Preferred clinical practice in convergence insufficiency in India: a survey.
Convergence insufficiency (CI) is a common binocular vision disorder. However, there is a lack of consensus regarding the treatment most appropriate for CI. The aim of the study was to investigate the treatment for CI by surveying the ophthalmologists regarding the most common treatment modalities used in India. Four hundred questionnaires were distributed amongst ophthalmologists attending different sessions of the Delhi Ophthalmological Society annual conference held in April 2007. Two hundred and three ophthalmologists responded (response rate 50.75%). The responders included 109 private practitioners, 57 consultants attached to teaching institutes and 37 residents. The majority of ophthalmologists (66.7%) claimed encountering > 5% outpatient department patients with CI. Pencil push-ups therapy (PPT) was the most common first line of treatment offered by ophthalmologists (79%) followed by synoptophore exercises (18%). Only 3% referred the patients to optometrists. Thirty per cent ophthalmologists claimed good results with PPT, which was significantly higher in private practitioners (35%). Only 26% ophthalmologists explained physiological diplopia to patients on a regular basis and reported significantly higher percentage of patients (46.3%) with good results. Only 12.3% ophthalmologists needed to refer > 30% patients for synoptophore exercises. For failure of PPT 86.7% considered lack of compliance as the major reason as perceived by ophthalmologists. This survey suggested that most ophthalmic practitioners prescribed PPT as the initial treatment for CI and had satisfactory results with PPT. The majority of the practitioners did not explain to the patient about physiological diplopia. Explaining physiological diplopia may improve outcome, as perceived from the survey.


Odour abatement in the integrated reactor concept for simultaneous treatment of liquid and solid pig manure fractions.
New technologies are needed for manure treatment that can capture nutrients, reduce emissions of ammonia and nuisance odours, and kill harmful pathogens. A reactor concept was developed for simultaneous treatment of separately collected liquid and solid fractions of pig manure. The liquid fraction is concentrated by evaporating the water using energy from the composting system and at the same time scrubbing ammonia from the composting off-gas by acidifying the urine to pH 4 with nitric acid. This results in two marketable products, a concentrated liquid nitrogen fertiliser (NH4NO3) without phosphorus, and a stabilised, solid organic fertiliser, which is free of pathogens and weeds. By connecting the two reactor systems, emissions of ammonia and odours are abated as ammonia emitted from the composting is trapped in the liquid fraction and odorous compounds emitted from the liquid are degraded in the composting reactor. The concept was physically simulated by coupling a 80-L compost reactor to a 10-L bubble column. Operation of the bench-scale system showed that the concept is very promising. All nutrients were captured, and emissions of ammonia and odours were almost completely abated.


Explaining the demand for pharmaceuticals in Spain: are there differences in drug consumption between foreigners and the Spanish population?
The aim of this study is to examine the factors driving the demand for drugs in Spain, focusing on the existence of disparities in pharmaceutical consumption between the Spanish and the foreign population. Our analysis is based on a multilevel multinomial probit model that compares three consumption options (no consumption, prescribed consumption and self-medicated consumption) on the five most consumed drugs in Spain. Data is taken from the adult sample of the 2006 Spanish National Health Survey, including 29,478 individuals over 15 years old. Overall, the findings show a lower consumption of medicines by some immigrants categories relative to Spaniards. In addition, the results indicate that the consumption of medicines is mainly related to variables associated to the specific cost sharing structure in Spain, such as health limitations and retirement status. Other variables found to explain the demand for drugs were: private health insurance, age, sex, alcohol and cigarette consumption and drug class. Further understanding of the reasons for the observed differences in drug consumption on the basis of country of birth would allow the health system to design more effective health policies aimed at ensuring equality of access to health resources to all population groups.


Are the conclusions of INTERSALT applicable to the German population?
We distinguish determinants of individual blood pressure elevations and those which influence shape and location of entire population distributions, i.e. epidemiological determinants. Individual and epidemiological determinants are not necessarily the same. Identification of the latter may be used to develop population wide prevention strategies that carry a great potential of reducing the public burden of cardiovascular morbidity and mortality. Salt has long but controversially been suspected as a major etiologic agent in hypertensive populations. For the first time the INTERSALT study tried in a systematic and standardized way to assess the salt-BP association in individuals and across 52 populations in 32 countries. The observed within center relations to systolic and more so to diastolic BP were largely inconsistent in direction and magnitude indicating probable non-uniformity of the salt effect. In this case, statistical pooling of single effect estimates may have lead to invalid conclusions. Across center analyses found no relevant relation of median sodium excretion to median BP values or hypertension prevalence and hence no evidence for salt as an epidemiologic BP determinant. It is concluded that the INTERSALT evidence is not sufficient to warrant salt restriction in the general population. This contrasts with consistent and quantitatively relevant individual and population associations of body mass index with blood pressure in INTERSALT. Considering its potentially multifactorial preventive effects, BMI reduction seems to be a more pragmatic public health measure for the German population.


Monitoring uranium, hydrogen, and lithium and their isotopes using a compact laser-induced breakdown spectroscopy (LIBS) probe and high-resolution spectrometer.
The development of field-deployable instruments to monitor radiological, nuclear, and explosive (RNE) threats is of current interest for a number of assessment needs such as the on-site screening of suspect facilities and nuclear forensics. The presence of uranium and plutonium and radiological materials can be determined through monitoring the elemental emission spectrum using relatively low-resolution spectrometers. In addition, uranium compounds, explosives, and chemicals used in nuclear fuel processing (e.g., tributyl-phosphate) can be identified by applying chemometric analysis to the laser-induced breakdown (LIBS) spectrum recorded by these spectrometers. For nuclear forensic applications, however, isotopes of U and Pu and other elements (e.g., H and Li) must also be determined, requiring higher resolution spectrometers given the small magnitude of the isotope shifts for some of these elements (e.g., 25 pm for U and 13 pm for Pu). High-resolution spectrometers will be preferred for several reasons but these must fit into realistic field-based analysis scenarios. To address the need for field instrumentation, we evaluated a previously developed field-deployable hand-held LIBS interrogation probe combined with two relatively new high-resolution spectrometers (λ/Δλ ~75,000 and ~44,000) that have the potential to meet field-based analysis needs. These spectrometers are significantly smaller and lighter in weight than those previously used for isotopic analysis and one unit can provide simultaneous wide spectral coverage and high resolution in a relatively small package. The LIBS interrogation probe was developed initially for use with low resolution compact spectrometers in a person-portable backpack LIBS instrument. Here we present the results of an evaluation of the LIBS probe combined with a high-resolution spectrometer and demonstrate rapid detection of isotopes of uranium and hydrogen and highly enriched samples of (6)Li and (7)Li.


Stigmatization toward People with Anorexia Nervosa, Bulimia Nervosa, and Binge Eating Disorder: A Scoping Review.
Research about stigmatization in eating disorders (EDs) has highlighted stereotypes, prejudices, and discrimination against people with EDs, as well as their harmful effects on them, including self-stigma and a difficult recovery process. Whereas a recent review focused on the consequences of ED stigma, our work aimed to provide a broader synthesis of ED stigma, including its consequences, but also its content and distribution. More precisely, we focused on three EDs-namely, anorexia nervosa, bulimia nervosa, and binge eating disorder. Based on a systematic search of four major databases in psychology, the present scoping review includes 46 studies published between 2004 and 2021. We did not conduct any quality assessment of the studies included, because our aim was to provide a wide-ranging overview of these topics instead of an appraisal of evidence answering a precise research question. The review confirmed the existence of a common ED stigma: all individuals affected by EDs reviewed here were perceived as responsible for their situation, and elicited negative emotions and social distance. However, our review also depicted a specific stigma content associated with each ED. In addition, the demographic characteristics of the stigmatizing individuals had a notable influence on the extent of ED stigma: men, young adults, and low-income individuals appeared to be the most stigmatizing toward individuals with EDs. It is important to note that ED stigma had a negative effect on individuals' eating disorders, psychological wellbeing, and treatment-seeking behavior. There is an urgent need for further research on the adverse effects of ED stigma and its prevention.


Functional insights into the activation mechanism of Ste20-related kinases.
Mammalian Ste20-related kinases modulate salt transport and ion homeostasis through physical interaction and phosphorylation of cation-chloride cotransporters. Identification of a sea urchin (Strongylocentrotus purpuratus) ortholog of the mouse Oxidative Stress Response 1 (OSR1) kinase prompted the cloning and testing of the functional effect of a non-mammalian kinase on a mammalian cotransporter. Heterologous expression of sea urchin OSR1 (suOSR1) cRNA with mouse WNK4 cRNA and mouse NKCC1 cRNA in Xenopus laevisoocytes activated the cotransporter indicating evolutionary conservation of the WNK4-OSR1-NKCC signaling pathway. However, expression of a suOSR1 kinase mutated to confer constitutive activity did not result in stimulation of the cotransporter. Using a chimeric strategy, we determined that both the mutated catalytic and regulatory domains of the suOSR1 kinase were functional, suggesting that the tertiary structure of full-length mutated suOSR1 must somehow adopt an inactive conformation. In order to identify the regions or residues which lock the suOSR1 kinase in an inactive conformation, we created and tested several additional chimeras by replacing specific portions of the suOSR1 gene with complimentary mouse OSR1 sequences. Co-expression of these chimeras identified several regions in both the catalytic and regulatory domain of suOSR1 which possibly prevented the kinase from acquiring an active conformation. Interestingly, non-functional suOSR1 chimeras were able to activate mouse NKCC1 when a mouse scaffolding protein, Cab39, was co-expressed in frog oocytes. Sea urchin/mouse OSR1 chimeras and kinase stabilization with mouse Cab39 has provided some novel insights into the activation mechanism of the Ste20-related kinases.


