Enhancing Person-Centered Audiologic Rehabilitation: Exploring the Use of an Interview Tool Based on the International Classification of Functioning, Disability, and Health Core Sets for Hearing Loss.
Health care interventions that are intended to improve hearing should be based on the results of individual patient assessments. To improve these assessments, the feasibility of an International Classification of Functioning, Disability, and Health (ICF)-based interview tool was tested in a single clinical setting in Sweden. Audiologists participating in the study used the interview tool during a four-week testing period and provided written reflections after each session. The use of this tool was also evaluated in a focus group interview that took place after the completion of the project. The results of this study identified both process-related and structure-related factors that were highly relevant to the implementation of this interview tool. Overall, the findings revealed that the use of this interview tool promoted person-centered care in encounters focused on clinical audiological rehabilitation. Specifically, the ICF-based holistic approach permitted the audiologists to acquire more comprehensive patient narratives. The use of the ICF interview tool facilitated patient participation and permitted the audiologist to collect more substantial and meaningful information from each patient.


Interleukin-10 has different effects on proliferation of Listeria monocytogenes in livers and spleens of mice.
The aim of this study was to investigate the effect of interleukin-10 (IL-10) on the course of Listeria monocytogenes infection in naive and immune mice. Treatment with IL-10 during the course of a primary infection significantly decreased the number of bacteria in the spleen and did not affect the number in the liver. During a secondary infection in immune mice treated with IL-10, the number of bacteria was significantly lower in the spleen but significantly higher in the liver in comparison to mock-treated immune mice. IL-10 treatment during a primary Listeria infection decreased the concentration of gamma interferon (IFN-gamma) in plasma and the toxoplasmastatic activity of macrophages, whereas it increased the percentage of mildly CD3-positive T cells in the spleen. During a secondary infection, the concentration of IFN-gamma in plasma was decreased on day 1 but remained unaffected during later days of infection. From these results, we conclude that IL-10 has different effects on the proliferation of L. monocytogenes in the spleen and liver during primary and secondary Listeria infections.


Rhombencephalosynapsis: a hindbrain malformation associated with incomplete separation of midbrain and forebrain, hydrocephalus and a broad spectrum of severity.
Rhombencephalosynapsis is a midline brain malformation characterized by missing cerebellar vermis with apparent fusion of the cerebellar hemispheres. Rhombencephalosynapsis can be seen in isolation or together with other central nervous system and extra-central nervous system malformations. Gómez-López-Hernández syndrome combines rhombencephalosynapsis with parietal/temporal alopecia and sometimes trigeminal anaesthesia, towering skull shape and dysmorphic features. Rhombencephalosynapsis can also be seen in patients with features of vertebral anomalies, anal atresia, cardiovascular anomalies, trachea-oesophageal fistula, renal anomalies, limb defects (VACTERL) association. Based on a comprehensive evaluation of neuroimaging findings in 42 patients with rhombencephalosynapsis, we propose a spectrum of severity, ranging from mild (the partial absence of nodulus, anterior and posterior vermis), to moderate (the absence of posterior vermis with some anterior vermis and nodulus present), to severe (the absence of posterior and anterior vermis with some nodulus present), to complete (the absence of the entire vermis including nodulus). We demonstrate that the severity of rhombencephalosynapsis correlates with fusion of the tonsils, as well as midbrain abnormalities including aqueductal stenosis and midline fusion of the tectum. Rhombencephalosynapsis is also associated with multiple forebrain abnormalities including absent olfactory bulbs, dysgenesis of the corpus callosum, absent septum pellucidum and, in rare patients, atypical forms of holoprosencephaly. The frequent association between rhombencephalosynapsis and aqueductal stenosis prompted us to evaluate brain magnetic resonance images in other patients with aqueductal stenosis at our institution, and remarkably, we identified rhombencephalosynapsis in 9%. Strikingly, subjects with more severe rhombencephalosynapsis have more severely abnormal neurodevelopmental outcome, as do subjects with holoprosencephaly and patients with VACTERL features. In summary, our data provide improved diagnostic and prognostic information, and support disruption of dorsal-ventral patterning as a mechanism underlying rhombencephalosynapsis.


Nano-La2O3 Induces Honeybee (Apis mellifera) Death and Enriches for Pathogens in Honeybee Gut Bacterial Communities.
Honeybees (Apis mellifera) can be exposed via numerous potential pathways to ambient nanoparticles (NPs), including rare earth oxide (REO) NPs that are increasingly used and released into the environment. Gut microorganisms are pivotal in mediating honeybee health, but how REO NPs may affect honeybee health and gut microbiota remains poorly understood. To address this knowledge gap, honeybees were fed pollen and sucrose syrup containing 0, 1, 10, 100, and 1000mgkg-1 of nano-La2O3 for 12days. Nano-La2O3 exerted detrimental effects on honeybee physiology, as reflected by dose-dependent adverse effects of nano-La2O3 on survival, pollen consumption, and body weight (p<0.05). Nano-La2O3 caused the dysbiosis of honeybee gut bacterial communities, as evidenced by the change of gut bacterial community composition, the enrichment of pathogenic Serratia and Frischella, and the alteration of digestion-related taxa Bombella (p<0.05). There were significant correlations between honeybee physiological parameters and the relative abundances of pathogenic Serratia and Frischella (p<0.05), underscoring linkages between honeybee health and gut bacterial communities. Taken together, this study demonstrates that nano-La2O3 can cause detrimental effects on honeybee health, potentially by disordering gut bacterial communities. This study thus reveals a previously overlooked effect of nano-La2O3 on the ecologically and economically important honeybee species Apis mellifera.


Alteration of the E-Cadherin/β-Catenin Complex Is an Independent Poor Prognostic Factor in Lung Adenocarcinoma.
Epithelial-mesenchymal transition (EMT) is an important step in the invasion and progression of cancer and in the development of chemoresistance by cancer cells. To address the clinical significance of the EMT pathway in lung adenocarcinoma and the association of the pathway with histological subtype, we examined 193 surgically resected lung adenocarcinoma samples for the expression of representative EMT-related proteins (E-cadherin, β-catenin, and vimentin) by immunohistochemistry. Histological subtypes were classified according to the 2011 International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification. The results for EMT-related protein expression were analyzed for correlation with clinicopathological features and with survival. The loss of E-cadherin expression and aberrant β-catenin expression were significantly associated with larger tumor size, pleural invasion, lymphatic/vascular invasion, and advanced pathological stage (p<0.05). The alteration of the E-cadherin/β-catenin complex was least frequently observed in the lepidic-predominant group, but these associations were not statistically significant. In the multivariate analysis, altered E-cadherin/β-catenin complex expression was found to be an independent poor prognostic factor (p=0.017; hazard ratio, 1.926; 95% confidence interval, 1.119 to 3.314). The alteration of the expression of the E-cadherin/β-catenin complex was associated with aggressive tumor behavior in lung adenocarcinoma.


Coronary heart disease case fatality in four countries. A community study. The Acute Myocardial Infarction Register Teams of Auckland, Augsburg, Bremen, FINMONICA, Newcastle, and Perth.
Community-based registers participating in the MONICA Project of the World Health Organization show markedly different attack and death rates of coronary heart disease. This variation is a function of both the incidence and case fatality occurring within countries. The contribution of case fatality to the international variation in coronary heart disease mortality rates is not well understood. The register data from eight study populations--Augsburg and Bremen in Germany, Auckland in New Zealand, Perth and Newcastle in Australia, and North Karelia, Kuopio, and Turku/Loimaa in Finland--were compared. All patients with definite myocardial infarction or coronary death aged 35 to 64 years occurring in the study populations in 1985 through 1989 are the basis for the case fatality calculations by different definitions: 28-day case fatality for all cases, for hospitalized cases, and for hospitalized 24-hour survivors; out-of-hospital case fatality; and 24-hour case fatality for hospitalized cases. Differences in case fatality were much smaller than differences in attack and mortality rates in these populations. About two thirds of deaths occurred before the patients reached a hospital. The 28-day case fatality ranged from 37% for men in Perth to 58% for women in Augsburg. Among those who reached the hospital alive, 28-day case fatality was 13% to 27% for men and 20% to 35% for women. In those who survived 24 hours from the onset of symptoms, 28-day case fatality was 8% to 17% for men and 12% to 26% for women. Differences in case fatality were not associated with differences in coronary mortality rates between these populations. As most deaths occurred before reaching a hospital, opportunities for reducing case fatality through improved hospital care are limited. This emphasizes the primary role of prevention in reducing coronary death rates.


Payment changes require integrating records.
The greatest challenges for healthcare organizations facing radical changes in their payment and reporting structures lie in finding ways to integrate various forms of patient information. An analysis of how three New York City hospitals dealt with their state's switch to an all-payer diagnosis related group-based payment system reveals strengths and weaknesses in their existing information systems and in steps taken to adapt to the change.


[Activity of blood interleukin-1 in dogs during work hyperthermia].
The activity of interleukin-1 (IL-1) in blood plasma of the dogs in conditions of working hyperthermia was studied. The animals performed static exercise of submaximal capacity. Data on IL-1 circulation at different time after the onset of physical exercise were obtained. Cessation of exercise is accompanied by degradation of an IL-1 molecule to shorter fragments. The existence of the reserve pool of this biologically active substance released during intense muscle activity is suggested.


Isolation and characterization of new polymorphic microsatellite loci in the mixotrophic orchid Limodorum abortivum L. Swartz (Orchidaceae).
Here, we report the isolation and characterization of 11 polymorphic microsatellites in Limodorum abortivum. Allele variability has been characterized in three populations from Southern Italy and France. The number of alleles ranged from one to six per locus with an average of 3.8 alleles per locus. Observed and expected heterozygosity values ranged from 0.000 to 1.000 and from 0.492 to 0.806, respectively, with striking differences among populations. These microsatellites should be valuable tools for studying fine-scale genetic structure of scattered Limodorum abortivum populations, patterns of relationship with closely related taxa and the evolutionary ecology of its mycorrhizal interactions.


