiwan. Despite a growing population of elders who live alone, research on their quality of life, important for policy decisions and health care provider interventions is virtually absent. A descriptive correlational design surveyed 192 Taiwanese elders living alone, selected at random from urban and rural areas. During home visits elders completed the WHO-QOL-BREF, Social Support Scale and Center for Epidemiological Studies Depression Scale (CES-D) in addition to providing demographic data. Multiple linear regressions showed that six variables predicted physical health and the psychological wellbeing QOL domains, accounting for 74.5 and 60.1% of the variance, respectively. Four variables predicted 46.7 and 34.3% of the environmental and the social relationship QOL domains, respectively. Elders who live alone in rural areas and suffer from depression are at high risk for a low quality of life. However, elders living alone reported a better quality of life than their institutionalized counterparts. Interventional research and policy decisions focused on treatment for depression and providing social support networks, as these elders age, will be particularly important. By understanding variables associated with elders' quality of life, nurses can coordinate interventions to improve their quality of life. Poorly educated rural women who live alone are particularly vulnerable. Nursing assessment of quality of life indicators and implementation of strategies for increased social support are needed for high-risk elders.


Flat amplitude multiwavelength Brillouin-Raman comb fiber laser in Rayleigh-scattering-enhanced linear cavity.
We investigate the amplitude flatness of Rayleigh-assisted Brillouin-Raman comb laser in a linear cavity in which feedbacks are formed by high-reflectivity mirror. The optimization of Brillouin pump power and wavelength is very crucial in order to obtain a uniform power level between Stokes lines. The Brillouin pump must have a relatively large power and its wavelength must be located closer to the Raman peak gain region. The flat-amplitude bandwidth is also determined by the choice of Raman pump wavelengths. A flat-amplitude bandwidth of 30.7 nm from 1527.32 to 1558.02 nm is measured when Raman pump wavelengths are set to 1435 and 1450 nm. 357 uniform Brillouin Stokes lines with 0.086 nm spacing are generated across the wavelength range. The average signal-to-noise ratio of 17 dB is obtained for all the Brillouin Stokes lines.


Effect of paternal age in achondroplasia, thanatophoric dysplasia, and osteogenesis imperfecta.
The paternal ages of nonfamilial cases of achondroplasia (AC) (n = 78), thanatophoric dysplasia (TD) (n = 64), and osteogenesis imperfecta (OI) (n = 106), were compared with those of matched controls, from an Italian Indagine Policentrica Italiana sulle Malformazioni Congenite and a South American Estudio Colaborativo Latinoamericano de Malformaciones Congénitas series. The degree of paternal age effect on the origin of these dominant mutations differed among the three conditions. Mean paternal age was highly elevated in AC, 36.30 +/- 6.74 years in the IPIMC, and 37.19 +/- 10.53 years in the ECLAMC; less consistently elevated in TD, 33.60 +/- 7.08 years in the IPIMC, and 36.41 +/- 9.38 years in the ECLAMC; and only slightly elevated in OI in the ECLAMC, 31.15 +/- 9.25 years, but not in the IPIMC, 32.26 +/- 6.07 years. Increased maternal age or birth order in these conditions disappeared when corrected for paternal age. Approximately 50% of AC and TD cases, and only 30% of OI cases, were born to fathers above age 35 years. For AC and TD, the increase in relative incidence with paternal age fitted an exponential curve. The variability of paternal age effect in these new mutations could be due, among other reasons, to the high proportion of germ-line mosaicism in OI parents, or to the localization of the AC gene, mapped to the 4p16.3 region, in the neighborhood of an unstable DNA area.


Thoracic Magnetic Resonance Imaging Applications in Children.
Lung pathologies in the pediatric population can usually be detected using chest radiography. Multidetector computed tomography (MDCT) imaging is often used as a supplementary method in the evaluation of lung diseases. Recently, magnetic resonance imaging (MRI) techniques were found to be reliable in the evaluation of pulmonary diseases in the pediatric population. This review study describes the routine application of MRI examinations and the use of thoracic MRI with a particular focus in pediatric patients.


Effect of calcium alginate concentration on viability and proliferation of encapsulated fibroblasts.
Alginate hydrogels have been used widely in tissue engineering for cell encapsulation for several reasons: low toxicity, the ability to gel under gentle condition and compatibility with cells. In this study, we determined the effect of different concentrations of alginate on encapsulation of 3T3 fibroblast cells at two different cell seeding densities. Live/dead staining and MTT assay were performed at regular intervals up to 4 weeks. A Hoechst 33258 assay was done to validate the MTT results. There were more dead cells on day 1 for the higher concentrations of alginate while at, the lower concentration of alginate, cell proliferation and spheroid formation occurred more quickly. Furthermore, at low cell seeding density, cell proliferation was prolonged compared to the intermediate seeding density. In conclusion, by altering both alginate concentration and cell seeding density, proliferation and spheroid formation can be controlled.


COVID-19 Daily Realities for Families: A South African Sample.
The COVID-19 pandemic affected families globally. Empirical research has been explored to understand the impact of COVID-19 on families across countries, however, there are limited findings of how COVID-19 has affected the daily realities of families in South Africa. This study used an exploratory qualitative research approach to explore the experiences of COVID-19 for South African families. Findings suggest that the negative outcomes of COVID-19 experienced by South African families included a shift in the daily routines, restrictions on family events, lack of socialization and loss of connections, family conflicts, financial constraints as well as psychological impacts. On the contrary, the positive outcomes included increased family time and communication, cleanliness, and good health status, and improved financial management. Implications for future research should include research focused on the health impacts of COVID-19 on diverse family structures, family compositions, and family dynamics. In-depth research and findings can assist in developing policies and interventions for families.


Control of Nonadiabatic Passage through a Conical Intersection by a Dynamic Resonance.
Nonadiabatic processes, dominated by dynamic passage of reactive fluxes through conical intersections (CIs), are considered to be appealing means for manipulating reaction paths, particularly via initial vibrational preparation. Nevertheless, obtaining direct experimental evidence of whether specific-mode excitation affects the passage at the CI is challenging, requiring well-resolved time- or frequency-domain experiments. Here promotion of methylamine-d2 (CH3ND2) molecules to spectral-resolved rovibronic states on the excited S1 potential energy surface, coupled to sensitive D photofragment probing, allowed us to follow the N-D bond fission dynamics. The branching ratios between slow and fast D photofragments and the internal energies of the CH3ND(X̃) photofragments confirm correlated anomalies for predissociation initiated from specific rovibronic states. These anomalies reflect the existence of a dynamic resonance that strongly depends on the energy of the initially excited rovibronic states, the evolving vibrational mode on the repulsive S1 part during N-D bond elongation, and the manipulated passage through the CI that leads to CH3ND radicals excited with C-N-D bending. This resonance plays an important role in the bifurcation dynamics at the CI and can be foreseen to exist in other photoinitiated processes and to control their outcome.


Cooking Frequency Associated With Dietary Quality in iCook-4H Youth Participants at Baseline.
Increased intakes of ready-made and fast foods paralleled with decreased homemade food consumption have been associated with increased rates of obesity. Researchers have shown associations between cooking self-efficacy (SE) and cooking frequency (CF) with dietary quality and weight status. Some cooking interventions have shown positive associations with dietary outcomes, such as increased fruit and vegetable intake and decreased fast food consumption. There is still much unknown about SE and CF, especially among youth. Determine baseline SE and CF and the associations with dietary quality and body mass index (BMI) of youth enrolled in iCook 4H. Youth (n = 228, ages 9-10 years) completed online surveys assessing SE, CF, dietary quality, and demographics. Anthropometrics were collected to calculate BMI-for-age percentiles and weight categories. Descriptive statistics were completed for CF, SE, BMI categories, and demographics. Differences in CF and SE by sex, race, and participation in government assistance programs were determined through independent-sample t tests. Pearson correlations were used to assess the association between dietary quality and CF and SE. Associations between CF and dietary quality were assessed further through 2-way analyses of variance (ANOVAs) that included CF and sex and CF and race as independent variables. Associations between SE and CF and BMI were assessed through ANOVAs. Thirty-seven percent of youth were overweight or obese. Females reported significantly higher CF than males (P = .042). Cooking frequency was positively associated with dietary quality (P < .001), but BMI was not associated with dietary quality. SE was not associated with dietary quality or BMI. Based on results, CF was positively associated with dietary quality among youth. More research is needed to assess how different types of cooking relate to diet and BMI. Interventions are needed to determine whether increasing CF leads to better diet outcomes.


PARTIE: a partition engine to separate metagenomic and amplicon projects in the Sequence Read Archive.
The Sequence Read Archive (SRA) contains raw data from many different types of sequence projects. As of 2017, the SRA contained approximately ten petabases of DNA sequence (10 16 bp). Annotations of the data are provided by the submitter, and mining the data in the SRA is complicated by both the amount of data and the detail within those annotations. Here, we introduce PARTIE, a partition engine optimized to differentiate sequence read data into metagenomic (random) and amplicon (targeted) sequence data sets. PARTIE subsamples reads from the sequencing file and calculates four different statistics: k -mer frequency, 16S abundance, prokaryotic- and viral-read abundance. These metrics are used to create a RandomForest decision tree to classify the sequencing data, and PARTIE provides mechanisms for both supervised and unsupervised classification. We demonstrate the accuracy of PARTIE for classifying SRA data, discuss the probable error rates in the SRA annotations and introduce a resource assessing SRA data. PARTIE and reclassified metagenome SRA entries are available from https://github.com/linsalrob/partie. firstname.lastname@example.com. Supplementary data are available at Bioinformatics online.