Male clients of male sex workers in West Africa: A neglected high-risk population.
Research on male clients of male sex workers (MCMSW) has been neglected for a long time globally. We aimed to characterize MCMSW and to identify factors associated with their sexual practices using data from the prospective cohort study CohMSM conducted in Burkina Faso, Côte d'Ivoire, Mali and Togo. Our study focused on HIV-negative men who have sex with other men (MSM), recruited between 06/2015 and 01/2018 by a team of trained peer educators. Scheduled study visits at 6, 12 and 18 months included medical examinations, HIV screening, risk-reduction counselling and face-to-face interviews to collect information on their sociodemographic characteristics, sexual behaviours, and HIV risk-reduction strategies (HIV-RRS). Three stigmatization sub-scores were constructed (experienced, perceived and internalized). Mixed-effects logistic regression was used for data analysis. Of the 280 participants recruited at baseline, 238, 211 and 118, respectively, had a follow-up visit at 6, 12 and 18 months. Over a total of 847 visits, 47 transactional sex (TS) encounters were reported by 38 MCMSW (13.6%). Of the latter, only one participant reported systematic TS (2.6%), 18 (47.4%) stopped reporting TS after baseline, while 6 (15.8%) reported TS after baseline. Thirteen participants (34.2%) reported occasional TS. After adjusting for country of study and age, the following self-reported factors were associated with a greater likelihood of being MCMSW: protected anal sex, exclusively insertive anal sex with male sexual partners, avoidance of sex after consuming psychoactive products and experiencing stigmatization (all during the previous 6 months). The majority of MCMSW in this study practiced HIV-RRS with male sexual partners, including engaging in protected anal sex, avoidance of sex when consuming psychoactive products, and practising exclusively insertive anal sex.


TGF-β1 Inhibits Human Trophoblast Cell Invasion by Upregulating Connective Tissue Growth Factor Expression.
Appropriate trophoblast invasion into the maternal endometrium is essential for successful human implantation and placentation. Connective tissue growth factor (CTGF), also known as CCN2, is a matricellular protein that is expressed in the placenta. Interestingly, the CTGF expression levels in the placenta and serum from patients with severe preeclampsia or fetal growth restriction are higher than those from healthy controls. However, to date, the role of CTGF in the regulation of trophoblast cell invasion remains unclear. Transforming growth factor-β1 (TGF-β1) is a potent stimulator of CTGF expression and has been shown to inhibit trophoblast cell invasiveness. However, whether CTGF mediates TGF-β1-inhibited human trophoblast cell invasion is unknown. In the present study, we show that treatment with TGF-β1 upregulates CTGF expression in a human trophoblast cell line, HTR-8/SVneo, and in primary human trophoblast cells. Our results also demonstrate that the SMAD2/3 signaling pathways are required for TGF-β1-induced upregulation of CTGF. Importantly, CTGF knockdown attenuates TGF-β1-inhibited cell invasion. Furthermore, cell invasiveness is decreased by treatment with recombinant CTGF. These results provide evidence that CTGF mediates TGF-β1-inhibited human trophoblast cell invasion.


Factors affecting employment at initiation of dialysis.
Half the individuals who reach ESRD are working age (< 65 years old) and many are at risk for job loss. Factors that contribute to job retention among working-age patients with chronic kidney disease before ESRD are unknown. The purpose of the study is to understand factors associated with maintaining employment among working-age patients with advanced kidney failure. In this retrospective study we reviewed the United States Renal Data System database (1992 through 2003) and selected all patients (n = 102,104) who were working age and employed 6 months before dialysis initiation. Factors that were examined for an association with maintaining employment status included demographics, comorbid conditions, ESRD cause, insurance, predialysis erythropoietin use, and dialysis modality. Maintaining employment at the same level during the final 6 months before dialysis was more likely among (1) white men ages 30 to 49 years; (2) patients with either glomerulonephritis, cystic, or urologic causes of renal failure; (3) patients choosing peritoneal dialysis for their first treatment; (4) those with employer group or other health plans; and (5) erythropoietin usage before ESRD. Maintaining employment status was less likely among patients with congestive heart failure, cardiovascular disease, cancer, and other chronic illnesses. The rate of unemployment in working-age patients with chronic kidney disease and ESRD is high compared with that of the general population. Treating anemia with erythropoietin before kidney failure and educating patients about work-friendly home dialysis options might improve job retention.


Curcumin protects mitochondria from oxidative damage and attenuates apoptosis in cortical neurons.
To investigate the effect of curcumin on tert-butyl hydroperoxide (t-BHP)-induced oxidative damage in rat cortical neurons and to explore the possible mechanism. Primary cultured rat cortical neurons were performed in vitro and cell viability was measured by MTT assay. DNA fragmentation was used to evaluate cell apoptosis. Intracellular reactive oxygen species (ROS) and mitochondrial membrane potential (Deltapsim) was determined by flow cytometric assay. Cellular glutathione (GSH) content was measured by spectrophotometer. Bcl-2 family proteins, cytochrome c, cleaved caspase-3, and poly (ADP-ribose) polymerase (PARP) were detected by Western blot. Exposure of tBHP 100 micromol/L to neurons for 60 min resulted in DYm loss and cytochrome c release from mitochondria and subsequent activation of caspase-3 and PARP cleavation, and cell apoptosis. After removal of tBHP and then further treatment with curcumin (2.5-20 micromol/L) for 18 h, curcumin abrogated Deltapsim loss and cytochrome c release, blocked activation of caspase 3, and altered the expression of Bcl-2 family. Further curcumin treatment also prevented cellular GSH and decreased intracellular ROS generation markedly. Curcumin eventually attenuated tBHP-induced apoptosis in cortical neurons. Curcumin may attenuate oxidative damages in cortical neurons by reducing intracellular production of ROS and protecting mitochondria from oxidative damage.


The role of prevalence in the diagnosis of prostate cancer.
The worldwide incidence of prostate cancer has been rising rapidly, likely due to intensified effort in early detection and screening. Intense effort is also directed at novel schemas of chemoprevention and therapy. Incidence data are insufficient to identify the true magnitude of prostate cancer in a given population. The true prevalence of prostate cancer must be identified. We reviewed the latest worldwide epidemiologic data and clinical studies on prostate cancer studying the true prevalence of this disease. The incidence of prostate cancer is increasing worldwide, with strong variation among regions. Prevalence studies based on autopsy data have confirmed a high frequency of latent prostate cancer in men of all ages. More aggressive screening measures using a lower prostate-specific antigen (PSA) threshold, together with an increasing number of biopsies, have escalated the detection of these latent cancers. Recent improvements in prostate cancer detection narrow the gap between the incidence and true prevalence of prostate cancer. This, however, raises concerns about the risk of over detection of latent cancers and thus identifying a need for improvement in screening strategies to better identify clinically significant disease.


Evaluation of Midterm Clinical and Radiographic Outcomes of Arthroscopically Repaired Vertical Longitudinal and Bucket-Handle Lateral Meniscal Tears.
Lateral meniscal tears in the stable knee are rare. There are few comparative studies evaluating functional and radiological outcomes of vertical longitudinal and bucket-handle lateral meniscal tears. To evaluate the midterm clinical and radiological outcomes of arthroscopically repaired traumatic vertical longitudinal and bucket-handle lateral meniscal tears. Case series; Level of evidence, 4. A total of 43 full-thickness lateral meniscal repairs, including 22 (51.2%) for vertical longitudinal tears and 21 (48.8%) for bucket-handle tears, were evaluated. A clinical assessment was performed according to the Barrett criteria, and patient outcomes were measured with the Lysholm knee score, Tegner activity scale, and overall satisfaction scale. Magnetic resonance imaging was used as the radiological re-examination method preoperatively and at final follow-up. A subgroup analysis examining isolated repair versus repair with concurrent anterior cruciate ligament (ACL) reconstruction was performed. The mean follow-up period was 63.2 months (range, 24-86 months). Based on clinical and radiological outcomes, 38 of the 43 repairs (88.3%) were successful, and the remaining 5 (11.6%) cases were considered to be failures. Overall, the combined results for both groups demonstrated an improvement in the Lysholm score, Tegner score, and patient satisfaction. There was no significant difference in the postoperative Lysholm score (91.4 vs 87.0, respectively; P = .223), Tegner score (5.4 vs 5.5, respectively; P = .872), or patient satisfaction (7.2 vs 7.4, respectively; P = .624) between bucket-handle repair and vertical longitudinal repair. The subgroup analysis demonstrated no difference in outcome scores for isolated repair versus repair with concurrent ACL reconstruction. Smoking was identified as a risk factor for repair failure. Comparable clinical and radiological outcomes were obtained after vertical longitudinal and bucket-handle lateral meniscal repairs using the all-inside or hybrid suture technique with different suture configurations, regardless of whether ACL reconstruction was performed. Smoking was identified as a risk factor for failure.