Dietary supplementation with dried chicory root triggers changes in the blood serum proteins engaged in the clotting process and the innate immune response in growing pigs.
The aim of the study was to characterize the systemic immune and metabolic alterations in the blood serum of growing pigs in response to a dietary supplementation with 4% of dried chicory roots. This was achieved by examining the influence of the experimental diet on serum protein changes especially these related with immunology and lipid metabolism. Serum proteins with the isoelectric point ranging from pH 3.0 to 10.0 were separated using high resolution two-dimensional electrophoresis. As a result, we found that experimental diet triggered significant changes in 37 protein spots. Of these, 14 were up-regulated, whereas 23 showed down-regulation. Of 37 significantly altered protein spots, 24 were successfully identified, representing 14 distinct gene products. Implementation of the dried chicory roots into the diet of growing pigs caused a significant down-regulation of apolipoprotein C-II complement component C6, C-reactive protein, CD14 antigen, C4b binding protein α and β chains, and fibrinogen. Piglets fed experimental diet had similar IgA, IgG and IgM concentrations, although the level of IgM tended to be lower compared to the control group. It is concluded that diet supplemented with 4% of dried chicory root may exert anti-inflammatory properties and affect lipid metabolism in growing pigs.


Unveiling Coherent Control of Halomethane Dissociation Induced by a Single Strong Ultraviolet Pulse.
We present a theoretical investigation into the coherent control of photodissociation reactions in halomethanes, specifically focusing on CH2BrCl by manipulating the spectral phase of a single femtosecond laser pulse. We examine the photodissociation of CH2BrCl under an ultrashort pulse with a quadratic spectral phase and reveal the sensitivity of both the total dissociation probability and the resulting radical products (Br+CH2Cl and Cl+CH2Br) to chirp rates. To gain insights into the underlying mechanism, we calculate the population distributions of excited vibrational states in the ground electronic state, demonstrating the occurrence of resonance Raman scattering (RRS) in the strong-field limit regime. By utilizing chirped pulses, we show that this RRS phenomenon can be suppressed and even eliminated through quantum destructive interference. This highlights the high sensitivity of photodissociation into Cl+CH2Br to the spectral phase, showcasing a phenomenon that goes beyond the traditional one-photon photodissociation of isolated molecules in the weak-field limit regime. These findings emphasize the importance of coherent control in the exploration and utilization of photodissociation in polyatomic molecules, paving the way for new advancements in chemical physics and femtochemistry.


Can the oxytocin challenge test serve as the primary method for managing high-risk pregnancies?
The purpose of this investigation was to determine whether the oxytocin challenge test (OCT) could serve as the primary method for managing pregnancies characterized by possible placental insufficiency. One hundred and five patients underwent 225 oxytocin challenge tests; no perinatal deaths occurred. Eight tests were positive, 21 suspicious, and 196 negative. Because of data obtained in a preliminary study, all 8 fetuses with positive tests were delivered by cesarean section. Four of the 8 had repetitive suspicious tests prior to a positive test, suggesting that utero-placental function may deteriorate gradually. Urinary excretion of estriol did not decrease significantly in any patient, suggesting that the OCT is a more sensitive indicator of placental function than excretion of estriol. Except for patients with preeclampsia who were induced for maternal indications, all pregnancies with a negative OCT were allowed to terminate spontaneously. Five of the 97 fetuses with negative tests developed late-onset deceleration patterns during labor. This indicates that a negative OCT will not necessarily predict fetal tolerance to labor, contrary to assertions made by some other investigators. It is concluded that the OCT can serve as the primary method for assessing the fetal status in pregnancies characterized by placental insufficiency.


Adrenal hormones and the anorectic response and adaptation of rats to amino acid imbalance.
The role of adrenal function in the anorectic response and adaptation of rats to a diet with an isoleucine (Ile) imbalance was investigated. In the first of four experiments, rats were fed a mildly Ile-imbalanced diet after treatment with metyrapone, and inhibitor of glucocorticoid synthesis. In two separate experiments, rats were presented with either a mildly or severely Ile-imbalanced diet (4.93 and 9.86% imbalanced amino acid mixture, respectively) after bilateral adrenalectomy. Finally, the effects of ICS 205-930, a serotonin-3 receptor antagonist, on the intake of mildly Ile-imbalanced diet were tested in adrenalectomized animals. In each experiment a 2 X 2 factorial design was used. Neither metyrapone nor adrenalectomy altered the initial depression in the intake of an imbalanced diet. The adaptation phase in the response of adrenalectomized rats fed a mildly Ile-imbalanced diet was not different from that of controls, but adrenalectomized rats fed severely Ile-imbalanced diets were unable to adapt. Adrenalectomy did not alter the anti-anoretic activity of ICS 205-930 in this model. These results suggest that adrenal hormones are not necessary for the initial anoretic response or adaptation of rats to an Ile-imbalanced diet, nor are they implicated in the anti-anorectic effect of serotonin-3 blockade.


Novelty detection is enhanced when attention is otherwise engaged: an event-related potential study.
Novel stimuli are detected and evaluated quickly, suggesting that processing them is a priority for the brain. In the present study, the effects of attention on this early visual novelty processing were investigated in two experiments using the event-related potential (ERP) technique. In the first experiment, participants performed two tasks that varied in the amount of attention available for novel stimuli. In the Visual Oddball task, participants responded to an infrequent target presented among standard and novel stimuli. In the Working Memory task, participants saw the same stimuli, but they could ignore them. Instead, participants had to keep six letters in working memory and report one of these letters at the end of the trial; attention was thus maximally allocated away from the visual oddball stimuli. In line with attention being fully occupied in the Working Memory task, the P3a to the visual oddball stimuli was smaller in the Working Memory than in the Visual Oddball task. In contrast, the anterior N2 component to task-irrelevant stimuli was enhanced in the Working Memory task. These findings suggest that the initial detection of novel stimuli is enhanced (large anterior N2) when few attentional resources are available, which is inconsistent with earlier findings that if anything, the N2 is enhanced by attention. In a second experiment, a condition was added in which working memory load was low, but visual oddball stimuli were task-irrelevant. Results from this experiment showed that while the reduction in P3a amplitude was due to task irrelevance, the enhanced anterior N2 was linked to a high working memory load. This suggests that novelty detection is enhanced when attention is otherwise engaged.


Decreased level of psychobiological factor novelty seeking and lower intelligence in men latently infected with the protozoan parasite Toxoplasma gondii Dopamine, a missing link between schizophrenia and toxoplasmosis?
Toxoplasma gondii, a parasitic protozoan, infects about 30-60% of people worldwide. The latent toxoplasmosis, i.e. life-long presence of cysts in the brain and muscular tissues, has no effect on human health. However, infected subjects score worse in psychomotor performance tests and have different personality profiles than Toxoplasma-negative subjects. The mechanism of this effect is unknown; however, it is supposed that presence of parasites' cysts in the brain induces an increase of the concentration of dopamine. Here we search for the existence of differences in personality profile between Toxoplasma-positive and Toxoplasma-negative subjects by testing 857 military conscripts using a modern psychobiological questionnaire, namely with Cloninger's Temperament and Character Inventory (TCI). ANCOVA showed that Toxoplasma-positive subjects had lower Novelty seeking (NS) scores (P=0.035) and lower scores for three of its four subscales, namely Impulsiveness (P=0.049), Extravagance (P=0.056) and Disorderliness (P=0.006) than the Toxoplasma-negative subjects. Differences between Toxoplasma-negative and positive subjects in NS was inversely correlated with duration of toxoplasmosis estimated on the basis of concentration anti-Toxoplasma antibodies (P=0.031). Unexpectedly, the infected subjects had also lower IQ (P(2)=0.003) and lower probability of achieving a higher education (P(2)<0.0000). Decrease of NS suggests that the increase of dopamine in brain of infected subjects can represent a missing link between toxoplasmosis and schizophrenia.


The implications of human metabolic network topology for disease comorbidity.
Most diseases are the consequence of the breakdown of cellular processes, but the relationships among genetic/epigenetic defects, the molecular interaction networks underlying them, and the disease phenotypes remain poorly understood. To gain insights into such relationships, here we constructed a bipartite human disease association network in which nodes are diseases and two diseases are linked if mutated enzymes associated with them catalyze adjacent metabolic reactions. We find that connected disease pairs display higher correlated reaction flux rate, corresponding enzyme-encoding gene coexpression, and higher comorbidity than those that have no metabolic link between them. Furthermore, the more connected a disease is to other diseases, the higher is its prevalence and associated mortality rate. The network topology-based approach also helps to uncover potential mechanisms that contribute to their shared pathophysiology. Thus, the structure and modeled function of the human metabolic network can provide insights into disease comorbidity, with potentially important consequences for disease diagnosis and prevention.


The Evolving Genomic Landscape of Esophageal Squamous Cell Carcinoma Under Chemoradiotherapy.
Esophageal squamous cell carcinoma (ESCC) often recurs after chemoradiotherapy, and the prognosis of ESCC after chemoradiotherapy has not improved over the past few decades. The mutation process in chemoradiotherapy-resistant clones and the functional relevance of genetic alterations remain unclear. To address these problems, we performed whole-exome sequencing of 52 tumor samples from 33 patients with ESCC who received radiotherapy combined with 5-fluorouracil/platinum. In multiregion analyses of pretreatment and locally recurrent lesions from five cases, most driver gene-altered clones remained under chemoradiotherapy selection pressure, while few driver gene alterations were acquired at recurrence. The mutation signatures of recurrent ESCC, including increased deletion frequency and platinum dose-dependent base substitution signatures, were substantially different from those of primary ESCC and reflected the iatrogenic impacts of chemoradiotherapy. Single-region analysis of 28 pretreatment tumors indicated that focal copy-number gain at the MYC locus was significantly associated with poor progression-free survival and overall survival after chemoradiotherapy. MYC gain remained throughout the chemoradiotherapy course and potentially contributes to intrinsic resistance to chemoradiotherapy. Consistent with these findings, MYC copy number and mRNA and protein levels in ESCC cell lines correlated positively with resistance to radiotherapy, and MYC knockdown improved sensitivity to radiotherapy. Overall, these data characterize the clonal evolution process induced by chemoradiotherapy and clinically relevant associations for genetic alterations in ESCC. These findings increase our understanding of therapeutic resistance and support the rationale for precision chemoradiotherapy. SIGNIFICANCE: Whole-exome sequencing reveals the genetic evolution of ESCC during chemoradiotherapy, highlighting MYC gain in pretreatment tumors as a potential marker of therapy resistance.