Feeding and smoking habits as cumulative risk factors for early childhood caries in toddlers, after adjustment for several behavioral determinants: a retrospective study.
Several maternal health determinants during the first period of life of the child, as feeding practice, smoking habit and socio-economic level, are involved in early childhood health problems, as caries development. The potential associations among early childhood caries, feeding practices, maternal and environmental smoking exposure, Socio-Economic Status (SES) and several behavioral determinants were investigated. Italian toddlers (n = 2395) aged 24-30 months were recruited and information on feeding practices, sweet dietary habit, maternal smoking habit, SES, and fluoride supplementation in the first year of life was obtained throughout a questionnaire administered to mothers. Caries lesions in toddlers were identified in visual/tactile examinations and classified using the International Caries Detection and Assessment System (ICDAS). Associations between toddlers' caries data and mothers' questionnaire data were assessed using chi-squared test. Ordinal logistic regression was used to analyze associations among caries severity level (ICDAS score), behavioral factors and SES (using mean housing price per square meter as a proxy). Caries prevalence and severity levels were significantly lower in toddlers who were exclusively breastfed and those who received mixed feeding with a moderate-high breast milk component, compared with toddlers who received low mixed feeding and those exclusively fed with formula (p < 0.01). No moderate and high caries severity levels were observed in an exclusively breastfed children. High caries severity levels were significantly associated with sweet beverages (p < 0.04) and SES (p < 0.01). Toddlers whose mothers smoked five or more cigarettes/day during pregnancy showed a higher caries severity level (p < 0.01) respect to those whose mothers did not smoke. Environmental exposure to smoke during the first year of life was also significantly associated with caries severity (odds ratio =7.14, 95% confidence interval = 6.07-7.28). No association was observed between caries severity level and fluoride supplementation. More than 50% of toddlers belonging to families with a low SES, showed moderate or high severity caries levels (p < 0.01). Higher caries severity levels were observed in toddlers fed with infant formula and exposed to smoke during pregnancy living in area with a low mean housing price per square meter.


[Surgical treatment of Hirschprung's disease total form in children].
It was analyzed the treatment results of 24 patients under the age of 2 years with total aganglionosis for the period from 2000 to 2013. Each of these patients underwent several surgical interventions (on the average 7.8±2.1). All children were operated radically. It was performed ileojejunorectal anastomosis at transitional fold of peritoneum in patients with concomitant short bowel syndrome. Soave's operation was done in 14 patients including by using of laparoscopic technique in 3 cases. Inflammatory complications (paraproctitis) developed in 2 children on maceration background. Perirectal fistula was observed in 1 patient subsequently. In long-term period liquid stool incontinence persisted up to 6 months in 28% of children. In terms of more than 1 year stool incontinence was observed in 12.6% of patients. Increased growth of D-lactate-producing gram-positive anaerobes was revealed during microbiological investigation of feces in 35% of patients in long-term period. Increased growth was accompanied by systemic acidosis and infectious enteritis clinically. Course monthly treatment with antibacterial drugs (Alpha-Normix, Trichopolum, Gentamicin) was prescribed in patients with short bowel syndrome and high frequent of enteritis recurrence. Treatment was used In terms from 6 to 12 months of longer if it was necessary. It was concluded that timely diagnosis and right tactic in neonatal period leads to decrease significantly the number of complications, vain interventions and to improve treatment outcomes. Our experience shows that the best results of surgical treatment were observed in children aged from 2.5-3 years when a child can control urination and defecation. The most mistakes are caused by wrong or failed morphological investigation of large bowel.


Healthy Tissue Uptake of 68Ga-Prostate-Specific Membrane Antigen, 18F-DCFPyL, 18F-Fluoromethylcholine, and 18F-Dihydrotestosterone.
PET is increasingly used for prostate cancer (PCa) diagnostics. Important PCa radiotracers include 68Ga-prostate-specific membrane antigen HBED-CC (68Ga-PSMA), 18F-DCFPyL, 18F-fluoromethylcholine (18F-FCH), and 18F-dihydrotestosterone (18F-FDHT). Knowledge on the variability of tracer uptake in healthy tissues is important for accurate PET interpretation, because malignancy is suspected only if the uptake of a lesion contrasts with its background. Therefore, the aim of this study was to quantify uptake variability of PCa tracers in healthy tissues and identify stable reference regions for PET interpretation. Methods: A total of 232 PCa PET/CT scans from multiple hospitals was analyzed, including 87 68Ga-PSMA scans, 50 18F-DCFPyL scans, 68 18F-FCH scans, and 27 18F-FDHT scans. Tracer uptake was assessed in the blood pool, lung, liver, bone marrow, and muscle using several SUVs (SUVmax, SUVmean, SUVpeak). Variability in uptake between patients was analyzed using the coefficient of variation (COV%). For all tracers, SUV reference ranges (95th percentiles) were calculated, which could be applicable as image-based quality control for future PET acquisitions. Results: For 68Ga-PSMA, the lowest uptake variability was observed in the blood pool (COV, 19.9%), which was significantly more stable than all other tissues (COV, 29.8%-35.2%; P = 0.001-0.024). For 18F-DCFPyL, the lowest variability was observed in the blood pool and liver (COV, 14.4% and 21.7%, respectively; P = 0.001-0.003). The least variable 18F-FCH uptake was observed in the liver, blood pool, and bone marrow (COV, 16.8%-24.2%; P = 0.001-0.012). For 18F-FDHT, low uptake variability was observed in all tissues, except the lung (COV, 14.6%-23.6%; P = 0.001-0.040). The different SUV types had limited effect on variability (COVs within 3 percentage points). Conclusion: In this multicenter analysis, healthy tissues with limited uptake variability were identified, which may serve as reference regions for PCa PET interpretation. These reference regions include the blood pool for 68Ga-PSMA and 18F-DCFPyL and the liver for 18F-FCH and 18F-FDHT. Healthy tissue SUV reference ranges are presented and applicable as image-based quality control.


A murine model of obesity implicates the adipokine milieu in the pathogenesis of severe acute pancreatitis.
Obesity is clearly an independent risk factor for increased severity of acute pancreatitis (AP), although the mechanisms underlying this association are unknown. Adipokines (including leptin and adiponectin) are pleiotropic molecules produced by adipocytes that are important regulators of the inflammatory response. We hypothesized that the altered adipokine milieu observed in obesity contributes to the increased severity of pancreatitis. Lean (C57BL/6J), obese leptin-deficient (LepOb), and obese hyperleptinemic (LepDb) mice were subjected to AP by six hourly intraperitoneal injections of cerulein (50 microg/kg). Severity of AP was assessed by histology and by measuring pancreatic concentration of the proinflammatory cytokines IL-1beta and IL-6, the chemokine MCP-1, and the marker of neutrophil activation MPO. Both congenitally obese strains of mice developed significantly more severe AP than wild-type lean animals. Severity of AP was not solely related to adipose tissue volume: LepOb mice were heaviest; however, LepDb mice developed the most severe AP both histologically and biochemically. Circulating adiponectin concentrations inversely mirrored the severity of pancreatitis. These data demonstrate that congenitally obese mice develop more severe AP than lean animals when challenged by cerulein hyperstimulation and suggest that alteration of the adipokine milieu exacerbates the severity of AP in obesity.


Comparison Between Radial Approach and Femoral Approach With Vascular Closure Devices on the Occurrence of Access-Site Complications and Periprocedural Bleeding After Percutaneous Coronary Procedures: A Systematic Review and Meta-Analysis.
Periprocedural bleedings, often related to vascular access site, represent an important drawback of percutaneous coronary procedures and are associated with worse outcomes. Radial access (RA) and, potentially, femoral access (FA) with vascular closure device (VCD) are useful strategies in order to mitigate periprocedural bleedings; nevertheless, their relative efficacy is largely undetermined. We aimed to perform a systematic review and meta-analysis of available studies comparing the efficacy of RA and FA with hemostasis by VCD (FA + VCD) on the reduction of access-site complications and/or periprocedural bleedings. Published studies reporting outcomes on access-site complications and periprocedural bleedings were included in the analysis. Data were extracted by two independent reviewers; odds ratio (OR) and 95% confidence interval (CI) were calculated by random-effects model and were used as summary statistics. We included in the analysis 13 studies, of which 5 were randomized. Access-site complications were reported by 11 studies, amounting to 157,031 patients (77,713 in the RA group and 79,318 in the FA + VCD group), whereas periprocedural bleedings were reported by 12 studies, amounting to 600,196 patients (137,277 in the RA group and 462,919 in the FA + VCD group). RA was associated with a significant reduction in access-site complications (OR, 0.25; 95% CI ,0.21-0.31; P<.001) and periprocedural bleedings (OR, 0.40; 95% CI, 0.34-0.48; P<.001) as compared with FA + VCD; the results were consistent among randomized and observational studies. This meta-analysis shows that RA is superior to FA + VCD in the reduction of access-site complications and periprocedural bleedings.


Susceptibility of Campylobacter jejuni to strain-specific bactericidal activity in sera of infected patients.
Campylobacter jejuni is a common cause of inflammatory enteritis, which in normal hosts is usually self-limited and resolves without antibiotic therapy. C. jejuni bacteremia is very rare. We examined sera for bactericidal activity that might be important in limiting the extent of C. jejuni infection in man. We studied the ability of nonimmune sera and homologous and heterologous immune sera from infected patients to kill different fresh case isolates of C. jejuni in vitro. The reduction of the log10 concentration of viable C. jejuni (log10 killing) by fresh sera from nonimmune donors was only 0.2. Log10 killing by homologous acute sera varied from 0 to 3.8 (mean, 1.8). Convalescent sera showed remarkable log10 killing of only homologous C. jejuni, with values of 2.7 to 4.4 (mean, 3.7). The bactericidal effects of acute and convalescent sera were abrogated by heat and EDTA chelation, indicating mediation by complement. The role of classical complement pathway activation was supported by chelating sera with magnesium EGTA [ethylene glycol-bis(beta-aminoethyl ether)-N, N, N', N'-tetraacetic acid] and by reconstitution experiments with heat-inactivated sera, C2-deficient serum, and purified C2. The requirement of specific antibody for the serum bactericidal effect was indicated by the loss of bactericidal activity when immune sera were absorbed with homologous but not heterologous whole C. jejuni isolates. The presence of specific antibodies was further documented by agglutination of only homologous C. jejuni suspensions by heat-inactivated immune sera. Studies with polymorphonuclear leukocytes suggested that ingestion and killing of two C. jejuni strains were modest and variable in the presence of heat-inactivated homologous serum. In summary, the data document a potent serum bactericidal effect that develops rapidly and specifically during C. jejuni enteritis and may be an important factor in host defense against C. jejuni.