Latinos' Access to Online and Formal Mental Health Support.
Research on mental health services disparities affecting minority populations of the USA tends to neglect online mental health support (OMHS). The main objective of this study was to investigate online mental health support and help-seeking of Latino citizens living in US communities by estimating associations linking OMHS with a selection of individual and community variables. In addition, the extent to which unmet mental health treatment needs among adults are associated with key variables was examined. Variables of interest included economic resources, health insurance and coverage, confidentiality, perceived stigma, and accessibility. Data are from 39,630 Latino adult participants in the National Surveys on Drug Use and Health (NSDUH), 2004-2010. Results indicate that for every 10,000 US Latino adults, fewer than 25 individuals received recent OMHS, as compared to a recently published estimate of 270-330 per 10,000 for the US population generally. Among Latinos with self-described unmet mental health needs, an estimated 40% identified cost of treatment as a prominent barrier that explained why they had not received formal mental health treatment services. Research and policy health disparities implications are discussed.


Hyaluronan-CD44 interactions as potential targets for cancer therapy.
It is becoming increasingly clear that signals generated in tumor microenvironments are crucial to tumor cell behavior, such as survival, progression and metastasis. The establishment of these malignant behaviors requires that tumor cells acquire novel adhesion and migration properties to detach from their original sites and to localize to distant organs. CD44, an adhesion/homing molecule, is a major receptor for the glycosaminoglycan hyaluronan, which is one of the major components of the tumor extracellular matrix. CD44, a multistructural and multifunctional molecule, detects changes in extracellular matrix components, and thus is well positioned to provide appropriate responses to changes in the microenvironment, i.e. engagement in cell-cell and cell-extracellular matrix interactions, cell trafficking, lymph node homing and the presentation of growth factors/cytokines/chemokines to co-ordinate signaling events that enable the cell responses that change in the tissue environment. The potential involvement of CD44 variants (CD44v), especially CD44v4-v7 and CD44v6-v9, in tumor progression has been confirmed for many tumor types in numerous clinical studies. The downregulation of the standard CD44 isoform (CD44s) in colon cancer is postulated to result in increased tumorigenicity. CD44v-specific functions could be caused by their higher binding affinity than CD44s for hyaluronan. Alternatively, CD44v-specific functions could be caused by differences in associating molecules, which may bind selectively to the CD44v exon. This minireview summarizes how the interaction between hyaluronan and CD44v can serve as a potential target for cancer therapy, in particular how silencing CD44v can target multiple metastatic tumors.


Circulatory changes during spontaneous motor activity: role of arterial baroreflexes.
Systemic arterial pressure (SAP) and heart rate (HR) were continuously measured in rabbits during spontaneous motor activity such as postural change, exploration, grooming, and eating, and during interposed periods of inactivity within which SAP and HR were defined as basal. Six rabbits were observed for 2 h under each of 3 conditions of arterial baroreceptor afferents: all intact (B4); one carotid sinus intact (B1); all interrupted (B0). In B4, SAP and HR were above basal levels 82% of the time; in B1, 64% and 76% of the time, respectively; in B0, only 21% and 28% of the time, respectively. Supplementary experiments in another six rabbits established that the activity-associated falls of SAP in condition B0 were independent of HR, were not due to engagement of cardiac receptor reflexes, and were not abolished by autonomic ganglion blockade. We conclude that the transient rises of SAP and HR that occur during everyday activity are associated with partial or complete suppression of the reflex effects of arterial baroreceptor input, and we suggest that this is due to transient upward resetting of the arterial baroreflex.


Translational Chemistry Meets Gluten-Related Disorders.
Gluten-related disorders are a complex group of diseases that involve the activation of the immune system triggered by the ingestion of gluten. Among these, celiac disease, with a prevalence of 1 %, is the most investigated, but recently, a new pathology, named nonceliac gluten sensitivity, was reported with a general prevalence of 7 %. Finally, there other less-prevalent gluten-related diseases such as wheat allergy, gluten ataxia, and dermatitis herpetiformis (with an overall prevalence of less than 0.1 %). As mentioned, the common molecular trigger is gluten, a complex mixture of storage proteins present in wheat, barley, and a variety of oats that are not fully degraded by humans. The most-studied protein related to disease is gliadin, present in wheat, which possesses in its sequence many pathological fragments. Despite a lot of effort to treat these disorders, the only effective method is a long-life gluten-free diet. This Review summarizes the actual knowledge of gluten-related disorders from a translational chemistry point of view. We discuss what is currently known from the literature about the interaction of gluten with the gut and the critical host responses it evokes and, finally, connect them to our current and novel molecular understanding of the supramolecular organization of gliadin and the 33-mer gliadin peptide fragment under physiological conditions.


Clinical value of serum glycoprotein galactosyltransferase levels in different histological types of ovarian carcinoma.
Serum glycoprotein galactosyltransferase levels were determined in 28 healthy women and 113 patients with ovarian carcinoma with various histological types, at different clinical stages. Ovomucoid, which possesses terminal N-acetylglucosaminyl residues, was used as glycoprotein acceptor. Clinical correlations between galactosyltransferase levels and tumor burden were examined, as well as the variations due to histology. Follow-up studies could be done for 60 patients, and correlations with clinical evolution, established. Galactosyltransferase might be a promising marker for the diagnosis and follow-up of ovarian carcinomas.


Satisfaction with food-related life and life satisfaction: a triadic analysis in dual-earner families.
This study explored the spillover and crossover associations between satisfaction with food-related life and life satisfaction in mothers, fathers and adolescent children in dual-earned families. This is a cross-sectional design study with mothers, fathers and children surveyed in Temuco, Chile. The participants were 303 dual-earner parents and their adolescent children (mean age 13.3 years, 51.5% female). Actor-partner Interdependence Model (APIM) and structural equation modeling were used to explore spillover (actor effect) and crossover (partner effect) associations among family members. As a result, fathers' satisfaction with food-related life was positively associated with their own life satisfaction (p ≤ 0.01), as well as with their partner's (mother's) satisfaction with life (p ≤ 0.05), but not with their adolescent child's life satisfaction (p > 0.1). Mothers and children presented positive spillovers between their own levels of satisfaction with food-related life and life satisfaction (p ≤ 0.01). No crossover effects were found between mothers and children (p > 0.1). This study results underscore the positive association between satisfaction with food-related life and life satisfaction among members of dual-earner families with adolescent children. Special efforts should be made by dual-earner parents to improve the variables related to their satisfaction with food-related life as well as their children's satisfaction.


Collective behavior of networks with linear (VLSI) integrate-and-fire neurons.
We analyze in detail the statistical properties of the spike emission process of a canonical integrate-and-fire neuron, with a linear integrator and a lower bound for the depolarization, as often used in VLSI implementations (Mead, 1989). The spike statistics of such neurons appear to be qualitatively similar to conventional (exponential) integrate-and-fire neurons, which exhibit a wide variety of characteristics observed in cortical recordings. We also show that, contrary to current opinion, the dynamics of a network composed of such neurons has two stable fixed points, even in the purely excitatory network, corresponding to two different states of reverberating activity. The analytical results are compared with numerical simulations and are found to be in good agreement.


Learning to integrate versus inhibiting information is modulated by age.
Cognitive training aiming at improving learning is often successful, but what exactly underlies the observed improvements and how these differ across the age spectrum are currently unknown. Here we asked whether learning in young and older people may reflect enhanced ability to integrate information required to perform a cognitive task or whether it may instead reflect the ability to inhibit task-irrelevant information for successful task performance. We trained 30 young and 30 aging human participants on a numerosity discrimination task known to engage the parietal cortex and in which cue-integration and inhibitory abilities can be distinguished. We coupled training with parietal, motor, or sham transcranial random noise stimulation, known for modulating neural activity. Numerosity discrimination improved after training and was maintained long term, especially in the training + parietal stimulation group, regardless of age. Despite the quantitatively similar improvement in the two age groups, the content of learning differed remarkably: aging participants improved more in inhibitory abilities, whereas younger subjects improved in cue-integration abilities. Moreover, differences in the content of learning were reflected in different transfer effects to untrained but related abilities: in the younger group, improvements in cue integration paralleled improvements in continuous quantity (time and space), whereas in the elderly group, improvements in numerosity-based inhibitory abilities generalized to other measures of inhibition and corresponded to a decline in space discrimination, possibly because conflicting learning resources are used in numerosity and continuous quantity processing. These results indicate that training can enhance different, age-dependent cognitive processes and highlight the importance of identifying the exact processes underlying learning for effective training programs.