Preliminary study of Malaysian fruit bats species diversity in Lenggong Livestock Breeding Center, Perak: Potential risk of spill over infection.
Farms that are neighboring wildlife sanctuaries are at risk of spillover infection from wildlife, and the objective of this research is to examine the species diversity of Malaysian fruit bats in livestock farm in determining the possible risk of spill over infection to livestock. Fifty individual fruit bats were captured using six mists net, from May to July 2017. The nets were set at dusk (1830 h) as bats emerge for foraging and monitored at every 30-min intervals throughout the night until dawn when they returned to the roost. The nets were closed for the day until next night, and captured bats were identified to species levels. All the captured bats were mega chiropterans, and Cynopterus brachyotis was the highest captured species, representing 40% of the total capture. Shannon-Weiner index is 2.80, and Simpson index is 0.2. Our result suggests that there is a degree of species dominance with low diversity in Lenggong Livestock Breeding Center. We concluded that fruit bats are indeed, encroaching livestock areas and the species identified could be a potential source of infection to susceptible livestock. Hence, an active surveillance should be embarked on farms that border wildlife sanctuaries.


p53 gene mutations and abnormal retinoblastoma protein in radiation-induced human sarcomas.
The potentially carcinogenic effect of therapeutic irradiation has been recognized for many years. Second malignancies, usually sarcomas, are known to arise within or at the edge of radiation fields after a period of several years after the initial radiation exposure. We analyzed tumor cells derived from seven radiation-induced tumors for abnormalities in tumor suppressor genes p53 and retinoblastoma at the DNA sequence and/or protein level. p53 mutations were detected by exon-specific polymerase chain reaction amplification and single-strand conformation polymorphism analysis of exons 5-8 followed by direct genomic sequencing of those tumors exhibiting a variant pattern. The p53 gene was abnormal in three of six sarcomas studied. Retinoblastoma gene analysis was performed by Western immunoblot; retinoblastoma protein was under-phosphorylated in three of seven tumors and absent in one other. In all, six of seven radiation-induced human tumors have abnormalities of one or both suppressor genes. Inactivation of tumor suppressor genes by ionizing radiation may contribute to radiation carcinogenesis.


High self-reported non-adherence to antiretroviral therapy amongst adolescents living with HIV in Malawi: barriers and associated factors.
Globally adolescents and young adults account for more than 40% of new HIV infections, and HIV-related deaths amongst adolescents increased by 50% from 2005 to 2012. Adherence to antiretroviral therapy (ART) is critical to control viral replication and preserve health; however, there is a paucity of research on adherence amongst the growing population of adolescents living with HIV/AIDS (ALHIV) in Southern Africa. We examined levels of self-reported ART adherence, barriers to adherence, and factors associated with non-adherence amongst ALHIV in Malawi. Cross-sectional study of 519 ALHIV (12-18 years) attending two large HIV clinics in central and south-eastern Malawi. Participants self-reported missed doses (past week/month), barriers to adherence, and completed questionnaires on past traumatic events/stressors, disclosure, depression, substance use, treatment self-efficacy, and social support. Biomedical data were retrieved from existing medical records. Multivariate logistic regression was performed to identify factors independently associated with self-reported ART adherence (7 day recall). The mean age of participants (SD) was 14.5 (2) years and 290 (56%) were female. Of the 519 participants, 153 (30%) reported having missed ART doses within the past week, and 234 (45%) in the past month. Commonly reported barriers to adherence included forgetting (39%), travel from home (14%), busy with other things (11%), feeling depressed/overwhelmed (6%), feeling stigmatized by people outside (5%) and within the home (3%). Factors found to be independently associated with missing a dose in the past week were drinking alcohol in the past month (OR 4.96, 95% CI [1.41-17.4]), missed clinic appointment in the past 6 months (OR 2.23, 95% CI [1.43-3.49]), witnessed or experienced violence in the home (OR 1.86, 95% CI [1.08-3.21]), and poor treatment self-efficacy (OR 1.55 95% CI [1.02-2.34]). Sex and age were not associated with adherence. In our study, nearly half of all ALHIV reported non-adherence to ART in the past month. Violence in the home or alcohol use in the past year as well as poor treatment self-efficacy were associated with worse adherence. Sub-optimal adherence is a major issue for ALHIV and compromise treatment outcomes. Programmes specifically tailored to address those challenges most pertinent to ALHIV may help improve adherence to ART.


Participation in online continuing education.
The ADAPT (ADapting pharmacists' skills and Approaches to maximize Patients' drug Therapy effectiveness) e-learning programme requires weekly participation in module activities and facilitated discussion to support skill uptake. In this study, we sought to describe the extent and pattern of, satisfaction with and factors affecting participation in the initial programme offering and reasons for withdrawal. Mixed methods - convergent parallel approach. Participation was examined in qualitative data from discussion boards, assignments and action plans. Learner estimations of time commitment and action plan submission rates were calculated. Surveys (Likert scale and open-ended questions) included mid-point and final, exit and participation surveys. Eleven of 86 learners withdrew, most due to time constraints (eight completed an exit survey; seven said they would take ADAPT again). Thirty-five of 75 remaining learners completed a participation survey. Although 50-60% of the remaining 75 learners actively continued participating, only 15/35 respondents felt satisfied with their own participation. Learners spent 3-5 h/week (average) on module activities. Factors challenging participation included difficulty with technology, managing time and group work. Factors facilitating participation included willingness to learn (content of high interest) and supportive work environment. Being informed of programme time scheduling in advance was identified as a way to enhance participation. This study determined extent of learner participation in an online pharmacist continuing education programme and identified factors influencing participation. Interactions between learners and the online interface, content and with other learners are important considerations for designing online education programmes. Recommendations for programme changes were incorporated following this evaluation to facilitate participation.


Production of Farmstead Lactose-Free Pecorino di Osilo and Ricotta Cheeses from Sheep's Milk.
The present work was aimed to define and validate farmstead production of lactose-free Pecorino di Osilo cheese, fresh ricotta cheese, and salted and smoked ricotta cheese (Ricotta mustia). The enzymatic activity of the commercial preparation containing lactase (1.1 g/mL), preliminarily tested using a spectrophotometric titration, showed activity equal to 4950±40 neutral lactase unit/g. The amount of lactase required to obtain the lactose-free milk was then established in triplicate laboratory trials, by adding the enzyme at concentrations of 0.7, 0.9 and 1.1 g/L in flasks containing 160 mL of raw sheep's milk. Samples were incubated under conditions expected during milk storage and cheese-making. The residual lactose content in milk was determined by enzymatic method. The addition of lactase at concentration of 1.1 g/L of milk reduced the lactose concentration below the limit of detection (LOD) of 0.06 g/L. The procedure was validated at a dairy farm, using three different batches of bulk raw sheep's lactose-free milk that were transformed into Pecorino di Osilo cheese. The resulting whey was used to produce fresh ricotta and Ricotta mustia cheese. Raw milk and whey samples were always below lactose detection limit. The residual lactose was measured in Pecorino di Osilo cheese, after 24 hours and 30 days from production; in fresh ricotta cheese, after 48 hours; in Ricotta mustia cheese after 7 days. The determination of lactose content in cheese samples was conducted by a gas chromatography-flame ionization detection method, which showed a LOD and limit of quantification respectively of 1.8 and 5.6 mg/kg for cheese, and 1.35 and 4.2 mg/kg for both ricotta cheeses. The lactose concentration was always below the relevant LOD values in all samples. The mean concentration of galactose and glucose were respectively 13,000±2000 and 11,000±2000 mg/kg in fresh Pecorino di Osilo, 1100±300 and 1200±300 mg/kg in fresh ricotta, and 950±400 and 750±250 mg/kg in Ricotta mustia. The results of the present study showed that the production of farmstead lactose-free Pecorino di Osilo cheese and ricotta cheeses from raw sheep's milk is easily achievable. The main issue for farmstead production of artisanal lactose-free products is the implementation of permanent procedures based on hazard-analysis and critical control principles aimed at guaranteeing the effectiveness of the process and at acquiring analytical evidences to demonstrate the fulfilment of law requirements for labelling.


Are Disposable and Standard Gonioscopy Lenses Comparable?
Gonioscopy is important in the evaluation and treatment of glaucoma. With increased scrutiny of acceptable sterilization processes for health care instruments, disposable gonioscopy lenses have recently been introduced. Single-time use lenses are theorized to decrease infection risk and eliminate the issue of wear and tear seen on standard, reusable lenses. However, patient care would be compromised if the quality of images produced by the disposable lens were inferior to those produced by the reusable lens. The purpose of this study was to compare the quality of images produced by disposable versus standard gonioscopy lenses. A disposable single mirror lens (Sensor Medical Technology) and a standard Volk G-1 gonioscopy lens were used to image 21 volunteers who were prospectively recruited for the study. Images of the inferior and temporal angles of each subject's left eye were acquired using a slit-lamp camera through the disposable and standard gonioscopy lens. In total, 74 images were graded using the Spaeth gonioscopic system and for clarity and quality. Clarity was scored as 1 or 2 and defined as either (1) all structures perceived or (2) all structures not perceived. Quality was scored as 1, 2, or 3, and defined as (1) all angle landmarks clear and well focused, (2) some angle landmarks clear, others blurred, or (3) angle landmarks could not be ascertained. The 74 images were divided into images taken with the disposable single mirror lens and images taken with the standard Volk G-1 gonioscopy lens. The clarity and quality scores for each of these 2 image groups were averaged and P-values were calculated. Average quality of images produced with the standard lens was 1.46±0.56 compared with 1.54±0.61 for those produced with the disposable lens (P=0.55). Average clarity of images produced with the standard lens was 1.47±0.51 compared with 1.49±0.51 (P=0.90) with the disposable lens. We conclude that there is no significant difference in quality of images produced with standard versus disposable gonioscopy lenses. Disposable gonioscopy lenses may be an acceptable alternative to standard reusable lenses, especially in conditions where sterilization is difficult.