Timing of regional left ventricular lengthening by pulsed tissue Doppler.
Pulsed tissue Doppler can measure myocardial velocities with high temporal resolution. Our aim was to determine the onset timing of the regional left ventricular longitudinal early lengthening (e) in relation to the mitral inflow (E) in acute coronary syndromes. We applied pulsed tissue Doppler to the septal, lateral, inferior, and anterior left ventricular basal walls of 160 patients with acute coronary syndromes and 60 control subjects. Maximum systolic and early diastolic velocities were lower for patient than for control walls (6.1 +/- 1.7 vs 7.9 +/- 1.4 cm/s, P <.0001, and 6.9 +/- 2.3 vs 10.0 +/- 2.3 cm/s, P <.0001, respectively) and e started later than E (12 +/- 30 vs 2 +/- 19 milliseconds later, P <.0001). All 3 variables related to the degree of visual left ventricular wall pathology. The intraindividual time range for all 4 e starts was wider for patients (43 +/- 27 vs 30 +/- 18 milliseconds, P <.0001). Our results show that pulsed tissue Doppler can identify a delayed and asynchronous initial wall lengthening in acute coronary syndromes.


Increase in Rate of Hospitalizations for Pediatric Intentional Acetaminophen Ingestion at a Single Center During the COVID-19 Pandemic.
Social disruption due to COVID-19 has detrimentally affected American adolescents' emotional well-being. Within our system, pediatric acetaminophen ingestions increased in 2020, compared with previous years. We sought to evaluate the rate of hospitalizations for acetaminophen self-harm ingestions and self-harm of adolescents during the COVID-19 pandemic. We identified patients (aged 0-23) from billing data with diagnosis of acetaminophen ingestion with self-harm intent (ICD-10 code T391X2A), from a multicenter urban, quaternary health care system. We performed retrospective chart review from 2016 to 2020 and performed statistics using a generalized estimating equation (GEE) logistic regression model. From 2016 to 2020, there were 25 790 discharges of adolescents with 65 acetaminophen self-harm ingestion and 148 self-harm discharges. Of the 65 acetaminophen patients, 75% identified as female and 54% identified as non-white; 71% with Medicaid insurance. The proportion of acetaminophen ingestion and self-harm admissions increased from 0.13% in 2016 to 0.46% by 2020 and 0.42% in 2016 to 0.73% by 2020, respectively. The odds of acetaminophen ingestion admission increased by 28% each additional year (odds ratio = 1.28; 95% confidence interval: 1.08, 1.53; P = .006). There was not enough evidence to conclude that the log-odds of a self-harm ingestion were linearly related to time (P = .06). Acetaminophen ingestion for self-harm has significantly increased, while overall self-harm has increased to a lesser, nonsignificant degree. Primarily females of color and those with Medicaid insurance are affected. It is important to note this growing, disturbing trend, and to continue to screen for depression in our adolescent community and ensure access to mental health resources.


Rapid narcotic detoxification in chronic pain patients treated with auricular electroacupuncture and naloxone.
Severe withdrawal signs which accompany the detoxification of narcotic addicts from opiate drugs are also a serious problem for chronic pain patients taking high levels of analgesic medications. A rapid narcotic detoxification procedure utilizing auricular electroacupuncture was applied to 14 chronic pain patients to be withdrawn from their opiate medications. All patients were first switched to oral methadone. They were then given bilateral electrical stimulation to needles inserted in the "lung" and "shen men" acupuncture points on the ear, followed by periodic intravenous injections of low doses of naloxone. Twelve of the patients, 85.7%, were completely withdrawn from narcotic medications within 2-7 days, and they experienced no to minimal side effects. These results are explained by the relationship of electroacupuncture to the release of endorphins.


Getting around an Early Lethal Phenotype in Mice with Chimeras.
The same gene can have many different functions in different places in the body and/or at different times in development and adult life. Often only one organ or one developmental stage is of particular interest to an investigator. If, however, lethality or severe detrimental effects of a mutation prevent the study of the organ or stage of interest, there are a number of ways to circumvent an early effect. In this overview, we discuss one way of getting around an early lethal phenotype by using chimeras, a method that is also useful for studying the mutant cells in the context of a wild-type host as part of the phenotypic analysis. The composition of chimeras with respect to embryonic cell lineages can be controlled to some extent to produce lineage-restricted chimeras with, for example, mutant cells restricted to certain lineages. Depending on the site of action of the mutant gene, this could result in chimeric "rescue." Details of how to distinguish mutant cells from wild type, an essential part of any chimera experiment, are discussed as well as methods to genotype the chimeras with respect to both component cell types.


Control of conformers combining cooling by supersonic expansion of seeded molecular beams with hexapole selection and alignment: experiment and theory on 2-butanol.
Selection and alignment of rotamers and, more in general, of conformers in the gas phase is a challenge that we tackle experimentally by supersonic expansion of seeded molecular beams and hexapolar electrostatic fields with quadrupole mass detection. The studied system involves the nine conformers of the asymmetric-top molecule 2-butanol, which coexist because of nearly free rotations around a CC and a CO bond. From the measured time-of-flight of a 2-butanol supersonic molecular beam seeded in either He or Ar, the corresponding velocity distributions are obtained. The different nature and masses of the seeding gas decrease selectively the vibrational temperature and determine the population of the conformers, which is assessed on the basis of their statistical distribution, derived from high level accompanying quantum mechanical calculations. The use of a hexapolar electrostatic field permits us to induce a variation of the population distribution as a function of the applied voltage and of the selective focusing and alignment of the conformers. A technique, recently developed for treating asymmetric tops and involving extensive trajectory simulations, is applied to obtain the link between the focusing curves, i.e. the dependence of the beam intensity on the hexapole voltage, and the conformers' populations and alignment. Perspectives are provided for photo- and stereo-dynamics experiments, particularly appealing also on account that 2-butanol is the simplest chiral alcohol.


On the medical edge: preparation of expatriates, refugee and disaster relief workers, and Peace Corps volunteers.
Travelers to extreme environments and those who spend long periods of time in settings with limited health care resources need to have more detailed pretravel screening and education than the routine short-term traveler. Expatriates, relief workers, and Peace Corps volunteers need to receive careful pretravel medical, dental, and psychologic screening before deployment. Knowledge of special risks associated with the environment in which they will be stationed is necessary to provide effective education about ways to reduce or eliminate the risk of illness and death. The travel medicine practitioner should also provide detailed, region-specific recommendations regarding emergency care while traveling in remote regions. Information on foreign medical facilities and practitioners should be gathered in advance and regularly updated. Many fee-for-service directories of overseas medical centers are often out of date and do not include emergency contact information. Once deployed, systems should be in place to ensure the traveler's continued personal safety and maintenance of good health. Although these systems are generally beyond the scope of work of travel medicine providers, it is important for the long-term traveler to be aware of the need to be prepared to deal with unexpected medical events. In the event of an overseas emergency, the travel medicine specialist may be called on to facilitate ground or air medical evacuation to the most appropriate medical center, to communicate treatment priorities and pertinent medical details to foreign medical providers, and to facilitate international air evacuation or repatriation if necessary. In each of these cases, the experience for the patient and the travel health professional is dramatically improved by adhering to risk-reduction measures, such as pretravel screening, pretravel health and safety education, and preparing for emergencies in advance.


Human papillomavirus vaccination series initiation and completion, 2008-2009.
The goal was to describe factors associated with human papillomavirus (HPV) vaccination series initiation (≥1 dose) and completion (≥3 doses) and parents' intent to have their daughters vaccinated. Data from the 2008 and 2009 National Immunization Survey-Teen were analyzed to estimate HPV vaccination coverage among girls 13 to 17 years of age (N = 18,228) and to examine associations of vaccination coverage with demographic characteristics. Overall, 40.5% of girls had received ≥1 HPV vaccine dose, and 53.3% of those girls completed the series. Factors independently associated with vaccination initiation included older age, having an 11- to 12-year preventive visit, insurance status, mother's age and marital status, not receiving all vaccines at public facilities, and provider recommendation, which was the factor most strongly associated with initiation (prevalence ratio: 2.6 [95% confidence interval: 2.4-2.9]). Compared with white girls (60.4%), black (46.0%) and Hispanic (40.3%) girls were less likely to complete the series. Lack of knowledge of the vaccine (19.4%), vaccination was not needed (18.8%), the daughter was not sexually active (18.3%), and a provider did not recommend (13.1%) were the most common reasons for parents' nonintent to have their daughters vaccinated. Although HPV vaccine coverage rates are increasing, they are still below target levels. Recommendations by providers to adolescent patients and parents likely would improve vaccine uptake. Parental education regarding disease risks and benefits of HPV vaccination before exposure is needed to promote vaccine uptake.


Mycobacterium tuberculosis infection modulates adipose tissue biology.
Mycobacterium tuberculosis (Mtb) primarily resides in the lung but can also persist in extrapulmonary sites. Macrophages are considered the prime cellular habitat in all tissues. Here we demonstrate that Mtb resides inside adipocytes of fat tissue where it expresses stress-related genes. Moreover, perigonadal fat of Mtb-infected mice disseminated the infection when transferred to uninfected animals. Adipose tissue harbors leukocytes in addition to adipocytes and other cell types and we observed that Mtb infection induces changes in adipose tissue biology depending on stage of infection. Mice infected via aerosol showed infiltration of inducible nitric oxide synthase (iNOS) or arginase 1 (Arg1)-negative F4/80+ cells, despite recruitment of CD3+, CD4+ and CD8+ T cells. Gene expression analysis of adipose tissue of aerosol Mtb-infected mice provided evidence for upregulated expression of genes associated with T cells and NK cells at 28 days post-infection. Strikingly, IFN-γ-producing NK cells and Mtb-specific CD8+ T cells were identified in perigonadal fat, specifically CD8+CD44-CD69+ and CD8+CD44-CD103+ subpopulations. Gene expression analysis of these cells revealed that they expressed IFN-γ and the lectin-like receptor Klrg1 and down-regulated CD27 and CD62L, consistent with an effector phenotype of Mtb-specific CD8+ T cells. Sorted NK cells expressed higher abundance of Klrg1 upon infection, as well. Our results reveal the ability of Mtb to persist in adipose tissue in a stressed state, and that NK cells and Mtb-specific CD8+ T cells infiltrate infected adipose tissue where they produce IFN-γ and assume an effector phenotype. We conclude that adipose tissue is a potential niche for Mtb and that due to infection CD8+ T cells and NK cells are attracted to this tissue.