The nicotinic acetylcholine receptor alpha5 subunit plays a key role in attention circuitry and accuracy.
Stimulation of the prefrontal cortex by acetylcholine is critical for attention; however, the cellular mechanisms underlying its influence on attention pathways within the brain are not well understood. Pyramidal neurons in layer VI of the prefrontal cortex are believed to play an important role in this process because they are excited by acetylcholine and provide a major source of feedback projections to the thalamus. Here, we show using whole-cell electrophysiology that the relatively rare alpha5 subunit of the nicotinic acetylcholine receptor powerfully enhances nicotinic currents in layer VI pyramidal neurons in prefrontal cortical brain slices from adult mice. In addition, behavioral experiments using the five-choice serial reaction time test show that the presence of the nicotinic receptor alpha5 subunit also increases the accuracy of adult mice on this visual attention task under highly demanding conditions. Together, these findings demonstrate a novel and important role for the nicotinic receptor alpha5 subunit in adult brain circuitry required for attentional performance.


Targeting TGF-β Signaling in Cancer.
The transforming growth factor (TGF)-β signaling pathway is deregulated in many diseases, including cancer. In healthy cells and early-stage cancer cells, this pathway has tumor-suppressor functions, including cell-cycle arrest and apoptosis. However, its activation in late-stage cancer can promote tumorigenesis, including metastasis and chemoresistance. The dual function and pleiotropic nature of TGF-β signaling make it a challenging target and imply the need for careful therapeutic dosing of TGF-β drugs and patient selection. We review here the rationale for targeting TGF-β signaling in cancer and summarize the clinical status of pharmacological inhibitors. We discuss the direct effects of TGF-β signaling blockade on tumor and stromal cells, as well as biomarkers that can predict the efficacy of TGF-β inhibitors in cancer patients.


[Ultrastructure and electron-histochemical properties of the glandular endometrial epithelium in women].
Ultrastructural and ultracytochemical characteristics of glandular epithelium of endometrium in 10 women with two-phase cycle were studied. Secretory transformation of glandular epithelium at ultrastructural level is manifested by deposits of glycogen in cytoplasm, giant mitochondria, hypertrophic Golgi complex and nuclear channel system. In organ endometrial cultures formation of the nuclear channel system at the stage of proliferation is induced by progesterone. Localization of ribonucleoproteins and activity of nucleoside phosphatases (ATPase and 5'-nucleotidase) in the nuclei and the channel system is described. Ultrastructural and ultracytochemical data permit to exclude nucleolar origin of the nucleolar channel system.


Hydrodynamic trapping of Tetrahymena thermophila for the long-term monitoring of cell behaviors.
Microfluidic trapping technology has been widely applied for single-cell observation in order to reveal characteristic cell behaviors. However, this strategy has yet to be tested for monitoring highly motile cells, which are often biologically important. In this paper, we seek the conditions that enable effective and long-term trapping of a prominent model ciliate Tetrahymena thermophila within a hydrodynamic microfluidic device. Although motility and flexibility of T. thermophila make it difficult to avoid escaping from the trap, we show that tuning some key parameters in the hydrodynamic circuit was effective to achieve approximately 40 h cell retention, which is long enough to monitor cell behaviors over several generations. Here, we demonstrate the real-time observation of cell division and phagocytic digestion, revealing interesting phenomena such as a wide distribution in doubling time in a poor synthetic medium and heterogeneous time courses in digestion processes. Our results present a strategy for trapping highly motile ciliate cells in order to study the dynamic behaviors of single cells.


Involvement of Pex13p in Pex14p localization and peroxisomal targeting signal 2-dependent protein import into peroxisomes.
Pex13p is the putative docking protein for peroxisomal targeting signal 1 (PTS1)-dependent protein import into peroxisomes. Pex14p interacts with both the PTS1- and PTS2-receptor and may represent the point of convergence of the PTS1- and PTS2-dependent protein import pathways. We report the involvement of Pex13p in peroxisomal import of PTS2-containing proteins. Like Pex14p, Pex13p not only interacts with the PTS1-receptor Pex5p, but also with the PTS2-receptor Pex7p; however, this association may be direct or indirect. In support of distinct peroxisomal binding sites for Pex7p, the Pex7p/Pex13p and Pex7p/ Pex14p complexes can form independently. Genetic evidence for the interaction of Pex7p and Pex13p is provided by the observation that overexpression of Pex13p suppresses a loss of function mutant of Pex7p. Accordingly, we conclude that Pex7p and Pex13p functionally interact during PTS2-dependent protein import into peroxisomes. NH2-terminal regions of Pex13p are required for its interaction with the PTS2-receptor while the COOH-terminal SH3 domain alone is sufficient to mediate its interaction with the PTS1-receptor. Reinvestigation of the topology revealed both termini of Pex13p to be oriented towards the cytosol. We also found Pex13p to be required for peroxisomal association of Pex14p, yet the SH3 domain of Pex13p may not provide the only binding site for Pex14p at the peroxisomal membrane.


[An autopsy case of multiple system atrophy with many Lewy bodies--striatonigral degeneration, olivo-ponto-cerebellar atrophy and autonomic nerve nucleus involvement in the spinal cord].
A 72 years old man developed slowness of the motion and orthostatic hypotension at the age of 69. Neurological examination showed slight finger tremor, rigidity of extremities, bradykinesia, and marked orthostatic hypotension. The illness progressed steadily and the patient died of pneumonia. At autopsy brain weighed 1220 g. Grossly the putamen was bilaterally shrunken, the color of the substantia nigra and locus ceruleus became pale. Base of the pons and the cerebellum were atrophic. Microscopically the most remarkable change was seen in the striato-nigral system. In the putamen, there were severe loss of small neurons and intense gliosis and brownish pigments were observed in the neuropil and within some of the astrocytes. There found neuronal loss and gliosis in the substantia nigra. A few Lewy bodies were seen in the substantia nigra. In the cerebellum there were slight loss of Purkinje cell and many torpedos were seen. There were demyelination and fibrirally gliosis in the cerebellar white matter except the hilus of dentate nucleus. The transverse pontocerebellar fibers were degenerated and fibrirally gliosis was seen there. The inferior olivary nuclei showed neuronal loss and astrocytosis. But the degeneration of the olivo-ponto-cerebellar system in this case was not so severe as the typical case of OPCA. In the spinal cord there was depletion of nerve cells in the intermediolateral nuclei and Onufrowitz nuclei. Slight neuronal loss and many spheroids were observed in the anterior horns and there was demyelination in the corticospinal tracts.(ABSTRACT TRUNCATED AT 250 WORDS)


Pharmaceutical Perspectives of Spices and Condiments as Alternative Antimicrobial Remedy.
Medicinal values of spices and condiments are being revived by biologists through in vitro and in vivo trials providing evidence for its antimicrobial activities. The essential oils and extracts of spices like black pepper, cloves, cinnamon, and nutmeg contain active compounds like piperine, eugenol, cinnamaldehyde, and lignans. Similarly, condiments like coriander, black cumin, turmeric, garlic, and ginger are recognized for constituents like linalool, thymoquinones, curcumin, allicin, and geranial respectively. These act as natural preventive components of several diseases and represent as antioxidants in body cells. Scientists have to investigate the biochemical nature, mode of action, and minimum concentration of administrating active ingredients effectively. This review reports findings of recent research carried out across South Asia and Middle East countries where spices and condiments form chief flavoring components of traditional foods. It narrates the history, myths, and facts people believe in these regions. There may not be scientific explanation but has evidence of cure for centuries.


[Cleavage of synthetic RNA-DNA hybrids with restriction endonucleases BamH1 and Sau3A].
Synthetic oligodeoxyribonucleotides, containing one or two ribonucleotides in the recognition sequence, and RNA--DNA hybrids were tested for their activity in cleavage with BamH1 and Sau3A endonucleases. The replacement of dG with G in the first position of BamH1-site (GGATCC) of one of the chains does not affect the rate of the BamH1 hydrolysis. The similar heteroduplex, containing G residue in the second position, displays a decreased rate of the BamH1 hydrolysis of the modified strand and, to a lesser extent, of the unmodified complementary strand. Oligodeoxyribonucleotides in complex with oligoribonucleotides can be cleaved with the excess of BamH1 and Sau3A, oligoribonucleotides remaining intact.