Two-dimensional gel electrophoresis, protein electroblotting and microsequencing: a direct link between proteins and genes.
We have used two-dimensional gel electrophoresis as a general "preparative" method to purify proteins for microsequencing analysis. In the first experiments, proteins derived from a total extract of Nicotiana tabacum leaf tissue were directly blotted from the gel onto poly(4-vinyl-N-methylpyridinium iodide)-coated glass fiber sheets. The major spots were excised and subjected to NH2-terminal sequence analysis, which made it possible to identify five of the eight selected proteins, while two more were recognized by generated internal sequences. In a second set of experiments, proteins of human origin were separated on multiple two-dimensional gels and the Coomassie Brilliant Blue-stained spots were excised from the gels. The combined spots were re-eluted and concentrated in a new gel and blotted on Immobilon. They were fragmented by in situ proteolysis and the generated peptides were separated by reverse phase-high performance liquid chromatography and sequenced. At the average, the internal sequences that were obtained covered 35 residues per protein and allowed unambiguous identification of 13 of the 23 proteins analyzed so far. The sequence information obtained of the unidentified proteins is sufficient for further cloning. These results demonstrate that systematic sequence analysis of the major proteins seen in two-dimensional gels is within the reach of current technologies. This offers a unique opportunity to link information contained in protein databases with known or forthcoming DNA sequence data.


Yeast dynamically modify their environment to achieve better mating efficiency.
The maintenance and detection of signaling gradients are critical for proper development and cell migration. In single-cell organisms, gradient detection allows cells to orient toward a distant mating partner or nutrient source. Budding yeast expand their growth toward mating pheromone gradients through a process known as chemotropic growth. MATα cells secrete α-factor pheromone that stimulates chemotropism and mating differentiation in MATa cells and vice versa. Paradoxically, MATa cells secrete Bar1, a protease that degrades α-factor and that attenuates the mating response, yet is also required for efficient mating. We observed that MATa cells avoid each other during chemotropic growth. To explore this behavior, we developed a computational platform to simulate chemotropic growth. Our simulations indicated that the release of Bar1 enabled individual MATa cells to act as α-factor sinks. The simulations suggested that the resultant local reshaping of pheromone concentration created gradients that were directed away from neighboring MATa cells (self-avoidance) and that were increasingly amplified toward partners of the opposite sex during elongation. The behavior of Bar1-deficient cells in gradient chambers and mating assays supported these predictions from the simulations. Thus, budding yeast dynamically remodel their environment to ensure productive responses to an external stimulus and avoid nonproductive cell-cell interactions.


Reevaluating the antiquity of the Palmrose site: Collections-based research of an early plank house on the northern Oregon Coast.
Large-scale excavations conducted by Smithsonian Institution archaeologists and avocational archaeologists during the 1960s and 1970s at three sites in Seaside, Oregon, resulted in the recovery of a diverse range of material culture curated by multiple institutions. One site, known as Palmrose (35CLT47), provides compelling evidence for the presence of one of the earliest examples of a rectangular plank house along the Oregon Coast. Previous research suggests habitation of the Palmrose site occurred between 2340 cal BC to cal AD 640. However, recent research highlights significant chronometric hygiene concerns of previously reported radiocarbon dates for the Seaside area, calling into question broader regional chronologies. This paper presents a revised chronology for the Palmrose site based on 12 new accelerator mass spectrometry (AMS) radiocarbon dates of ancient cervid bones. I evaluate these new dates and previously reported radiocarbon dates from the site, applying chronometric hygiene assessments and Bayesian statistics to build a refined chronology for the Palmrose site. Calibration of the 12 AMS radiocarbon dates suggests an initial occupation range from 345-55 cal BC and a terminal occupation range from cal AD 225-340-. Bayesian modeling of the Palmrose sequence suggests initial occupation may have spanned from 195-50 cal BC and the terminal occupation from cal AD 210-255. Modeling suggests the maximum range of occupation may span from 580-55 cal BC to cal AD 210-300 based on the start and end boundary calculations. Bayesian modeling of radiocarbon dates directly associated with the plank house deposits suggests the plank house's occupation may have spanned from 160-1 cal BC to cal AD 170-320. The new radiocarbon dates significantly constrain the Palmrose habitation and alter regional chronologies.


A glycoprotein specified by spleen focus-forming virus in three cell lines varies on molecular size and peptide composition, but retains both xenotropic and ecotropic MuLV antigenicity.
A glycoprotein with an approx. mol. wt. of 55000, encoded by spleen focus-forming virus (SFFV), was detected with an antiserum against xenotropic murine leukaemia virus (MuLV) in various cell lines infected with the Friend strain of SFFV, suggesting that the SFFV-specific RNA coding for gp55 is related to the xenotropic virus. The proteins from three cell lines differed from each other in molecular size and gave different peptide maps. The differences in the gp55 molecules were shown to depend on differences in the SFFV genome, but not on differences in glycosylation or processing of the precursor polypeptides of gp55 in the different cells. These results indicate virus strain specificity of SFFV in gp55 formation.


An international external quality assessment for laboratory diagnosis of heparin-induced thrombocytopenia.
Essentials A pilot study for External Quality Assessment for testing of HIT is described. The qualitative accordance for the PF4/heparin IgG test was 97.6%. The qualitative accordance for functional HIT tests was considerably lower. External Quality Assessment for functional HIT tests is required. SUMMARY: Objective Heparin-induced thrombocytopenia (HIT) is a potentially life-threatening complication of heparin exposure. Diagnosis is most reliable using a combination of an enzyme immunoassay (EIA) that detects antibodies against platelet factor 4 (PF4)/heparin complexes ("antigen" assay) and a "functional" assay that detects platelet-activating properties of the pathogenic HIT antibodies. No External Quality Assessment (EQA) is available for a combination of the tests. Here we report on the results of the first international EQA. Methods The pilot EQA was organized by the Department of Transfusion Medicine, Universitätsmedizin Greifswald, Germany. Six serum samples of patients, which were referred to Greifswald for HIT diagnosis, and one negative control sample were distributed to seven participants in Germany, Canada, and Singapore. Participants were asked to report the optical density (OD) values of their local EIA test for IgG-specific antibodies against the PF4/heparin complexes and the results for a functional assay (HIPA or SRA). Consensus was defined as a minimum 70% agreement, i.e., agreement among at least five of the seven participating laboratories. Results and conclusion Six out of seven participants reported results for EIA, with a high quantitative accordance (97.6%). For the functional assay, consensus was reached for all samples except the negative control, for which some participants reported nonspecific reactivity. All HIT-negative samples were correctly diagnosed by all participants; for HIT-positive samples, consensus of 70% was reached. Although the limited availability of sample material is an obstacle to overcome, an EQA combining both EIA and functional testing is feasible.


Young children experience both regret and relief in a gain-or-loss context.
Recent research has provided compelling evidence that children experience the negative counterfactual emotion of regret, by manipulating the presence of a counterfactual action that would have led to participants receiving a better outcome. However, it remains unclear if children similarly experience regret's positive counterpart, relief. The current study examined children's negative and positive counterfactual emotions in a novel gain-or-loss context. Four- to 9-year-old children (N = 136) were presented with two opaque boxes concealing information that would lead to a gain or loss of stickers, respectively. Half of the children chose between two keys that matched each box, whereas the other half were compelled to select one box because only one of the two keys matched. After seeing inside the alternative, non-chosen box, children were significantly more likely to report a change in emotion when they could have opened that box than when they could not have. The effects were similar for children who lost stickers and won stickers, and neither effect varied with age. These findings suggest that children may become capable of experiencing regret and relief around the same time, although their expression of these counterfactual emotions may vary with actual and counterfactual gains and losses.


Congenital dengue in a Saudi neonate: A case report.
Dengue fever is a mosquito-borne viral illness with 100 million new cases occurring worldwide. The vectors involved are mainly Aedes aegypti and Aedes albopictus. Dengue infection is associated with maternal as well as fetal morbidities, like stillbirth, preterm birth, and low birth weight. We report a case of dengue fever occurring during early pregnancy and subsequent congenital neurologic malformation in the neonate as a result of vertical transmission. To our knowledge, this is the first case of confirmed congenital dengue in Saudi Arabia. Dengue infection is not commonly associated with congenital anomalies and no biologic mechanism has yet been established for its teratogenicity. Congenital dengue in neonates can be confirmed by identification of the dengue virus in cord blood samples. The positive dengue serology within the first week of life, together with the confirmed maternal dengue infection during pregnancy, supports the diagnosis of vertical transmission in the presence of clinical manifestations. A high index of suspicion, early diagnosis, and close monitoring is needed in these cases.


Expression of interleukin 1 receptors on human peripheral T cells.
The expression of interleukin 1 receptors (IL 1R) on human peripheral T cells was studied by the binding assay with 125I-labeled recombinant human interleukin 1 (IL 1) alpha and IL 1 beta and by the flow cytofluorometry with the fluorescein isothiocyanate (FITC)-conjugated IL 1 alpha. Peripheral blood lymphocytes expressed only few IL 1R without any stimulations. When they were stimulated with concanavalin A (Con A), IL 1R-positive cells began to increase by 4 hr, reached the maximum level at 48 hr, and then gradually decreased. The kinetics of the expression of IL 1 alpha R and IL 1 beta R showed the same pattern. Furthermore the binding of 125I-labeled IL 1 alpha to IL 1R on T cells was inhibited by the addition of either cold IL 1 alpha or IL beta, but not by interleukin 2 or interferons. The similar results were observed in the binding of 125I-labeled IL 1 beta. These results suggest that IL 1R on human peripheral T cells reactive for IL 1 alpha and IL 1 beta were identical. By Scatchard plot analysis, the numbers of IL 1R were estimated as 40 and 350 molecules per cell before and after Con A stimulation, respectively, and their Kd values were 3.1 X 10(-10) M and 2.8 X 10(-10) M. When purified T cells alone were stimulated with Con A, IL 1R were only marginally expressed. However, by the addition of monocytes, IL 1R were expressed on T cells in a dose-dependent manner. The maximum response was induced in the presence of 10% monocytes. The maximum IL 1R-positive T cells were approximately 30% by the detection of the flow cytofluorometry with FITC-conjugated IL 1 alpha. This enhancing activity of IL 1R expression on T cells by monocytes was inhibited by the addition of an anti-HLA-DR antibody or by the treatment of monocytes with the anti-HLA-DR antibody and complement. Furthermore T cell proliferative responses induced with IL 1 and Con A were also enhanced by the addition of HLA-DR-positive monocytes. These results suggest that IL 1R are expressed as the result of monocyte-T cell interaction in the early stage of T cell activation, and the expression of IL 1R on T cells and the responsiveness of T cells for IL 1 require the accessory function of HLA-DR-positive monocytes.