IMPACT-III is a valid and reliable questionnaire for assessing health-related quality of life in Swedish children with inflammatory bowel disease.
This study examined the reliability, validity and factor structure of the Swedish version of the IMPACT-III questionnaire for assessing health-related quality of life in children with inflammatory bowel disease. We recruited 202 participants aged eight to 18 years, who were enrolled from 16 of the 23 paediatric gastroenterology clinics across Sweden during 2010-2013. This cross-sectional study compared two versions of the IMPACT-III questionnaire - one with six factors and 35 items and one with four factors and 19 items - plus the Paediatric Quality of Life Inventory 4.0 Generic Core Scale. Disease activity was assessed and defined as active or inactive. The mean total score for the six-factor IMPACT-III scale was 143.7/175, with a standard deviation (SD) of 17.9. There was a significant difference in mean total scores between the 133 children with inactive disease (147.8, SD: 14.9) and the 52 with active disease (133.0, SD: 20.3). Confirmatory factor analysis showed that the four-factor scale was more robust than the original six-factor scale. Concurrent validity and discriminant validity were high for both versions. The Swedish version of the IMPACT-III questionnaire was valid and reliable, but the shorter, four-factor version is quicker and may be more convenient in clinical settings.


Effects of pituitary adenylate cyclase-activating polypeptide (PACAP) on cyclic AMP formation in the duck and goose brain.
Two molecular forms of pituitary adenylate cyclase-activating polypeptide (PACAP), i.e., PACAP27 and PACAP38 (0.0001-1 microM), as well as vasoactive intestinal polypeptide (VIP; 0.1-3 microM), have been studied for their effects on cyclic AMP formation in the hypothalamus and cerebral cortex of duck and goose. All three peptides concentration-dependently stimulated cyclic AMP production in the tested brain regions of 2-3-weeks-old (young) ducks, with VIP showing at least one order of magnitude weaker activity than PACAP. This characteristics suggests the existence in the duck's brain of adenylyl cyclase-linked PAC1 receptors. Both forms of PACAP also stimulated the nucleotide formation in the cerebral cortex and hypothalamus of 5-6-months-old (adult) ducks or geese grown under natural environment. The peptides-evoked effects in adult and young ducks were comparable, and clearly greater than those found in adult geese. The present data extend our recent observations made on chicks, and suggest PACAP to be a potent stimulator of the cyclic AMP generation in the avian central nervous system.


Inducibility and negative autoregulation of CREM: an alternative promoter directs the expression of ICER, an early response repressor.
cAMP-responsive element modulator (CREM) expression is tissue specific and developmentally regulated. Here we report that CREM is unique within the family of cAMP-responsive promoter element (CRE)-binding factors since it is inducible by activation of the cAMP signaling pathway. The kinetic of expression is characteristic of an early response gene. The induction is transient and cell specific, does not involve increased transcript stability, and does not require protein synthesis. Significantly, the subsequent decline in CREM expression requires de novo protein synthesis. The induced transcript encodes a novel repressor, inducible cAMP early repressor (ICER), and is generated from an alternative intronic promoter. A cluster of four CREs in this promoter directs cAMP inducibility. ICER binds to these elements and thereby represses the activity of its own promoter, thus constituting a negative autoregulatory loop.


Internal jugular vein sampling in adrenocorticotropic hormone-dependent Cushing's syndrome: a comparison with inferior petrosal sinus sampling.
Distinguishing between pituitary-dependent Cushing's syndrome (CS) and occult ectopic ACTH syndrome can be extremely difficult. Bilateral inferior petrosal sinus sampling has been shown to have the highest diagnostic accuracy in this subtype evaluation. Internal jugular vein sampling (IJVS) has been reported as a potentially safer invasive alternative, but data are limited. Our objective was to compare the sensitivity and specificity of bilateral IJVS and bilateral inferior petrosal sinus sampling (IPSS) in patients with ACTH-dependent CS. We prospectively collected blood samples from the inferior petrosal sinus and internal jugular vein of consecutive patients with ACTH-dependent CS. The study group included 35 patients: 32 with pituitary-dependent CS (positive immunohistochemical findings for ACTH pituitary tumour or biochemical cure after pituitary surgery) and three with histologically proven ectopic ACTH syndrome. Inferior petrosal sinus sampling and bilateral IJVS were performed simultaneously before and after administration of corticotropin-releasing hormone (CRH), and ratios of central-to-peripheral ACTH concentrations were calculated. The basal IJVS central-to-peripheral ACTH ratios were diagnostic for pituitary-dependent CS (> 2) in 15 patients (46.9%), as were basal inferior petrosal sinus sampling central-to-peripheral ACTH ratios in 29 patients (90.6%). The post-CRH IJVS central-to-peripheral ACTH ratios were diagnostic for pituitary-dependent disease (> 3) in 24 patients (75%), as were post-CRH inferior petrosal sinus sampling central-to-peripheral ACTH ratios in 28 patients (87.5%). In the three patients with ectopic ACTH CS, the IJVS and inferior petrosal sinus sampling pre- and post-CRH ACTH ratios were correctly negative. The overall sensitivity of combined pre- or post-CRH was 81.3% for IJVS and 93.8% for inferior petrosal sinus sampling. Because of the difference between mean ratios in the two techniques, new criteria for IJVS were mathematically calculated: a pre-CRH central-to-peripheral ACTH ratio of 1.59 and a post-CRH central-to-peripheral ACTH ratio of 2.47 maximized sensitivity and specificity when both of these are equally taken into consideration. In conclusion, IJVS is not superior to inferior petrosal sinus sampling for establishing the cause of ACTH-dependent CS. When new criteria of basal (> 1.6) and post-CRH (> 2.5) central-to-peripheral ACTH gradients were applied to ACTH ratios from IJVS, the sensitivity of this test was maximized. However, confirmatory inferior petrosal sinus sampling is recommended when there is a lack of a central-to-peripheral ACTH gradient and when there is only a gradient above the cut-off on basal (pre-CRH) sampling.


Ruptured mycotic aneurysm of a coronary artery. A fatal complication of Salmonella infection.
A 53-year-old man with a kidney transplant was hospitalized because of back pain, fever, and an enlarging heart size. Cultures of blood and stool yielded Salmonella enteritidis (group D, serotype enteritidis). Despite appropriate antibiotic therapy, the patient died of cardiac arrest on the seventh hospital day. Autopsy revealed a ruptured mycotic aneurysm of the right coronary artery with hemopericardium. In addition, a ruptured aneurysm of the abdominal aorta was present. To our knowledge, ruptured mycotic aneurysm involving a coronary artery owing to Salmonella infection has not been described previously.


Oxygen-plasma-modified biomimetic nanofibrous scaffolds for enhanced compatibility of cardiovascular implants.
Electrospun nanofibrous scaffolds have been extensively used in several biomedical applications for tissue engineering due to their morphological resemblance to the extracellular matrix (ECM). Especially, there is a need for the cardiovascular implants to exhibit a nanostructured surface that mimics the native endothelium in order to promote endothelialization and to reduce the complications of thrombosis and implant failure. Thus, we herein fabricated poly-ε-caprolactone (PCL) electrospun nanofibrous scaffolds, to serve as coatings for cardiovascular implants and guide tissue regeneration. Oxygen plasma treatment was applied in order to modify the surface chemistry of the scaffold and its effect on cell attachment and growth was evaluated. The conditions of the surface modification were properly adjusted in order to define those conditions of the treatment that result in surfaces favorable for cell growth, while maintaining morphological integrity and mechanical behavior. Goniometry (contact angle measurements), scanning electron microscopy (SEM), atomic force microscopy (AFM), and X-ray photoelectron spectroscopy (XPS) measurements were used to evaluate the morphological and chemical changes induced by the plasma treatment. Moreover, depth-sensing nanoindentation was performed to study the resistance of the plasma-treated scaffolds to plastic deformation. Lastly, the cell studies indicated that all scaffolds were cytocompatible, with the plasma-treated ones expressing a more pronounced cell viability and adhesion. All the above findings demonstrate the great potential of these biomimetic tissue-engineering constructs as efficient coatings for enhanced compatibility of cardiovascular implants.


Attenuation of the midbrain-evoked defense reaction by selective stimulation of medullary raphe neurons in rats.
In rats anesthetized with alfaxalone/alfadolone, electrical stimulation in the dorsal periaqueductal gray matter (PAG) evoked a cardiovascular defense reaction with increases in blood pressure, heart rate, femoral conductance, and respiratory activity but a decrease in renal conductance. These responses were attenuated significantly after microinjection of 200 nl 0.1 M DL-homocysteic acid (DLH) into nucleus raphe magnus (NRM, n = 12) or nucleus raphe obscurus (NRO, n = 22). The maximum reduction in the pressor response was similar after stimulation in NRM (-36.3%) and NRO (-37.3%). The reduction of the tachycardia, however, was greater after stimulation in NRM (-78.1%) compared with NRO (-34.6%). The maximum reduction in the PAG-evoked vasodilation of the hindlimb averaged -55.7% and -55.3% after stimulation of NRM and NRO, respectively, whereas the renal vasoconstriction was reduced by -66.4% and -79.0%. The PAG-evoked increase in respiratory amplitude was attenuated only after stimulation of NRO. It is concluded that neurons in NRM and NRO may be involved in modulating the level of excitability of neurons in the midbrain defense area and/or in its efferent pathway.


Context-Dependent Upper Limb Prosthesis Control for Natural and Robust Use.
Pattern recognition and regression methods applied to the surface EMG have been used for estimating the user intended motor tasks across multiple degrees of freedom (DOF), for prosthetic control. While these methods are effective in several conditions, they are still characterized by some shortcomings. In this study we propose a methodology that combines these two approaches for mutually alleviating their limitations. This resulted in a control method capable of context-dependent movement estimation that switched automatically between sequential (one DOF at a time) or simultaneous (multiple DOF) prosthesis control, based on an online estimation of signal dimensionality. The proposed method was evaluated in scenarios close to real-life situations, with the control of a physical prosthesis in applied tasks of varying difficulties. Test prostheses were individually manufactured for both able-bodied and transradial amputee subjects. With these prostheses, two amputees performed the Southampton Hand Assessment Procedure test with scores of 58 and 71 points. The five able-bodied individuals performed standardized tests, such as the box&block and clothes pin test, reducing the completion times by up to 30%, with respect to using a state-of-the-art pure sequential control algorithm. Apart from facilitating fast simultaneous movements, the proposed control scheme was also more intuitive to use, since human movements are predominated by simultaneous activations across joints. The proposed method thus represents a significant step towards intelligent, intuitive and natural control of upper limb prostheses.