Bisphosphonate-Functionalized Hydroxyapatite Nanoparticles for the Delivery of the Bromodomain Inhibitor JQ1 in the Treatment of Osteosarcoma.
Osteosarcoma (OS) is one of the most common neoplasia among children, and its survival statistics have been stagnating since the combinatorial anticancer therapy triad was first introduced. Here, we report on the assessment of the effect of hydroxyapatite (HAp) nanoparticles loaded with medronate, the simplest bisphosphonate, as a bone-targeting agent and JQ1, a small-molecule bromodomain inhibitor, as a chemotherapeutic in different 2D and 3D K7M2 OS in vitro models. Both additives decreased the crystallinity of HAp, but the effect was more intense for medronate because of its higher affinity for HAp. As the result of PO43--NH+ binding, JQ1 shielded the surface phosphates of HAp and pushed its surface charge to more positive values, exhibiting the opposite effect from calcium-blocking medronate. In contrast to the faster and more exponential release of JQ1 from monetite, its release from HAp nanoparticles followed a zero-order kinetics, but 98% of the payload was released after 48 h. The apoptotic effect of HAp nanoparticles loaded with JQ1, with medronate and with both JQ1 and medronate, was selective in 2D culture: pronounced against the OS cells and nonexistent against the healthy fibroblasts. While OS cell invasion was significantly inhibited by all of the JQ1-containing HAp formulations, that is, with and without medronate, all of the combinations of the targeting compound, medronate, and the chemotherapeutic, JQ1, delivered using HAp, but not HAp alone, inhibited OS cell migration from the tumor spheroids. JQ1 delivered using HAp had an effect on tumor migration, invasion, and apoptosis even at extremely low, subnanomolar concentrations, at which no effect of JQ1 per se was observed, meaning that this form of delivery could help achieve a multifold increase of this drug's efficacy. More than 80% of OS cells internalized JQ1-loaded HAp nanoparticles after 24 h of coincubation, suggesting that this augmentation of the activity of JQ1 may be due to the intracellular delivery and sustained release of the drug enabled by HAp. In addition to the reduction of the OS cell viability, the reduction of the migration and invasion radii was observed in OS tumor spheroids challenged with even JQ1-free medronate-functionalized HAp nanoparticles, demonstrating a definite anticancer activity of medronate alone when combined with HAp. The effect of medronate-functionalized JQ1-loaded HAp nanoparticles was most noticeable against OS cells differentiated into an osteoblastic lineage, in which case they surpassed in effect pure JQ1 and medronate-free compositions. The activity of JQ1 was mediated through increased Ezrin expression and decreased RUNX2 expression and was MYC and FOSL1 independent, but these patterns of gene expression changed in cells challenged with the nanoparticulate form of delivery, having been accompanied by the upregulation of RUNX2 and downregulation of Ezrin in OS cells treated with medronate-functionalized JQ1-loaded HAp nanoparticles.


Homeless women and children's access to health care: a paradox.
Homeless women and children who reside in shelters experience many health-related problems. The aim of the qualitative study reported here was to (a) explore how shelter staffs manage health problems among their residents and assist them in accessing health services, and (b) identify clinical strategies for community health nurses working with this population. Findings demonstrate a paradox whereby homeless shelter staffs try to gain access to care for their residents through a system that is designed to keep them out. In addition, findings indicate a need for increased community health nursing services in homeless shelters. Strategies for resolving this paradox include providing assessment, policy development, and assurance of health care for homeless women and children.


Deep learning for early warning signals of tipping points.
Many natural systems exhibit tipping points where slowly changing environmental conditions spark a sudden shift to a new and sometimes very different state. As the tipping point is approached, the dynamics of complex and varied systems simplify down to a limited number of possible "normal forms" that determine qualitative aspects of the new state that lies beyond the tipping point, such as whether it will oscillate or be stable. In several of those forms, indicators like increasing lag-1 autocorrelation and variance provide generic early warning signals (EWS) of the tipping point by detecting how dynamics slow down near the transition. But they do not predict the nature of the new state. Here we develop a deep learning algorithm that provides EWS in systems it was not explicitly trained on, by exploiting information about normal forms and scaling behavior of dynamics near tipping points that are common to many dynamical systems. The algorithm provides EWS in 268 empirical and model time series from ecology, thermoacoustics, climatology, and epidemiology with much greater sensitivity and specificity than generic EWS. It can also predict the normal form that characterizes the oncoming tipping point, thus providing qualitative information on certain aspects of the new state. Such approaches can help humans better prepare for, or avoid, undesirable state transitions. The algorithm also illustrates how a universe of possible models can be mined to recognize naturally occurring tipping points.


Human cholesterol 7alpha-hydroxylase (CYP7A1) deficiency has a hypercholesterolemic phenotype.
Bile acid synthesis plays a critical role in the maintenance of mammalian cholesterol homeostasis. The CYP7A1 gene encodes the enzyme cholesterol 7alpha-hydroxylase, which catalyzes the initial step in cholesterol catabolism and bile acid synthesis. We report here a new metabolic disorder presenting with hyperlipidemia caused by a homozygous deletion mutation in CYP7A1. The mutation leads to a frameshift (L413fsX414) that results in loss of the active site and enzyme function. High levels of LDL cholesterol were seen in three homozygous subjects. Analysis of a liver biopsy and stool from one of these subjects revealed double the normal hepatic cholesterol content, a markedly deficient rate of bile acid excretion, and evidence for upregulation of the alternative bile acid pathway. Two male subjects studied had hypertriglyceridemia and premature gallstone disease, and their LDL cholesterol levels were noticeably resistant to 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors. One subject also had premature coronary and peripheral vascular disease. Study of the kindred, which is of English and Celtic background, revealed that individuals heterozygous for the mutation are also hyperlipidemic, indicating that this is a codominant disorder.


The remedial effect of Thymus vulgaris extract against lead toxicity-induced oxidative stress, hepatorenal damage, immunosuppression, and hematological disorders in rats.
The Thymus vulgaris (T. vulgaris) has been used in foods for the flavor, aroma, and preservation and in folk medicines. The objective of the present work was to determine the antioxidant and protective effects of T. vulgaris extract against lead (Pb)-intoxicated rats. A thirty-two male Sprague-Dawley were randomly assigned into 4 equal groups and treated for six weeks as follows: group I (GP-I), served as negative control; GP-II, -III, and -IV received either Pb acetate in drinking water (500 mg/L), T. vulgaris extract (500 mg/kg/day) by oral gavage or Pb acetate with T. vulgaris extract, respectively. Blood samples were collected at the end of the study week 6 to measure the hepatic and renal biochemical markers, complete blood count alongside the serum levels of interleukin (IL)-1β, IL-6, IL-10, tumor necrosis (TNF)-α, and interferon (IFN)-γ. Additionally, liver and kidney tissue specimens were collected for histopathology as well as to measure the antioxidant-reduced glutathione (GSH), glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD) alongside the lipid peroxidation marker, malonaldehyde (MDA). The results indicated that Pb toxicity increased the serum levels of IL-1β, IL-6, and TNF-α, whereas IL-10 and IFN-γ were reduced. The results showed disturbed liver and renal functions; increased serum levels of ALT, AST, ALP, total bilirubin, creatinine, and urea; and decreased total protein, albumin, and calcium. The GSH, Gpx, and CAT levels were significantly decreased in the Pb-administrated group, while MDA was increased. However, regarding the hepatorenal markers, those animals treated with T. vulgaris alone did not induce any significant changes. Moreover, the combined treatment with T. vulgaris extract together with Pb showed significant improvement in Pb-induced toxicity in all the tested parameters compared to the negative control group. We investigated the potential protective effects of the medicinal plant T. vulgaris in vivo, since there are no publications that address the potential protective effect of this leaf extract against Pb-induced hepatorenal toxicity. Our studies concluded that the T. vulgaris extract reduces Pb overload in hepatorenal tissues, and that this has a potential immunomodulatory role, antioxidant activity, and a protective effect against Pb toxicity.


Sleep Disorders in Parkinsonian and Nonparkinsonian LRRK2 Mutation Carriers.
In idiopathic Parkinson disease (IPD) sleep disorders are common and may antedate the onset of parkinsonism. Based on the clinical similarities between IPD and Parkinson disease associated with LRRK2 gene mutations (LRRK2-PD), we aimed to characterize sleep in parkinsonian and nonmanifesting LRRK2 mutation carriers (NMC). A comprehensive interview conducted by sleep specialists, validated sleep scales and questionnaires, and video-polysomnography followed by multiple sleep latency test (MSLT) assessed sleep in 18 LRRK2-PD (17 carrying G2019S and one R1441G mutations), 17 NMC (11 G2019S, three R1441G, three R1441C), 14 non-manifesting non-carriers (NMNC) and 19 unrelated IPD. Sleep complaints were frequent in LRRK2-PD patients; 78% reported poor sleep quality, 33% sleep onset insomnia, 56% sleep fragmentation and 39% early awakening. Sleep onset insomnia correlated with depressive symptoms and poor sleep quality. In LRRK2-PD, excessive daytime sleepiness (EDS) was a complaint in 33% patients and short sleep latencies on the MSLT, which are indicative of objective EDS, were found in 71%. Sleep attacks occurred in three LRRK2-PD patients and a narcoleptic phenotype was not observed. REM sleep behavior disorder (RBD) was diagnosed in three LRRK2-PD. EDS and RBD were always reported to start after the onset of parkinsonism in LRRK2-PD. In NMC, EDS was rarely reported and RBD was absent. When compared to IPD, sleep onset insomnia was more significantly frequent, EDS was similar, and RBD was less significantly frequent and less severe in LRRK2-PD. In NMC, RBD was not detected and sleep complaints were much less frequent than in LRRK2-PD. No differences were observed in sleep between NMC and NMNC. Sleep complaints are frequent in LRRK2-PDand show a pattern that when compared to IPD is characterized by more frequent sleep onset insomnia, similar EDS and less prominent RBD. Unlike in IPD, RBD and EDS seem to be not markers of the prodromal stage of LRRK2-PD.