Evaluation of the Relationship Between Maxillary Sinus Wall and Maxillary Canines and Posterior Teeth Using Cone-Beam Computed Tomography.
BACKGROUND The proximity between the maxillary sinus and dental roots may impede orthodontic tooth movement. This study aimed to explore the relationship between the maxillary sinus wall (MSW) and maxillary canines and posterior teeth using cone-beam computed tomography (CBCT). MATERIAL AND METHODS CBCT images (317) were examined for whether the mesial, distal, buccal, and palatal surfaces of the examined root contacted the MSW, and the contact distance of each root surface with the MSW was measured. The effects of age and sex were analyzed using logistic regression and linear regression analyses. RESULTS The highest contact ratios with the MSW (ranging from 62.0% to 73.2%) were observed at the palatal root surfaces of the first molar mesiobuccal and distobuccal roots (1M MB and DB), the buccal root surface of the first molar palatal roots (1M P), and the mesial and buccal root surfaces of the second molars (2M), followed by the distal root surface of the second premolars (2PM) and the mesial root surfaces of the 1M MB and P (ranging from 49.2% to 59.3%). At these root surfaces, the contact ratios decreased with age (P<0.05), but the lowest still reached a range of 29.4% to 57.9% in the 30- to 47-year-old group. CONCLUSIONS The 2PM distal root surface, the 1M MB mesial and palatal root surfaces, the 1M DB palatal root surface, and the 1M P and 2M mesial and buccal root surfaces most frequently contacted the MSW. Clinicians should observe the contact of root surfaces with the MSW, even in aged patients.


Quantitation of soybean allergens using tandem mass spectrometry.
Soybean (Glycine max) seed contain some proteins that are allergenic to humans and animals. However, the concentration of these allergens and their expression variability among germplasms is presently unknown. To address this problem, 10 allergens were quantified from 20 nongenetically modified commercial soybean varieties using parallel, label-free mass spectrometry approaches. Relative quantitation was performed by spectral counting and absolute quantitation was performed using multiple reaction monitoring (MRM) with synthetic, isotope-labeled peptides as internal standards. During relative quantitation analysis, 10 target allergens were identified, and five of these allergens showed expression levels higher than technical variation observed for bovine serum albumin (BSA) internal standard (∼11%), suggesting expression differences among the varieties. To confirm this observation, absolute quantitation of these allergens from each variety was performed using MRM. Eight of the 10 allergens were quantified for their concentration in seed and ranged from approximately 0.5 to 5.7 μg/mg of soy protein. MRM analysis reduced technical variance of BSA internal standards to approximately 7%, and confirmed differential expression for four allergens across the 20 varieties. This is the first quantitative assessment of all major soybean allergens. The results show the total quantity of allergens measured among the 20 soy varieties was mostly similar.


Identifying the barriers and perceptions of non-Hispanic black and Hispanic/Latino persons with uncontrolled type 2 diabetes for participation in a home Telemonitoring feasibility study: a quantitative analysis of those who declined participation, withdrew or were non-adherent.
Objectives: Type 2 Diabetes Mellitus and its complications disproportionately affect non-Hispanic blacks and Hispanic/Latinos more than non-Hispanic whites. These disparities stem from complex interactions between biological, behavioral and socioeconomic factors. In recent years, telemedicine has been used to manage Type 2 Diabetes; however limited recruitment and retention of black and Hispanic/Latino patients into clinical trials exploring the use of telemedicine have necessitated the elucidation of their perceptions regarding participation in such trials. This study investigated patient-reported reasons for declining participation, prematurely terminating participation or demonstrating poor adherence to the study protocol in an ongoing randomized clinical trial, 'Feasibility of Telehealth Management of Diabetes Mellitus type 2 (T2DM) in Black and Hispanic Minority Patients'.Design: Semi-structured interviews comprised of open-ended questions and prompts were conducted by telephone to gauge patients' actual and perceived challenges to participating in the trial and using telemedicine to manage their diabetes. Data were collated with that of the original clinical trial and subsequently content analyzed for overarching themes and trends.Results: Eight semi-structured interviews were completed telephonically. Themes that emerged from analysis included disinterest (47%), inconvenience (33%), lack of perceived benefit (13%), lack of awareness of diabetes diagnosis (7%) and perceived lack of ability to fully participate in the study (7%).Conclusion: Adoption of telemedicine to help minority patients manage diabetes holds promise but is limited by patient factors such as disinterest, inconvenience and lack of perceived benefit. Greater awareness and understanding of these issues will be critical as we strive for greater health equity in disparity patients with uncontrolled diabetes.


Super-Resolution Microscopy and Single-Molecule Tracking Reveal Distinct Adaptive Dynamics of MreB and of Cell Wall-Synthesis Enzymes.
The movement of filamentous, actin-like MreB and of enzymes synthesizing the bacterial cell wall has been proposed to be highly coordinated. We have investigated the motion of MreB and of RodA and PbpH cell wall synthesis enzymes at 500 ms and at 20 ms time scales, allowing us to compare the motion of entire MreB filaments as well as of single molecules with that of the two synthesis proteins. While all three proteins formed assemblies that move with very similar trajectory orientation and with similar velocities, their trajectory lengths differed considerably, with PbpH showing shortest and MreB longest trajectories. These experiments suggest different on/off rates for RodA and PbpH at the putative peptidoglycan-extending machinery (PGEM), and during interaction with MreB filaments. Single molecule tracking revealed distinct slow-moving and freely diffusing populations of PbpH and RodA, indicating that they change between free diffusion and slow motion, indicating a dynamic interaction with the PGEM complex. Dynamics of MreB molecules and the orientation and speed of filaments changed markedly after induction of salt stress, while there was little change for RodA and PbpH single molecule dynamics. During the stress adaptation phase, cells continued to grow and extended the cell wall, while MreB formed fewer and more static filaments. Our results show that cell wall synthesis during stress adaptation occurs in a mode involving adaptation of MreB dynamics, and indicate that Bacillus subtilis cell wall extension involves an interplay of enzymes with distinct binding kinetics to sites of active synthesis.


The role of reducible oxide-metal cluster charge transfer in catalytic processes: new insights on the catalytic mechanism of CO oxidation on Au/TiO2 from ab initio molecular dynamics.
To probe metal particle/reducible oxide interactions density functional theory based ab initio molecular dynamics studies were performed on a prototypical metal cluster (Au20) supported on reducible oxides (rutile TiO2(110)) to implicitly account for finite temperature effects and the role of excess surface charge in the metal oxide. It is found that the charge state of the Au particle is negative in a reducing chemical environment whereas in the presence of oxidizing species coadsorbed to the oxide surface the cluster obtained a net positive charge. In the context of the well-known CO oxidation reaction, charge transfer facilitates the plasticization of Au20, which allows for a strong adsorbate induced surface reconstruction upon addition of CO leading to the formation of mobile Au-CO species on the surface. The charging/discharging of the cluster during the catalytic cycle of CO oxidation enhances and controls the amount of O2 adsorbed at oxide/cluster interface and strongly influences the energetics of all redox steps in catalytic conversions. A detailed comparison of the current findings with previous studies is presented, and generalities about the role of surface-adsorbate charge transfer for metal cluster/reducible oxide interactions are discussed.


A fast and exhaustive method for heterogeneity and epistasis analysis based on multi-objective optimization.
The existing epistasis analysis approaches have been criticized mainly for their: (i) ignoring heterogeneity during epistasis analysis; (ii) high computational costs; and (iii) volatility of performances and results. Therefore, they will not perform well in general, leading to lack of reproducibility and low power in complex disease association studies. In this work, a fast scheme is proposed to accelerate exhaustive searching based on multi-objective optimization named ESMO for concurrently analyzing heterogeneity and epistasis phenomena. In ESMO, mutual entropy and Bayesian network approaches are combined for evaluating epistatic SNP combinations. In order to be compatible with heterogeneity of complex diseases, we designed an adaptive framework based on non-dominant sort and top k selection algorithm with improved time complexity O(k*M*N) . Moreover, ESMO is accelerated by strategies such as trading space for time, calculation sharing and parallel computing. Finally, ESMO is nonparametric and model-free. We compared ESMO with other recent or classic methods using different evaluating measures. The experimental results show that our method not only can quickly handle epistasis, but also can effectively detect heterogeneity of complex population structures. https://github.com/XiongLi2016/ESMO/tree/master/ESMO-common-master . email@example.com.


Relationship of plasma lipid concentrations to fat deposition in pigs.
The time course for changes in plasma free fatty acid and triglyceride concentration after removal of feed was established. Genetically obese and lean lines of pigs, two types of crossbred female pigs and a group of male pigs were used to establish the relationship between circulating free fatty acid or triglyceride concentrations and adiposity. Pigs were weighed, ultrasonically probed for backfat thickness, bled in a fed state and again in the fasted state. Plasma was analyzed for free fatty acid and triglyceride concentration. Fasting increased plasma free fatty acid, but only slightly increased triglyceride concentrations. There were several significant correlations between backfat thickness and plasma lipid concentrations; however, the low magnitude and inconsistency of these correlations precludes use of plasma lipid concentrations as indicators of adiposity in swine. Fasted obese pigs had lower plasma fatty acid concentrations than lean pigs at 2, 4 and 6 mo of age. If these plasma levels represent in vivo mobilization of fat, the results probably contrast with previously reported in vitro results wherein adipose tissue from obese pigs had lipolytic rates expressed on a cellular basis that were equal to or greater than those form lean pigs.