Further Optimization and Validation of the Classical Drude Polarizable Protein Force Field.
The CHARMM Drude-2013 polarizable force field (FF) was developed to include the explicit treatment of induced electronic polarizability, resulting in a more accurate description of the electrostatic interactions in molecular dynamics (MD) simulations. While the Drude-2013 protein FF has shown success in improving the folding properties of α-helical peptides and to reproduce experimental observables in simulations up to 1 μs, some limitations were noted regarding the stability of β-sheet structures in simulations longer than 100 ns as well as larger deviations from crystal structures in simulations of a number of proteins compared to the additive CHARMM36 protein FF. The origin of the instability has been identified and appears to be primarily due to overestimated atomic polarizabilities and induced dipole-dipole interactions on the Cβ, Cγ, and Cδ side chain atoms. To resolve this and other issues, a number of aspects of the model were revisited, resulting in Drude-2019 protein FF. Backbone parameters were optimized targeting the conformational properties of the (Ala)5 peptide in solution along with gas phase properties of the alanine dipeptide. Dipeptides that contain N-acetylated and N'-methylamidated termini, excluding Gly, Pro, and Ala, were used as models to optimize the atomic polarizabilities and Thole screening factors on selected Cβ, Cγ, and Cδ carbons by targeting quantum mechanical (QM) dipole moments and molecular polarizabilities. In addition, to obtain better conformational properties, side chain χ1 and χ2 dihedral parameters were optimized targeting QM data for the respective side chain dipeptide conformations as well as Protein Data Bank survey data based on the χ1, χ2 sampling from Hamiltonian replica-exchange MD simulations of (Ala)4-X-(Ala)4 in solution, where X is the amino acid of interest. Further improvements include optimizing nonbonded interactions between charged residues to reproduce QM interaction energies of the charged-protein model compounds and experimental osmotic pressures. Validation of the optimized Drude protein FF includes MD simulations of a collection of peptides and proteins including β-sheet structures, as well as transmembrane ion channels. Results showed that the updated Drude-2019 protein FF yields smaller overall root-mean-square differences of proteins as compared to the additive CHARMM36m and Drude-2013 FFs as well as similar or improved agreement with experimental NMR properties, allowing for long time scale simulation studies of proteins and more complex biomolecular systems in conjunction with the remainder of the Drude polarizable FF.


Biomass and nutrient concentration of sweet corn roots and shoots under organic amendments application.
Two field experiments were conducted at the Waimanalo research station on the island of O'ahu, Hawaii to study the effect of chicken (CM) and dairy (DM) manures on biomass and nutrient concentration in sweet corn roots and shoots. Sweet corn (super sweet 10, Zea Mays L. subsp. mays) was grown for two consecutive growing seasons under four rates of application (0, 168, 337, and 672 kg ha(-1) total N equivalent) and one time (OTA) or two time (TTA) applications of organic manure types and rates. There were significant effects of types, rates, and number of manure applications on dry biomass and macro- and micro-nutrient concentration in roots and shoots tissues. Results of root tissue indicated a significant accumulation of N and C under CM and DM treatments compared with the control treatment. Manure application rates significantly increased the accumulation of N and C in root tissue. Dry weight of roots and shoots and both macro- and micro-nutrient contents in the plant tissues significantly increased under TTA treatment compared with OTA treatment. There was a significant correlation (r(2) = 0.46 to 0.81) between root biomass, macro-, and micro-nutrient contents during both growing seasons. The results of the study indicates that amending soils with CM at the highest application rate provided the best crop performance in terms of root and shoot biomass, crop N, C, and other macro- and micro-nutrients.


Correcting global solar ultraviolet spectra recorded by a brewer spectroradiometer for its angular response error.
We present a methodology for correcting the global UV spectral measurements of a Brewer MKIII spectroradiometer for the error introduced by the deviation of the angular response of the instrument from the ideal response. This methodology is applicable also to other Brewer spectroradiometers that are currently in operation. The various stages of the methodology are described in detail, together with the uncertainties involved in each stage. Finally global spectral UV measurements with and without the application of the correction are compared with collocated measurements of another spectroradiometer and with model calculations, demonstrating the efficiency of the method. Depending on wavelength and on the aerosol loading, the cosine correction factors range from 2% to 7%. The uncertainties involved in the calculation of these correction factors were found to be relatively small, ranging from ~0.2% to ~2%.


Bacterial fitness shapes the population dynamics of antibiotic-resistant and -susceptible bacteria in a model of combined antibiotic and anti-virulence treatment.
Bacterial resistance to antibiotic treatment is a huge concern: introduction of any new antibiotic is shortly followed by the emergence of resistant bacterial isolates in the clinic. This issue is compounded by a severe lack of new antibiotics reaching the market. The significant rise in clinical resistance to antibiotics is especially problematic in nosocomial infections, where already vulnerable patients may fail to respond to treatment, causing even greater health concern. A recent focus has been on the development of anti-virulence drugs as a second line of defence in the treatment of antibiotic-resistant infections. This treatment, which weakens bacteria by reducing their virulence rather than killing them, should allow infections to be cleared through the body׳s natural defence mechanisms. In this way there should be little to no selective pressure exerted on the organism and, as such, a predominantly resistant population should be less likely to emerge. However, before the likelihood of resistance to these novel drugs emerging can be predicted, we must first establish whether such drugs can actually be effective. Many believe that anti-virulence drugs would not be powerful enough to clear existing infections, restricting their potential application to prophylaxis. We have developed a mathematical model that provides a theoretical framework to reveal the circumstances under which anti-virulence drugs may or may not be successful. We demonstrate that by harnessing and combining the advantages of antibiotics with those provided by anti-virulence drugs, given infection-specific parameters, it is possible to identify treatment strategies that would efficiently clear bacterial infections, while preventing the emergence of antibiotic-resistant subpopulations. Our findings strongly support the continuation of research into anti-virulence drugs and demonstrate that their applicability may reach beyond infection prevention.


Effects of a high-sucrose diet on the development of enzyme-altered foci in chemical hepatocarcinogenesis in rats.
Dietary factors can modify metabolic events involved in the initiation, promotion, or progression of tumors. To determine whether a high-sucrose diet has any effect on the development of enzyme-altered foci during the promotion step of chemical hepatocarcinogenesis in rats, 1-day-old Sprague-Dawley rats were given a single i.p. dose of diethylnitrosamine; controls received an equivalent i.p. volume of 0.9% NaCl solution. At 21 days of age, the rats were weaned, segregated by sex, separated in groups, and fed modified AIN76A diets containing either 65% glucose or 65% sucrose, with or without 0.05% phenobarbital. At the end of a 4-week treatment period, the sucrose-fed control rats of either sex had significantly heavier livers than did those on the glucose diet. Enlarged livers were found also in the sucrose-fed diethylnitrosamine-treated female rats, which developed twice as many gamma-glutamyltranspeptidase-positive foci per sq cm of liver section than did those on the glucose diet. Addition of phenobarbital augmented the number of foci 3-fold in the sucrose group and 5-fold in the glucose group. Focus count per sq cm was similar in animals on the two phenobarbital-supplemented diets. Despite the absence of statistically significant liver enlargement, results analogous to those in females were obtained in carcinogen-treated males. Differences between treatments, however, were smaller. In both female and male rats, the DNA-synthesizing activity of hepatocytes in enzyme-altered foci was significantly higher than in the surrounding normal parenchymal cells, as determined by autoradiography. These studies indicate that a high-sucrose diet has a promoting effect during hepatocarcinogenesis induced in the rat by diethylnitrosamine and that this effect is weaker than that of 0.05% phenobarbital.


[Pregnancy complicated by ovarian cysts].
This study included all the patients with ovarial cysts > or = 6 cm that were persisted during pregnancy in the 1st. Department of Obstetrics and Gynecology of Semmelweis University Medical School between 1. January 1991. and 31. December 1996. There were 14,640 deliveries and 15 cases which presented by above mentioned criteria with 1/976 incidency and 3 cases from all were malignant tumor with 1/4880 incidency. All patients underwent surgical intervention. Surgical management were spreaded on one adnexa in 12 cases of all, on both adnexum in only 3 cases and hysterectomy with both side adnexectomies was performed in only one case. Based on complications in two cases emergency laparotomies and in 13 cases elective extirpation of ovarial cysts were performed. There was no loss of pregnancy in the postoperative period. Because of the high risk of complications and malignancy we supported that surgical intervention in the second trimester is a definitive therapy for ovarial cysts complicated pregnancy.


Skeletal muscle insulin resistance promotes increased hepatic de novo lipogenesis, hyperlipidemia, and hepatic steatosis in the elderly.
Aging is closely associated with muscle insulin resistance, hyperlipidemia, nonalcoholic fatty liver disease (NAFLD), and type 2 diabetes. We examined the hypothesis that muscle insulin resistance in healthy aging promotes increased hepatic de novo lipogenesis (DNL) and hyperlipidemia by altering the distribution pattern of postprandial energy storage. Healthy, normal weight, sedentary elderly subjects pair-matched to young subjects were given two high-carbohydrate meals followed by ¹³C/¹H magnetic resonance spectroscopy measurements of postprandial changes in muscle and liver glycogen and lipid content, and assessment of DNL using ²H₂O. Net muscle glycogen synthesis was reduced by 45% (P < 0.007) in the elderly subjects compared with the young, reflecting severe muscle insulin resistance. Net liver glycogen synthesis was similar between groups (elderly, 143 ± 23 mmol/L vs. young, 138 ± 13 mmol/L; P = NS). Hepatic DNL was more than twofold higher in the elderly than in the young subjects (elderly, 14.5 ± 1.4% vs. young, 6.9 ± 0.7%; P = 0.00015) and was associated with approximately threefold higher postprandial hepatic triglyceride (TG) content (P < 0.005) and increased fasting plasma TGs (elderly, 1.19 ± 0.18 mmol/L vs. young, 0.74 ± 0.11 mmol/L; P = 0.02). These results strongly support the hypothesis that muscle insulin resistance in aging promotes hyperlipidemia and NAFLD by altering the pattern of postprandial carbohydrate storage away from muscle glycogen and into hepatic DNL.