Clinical pharmacology of the ACE inhibitors.
The central role of the renin-angiotensin-aldosterone system in the regulation of fluid balance and haemodynamics was not fully appreciated until the discovery and clinical application of inhibitors of the angiotensin-converting enzyme (ACE). Captopril, the first orally active compound has proved to be highly effective in mild, intermediate and severe hypertension and in congestive heart failure. This is also true for enalapril, the first of the second generation (non-sulfhydryl) of ACE inhibitors. Both compounds combine a high degree of clinical efficacy with a low rate of side effects, and both are eliminated via renal excretion. Thus, reduced doses are required in renal failure. Captopril has a shorter half-life and requires more frequent dosing than enalapril. Whether long-acting ACE inhibitors carry distinct advantages or disadvantages compared with short-acting ones is not clear, but both possibilities must be considered. Among many new ACE inhibitors being developed, compounds eliminated via hepatic routes, such as fosfenopril and zofenopril, may prove advantageous in renal failure. Very long-acting ones, such as lisinopril, a potent ACE inhibitor already shown to be clinically effective, may add value to this group of therapeutic agents. Drug compliance may be easily tested by measuring ACE activity in serum from patients treated with stable ACE inhibitors, such as enalapril and lisinopril, which is an obvious advantage compared with other antihypertensive compounds. The presence of ACE in sites not associated with regulation of fluid balance or blood pressure, such as macrophages and reproductive organs, and the possibility that new functions of ACE may be discovered, call for vigilance regarding possible long term side effects of ACE inhibitors.


Low infant mortality among Palestine refugees despite the odds.
To present data from a 2008 infant mortality survey conducted in Jordan, Lebanon, the Syrian Arab Republic, the Gaza Strip and the West Bank and analyse infant mortality trends among Palestine refugees in 1995-2005. Following the preceding birth technique, mothers who were registering a new birth were asked if the preceding child was alive or dead, the day the child was born and the date of birth of the neonate whose birth was being registered. From this information, neonatal, infant and early child mortality rates were estimated. The age at death for early child mortality was determined by the mean interval between successive births and the mean age of neonates at registration. In 2005-2006, infant mortality among Palestine refugees ranged from 28 deaths per 100 000 live births in the Syrian Arab Republic to 19 in Lebanon. Thus, infant mortality in Palestine refugees is among the lowest in the Near East. However, infant mortality has stopped decreasing in recent years, although it remains at a level compatible with the attainment of Millennium Development Goal 4. Largely owing to the primary health care provided by the United Nations Relief and Works Agency (UNRWA) for Palestine Refugees in the Near East and other entities, infant mortality among Palestine refugees had consistently decreased. However, it is no longer dropping. Measures to address the most likely reasons - early marriage and childbearing, poor socioeconomic conditions and limited access to good perinatal care - are needed.


Insights Into Veterans' Perspectives on a Peer Support Program for Glycemic Management.
The purpose of this study was to explore the mentor-mentee relationship in veterans with type 2 diabetes and gain insight into successful pairings. Qualitative semistructured interviews were conducted as part of a peer mentoring randomized controlled trial to understand participants' experiences, their relationship with their partner, and how the intervention affected self-care behaviors. Purposive sampling was done to ensure adequate representation of mentees who made large strides in reaching their glycemic targets, those who made marginal improvements toward their glycemic goals, and those who got worse. All interviews were audio-recorded, transcribed, and analyzed for salient themes. The intervention was well received, with most participants describing it as valuable. Participants perceived the intervention to have a number of benefits, including accessible support, enhanced self-confidence, increased accountability, better self-efficacy, improved glycemic management, and a fulfilled sense of altruism. Participants did encounter barriers, including logistical, interpersonal, and individual obstacles. The more successful mentees tended to be more effusive in their description of their mentors, endorsed a stronger sense of connection to their mentor, described a more structured interaction with their mentor, and tended to be more complimentary of the intervention. Large peer support programs are appealing and well received. These programs can be optimized by selecting naturally inclined mentors, providing additional training to introduce more structure into mentorship interactions, and targeting mentees who are not struggling with overwhelming comorbidities.


The proper timing of Atoh1 expression is pivotal for hair cell subtype differentiation and the establishment of inner ear function.
Atoh1 overexpression is essential for hair cell (HC) regeneration in the sensory epithelium of mammalian auditory and vestibular organs. However, Atoh1 overexpression alone cannot induce fully mature and functional HCs in the mammalian inner ear. In the current study, we investigated the effect of Atoh1 constitutive overexpression in native HCs by manipulating Atoh1 expression at different developmental stages. We demonstrated that constitutive overexpression of Atoh1 in native vestibular HCs did not affect cell survival but did impair vestibular function by interfering with the subtype differentiation of HCs and hair bundle development. In contrast, Atoh1 overexpression in cochlear HCs impeded their maturation, eventually leading to gradual HC loss in the cochlea and hearing dysfunction. Our study suggests that time-restricted Atoh1 expression is essential for the differentiation and survival of HCs in the inner ear, and this is pivotal for both hearing and vestibular function re-establishment through Atoh1 overexpression-induced HC regeneration strategies.


Should we blame the rich for clogging our landfills?
Conventional wisdom often holds that relatively high consumption levels among the affluent contributes to the generation of high volumes of municipal solid waste (MSW). Comparing data from different cities in Israel suggests otherwise. Regression analysis reveals that aggregate per capita waste outputs of cities are only vaguely correlated with their socio-economic indicators. In fact, the apparent 'hedonic' waste of the richest cities, compared with the average ones, accounts for only about 2% of the total waste production. Israel's main economic area, the Tel Aviv district, produces a quarter more MSW per capita than other districts, suggesting a need for special attention by policy makers. A surprisingly strong predicator of MSW per capita is water consumption by municipalities, dedicated for public gardening. The trimmings of the municipal landscape constituting an unobserved fraction of total MSW data, are estimated to be responsible for 15% of Israel's MSW, making it an additional target area for consideration and intervention.


Integrated approach to malaria control.
Malaria draws global attention in a cyclic manner, with interest and associated financing waxing and waning according to political and humanitarian concerns. Currently we are on an upswing, which should be carefully developed. Malaria parasites have been eliminated from Europe and North America through the use of residual insecticides and manipulation of environmental and ecological characteristics; however, in many tropical and some temperate areas the incidence of disease is increasing dramatically. Much of this increase results from a breakdown of effective control methods developed and implemented in the 1960s, but it has also occurred because of a lack of trained scientists and control specialists who live and work in the areas of endemic infection. Add to this the widespread resistance to the most effective antimalarial drug, chloroquine, developing resistance to other first-line drugs such as sulfadoxine-pyrimethamine, and resistance of certain vector species of mosquito to some of the previously effective insecticides and we have a crisis situation. Vaccine research has proceeded for over 30 years, but as yet there is no effective product, although research continues in many promising areas. A global strategy for malaria control has been accepted, but there are critics who suggest that the single strategy cannot confront the wide range of conditions in which malaria exists and that reliance on chemotherapy without proper control of drug usage and diagnosis will select for drug resistant parasites, thus exacerbating the problem. An integrated approach to control using vector control strategies based on the biology of the mosquito, the epidemiology of the parasite, and human behavior patterns is needed to prevent continued upsurge in malaria in the endemic areas.


Soft-tissue sarcomas: Overview of management, with a focus on surgical treatment considerations.
Patients with soft-tissue sarcomas generally present with a mass that is increasing in size; the presence or absence of pain is not typically predictive of malignancy. While magnetic resonance imaging (MRI) can identify a few soft-tissue lesion types as benign, diagnosis of most lesions requires a careful biopsy, preferably performed by or in consultation with the surgeon who would do an eventual resection. If biopsy confirms a diagnosis of sarcoma, MRI-guided surgical resection with a wide margin is the mainstay of treatment. Neoadjuvant radiation therapy and chemotherapy have not been of proven benefit in well-controlled studies but are frequently used as adjuncts. Resections with wide margins are generally associated with a low (< 10%) risk of recurrence.