"Falling between the cracks": Experiences of Black dementia caregivers navigating U.S. health systems.
In addition to numerous care responsibilities, family caregivers are expected to navigate health systems and engage in healthcare management tasks on behalf of their persons living with dementia (PLWD). These challenging tasks pose additional difficulties for Black dementia caregivers. Due to the centuries-old, disadvantaged social history of Black Americans, several unique stressors, vulnerabilities, and resources have emerged which inform and affect Black dementia caregivers' experiences and well-being. Focus groups were held with Black caregivers (N = 19) from the United States to explore the unique experiences and perspectives of this population navigating the U.S. health system on behalf of their PLWD. Five overarching themes were constructed during thematic analysis: Forced Advocacy, Poor Provider Interaction, Payor Source Dictates Care, Discrimination, and Broken Health System. Black dementia caregivers unanimously concurred that the health system that they experience in America is "broken." Gaps in the health system can lead to people [as one caregiver passionately expressed] "falling between the cracks," in terms of care, services, and resources needed. Caregivers agreed that class, sex, utilizing public health insurance, and being a "person of color" contribute to their difficulties navigating the health system. Caregivers perceived being dismissed by providers, forcing them to advocate for both themselves and their PLWD. Healthcare providers and researchers can utilize these findings to improve the experiences and healthcare outcomes of Black persons living with dementia and their caregivers. Additionally, these findings can lead to the development of culturally tailored caregiver education programs.


Black college students at elevated risk for suicide: Barriers to mental health service utilization.
To examine differences between Black students who do and do not screen positive for suicide risk; to describe barriers to mental health service utilization (MHSU) among participants with a positive screen and no current MHSU and; to determine if barriers vary by student characteristics. Participants: 1,559 Black students (66% female), ages 18 years and older (M = 21 years, SD = 2.61) recruited from September 2015 to October 2017 across four universities. Method: Participants completed an online survey assessing demographics, suicide risk, MHSU, and barriers to MHSU. Results: Seventeen percent of students screened positive for risk; 66% of these students were not receiving MHS. Students who screened positive were female and younger. Perceived problem severity (74%) was reported most frequently. Conclusions: Efforts to improve MHSU among Black college students at risk for suicide should address students' awareness of treatable MH problems and time concerns.


Behavioural treatment for chronic low-back pain.
Behavioural treatment is commonly used in the management of chronic low-back pain (CLBP) to reduce disability through modification of maladaptive pain behaviours and cognitive processes. Three behavioural approaches are generally distinguished: operant, cognitive, and respondent; but are often combined as a treatment package. To determine the effects of behavioural therapy for CLBP and the most effective behavioural approach. The Cochrane Back Review Group Trials Register, CENTRAL, MEDLINE, EMBASE, and PsycINFO were searched up to February 2009. Reference lists and citations of identified trials and relevant systematic reviews were screened. Randomised trials on behavioural treatments for non-specific CLBP were included. Two review authors independently assessed the risk of bias in each study and extracted the data. If sufficient homogeneity existed among studies in the pre-defined comparisons, a meta-analysis was performed. We determined the quality of the evidence for each comparison with the GRADE approach. We included 30 randomised trials (3438 participants) in this review, up 11 from the previous version. Fourteen trials (47%) had low risk of bias. For most comparisons, there was only low or very low quality evidence to support the results. There was moderate quality evidence that:i) operant therapy was more effective than waiting list (SMD -0.43; 95%CI -0.75 to -0.11) for short-term pain relief;ii) little or no difference exists between operant, cognitive, or combined behavioural therapy for short- to intermediate-term pain relief;iii) behavioural treatment was more effective than usual care for short-term pain relief (MD -5.18; 95%CI -9.79 to -0.57), but there were no differences in the intermediate- to long-term, or on functional status;iv) there was little or no difference between behavioural treatment and group exercise for pain relief or depressive symptoms over the intermediate- to long-term;v) adding behavioural therapy to inpatient rehabilitation was no more effective than inpatient rehabilitation alone. For patients with CLBP, there is moderate quality evidence that in the short-term, operant therapy is more effective than waiting list and behavioural therapy is more effective than usual care for pain relief, but no specific type of behavioural therapy is more effective than another. In the intermediate- to long-term, there is little or no difference between behavioural therapy and group exercises for pain or depressive symptoms. Further research is likely to have an important impact on our confidence in the estimates of effect and may change the estimates.


Enabling reproductive, maternal, neonatal and child health interventions: Time trends and driving factors of health expenditure in the successful story of Peru.
We compared expenditure trends for reproductive, maternal, neonatal and child health (RMNCH) with trends in RMNCH service coverage in Peru. We used National Health Accounts data to report on total health expenditure by source; the Countdown database for trends in external funding to RMNCH, and Ministry of Finance data for trends in domestic funding to RMNCH. We undertook over 170 interviews and group discussions to explore factors explaining expenditure trends. We describe trends in total health expenditure and RMNCH expenditure in constant 2012 US$ between 1995 and 2012. We estimated expenditure to coverage ratios. There was a substantial increase in domestic health expenditure over the period. However, domestic health expenditure as share of total government spending and GDP remained stable. Out-of-pocket health spending (OOPS) as a share of total health expenditure remained above 35%, and increased in real terms. Expenditure on reproductive health per woman of reproductive age varied from US$ 1.0 in 2002 to US$ 6.3 in 2012. Expenditure on maternal and neonatal health per pregnant woman increased from US$ 34 in 2000 to US$ 512 in 2012, and per capita expenditure on under-five children increased from US$ 5.6 in 2000 to US$ 148.6 in 2012. Increased expenditure on RMNCH reflects a greater political support for RMNCH, along with greater emphasis on social assistance, family planning, and health reforms targeting poor areas, and a recent emphasis on antipoverty and crosscutting equitable policies and programmes focused on nutrition and maternal and neonatal mortality. Increasing domestic RMNCH expenditure likely enabled Peru to achieve substantial health gains. Peru can provide useful lessons to other countries struggling to achieve sustained gains in RMNCH by relying on their own health financing.


Pharmacological classification of herbal extracts by means of comparison to spectral EEG signatures induced by synthetic drugs in the freely moving rat.
Herbal extracts targeting at the brain remain a continuous challenge to pharmacology. Usually, a number of different animal tests have to be performed in order to find a potential clinical use. Due to manifold possibly active ingredients biochemical approaches are difficult. A more holistic approach using a neurophysiological technique has been developed earlier in order to characterise synthetic drugs. Stereotactic implantation of four semi-microelectrodes into frontal cortex, hippocampus, striatum and reticular formation of rats allowed continuous wireless monitoring of field potentials (EEG) before and after drug intake. After frequency analysis (Fast Fourier Transformation) electric power was calculated for 6 ranges (delta, theta, alpha1, alpha2, beta1 and beta2). Data from 14 synthetic drugs - tested earlier and representative for different clinical indications - were taken for construction of discriminant functions showing the projection of the frequency patterns in a six-dimensional graph. Quantitative analysis of the EEG frequency pattern from the depth of the brain succeeded in discrimination of drug effects according to their known clinical indication (Dimpfel and Schober, 2003). Extracts from Valerian root, Ginkgo leaves, Paullinia seed, Hop strobile, Rhodiola rosea root and Sideritis scardica herb were tested now under identical conditions. Classification of these extracts based on the matrix from synthetic drugs revealed that Valerian root and hop induced a pattern reminiscent of physiological sleep. Ginkgo and Paullinia appeared in close neighbourhood of stimulatory drugs like caffeine or to an analgesic profile (tramadol). Rhodiola and Sideritis developed similar frequency patterns comparable to a psychostimulant drug (methylphenidate) as well to an antidepressive drug (paroxetine).


[Congenital Wilms' tumors are mostly (benign) mesoblastic nephromas--significance of prenatally detected solid kidney tumors].
In a nationwide study (1980-1988) for the diagnosis and treatment of Wilms' tumours (nephroblastomas), which are highly malignant embryonal mixed tumours of the kidney and show distant metastases at the time of diagnosis in 10-20% of cases, 78% of 373 children had a standard type Wilms' tumour, 7% had benign variants and 14% had high grade malignancy variants of the classical type. 20 of the 25 benign variants occurred in infants. From the 25, 16 tumours were congenital mesoblastic nephromas, 14 of which occurred in infants. As the detection of a solid renal tumour mass in the prenatal sonogram (showing an echotexture resembling that of the liver) may suggest Wilms' tumour, we analysed 11 neonates (1-14 days old), in which Wilms' tumours had been diagnosed (n = 11; 2.9%) for the histological subtype. In 9 of the 10 neonates, the final diagnosis was congenital mesoblastic nephroma. These congenital mesoblastic nephromas are cured by surgery alone. Thus, if a solid renal tumour suspected as a Wilms' tumour, is prenatally detected, the most probable diagnosis is that of the benign variant congenital mesoblastic nephroma, and, in this case, preterm delivery (e.g. to prevent metastasising and to start treatment as early as possible) is not indicated.


The Moderating Role of Deviant Peer Affiliation in the Relation between Cyber-Victimization, Tobacco and Alcohol Use, and Age Differences.
Cyber-victimization, tobacco and alcohol use are all prominent public health problems among adolescents throughout the world. Against this background, this study examined the association between cyber-victimization and tobacco and alcohol use, as well as the moderating role of deviant peer affiliation and the potential age differences among elementary, middle, and high school students. A survey conducted among 1488 school students (aged 9-19 years, consisting of 702 elementary school students, 318 middle school students, and 468 high school students) found that cyber-victimization was positively correlated with tobacco and alcohol use among students of all stages. However, the moderating mechanism was different. Among elementary school students, deviant peer affiliation played a positive moderating role. For individuals with high deviant peer affiliation, this association was stronger. Among middle school students, the moderating role of deviant peer affiliation was insignificant. Among high school students, deviant peer affiliation played a negative moderating role; this association was significant for individuals with low deviant peer affiliation. The results of this study clarify the relationship between cyber-victimization and tobacco and alcohol use by examining the moderating role of deviant peer affiliation and age differences, providing intervention guidance for reducing the negative influences of cyber-victimization on children and adolescents with respect their use of tobacco and alcohol.


Online sonification for golf putting gesture: reduced variability of motor behaviour and perceptual judgement.
This study investigates whether real-time auditory feedback has a direct behavioural or perceptual effect on novices performing a golf putting task with limited visual feedback. Due to its significant role in the success of a putt, club head speed was selected as the parameter for sonification. Different combinations of synthesisers, timbral modulations, scales, and mappings were developed to examine whether particular sound classes influenced performance. When compared to trials with static pink noise, we found that, despite their vision being limited at impact, participants were able to use different types of sonification to significantly reduce variability in their distance from the target and ball location estimation. These results suggest that concurrent sound can play an important role in reducing variability in behavioural performance and related perceptual estimations. In addition, we found that, when compared to trials with static pink noise, participants were able to use sonification to significantly lower their average impact velocity. In the discussion, we offer some trends and observations relative to the different sound synthesis parameters and their effects on behavioural and perceptual performance.