Cusp catastrophe model: a nonlinear model for health outcomes in nursing research.
Although health outcomes may have fundamentally nonlinear relationships with relevant behavioral, psychological, cognitively, or biological predictors, most analytical models assume a linear relationship. Furthermore, some health outcomes may have multimodal distributions, but most statistical models in common use assume a unimodal, normal distribution. Suitable nonlinear models should be developed to explain health outcomes. The aim of this study is to provide an overview of a cusp catastrophe model for examining health outcomes and to present an example using grip strength as an indicator of a physical functioning outcome to illustrate how the technique may be used. Results using linear regression, nonlinear logistic model, and the cusp catastrophe model were compared. Data from 935 participants from the Survey of Midlife Development in the United States (MIDUS) were analyzed. The outcome was grip strength; executive function and the inflammatory cytokine interleukin-6 were predictor variables. Grip strength was bimodally distributed. On the basis of fit and model selection criteria, the cusp model was superior to the linear model and the nonlinear logistic regression model. The cusp catastrophe model identified interleukin-6 as a significant asymmetry factor and executive function as a significant bifurcation factor. The cusp catastrophe model is a useful alternative for explaining the nonlinear relationships commonly seen between health outcome and its predictors. Considerations for the use of cusp catastrophe model in nursing research are discussed and recommended.


Malignant urachal lesions.
Urachal cancers are uncommon malignancies with a location that often permits considerable local extension before they are discovered. The most common histological type is adenocarcinoma, which may produce mucus that is a valuable aid in diagnosis. The presence of stippled calcification in a midline abdominal wall mass is almost pathognomonic for urachal carcinoma. More commonly, however, the symptoms are less specific, such as hematuria and an abdominal mass. Many lesions are visible endoscopically and, thus, the diagnosis can be made preoperatively from a biopsy. Most treatment failures occur because the tumor is not controlled locally by the initial operation and, therefore, we recommend en bloc cystectomy with umbilectomy and pelvic lymphadenectomy unless the tumor is known to be a sarcoma or early stage (I) carcinoma. If these patients are undertreated and there is a local recurrence then the patient usually is not salvageable. Because of the difficulty in identifying the origin of a bladder adenocarcinoma, any tumor on the dome or anterior wall should be approached initially as if it were a urachal tumor.


Effect of betamethasone and betamethasone with neomycin nasal drops on human nasal mucociliary clearance and ciliary beat frequency.
The effects of two topical nasal preparations on human nasal ciliary beat frequency in vitro and on nasal mucociliary clearance in vivo were investigated. Betamethasone and betamethasone with neomycin drops were found to be ciliotoxic when ciliated epithelium was exposed to them in vitro, mainly owing to the effects of the preservatives benzalkonium chloride and thiomersal. The nasal mucociliary clearance and in vitro ciliary beat frequency of nasal ciliated epithelium taken from healthy subjects were not adversely affected after topical application; neither did treatment with betamethasone, with or without neomycin, for four weeks affect these indices in two groups of patients with rhinitis. Thus, despite a ciliotoxic effect when ciliated epithelium is exposed to these preparations in vitro, they do not affect nasal clearance or ciliary beat frequency (as measured in vitro) adversely when administered topically to the nose.


Preliminary data on the genetic differentiation of Onchocerca volvulus in Africa (Nematoda: Filarioidea).
Data are reported on the genetic structure of three Onchocerca volvulus populations, respectively from Mali (savanna), Ivory Coast (forest), and Zaire (forest gallery in savanna). Electrophoretic analysis, carried out on 25 gene-enzyme systems, has shown a remarkable genetic heterogeneity existing within O.volvulus. Zaire and West Africa populations appear chiefly differentiated at Mdh-1 and 6Pgdh loci, their average Nei's genetic distance being 0.11. In West Africa Nei's D found between the savanna and forest samples is 0.04. The savanna population from Zaire is more similar to the savanna one from Mali (D = 0.09) than to the forest one from Ivory Coast (D = 0.13). This appears mainly due to the loci Ldh and Hbdh (possibly linked), some alleles of which seem to be selected for in forest populations (Ldh110, Hbdh108), while others in the savanna ones (Ldh100, Hbdh100). The hypothesis that the discrepant epidemiological patterns of human onchocerciasis are related to intrinsic differences in the parasite seems supported by the obtained data. The differences in allele frequencies found at the reported loci appear strong enough to allow biochemical identification of O. volvulus populations from different geographic regions and different habitats.


National oral health survey Zimbabwe 1995: quality of restorations.
In 1995, a second national oral health survey was carried out, ten years after the first. Application of a multi-stage sampling procedure resulted in 3709 persons being examined. The restorations were assessed using the criteria described by Kroeze et al (1990). Only ditches on the tooth/restoration margins that were wider than 0.4 mm were considered to be carious. The background variables studied were age, gender, type of location, socioeconomic status (SES) and level of education. The prevalence of restorations in all persons examined was 3.4 per cent. Restorations were found much more often among urban (95.5 per cent) than rural people (4.5 per cent) and also among those living in high (75 per cent) compared to low SES suburbs (25 per cent). Amalgam was more often used (89 per cent) than composite resin (10 per cent). The most frequently observed type of restoration was Class I (45 per cent) followed by Class II (39 per cent) and Class III (7 per cent). The prevalence of satisfactory restorations was 83.9 per cent. Failures were due to 'fractured restorations' (6.3 per cent), 'caries at the margin' and 'breakdown of restoration margin', both 4 per cent. Amongst adults, multiple-surface amalgam restorations failed more often than single-surface ones. It is concluded that the prevalence of restorations found was very low. There is a need to extend the provision of preventive and restorative oral health care by a more equitable distribution of oral health personnel and by making more finance available to rural and low-SES suburban areas.


Immunomodulatory activities of the somatostatin analogue BIM 23014c: effects on murine lymphocyte proliferation and natural killer activity.
We have examined the effect of somatostatin and its octapeptide analogue BIM 23014c on concanavalin A-induced lymphocyte proliferation and target-specific natural killer activity both in vitro and in vivo. Using Peyer's patches and spleen as a source of lymphocytes, we found that both peptides modulated immunity in a dose-dependent manner. Comparatively, there was no significant difference between the activity of somatostatin or BIM 23014c in the modulation of immunity. Proliferation, both in vitro and in vivo, was significantly inhibited by both peptides in each organ with a higher specificity towards the Peyer's patch lymphocytes. Natural killer activity was also inhibited in both organs in vivo and in vitro. Thus, not only did somatostatin and BIM 23014c have similar effects on proliferation and natural killer activity, but their effect was organ specific. Preliminary data suggest that BIM 23014c works via the same receptor as somatostatin, therefore intimating that these two peptides are both clinically and immunologically similar.


The effects of burial on drug detection in skeletal tissues.
Skeletal tissues have recently been investigated for use in post-mortem toxicology. Variables affecting drug concentration in these tissues, however, are still poorly characterized. In this work, the relative effects of burial on the response of enzyme-linked immunosorbent assay (ELISA) and gas chromatography-mass spectrometry (GC-MS) assays were examined. Rats were acutely exposed to ketamine or diazepam, euthanized and buried outdoors. After one month, the remains were exhumed and skeletal tissue drug levels were compared those of non-buried rats. A climate-controlled burial was also undertaken using defleshed bones to approximate an extended decomposition. Long bones (femora, tibiae) were isolated and separated into tissue type (diaphyseal bone, epiphyseal bone, and marrow), and according to treatment (i.e. buried or non-buried). Following methanolic extraction (bone) or simple homogenization (marrow), samples were analyzed with ELISA. Samples were then pooled according to treatment, extracted by solid phase extraction (SPE) and confirmed with GC-MS. Under the conditions examined, the effects of burial appear to be drug and tissue dependent. Ketamine-exposed tissues demonstrated the greatest differences, especially in bone marrow. In diazepam-exposed tissues, burial did not seem to greatly affect drug response and some gave greater assay response compared to the non-buried set. Overall, the data suggest that fresh tissue samples may not be representative of decomposed samples in terms of skeletal tissue drug levels.


Molecular defects in the E1 alpha subunit of the branched-chain alpha-ketoacid dehydrogenase complex that cause maple syrup urine disease.
Maple syrup urine disease (MSUD) results from an inborn metabolic error caused by a deficiency of the branched-chain alpha-ketoacid dehydrogenase complex (BCKDC). cDNA clones encoding the E1 alpha subunit of BCKDC from rat and human liver have been isolated and characterized. The chromosomal location of E1 alpha on chromosome 19q13.1-13.2 has been determined using complementary methods. The etiology of MSUD has been studied by determining the enzyme activity, protein mass and mRNA level of BCKDC in fibroblasts from a human family and Polled Hereford calves, both with classic MSUD. A TACTyr to AACAsn substitution at residue 394 of the E1 alpha subunit was identified in the human patient by using enzymatic amplification of mRNA followed by DNA sequencing. Amplification of both mRNA and genomic DNA, in combination with allele-specific oligonucleotide hybridization, demonstrated that the patient was a compound heterozygote, inheriting an allele with a structural mutation from the father, and an allele from the mother containing a presumably cis-acting defect in regulation that abolished the expression of one of the E1 alpha alleles. The results revealed for the first time that a case of MSUD was caused by structural and regulatory mutations involving the E1 alpha subunit. Recent studies by others have demonstrated that the same structural mutation as is found in this patient is responsible for the high incidence of MSUD in the Philadelphia Mennonite population.(ABSTRACT TRUNCATED AT 250 WORDS)


[Effect of GABA-ergic substances on the conditioned avoidance reaction in rats].
The effect of GABA-ergic substances on the production and latent period of the conditioned reflex of avoidance in rats has been studied. The inhibitor of GABA-transaminase n-dipropylacetate (depakin) deteriorates the reflex production. Fenibut and amino oxyacetic acid significantly prolong the latent period of the produced conditioned reflex of avoidance. The effect of amino oxyacetic acid on the conditioned reflex is abolished by bicuculline and is likely to be related to the increased brain GABA content.


Plasma levels of apolipoprotein A1 in malaria-exposed primigravidae are associated with severe anemia.
Plasmodium falciparum placental malaria (PM) contributes to 10,000 maternal deaths due to severe anemia (SA) each year in Africa, primarily among primigravid women who are most susceptible. Increased levels of proinflammatory cytokines like TNF-alpha are associated with maternal anemia in first time mothers but not in other women. Here we aimed to identify additional changes in the plasma proteome associated with pregnancy malaria that may contribute to the development of malaria-related maternal anemia. A semi-quantitative mass spectrometry approach was used to compare the relative abundance of plasma proteins in anemic versus non-anemic women with PM. Levels of 24 proteins differed significantly between anemic and non-anemic primigravidae, including several lipid metabolism proteins and molecular transport proteins involved in the acute phase response signaling network. These differences were not observed in multigravid women who enjoy specific immunity that protect them from PM. In a confirmatory study of a larger cohort of primigravid women, levels of the lipid metabolism protein Apolipoprotein (Apo)-AI were significantly lower in PM+ women with SA. Apo-AI levels are significantly lower in severely anemic primigravidae with PM, and ApoA1 levels positively correlate with hemoglobin levels in primigravid but not multigravid women. Apo-AI is known to have anti-inflammatory effects, and thus Apo-AI reductions may contribute to the inflammatory processes that result in SA.