Different effects of soluble and aggregated amyloid β42 on gene/protein expression and enzyme activity involved in insulin and APP pathways.
Although Alzheimer's dementia (AD) is not characterised any longer simply as the accumulation and deposition of amyloid beta (Aβ) peptides and hyperphosphorylation of tau proteins within the brain, excessive Aβ(42) deposition is still considered to play a major role in this illness. Aβ are able to adopt many differently aggregate forms, including amyloid fibrils as well as nonfibrillar structures (soluble Aβ(42) oligomers). It is not well-established that which Aβ(42) state is most responsible for AD or why. We wanted to verify which effects Aβ(42) oligomers and aggregated peptides have on gene expression, protein level and enzyme activity of insulin and amyloid precursor protein (APP) pathways in vitro. Human neuroblastoma cells (SH-SY5Y) were treated with varying concentrations of soluble and aggregated Aβ(42). Treatment effects on β-secretase (BACE), glycogen synthase kinase 3α (GSK3α), glycogen synthase kinase 3β (GSK3β), phosphatidylinositol-3 kinase (PI-3K), insulin-degrading enzyme (IDE), insulin-receptor substrate 1 (IRS1), insulin receptor (INSR) and monoamine oxidase B (MAO-B) were investigated via quantitative-PCR, western blot, ELISA and enzyme activity assay. We could find different effects of soluble and aggregated peptides especially on gene/protein expression of GSK3β and INSR and on GSK3β and MAO-B activity. Soluble peptides showed significant effects leading to increased gene expression and protein amount of GSK3β and to decreased level of gene and protein expression of INSR. MAO-B activity was enhanced after treatment with aggregated peptides and strongly inhibited after soluble Aβ(42) treatment. Our data might provide insights into selective effects of specific forms of Aβ(42) aggregates in AD.


Characterization of a beta 3-adrenoceptor stimulating gastrin and somatostatin secretions in rat antrum.
The beta 3-adrenoceptor (beta 3-AR) agonist SR-58611A {ethyl-[(7s)-7-[[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]5, 6,7,8-tetrahydronaphth-2-yl]oxyacetate hydrochloride} stimulated somatostatin and gastrin releases in isolated rat gastric antral epithelial cells. Stimulation was a concentration-dependent process with 50% effective concentrations of 2.7 +/- 1.1 and 3.8 +/- 1.9 nM compared with 209 +/- 71 and 230 +/- 51 nM for isoproterenol, respectively. It was inhibited by selective beta-AR antagonists with the following rank order of potency: SR-59230A 3-(2-ethylphenoxy)1-[(1S)-1,2,3,4-tetrahydronaphth- 1-ylamino]-(2S)-2-propranol oxalate; beta 3-AR antagonist > ICI-118551[erythro-(+/-)-1-(7-methylindan-4-yloxy)-3- isopropylaminobutan-2-ol-hydrochloride; beta 2-AR antagonist > CGP-20712A[(+/-)-[2-(3-carbarmoyl-4-hydroxyphenoxy)-et hyl- amino]-3-[4 (1-methyl-4-trifluoromethyl-2-imidazolyl)-phenoxy]- 2-propranol; beta 1-AR antagonist]. Furthermore, specific binding of 125I-cyanopindolol to the isolated cells was demonstrated and was displaced by the beta-AR antagonists according to the same rank order of potency and with apparent dissociation constants consistent with the 50% inhibitory concentrations for SR-58611A-stimulated somatostatin and gastrin releases. In addition, the presence of beta 3-AR mRNA was detected by reverse transcriptase polymerase chain reaction. These findings provide the first evidence for a gastric beta 3-AR mediating catecholamine stimulation of gastrin and somatostatin releases from antral cells.


Plasma beta-endorphin levels in anovulatory states: changes after treatments for the induction of ovulation.
The goal of this study was to evaluate the effects of menstrual cyclicity on plasma beta-endorphin (beta-EP) levels. For this purpose, beta-EP and cortisol plasma concentrations were measured during the menstrual cycle in healthy control subjects (n = 12), in patients affected by anovulatory syndrome (n = 6), and in amenorrheic patients (n = 8). In the same patients, beta-EP and cortisol were also measured under treatment for the induction of ovulation with pulsatile luteinizing hormone-releasing hormone or human menopausal gonadotropin plus human chorionic gonadotropin administration. In spontaneous and pharmacologically induced ovulatory cycles, a significant preovulatory rise of plasma beta-EP levels was always evident. Constant levels were found in the other periods of ovulatory cycles and in the patients affected by anovulatory syndrome and primary amenorrhea. Cortisol levels did not show any significant change throughout the cycle, either in controls or in patients before or after treatment. This result suggests that when ovulation occurs, plasma beta-EP levels show a relevant rise, the physiologic significance of which remains to be elucidated.


[Perfusion brain imaging with SPECT-technique. German Guideline S1].
This paper describes the guideline for perfusion brain imaging with SPECT-technique published by the Association of the Scientific Medical Societies in Germany (AWMF).The purpose of this guideline is to provide practical assistance for indication, examination procedures, findings and their interpretation also reflecting the present state of the art. Information and instruction are given regarding indication, preparation of the patients and examination procedures of brain perfusion SPECT, including preparation and quality control of the tracer as well as the radiation dosimetry, technical performance of image acquisition with the gamma-camera and image processing. Also advices for interpretation of findings are given. In addition, possible pitfalls are described.


Pancreatic Neuroendocrine Tumor With Humoral Hypercalcemia and High Tumor PD-L1 Score.
Pancreatic neuroendocrine tumors (NETs) are a heterogeneous group of neoplasms. They can be functioning tumors with secretion of a variety of peptide hormones, or nonfunctioning tumors with metastases to the liver at the time of diagnosis. Well-differentiated tumors tend to be slow-growing and characterized by low tumor mutational burden (TMB) and lower propensity to express PD-L1. Hypercalcemia due to malignancy can occur in about 20% to 30% of patients with cancer. The secretion of parathyroid hormone-related protein (PTH-rP) is among the causes of malignant hypercalcemia and has seldom been associated with hypercalcemia of NETs. Although the therapeutic landscape for neuroendocrine neoplasms has evolved substantially over the past decade, the role of immunotherapy has not yet been completely explored in this group of patients. We present a rare case of a metastatic pancreatic NET with high TMB, high PD-L1 tumor proportion score, and high PTH-rP related hypercalcemia.


Tau suppresses microtubule-regulated pancreatic insulin secretion.
Tau protein is implicated in the pathogenesis of Alzheimer's disease (AD) and other tauopathies, but its physiological function is in debate. Mostly explored in the brain, tau is also expressed in the pancreas. We further explored the mechanism of tau's involvement in the regulation of glucose-stimulated insulin secretion (GSIS) in islet β-cells, and established a potential relationship between type 2 diabetes mellitus (T2DM) and AD. We demonstrate that pancreatic tau is crucial for insulin secretion regulation and glucose homeostasis. Tau levels were found to be elevated in β-islet cells of patients with T2DM, and loss of tau enhanced insulin secretion in cell lines, drosophila, and mice. Pharmacological or genetic suppression of tau in the db/db diabetic mouse model normalized glucose levels by promoting insulin secretion and was recapitulated by pharmacological inhibition of microtubule assembly. Clinical studies further showed that serum tau protein was positively correlated with blood glucose levels in healthy controls, which was lost in AD. These findings present tau as a common therapeutic target between AD and T2DM.


Colloid solutions for fluid resuscitation.
Colloids are widely used in the replacement of fluid volume. However, doubts remain as to which colloid is best. Different colloids vary in their molecular weight and therefore in the length of time they remain in the circulatory system. Because of this, and their other characteristics, they may differ in their safety and efficacy. To compare the effects of different colloid solutions in patients thought to need volume replacement. We searched the Cochrane Injuries Specialised Register (searched 1 December 2011), the Cochrane Central Register of Controlled Trials 2011, issue 4 (The Cochrane Library); MEDLINE (Ovid) (1948 to November Week 3 2011); EMBASE (Ovid) (1974 to 2011 Week 47); ISI Web of Science: Science Citation Index Expanded (1970 to 1 December 2011); ISI Web of Science: Conference Proceedings Citation Index-Science (1990 to 1 December 2011); CINAHL (EBSCO) (1982 to 1 December 2011); National Research Register (2007, Issue 1) and PubMed (searched 1 December 2011). Bibliographies of trials retrieved were searched, and for the initial version of the review drug companies manufacturing colloids were contacted for information (1999). Randomised controlled trials comparing colloid solutions in critically ill and surgical patients thought to need volume replacement. Two review authors independently extracted the data and assessed the quality of the trials. The outcomes sought were death, amount of whole blood transfused, and incidence of adverse reactions. Eighty-six trials, with a total of 5,484 participants, met the inclusion criteria. Quality of allocation concealment was judged to be adequate in 33 trials and poor or uncertain in the rest.Deaths were reported in 57 trials. For albumin or plasma protein fraction (PPF) versus hydroxyethyl starch (HES) 31 trials (n = 1719) reported mortality. The pooled relative risk (RR) was 1.06 (95% confidence interval (CI) 0.86 to 1.31). When the trials by Boldt were removed from the analysis the pooled RR was 0.90 (95% CI 0.68 to 1.20). For albumin or PPF versus gelatin, nine trials (n = 824) reported mortality. The RR was 0.89 (95% CI 0.65 to 1.21). Removing the study by Boldt from the analysis did not change the RR or CIs. For albumin or PPF versus dextran four trials (n = 360) reported mortality. The RR was 3.75 (95% CI 0.42 to 33.09). For gelatin versus HES 22 trials (n = 1612) reported mortality and the RR was 1.02 (95% CI 0.84 to 1.26). When the trials by Boldt were removed from the analysis the pooled RR was 1.03 (95% CI 0.84 to 1.27). RR was not estimable in the gelatin versus dextran and HES versus dextran groups.Forty-one trials recorded the amount of blood transfused; however, quantitative analysis was not possible due to skewness and variable reporting. Twenty-four trials recorded adverse reactions, with two studies reporting possible adverse reactions to gel and one to HES. From this review, there is no evidence that one colloid solution is more effective or safe than any other, although the CIs were wide and do not exclude clinically significant differences between colloids. Larger trials of fluid therapy are needed if clinically significant differences in mortality are to be detected or excluded.