Species difference in glucuronidation formation kinetics with a selective mTOR inhibitor.
The mammalian target of rapamycin (mTOR) is a protein kinase that shows key involvement in age-related disease and promises to be a target for treatment of cancer. In the present study, the elimination of potent ATP-competitive mTOR inhibitor 3-(6-amino-2-methylpyrimidin-4-yl)-N-(1H-pyrazol-3-yl)imidazo[1,2-b]pyridazin-2-amine (compound 1) is studied in bile duct-cannulated rats, and the metabolism of compound 1 in liver microsomes is compared across species. Compound 1 was shown to undergo extensive N-glucuronidation in bile duct-catheterized rats. N-glucuronides were detected on positions N1 (M2) and N2 (M1) of the pyrazole moiety as well as on the primary amine (M3). All three N-glucuronide metabolites were detected in liver microsomes of the rat, dog, and human, while primary amine glucuronidation was not detected in cynomolgus monkey. In addition, N1- and N2-glucuronidation showed strong species selectivity in vitro, with rat, dog, and human favoring N2-glucuronidation and monkey favoring N1-glucuronide formation. Formation of M1 in monkey liver microsomes also followed sigmoidal kinetics, singling out monkey as unique among the species with regard to compound 1 N-glucuronidation. In this respect, monkeys might not always be the best animal model for N-glucuronidation of uridine diphosphate glucuronosyltransferase (UGT) 1A9 or UGT1A1 substrates in humans. The impact of N-glucuronidation of compound 1 could be more pronounced in higher species such as monkey and human, leading to high clearance in these species. While compound 1 shows promise as a candidate for investigating the impact of pan-mTOR inhibition in vivo, opportunities may exist through medicinal chemistry efforts to reduce metabolic liability with the goal of improving systemic exposure.


Transferrin saturation studies in male adults showing high prevalence of iron deficiency.
Estimation of serum iron, total iron binding capacity (TIBC) and transferrin saturation was performed in 62 apparently healthy male medical students. All had haemoglobin over 140 g/1. Low serum iron, elevated level of TIBC and transferrin saturation under 20% indicating iron deficiency state was found in 2 subjects. Elevated values of TIBC was found in 25 (40.32%) students as evidence of latent iron deficiency. Such high prevalence of iron deficiency in an affluent group indicates widespread iron deficiency in the general population.


Impact of day of admission on in-hospital outcomes of cardiogenic shock.
The management of cardiogenic shock (CS) requires attentiveness to details and in some cases, invasive interventions. In the past, studies have shown relationships between the day of admission and cardiovascular outcomes. We aim to analyze the trends and in-hospital outcomes of patients admitted with CS over the weekends compared to weekdays. We identified all patients with CS from the National Inpatient Sample (NIS) database between 2016 and 2020. Using multivariate logistic regression analysis, baseline demographics and in-hospital outcomes were obtained and compared by weekend or weekday admission. Out of 854,684 CS admissions, 199,255 (23.6%) occurred on weekends. Patients admitted over the weekend had worse outcomes, including higher rates of mortality (aOR 1.09 CI 1.05 - 1.11, p<0.001), cardiac arrest (aOR 1.09 CI 1.04 -1.14, p<0.001), and respiratory failure. We also noted higher percutaneous coronary intervention (PCI) rates (aOR 1.2 CI 1.16 - 1.25, p<0.001) but lower rates of pulmonary artery catheterization (PAC) and post-procedure pneumothorax. Weekend admissions had shorter hospital lengths of stay, and they incurred lower charges ($223,222 vs. $247,908). Between 2016 and 2020, we observed a consistent downward trend in the mortality rates of the weekend and weekday CS admissions, with consistently higher weekend than weekday admissions. Weekend admissions for CS are associated with worse outcomes, which have persisted for years. This now begs the question of whether physician dissatisfaction, understaffing, or burn-out are responsible for this finding.


Flow cytometry analysis reveals that only a subpopulation of mouse sperm undergoes hyperpolarization during capacitation.
To gain fertilizing capacity, mammalian sperm should reside in the female tract for a period of time. The physiological changes that render the sperm able to fertilize are known as capacitation. Capacitation is associated with an increase in intracellular pH, an increase in intracellular calcium, and phosphorylation of different proteins. This process is also accompanied by the hyperpolarization of the sperm plasma membrane potential (Em). In the present work, we used flow cytometry to analyze changes in sperm Em during capacitation in individual cells. Our results indicate that a subpopulation of hyperpolarized mouse sperm can be clearly distinguished by sperm flow cytometry analysis. Using sperm bearing green fluorescent protein in their acrosomes, we found that this hyperpolarized subpopulation is composed of sperm with intact acrosomes. In addition, we show that the capacitation-associated hyperpolarization is blocked by high extracellular K(+), by PKA inhibitors, and by SLO3 inhibitors in CD1 mouse sperm, and undetectable in Slo3 knockout mouse sperm. On the other hand, in sperm incubated in conditions that do not support capacitation, sperm membrane hyperpolarization can be induced by amiloride, high extracellular NaHCO3, and cAMP agonists. Altogether, our observations are consistent with a model in which sperm Em hyperpolarization is downstream of a cAMP-dependent pathway and is mediated by the activation of SLO3 K(+) channels.


Disparities in adverse childhood experiences among individuals with a history of military service.
Adverse childhood experiences (ACEs) are associated with several adulthood health problems, such as self-directed violence. For some individuals, enlistment in the military may be an instrumental act to escape adverse household environments; however, to our knowledge prevalence of ACEs among persons with a history of military service has not been documented in the United States using population-based data. To compare the prevalence of ACEs among individuals with and without a history of military service. Data are from the 2010 Behavioral Risk Factor Surveillance System. Computer-assisted telephone interviews were conducted with population-based samples of noninstitutionalized US adults from January 1 through December 31, 2010. Analyses were limited to respondents who received the ACE module (n = 60,598). Participants were categorized by history of military service and whether a respondent was 18 years of age in 1973. History of military service was defined by active duty service, veteran status, or training for the Reserves or National Guard. The ACE inventory assessed 11 negative experiences before the age of 18 years. Weighted χ2 tests and multiple logistic regression analyses were used to examine differences in ACEs by history of military service, era of service, and sex. Those with military experience had greater odds of any difference in prevalence of ACEs. In the all-volunteer era, men with military service had a higher prevalence of ACEs in all 11 categories than men without military service. Notably, in the all-volunteer era, men with military service had twice the odds of reporting forced sex before the age of 18 years (odds ratio, 2.19; 95% CI, 1.34-3.57) compared with men without military service. In the draft era, the only difference among men was household drug use, in which men with a history of military service had a significantly lower prevalence than men without a history of military service (2.1% vs. 3.3%; P = .003). Fewer differences were observed among women in the all-volunteer and draft eras. Differences in ACEs by era and sex lend preliminary support that enlistment may serve as an escape from adversity for some individuals, at least among men. Further research is needed to understand how best to support service members and veterans who may have experienced ACEs.


Endothelial modulation of renal interlobar arteries from pregnant rats.
The purpose of this study was to determine whether there are gestational effects on 1) the response of resistance arteries from the renal vasculature to phenylephrine and 2) the endothelial modulation of these arteries. Interlobar arteries (200-300 microns ID) were isolated from the kidneys of virgin and pregnant rats at 18-20 days of gestation (term, 22 +/- 1 days) and studied in a pressurized arteriograph system. Intact arteries from virgin and pregnant rats did not differ in sensitivity to phenylephrine. Arteries without endothelium from both groups were more sensitive to phenylephrine than arteries with endothelium. Sensitivity was increased 3.4-fold by endothelial removal in arteries from virgin rats and 1.5-fold in the pregnant group. Concentration-response relationships to phenylephrine were determined in arteries with endothelium and then repeated in the presence of 2.5 x 10(-4) M N omega-nitro-L-arginine (L-NNA), an inhibitor of nitric oxide synthase. All arteries were more sensitive to phenylephrine in the presence of L-NNA, with an average increase of 3.2-fold for the arteries from virgin rats and 1.6-fold from pregnant rats. These results indicate that the increased sensitivity to phenylephrine is primarily due to elimination of endothelium-derived relaxing factor (EDRF) and that basal EDRF activity is decreased during late gestation. To determine whether stimulated endothelium-dependent relaxation is enhanced in pregnancy, arteries with endothelium were constricted with phenylephrine to 50% of their maximum and relaxed to increasing concentrations of methacholine.(ABSTRACT TRUNCATED AT 250 WORDS)


A Seat at the Table: Strategic Engagement in Service Activities for Early-Career Faculty From Underrepresented Groups in the Academy.
Many academic institutions strive to promote more diverse and inclusive campuses for faculty, staff, and students. As part of this effort, these institutions seek to include individuals from historically underrepresented groups (URGs)-such as women, people from racial/ethnic minority populations, persons with disabilities-on committees and in other service activities. However, given the low number of faculty members from URGs at many institutions, these faculty members tend to receive more requests to provide service to the institution or department (e.g., serving on committees, mentoring) than their counterparts from majority groups. Faculty members from URGs, especially early-career faculty, thus risk becoming overburdened with providing service at the expense of working on other scholarly activities required for promotion and tenure (i.e., conducting research, publishing). Although many scholars and others have written about this "minority tax" and its implications for early-career faculty from underrepresented racial/ethnic minority groups, fewer have published about how this tax extends beyond racial/ethnic minorities to women and persons with disabilities. Further, the literature provides scant practical advice on how to avoid overburdening early-career faculty from URGs. Here, a group of multidisciplinary early- and mid-career faculty members from URGs seek to provide their peers from URGs with practical strategies for both evaluating the appropriateness of service requests and declining those that are not a good fit. The authors also provide institutional leaders with actionable recommendations to prevent early-career faculty from URGs from becoming overburdened with service.