Differential prognosis of metastatic colorectal cancer patients post-progression to first-line triplet chemotherapy plus bevacizumab, FIr-B/FOx, according to second-line treatment and KRAS genotype.
Clinical outcome post-progression to first-line triplet chemotherapy (CT) plus bevacizumab (FIr-B/FOx) was evaluated in metastatic colorectal cancer (MCRC) patients (pts). Second-line treatment was selected according to fitness, KRAS genotype, previous efficacy and safety. Efficacy was evaluated and compared according to treatment or KRAS genotype, using log-rank analysis. Among 54 pts, median overall survival (OS) post-progression was 12 months, significantly better in 40 (74.1%) treated compared to 14 (25.9%) who died without further treatment. Second-line surgical treatment, 4 pts (7.4%), medical treatment, 36 pts (66.7%): triplet CT plus targeted agent, 10 (18.5%); triplet regimens, 19 (35.2%); doublet/monotherapy, 7 (13%). At follow-up of 14 months, objective response rate (ORR) was 38%, metastasectomies 12.5%, progression-free survival (PFS) 10 months, OS 14 months. According to treatment, ORR, metastasectomies, PFS and OS were significantly favourable in triplet CT plus targeted agent compared to triplet, respectively: 80%, 40%, 13 months, not reached; 28%, 6%, 8 months, 11 months. PFS and OS were significantly worse in c.35 G>A mutant compared to wild-type and/or other mutant patients. Prognosis after progression to first‑line FIr-B/FOx may be significantly favourable in MCRC pts re-challenged with intensive regimens, and unfavourable in c.35 G>A KRAS mutant patients.


[Dermatoglyphics of deformed hands].
Palmar and finger prints are recovered in children with congenital malformed hands. The skin ridges of various hand abnormalities are compared with normal dermatoglyphics. We have found a relationship between the embryogenesis of the hand and the epidermal ridge arrangement. Dermatoglyphics are a clinically useful information for the diagnosis of amniotic disease or agenesis and for the chronology of the congenital malformation of limbs.


Phosphorylated tau/amyloid beta 1-42 ratio in ventricular cerebrospinal fluid reflects outcome in idiopathic normal pressure hydrocephalus.
Idiopathic normal pressure hydrocephalus (iNPH) is a potentially reversible cause of dementia and gait disturbance that is typically treated by operative placement of a ventriculoperitoneal shunt. The outcome from shunting is variable, and some evidence suggests that the presence of comorbid Alzheimer's disease (AD) may impact shunt outcome. Evidence also suggests that AD biomarkers in cerebrospinal fluid (CSF) may predict the presence of AD. The aim of this study was to investigate the relationship between the phosphorylated tau/amyloid beta 1-42 (ptau/Aβ1-42) ratio in ventricular CSF and shunt outcome in patients with iNPH. We conducted a prospective trial with a cohort of 39 patients with suspected iNPH. Patients were clinically and psychometrically assessed prior to and approximately 4 months after ventriculoperitoneal shunting. Lumbar and ventricular CSF obtained intraoperatively, and tissue from intraoperative cortical biopsies were analyzed for AD biomarkers. Outcome measures included performance on clinical symptom scales, supplementary gait measures, and standard psychometric tests. We investigated relationships between the ptau/Aβ1-42 ratio in ventricular CSF and cortical AD pathology, initial clinical features, shunt outcome, and lumbar CSF ptau/Aβ1-42 ratios in the patients in our cohort. We found that high ptau/Aβ1-42 ratios in ventricular CSF correlated with the presence of cortical AD pathology. At baseline, iNPH patients with ratio values most suggestive of AD presented with better gait performance but poorer cognitive performance. Patients with high ptau/Aβ1-42 ratios also showed a less robust response to shunting on both gait and cognitive measures. Finally, in a subset of 18 patients who also underwent lumbar puncture, ventricular CSF ratios were significantly correlated with lumbar CSF ratios. Levels of AD biomarkers in CSF correlate with the presence of cortical AD pathology and predict aspects of clinical presentation in iNPH. Moreover, preliminary evidence suggests that CSF biomarkers of AD may prove useful for stratifying shunt prognosis in patients being evaluated and treated for this condition.


Correlation between arrhythmias and abnormal systolic blood pressure response to exercise in mitral valve prolapse patients.
A wide variety of arrhythmias as well as exercise induced hypotension were described in some Mitral Valve Prolapse (MVP) patients. The aim of our study was to evaluate the correlation between the incidence of arrhythmias and the decrease of Systolic Blood Pressure (SBP), ST-T changes and prolonged QTc interval. 50 MVP patients (diagnosis confirmed by M-mode and 2-D echocardiography) underwent a complete clinical evaluation, 12 lead standard ECG, 24 hr. monitoring ECG and a submaximal exercise test. On the basis of the SBP response to effort, the patients were divided into 2 groups (gr.): gr. A, 18 patients with a decrease of the SBP during effort, mean 135 +/- 16.5 mmHg and gr. B, 32 patients with a normal increase of the SBP at the end of the effort, mean 168 +/- 14.7 mmHg (p less than 0.001). Arrhythmias were found in 83.33% among patients in gr. A and in 50% in gr. B (p less than 0.05). We did not find a significant difference concerning the types of arrhythmias between the 2 groups. Exercise induced ST-T changes, appeared in 55.55% in gr. A and in 25% in gr. B (p less than 0.05) but the incidence of arrhythmias in patients with ST-T changes was not significantly different between the 2 groups (5.55% and 6.25% respectively). Rhythm disturbances were found in 3 out of 4 patients with prolonged QTc in gr. A and in 2 out of 4 patients in gr. B (p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)


Peroxynitrite and oxidative damage in experimental autoimmune uveitis.
Results of a previous study demonstrated the presence of superoxide and nitric oxide in experimental autoimmune uveitis (EAU). These two chemical entities have recently been shown to combine rapidly to form one of the most potent known biologic oxidants, peroxynitrite. As an extension of the previous study, the current study was proposed to determine whether peroxynitrite is generated in EAU and the site and extent of any oxidative damage thereby inflicted. Experimental uveitis was induced in Lewis rats with retinal S-antigen. The localization of peroxynitrite was carried out by immunohistochemical detection of its nitration product, nitrotyrosine, using polyclonal rabbit antinitrotyrosine antibody. The lipid peroxides in the membrane were detected by fluorescent labeling of their secondary carbonyl products with 3-hydroxy-2-naphthoic acid hydrazide. This fluorescent product was also visualized by coupling with Fast Blue B. A confocal laser scanning microscope was used for detection. In EAU, the peroxynitrite plaques were observed to concentrate in the photoreceptors but were also visible in some inner retinal areas, including ganglion cell layers, nerve fiber layers, and retinal blood vessels. The lipid peroxides were localized exclusively in the photoreceptors, concentrating in the vicinity of the infiltrating phagocytes but not localized on the phagocytic cells themselves. Similar peroxide lesions in the photoreceptors were also generated by aerobically exposing the naive, open eyecups to a radical generator, 2,2'azobis(2-amidinopropane) hydrochloride. In EAU, there was a substantial concentration of peroxynitrite in the photoreceptors. The presence of this oxidant appears to correlate with the pathologic oxidation demonstrated in this area. The photoreceptors are especially prone to radical-induced lipid peroxidation caused by the high concentration of docasahexaenoic acid that is contained in these structures.


In silico virtual screening of lead compounds for major antigenic sites in respiratory syncytial virus fusion protein.
Human respiratory syncytial virus (RSV) is a leading ubiquitous respiratory pathogen in newborn infants, young children, and the elderly, with no vaccine available to date. The viral fusion glycoprotein (RSV F) plays an essential role in the infection process, and it is a primary target of neutralizing antibodies, making it an attractive site for vaccine development. With this in view, there is a persistent need to identify selective antiviral drugs against RSV, targeting the major antigenic sites on the F protein. We aimed to conduct a robust in silico high-throughput drug screening of one million compounds to explore potential inhibitors that bind the major antigenic site Ø and site II on RSV F protein, which are the main target of neutralizing antibodies (NAb). We utilized the three-dimensional crystallographic structure of both antigenic site Ø on pre-F and antigenic II on post-F to screen for potential anti-RSV inhibitors. A library of one million small compounds was docked to explore lead binders in the major antigenic sites by using virtual lab bench CLC Drug Discovery. We also performed Quantitative Structure-Activity and Relationship (QSAR) for the lead best binders known for their antiviral activity. Among one million tested ligands, seven ligands (PubChem ID: 3714418, 24787350, 49828911, 24802036, 79824892, 49726463, and 3139884) were identified as the best binders to neutralizing epitopes site Ø and four ligands (PubChem ID: 865999, 17505357, 24802036, and 24285058) to neutralizing epitopes site II, respectively. These binders exhibited significant interactions with neutralizing epitopes on RSV F, with an average of six H bonds, docking energy of - 15.43 Kcal·mol-1, and minimum interaction energy of - 7.45 Kcal·mol-1. Using in silico virtual screening, we identified potential RSV inhibitors that bind two major antigenic sites on the RSV F protein. Using structure-based design and combination-based drug therapy, identified molecules could be modified to generate the next generation anti-RSV drugs. The online version contains supplementary material available at 10.1007/s42247-021-00213-6.


Molecular shape as a means to control the incidence of the nanostructured twist bend phase.
Liquid crystalline phases with a spontaneous twist-bend modulation are most commonly observed for dimers and bimesogens with nonamethylene spacers. In order to redress this balance we devised a simple chemical intermediate that can be used to prepare unsymmetrical bimesogens; as a proof of concept we prepared and studied eleven novel materials with all found to exhibit the twist-bend phase and exhibit a linear relationship between TN-I and TTB-N. A computational study of the conformational landscape reveals the octamethyleneoxy spacer to have a broader distribution of bend-angles than the nonamethylene equivalent, leading to reductions in the thermal stability of the TB phase. This result indicates that a tight distribution of bend-angles should stabilise the TB phase and lead to direct TB-Iso phase transitions, and conversely a broader distribution should destabilise the TB phase which may allow new states of matter that are occluded by the incidence of this phase to be revealed.


Central and peripheral mechanisms by which ghrelin regulates gut motility.
Ghrelin is the recently discovered endogenous ligand for the growth hormone secretagogue receptor. This receptor had previously been characterized based on the stimulatory effect of synthetic peptides, enkephalin analogues, on growth hormone secretion by pituitary somatotrophs. Surprisingly, ghrelin is most abundant in the stomach, suggesting that it may have effects beyond the stimulation of growth hormone in the pituitary and that it is a new brain-gut peptide. There is now increasing evidence that ghrelin stimulates motor activity in the gastrointestinal tract. Thus ghrelin induces the migrating motor complex and accelerates gastric emptying. These are effects typical for motilin, the only peptide structurally related to ghrelin. Moreover, the receptors of both peptides are structurally related as well. The motor effects of ghrelin require rather high concentrations, while motilin at high concentrations stimulates growth hormone release. These data suggest cross-reactivity. However, in vitro binding and contractility studies in the rabbit, the classical model to study motilin agonists, show that ghrelin has very weak if any interaction with the motilin receptor. Similarly, in cell lines expressing the receptors for both peptides there is no evidence for cross-reactivity. This corresponds to the fact that the pharmacophore of both peptides is quite different. Therefore, the motor effects must be due to the stimulation of specific central or peripheral ghrelin receptors. In the guinea pig there is evidence from electrophysiology, immunohistochemistry and calcium imaging studies for ghrelin receptors on myenteric neurons. This provides the morphological basis for peripheral effects of ghrelin. In rats, ghrelin, but not motilin, enhances the response of muscle strips to electrical field stimulation by activating cholinergic pathways. In rabbits the opposite is true but some synthetic ghrelin agonists have weak effects which cannot be blocked by motilin antagonists. Apparently ghrelin is the functional equivalent of motilin in the rat, but in rabbits the motilin-ghrelin family may have yet unknown members. In vivo the effect of ghrelin can be blocked by vagotomy and there is evidence for ghrelin receptors on vagal afferents and in the nodose ganglion. Studies in the rat suggest that under physiological conditions circulating ghrelin does not activate the myenteric plexus, but is able to do so following vagotomy. Finally, centrally administered ghrelin also accelerates gastric emptying and ghrelin changes the activity of neurons of the central nuclei involved in signalling information from the gastrointestinal tract. It is concluded that ghrelin may affect gastrointestinal motility via specific ghrelin receptors located on myenteric, vagal and central neurons. Vagal and central pathways appear to be most important. The fact that ghrelin may reverse the effect of ileus on gastric emptying suggests that ghrelin agonists could find therapeutical application as prokinetics.


A systematic review of satisfaction with teledermatology.
Background The two most commonly used modalities of teledermatology (TD) are store-and-forward (SF) and live-interactive (LI) TD. Existing studies have not compared these tools with respect to patient and provider satisfaction. Objective To systematically review all published studies of patient and provider satisfaction with SF and LI TD. Methods PubMed, EMBASE, and Cochrane databases were systematically searched for studies on provider or patient satisfaction with SF or LI TD between January 2000 and June 2016. Results Forty eligible studies were identified: 32 with SF TD, 10 with LI TD, and 2 evaluating both. With SF TD, 96% of studies assessing patient satisfaction and 82% of studies assessing provider satisfaction demonstrated satisfaction ( n = 24 and 17, respectively). With LI TD, 89% of studies assessing patient satisfaction and all studies assessing provider satisfaction revealed satisfaction (n = 9 and 6, respectively). Conclusion Patients and providers are satisfied with both SF and LI TD. Studies assessing satisfaction with LI have not been conducted in recent years, and have only been conducted in limited geographic patient populations. Further research assessing satisfaction with TD will help address any dissatisfaction with its uses and allow for increased support and funding of future programmes.


MBD4 cooperates with DNMT1 to mediate methyl-DNA repression and protects mammalian cells from oxidative stress.
Oxidative stress induces genome-wide remodeling of the chromatin structure. In this study, we identify Methyl-CpG Binding Protein 4 (MBD4), a multifunctional enzyme involved in DNA demethylation, base excision repair, and gene expression regulation, as an essential factor in response to oxidative stress. We provide evidence that MBD4 is upregulated at the protein level upon oxidative stress, and that MBD4 is essential for cell survival following oxidative stress. In these cells, MBD4 and DNMT1 are recruited at sites of oxidation-induced DNA damage, where we speculate they participate in DNA repair. MBD4 and DNMT1 also share genomic targets in unstressed cells. Using genome-wide analysis of MBD4 binding sites, we identified new targets potentially co-regulated by MBD4 and DNA methylation. We identified two new binding sites for MBD4 and DNMT1 at methylated CpG islands of CDKN1A/p21 and MSH4, where they synergistically mediate transcriptional repression. Our study provides evidence that the interaction between DNMT1 and MBD4 is involved in controlling gene expression and responding to oxidative stress.


Oleocanthal Modulates Estradiol-Induced Gene Expression Involving Estrogen Receptor α.
Oleocanthal is a bioactive compound from olive oil. It has attracted considerable attention as it is anti-inflammatory, antiproliferative, and has been shown to possess neuroprotective properties in vitro and in vivo. Delineated from its polyphenolic structure, the aim of this study was to characterize oleocanthal towards estrogenic properties. This might contribute to partly explain the beneficial effects described for the Mediterranean diet. Estrogenic properties of oleocanthal were assessed by different methods: a) stimulation of reporter gene activity in MVLN or RNDA cells either expressing estrogen receptor α or β, b) stimulation of luciferase reporter gene activity in U2OS osteosarcoma cells expressing estrogen receptor α or β, and c) elucidation of the impact on estradiol-induced gene expression in U2OS cells transduced with both estrogen receptors. Depending on the cell line origin, oleocanthal inhibited luciferase activity (MVLN, U2OS-estrogen receptor β) or weakly induced reporter gene activity at 10 µM in U2OS-estrogen receptor α cells. However, oleocanthal inhibited stimulation of luciferase activity by estradiol from both estrogen receptors. Oleocanthal, if given alone, did not stimulate gene expression in U2OS cells, but it significantly modulated the response of estradiol. Oleocanthal enhanced the effect of estradiol on the regulation of those genes, which are believed to be regulated through heterodimeric estrogen receptors. As the estrogenic response pattern of oleocanthal is rather unique, we compared the results obtained with oleacein. Oleocanthal binds to both estrogen receptors inducing estradiol-agonistic or antiagonistic effects depending on the cell line. Regarding regulation of gene expression in U2OS-estrogen receptor α/β cells, oleocanthal and oleacein enhanced estradiol-mediated regulation of heterodimer-regulated genes.


The effect of poverty-influenced, food-related consumer behaviors on obesity: An analysis of the NHANES flexible consumer behavioral module.
Despite extensive research investigating obesity, the problem continues to increase, particularly in poor, minority, and under-resourced communities. However, the literature continues to demonstrate many obesity-predicating variables are outside of personal volitional control, such as food-related consumer behaviors, which are strongly influenced by income and environment. This cross-sectional study (n = 5,109) employed secondary data analysis to quantitatively examine the effect of food-related consumer variables on obesity while controlling for covariates. Participants answered questions regarding money spent on food, time preparing meals, number of meals eaten at home and away from home, and types of food products consumed (frozen/fast foods, sodas, salty snacks, etc.) In this study, 48.9% of respondents were either overweight or obese. No significant differences were noted between the contextual variables examined and BMI scores. However, given the sample's limitations illuminated in the study, further research regarding the relationship between obesity and poverty-influenced, food-related consumer behaviors is warranted.


Salvia officinalis attenuates bleomycin-induced oxidative stress and lung fibrosis in rats.
Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease characterized by progressive and irreversible fibroblasts proliferation leading to significant respiratory insufficiency. This study was designed to investigate the effect of sage infusion against bleomycin (BLM)-induced lung fibrosis in rats. Male Wistar rats were given a single dose of BLM (4 mg/kg, intratracheal), while sage infusion (50, 100 and 150 mg/kg, intraperitoneal) was administered 3 day later and continued for 4 weeks. We reveled by HPLC and LC-MS methods an important amount of phenolic bioactive compounds such as vanillic, gallic, ellagic, rosmarinic and carnosic acids. BLM induced collagen deposition, increased lipid peroxidation (MDA) and decreased superoxide dismutase (SOD) and catalase (CAT) activities. Only sage infusion at 150 mg/kg normalized MDA and antioxidant enzyme levels (SOD and CAT) and reduced significantly lung fibrosis. Our results showed also that this high dose have no renal or hepatic cytotoxic effect. In conclusion, sage can protect against BLM-induced murine lung fibrosis and oxidative stress due to the large content of bioactive phenolic compounds.


Systematic sequence analysis and identification of tissue-specific or stress-responsive genes of NAC transcription factor family in rice.
NAM, ATAF, and CUC (NAC) transcription factors comprise a large plant-specific gene family and a few members of this family have been characterized for their roles in plant growth, development, and stress tolerance. In this study, systematic sequence analysis revealed 140 putative NAC or NAC-like genes (ONAC) in rice. Phylogenetic analysis suggested that NAC family can be divided into five groups (I-V). Among them, all the published development-related genes fell into group I, and all the published stress-related NAC genes fell into the group III (namely stress-responsive NAC genes, SNAC). Distinct compositions of the putative motifs were revealed on the basis of NAC protein sequences in rice. Most members contained a complete NAC DNA-binding domain and a variable transcriptional regulation domain. Sequence analysis, together with the organization of putative motifs, indicated distinct structures and potential diverse functions of NAC family in rice. Yeast one-hybrid analysis confirmed that 12 NAC proteins representing different motif compositions can bind the NAC core DNA-binding site. Real-time polymerase chain reaction (PCR) analysis revealed 12 genes with different tissue-specific (such as callus, root, stamen, or immature endosperm) expression patterns, suggesting that these genes may play crucial regulatory roles during growth and development of rice. The expression levels of this family were also checked under various abiotic stresses including drought, salinity, and low temperature. A preliminary check based on our microarray data suggested that more than 40 genes of this family were responsive to drought and/or salt stresses. Among them, 20 genes were further investigated for their stress responsiveness in detail by real-time PCR analysis. Most of these stress-responsive genes belonged to the group III (SNAC). Considering the fact that a very limited number of genes of the NAC family have been characterized, our data provide a very useful reference for functional analysis of this family in rice.