CRISPR/Cas9-based split homing gene drive targeting doublesex for population suppression of the global fruit pest Drosophila suzukii.
Genetic-based methods offer environmentally friendly species-specific approaches for control of insect pests. One method, CRISPR homing gene drive that target genes essential for development, could provide very efficient and cost-effective control. While significant progress has been made in developing homing gene drives for mosquito disease vectors, little progress has been made with agricultural insect pests. Here, we report the development and evaluation of split homing drives that target the doublesex (dsx) gene in Drosophila suzukii, an invasive pest of soft-skinned fruits. The drive component, consisting of dsx single guide RNA and DsRed genes, was introduced into the female-specific exon of dsx, which is essential for function in females but not males. However, in most strains, hemizygous females were sterile and produced the male dsx transcript. With a modified homing drive that included an optimal splice acceptor site, hemizygous females from each of the four independent lines were fertile. High transmission rates of the DsRed gene (94 to 99%) were observed with a line that expressed Cas9 with two nuclear localization sequences from the D. suzukii nanos promoter. Mutant alleles of dsx with small in-frame deletions near the Cas9 cut site were not functional and thus would not provide resistance to drive. Finally, mathematical modeling showed that the strains could be used for suppression of lab cage populations of D. suzukii with repeated releases at relatively low release ratios (1:4). Our results indicate that the split CRISPR homing gene drive strains could potentially provide an effective means for control of D. suzukii populations.


Hypertension, coronary artery disease and myocardial ischemic syndromes.
Hypertension represents a major contributor to the development of coronary artery disease. The pathophysiological mechanisms underlying the link between hypertension and CAD are complex and include overactivation of neurohormones, accelerated development of the atherosclerotic plaque, endothelial dysfunction, altered intramyocardial coronary circulation, hypertension-mediated cardiac and vascular damage and the relationship between arterial stiffness and coronary perfusion. Blood pressure (BP) reduction is associated with a significant decrease of the risk of coronary events. Therapeutic interventions targeted to reduce BP and to improve endothelial function and coronary microvascular dysfunction, as well as to prevent left ventricular hypertrophy and dysfunction, contribute to reduce the burden of coronary disease and its acute ischemic manifestations.


Computed Tomographic Evaluation of Condylar Symmetry and Condyle-Fossa Relationship of the Temporomandibular Joint in Subjects with Normal Occlusion and Malocclusion: A Comparative Study.
The relationship of the condyle and the mandibular fossa differs in shape with type of malocclusion and skeletal pattern. A review of literature shows till date there are no studies on Temporomandibular Joint (TMJ) condyle-fossa relation to the type of malocclusion based on growth pattern. Computed Tomography (CT) provides optimal imaging of the osseous components of the TMJ. The purpose of this study was to investigate the condyle-fossa relationship and the dimensional and positional symmetries between the right and left condyles in subjects with normal occlusion and malocclusion in different growth patterns utilizing the CT scans of the TMJ. Sixty subjects with age group of 18-30 years were selected for the study. The sample was divided into three groups based on overbite and growth pattern. The groups included 20 subjects with normal occlusion and average growth pattern, 20 patients with horizontal growth pattern and deep bite, 20 patients with vertical growth pattern and deep bite. The depth of the mandibular fossa, the condyle-fossa relationship, and the concentric position of the condyles were evaluated by the images obtained from the sagittal slices. ANOVA was performed to assess the significance. If it was found significant, post-hoc Tukey's test was performed to see which two groups were statistically significant. No statistically significant difference was found in the anterior joint space and the superior joint space in horizontal and vertical growers with deep bite. Statistically significant (p <0.05) posterior positioning of the condyles was observed (nonconcentric positioning) in vertical growers with deep bite. There is a significant change in the position of the condyle in vertical growers compared to average and horizontal growers. Left condyle is more anteriorly placed than the right condyle in all the three groups. There is no significant change in the vertical depth of the mandibular fossa in all the three groups.


miR-200c regulates induction of apoptosis through CD95 by targeting FAP-1.
Tumor progression shares many characteristics with the process of epithelial-to-mesenchymal transition (EMT). Cells that have undergone an EMT are known to have an increased resistance to apoptosis. CD95/Fas is an apoptosis-inducing receptor expressed on many tissues and tumor cells. During tumor progression CD95 is frequently downregulated, and tumor cells lose apoptosis sensitivity. miR-200 microRNAs repress both the EMT-inducing ZEB1 and ZEB2 transcription factors. We now demonstrate that miR-200c sensitizes cells to apoptosis mediated by CD95. We have identified the apoptosis inhibitor FAP-1 as a target for miR-200c. FAP-1 was demonstrated to be responsible for the reduced sensitivity to CD95-mediated apoptosis in cells with inhibited miR-200. The identification of FAP-1 as an miR-200c target provides a molecular mechanism to explain both the downregulation of CD95 expression and the reduction in sensitivity of cells to CD95-mediated apoptosis that is observed in the context of reduced miR-200 expression during tumor progression.


A fully verified theoretical analysis of strain-photonic coupling for quantum wells embedded in wavy nanoribbons.
For optoelectronic devices, an attractive research field involves the flexible adjustment of the band gap in semiconductor quantum well (QW) structures by strain engineering. However, rigid wafer-based technology enables lattice-misfit strain during epitaxial growth, which is biaxial, unchangeable, and not sufficient for the devices fitted on various irregular surfaces. Therefore, exploiting the strain produced by externally deformed configurations offers unique opportunities to continuously and non-defectively tune the QW's band structure. Here, we propose a strategy to induce uniaxially distributed strain in elaborately designed wavy quantum well nanoribbons (QWNRs). Meanwhile, a numerically solved strain-photonic coupling model based on the theory of elasticity and the eight-band k·p method is established to illustrate the strain distribution coupled with the strain-induced band gap shift of the wavy QWNR. The μ-photoluminescence measurements reveal a periodically varied band gap in the QW along the uniaxial tensile direction, which is consistent with the result of theoretical calculations. This model demonstrates the potential application of a wrinkled configuration in arbitrarily controlling and tuning the band gap and thus the optoelectronic performances of quantum well systems.


A continuous flow microfluidic device based on contactless dielectrophoresis for bioparticles enrichment.
In recent years, applications of dielectrophoresis-based platforms have been recognized as effective and dependable approach to separate cells and bioparticles, suspended in different carrier fluids, based on particle size and electrical properties. In this study, a microfluidic device was fabricated by an unprecedented electrode pattern, and several experiments were performed to enrich samples including either of yeast, Escherichia coli, or latex particles. A chemical deposition-based method was employed for fabrication of microelectrodes, inducing nonuniform electric field required for dielectrophoresis-based separation. One major advantage of our employed method is low fabrication cost, in addition to its accuracy and operation at low voltages. The performance of the microfluidic device in enriching either of injected samples was studied using spectrophotometric techniques. The effects of experimentally controllable parameters (applied-voltage amplitude and frequency, and flow rate) were studied by changing a parameter while keeping the others constant. It became evident that all the aforementioned parameters had modulating impact on the performance of the microfluidic device. Furthermore, to investigate binary interactions among the parameters, response surface methodology was exploited, resulting in a second-order polynomial model for the performance of the device as a function of the parameters. The model was employed for finding the optimum values of the parameters at which the performance of the device is the highest. At optimum values for the experimentally controllable parameters, enrichment efficiencies of 87 ± 2, 82 ± 4, and 86 ± 3% for, respectively, yeast, E. coli, and latex particles were obtained experimentally, confirming the ability of the proposed method for biological and polymeric particles enrichment.


Impact of Obesity and Ozone on the Association Between Particulate Air Pollution and Cardiovascular Disease and Stroke Mortality Among US Adults.
Cardiovascular diseases (CVDs) and stroke are the highest and third highest causes of death, respectively, in the whole United States. It is well established that both long- and short-term exposure to particulate air pollution (particulate matter with diameters <2.5 μm [PM2.5]) increases the risks of both CVD and stroke mortality. We combined county-level data for CVD and stroke mortality, and prevalence of hypertension and obesity, with spatial patterns of PM2.5 and ozone in a cross-sectional ecological study. We found significant positive associations between both CVD (β=15.4, P<0.001) and stroke (β=2.7, P<0.001) mortality with PM2.5. Ozone had significant link with just CVD (β=1372.1, P<0.001). Once poverty, ethnicity, and education were taken into account, there were still significant positive associations between PM2.5 and both CVD (β=1.2, P<0.001) and stroke (β=1.1, P<0.001) mortality. Moreover, the association between CVD and ozone remained after adjustment for these factors (β=21.8, P<0.001). PM2.5 and ozone were independent risk factors. The impact of PM2.5 on CVD and stroke mortality was strongly dependent on the prevalence of obesity. Hypertension partially mediated the associations of PM2.5 and mortality from CVD and stroke. There was a spatial association between PM2.5 exposure and the leading causes of death and disability in United States. The effect of PM2.5 was considerably greater in areas where obesity is more prevalent. Hypertension is a possible mediator of the association of PM2.5 and both CVD and stroke.


Alu-DNA repeat-binding protein p68 is a part of Alu-RNA containing alpha-RNP.
An Alu-DNA repeat-binding protein with a molecular mass of 68 kDa (p68) is identified in the somatic human cell nucleoplasm. Gel mobility shift assay (GMSA), South-western blotting and affinity purification on DNA attached to the carrier were used in the identification. GMSA revealed multiple complexes with the exponential dependence of their relative mobility. A narrow binding site of the p68 was revealed using synthetic oligonucleotides. It is located between the A-box and B-box of the RNA polymerase III promoter and is identical to that reported for the Alu-binding protein from human spermatozoids. The same narrow binding site, the similarity of the isolation procedure from germ and somatic cells, and similar binding properties and molecular masses suggest homology of the two proteins. Antibodies raised against Alu-protein complexes led to hypershift of the complexes in GMSA and stained p68 in active fractions in human spermatozoids and in Alu-RNA-containing alpha-RNP particles. Immunofluorescence of a HeLa cell monolayer revealed an intranuclear dot pattern with the dots corresponding to euchromatin areas and some dots located at the cell periphery in the cytoplasm. alpha-RNP particles bound Alu-DNA in vitro and contained p68 as shown using the immunogold procedure. Alu-DNA binding activity was revealed in cytoplasm as well as in nucleoplasm. The possible nature of the main Alu-DNA binding protein and its involvement in the particle structure are discussed.