Criteria-based DUE aids in selection of preferred agent.
The combination of a criteria-based drug utilization evaluation and a comprehensive drug literature review can be effectively used to reach therapeutically sound, cost-efficient formulary decisions. This report describes the approach to evaluating the available H2-receptor antagonists used by the Pharmacy & Therapeutics Committee of Memorial Medical Center, a 550-bed, community-based teaching hospital affiliated with the Southern Illinois University School of Medicine in Springfield.


Fighting the COVID-19 pandemic in Ghana: a report from the Kwame Nkrumah University of Science and Technology, Kumasi.
The corona virus disease 2019 (COVID-19) has stretched the resources of health facilities but there is a lack of context-specific reports across Africa. Since February, 2020, the university hospital, Kwame Nkrumah University of Science and Technology (KNUST), a district-level institution, has been at the forefront in contributing to efforts in Ghana to fight the global pandemic. As of 16th August, 2020, 1755 individual samples have been taken at the hospital for COVID-19 out of which 629 (35.8%) tested positive, 414 (65.9%) recoveries and 6 (0.95%) deaths. The hospital's out-patient attendance has reduced by almost 50% with attendant loss of revenue. Here in, we present a report on our activities, highlight lessons and recommendations that other health facilities can glean from.


Cardiac macrophage biology in the steady-state heart, the aging heart, and following myocardial infarction.
Macrophages play critical roles in homeostatic maintenance of the myocardium under normal conditions and in tissue repair after injury. In the steady-state heart, resident cardiac macrophages remove senescent and dying cells and facilitate electrical conduction. In the aging heart, the shift in macrophage phenotype to a proinflammatory subtype leads to inflammaging. Following myocardial infarction (MI), macrophages recruited to the infarct produce both proinflammatory and anti-inflammatory mediators (cytokines, chemokines, matrix metalloproteinases, and growth factors), phagocytize dead cells, and promote angiogenesis and scar formation. These diverse properties are attributed to distinct macrophage subtypes and polarization status. Infarct macrophages exhibit a proinflammatory M1 phenotype early and become polarized toward an anti-inflammatory M2 phenotype later post-MI. Although this classification system is oversimplified and needs to be refined to accommodate the multiple different macrophage subtypes that have been recently identified, general concepts on macrophage roles are independent of subtype classification. This review summarizes current knowledge about cardiac macrophage origins, roles, and phenotypes in the steady state, with aging, and after MI, as well as highlights outstanding areas of investigation.


Antifungal prophylaxis in adult patients with acute myeloid leukaemia treated with novel targeted therapies: a systematic review and expert consensus recommendation from the European Hematology Association.
On the basis of improved overall survival, treatment guidelines strongly recommend antifungal prophylaxis during remission induction chemotherapy for patients with acute myeloid leukaemia. Many novel targeted agents are metabolised by cytochrome P450, but potential drug-drug interactions (DDIs) and the resulting risk-benefit ratio have not been assessed in clinical trials, leading to uncertainty in clinical management. Consequently, the European Haematology Association commissioned experts in the field of infectious diseases, haematology, oncology, clinical pharmacology, and methodology to develop up-to-date recommendations on the role of antifungal prophylaxis and management of pharmacokinetic DDIs with triazole antifungals. A systematic literature review was performed according to Cochrane methods, and recommendations were developed by use of the Grading of Recommendations Assessment, Development and Evaluation Evidence to Decision framework. We searched MEDLINE, Embase, and Cochrane Library, including Central Register of Controlled Trials, for randomised controlled trials and systematic reviews published from inception to March 10, 2020. We excluded studies that were not published in English. Evidence for any identified novel agent that is active against acute myeloid leukaemia was reviewed for the following outcomes: incidence of invasive fungal disease, prolongation of hospitalisation, days spent in intensive-care unit, mortality due to invasive fungal disease, quality of life, and potential DDIs. Recommendations and consensus statements were compiled for each targeted drug for patients with acute myeloid leukaemia and each specific setting. Evidence-based recommendations were developed for hypomethylating agents, midostaurin, and the venetoclax-hypomethylating agent combination. For all other agents, consensus statements were given for specific therapeutic settings, specifically for the management of patients with relapsed or refractory acute myeloid leukaemia, monotherapy, and combination with chemotherapy. Antifungal prophylaxis is recommended with moderate strength in most settings, and strongly recommended if the novel acute myeloid leukaemia agent is administered in combination with intensive induction chemotherapy. For ivosidenib, lestaurtinib, quizartinib, and venetoclax, we moderately recommend adjusting the dose of the antileukaemic agent during administration of triazoles. This is the first guidance supporting clinical decision making on antifungal prophylaxis in recipients of novel targeted drugs for acute myeloid leukaemia. Future studies including therapeutic drug monitoring will need to determine the role of dosage adjustment of novel antileukaemic drugs during concomitant administration of CYP3A4-inhibiting antifungals with respect to adverse effects and remission status.


Effects of Three Lipidated Oxytocin Analogs on Behavioral Deficits in CD38 Knockout Mice.
Oxytocin (OT) is a nonapeptide that plays an important role in social behavior. Nasal administration of OT has been shown to improve trust in healthy humans and social interaction in autistic subjects. As is consistent with the nature of a peptide, OT has some unfavorable characteristics: it has a short half-life in plasma and shows poor permeability across the blood-brain barrier. Analogs with long-lasting effects may overcome these drawbacks. To this end, we have synthesized three analogs: lipo-oxytocin-1 (LOT-1), in which two palmitoyl groups are conjugated to the cysteine and tyrosine residues, lipo-oxytocin-2 (LOT-2) and lipo-oxytocin-3 (LOT-3), which include one palmitoyl group conjugated at the cysteine or tyrosine residue, respectively. The following behavioral deficits were observed in CD38 knockout (CD38-/-) mice: a lack of paternal nurturing in CD38-/- sires, decreased ability for social recognition, and decreased sucrose consumption. OT demonstrated the ability to recover these disturbances to the level of wild-type mice for 30 min after injection. LOT-2 and LOT-3 partially recovered the behaviors for a short period. Conversely, LOT-1 restored the behavioral parameters, not for 30 min, but for 24 h. These data suggest that the lipidation of OT has some therapeutic benefits, and LOT-1 would be most useful because of its long-last activity.


Photothermal behaviour of titanium nitride nanoparticles evaluated by transient X-ray diffraction.
The photothermal properties of metal nitrides have recently received significant attention owing to diverse applications in solar energy conversion, photothermal therapies, photoreactions, and thermochromic windows. Here, the photothermal response of titanium nitride nanoparticles is examined using transient X-ray diffraction, in which optical excitation is synchronized with X-ray pulses to characterize dynamic changes in the TiN lattice. Photoinduced diffraction data is quantitatively analyzed to determine increases in the TiN lattice spacing, which are furthermore calibrated against static, temperature-dependent diffraction patterns of the same samples. Measurements of 20 nm and 50 nm diameter TiN nanoparticles reveal transient lattice heating from room temperature up to ∼175 °C for the highest pump fluences investigated here. Increasing excitation intensity drives sublinear increases in lattice temperature, due to increased heat capacity at the higher effective temperatures achieved at higher powers. Temporal dynamics show that higher excitation intensity drives not only higher lattice temperatures, but also unexpectedly slower cooling of the TiN nanoparticles, which is attributed to heating of the solvent proximal to the nanoparticle surface.


Optimized design of fluorinated polyimide based interleaver.
Statistical optimization method for the design of a fluorinated polyimide wavelength division element for optical communication is proposed. The opitimized device is an interleaver element suitable for dividing over 40 wavelengths in the 1550 nm band. Optimization considers the inherent polarization dependence of fluorinated polyimide based on measurements of the dispersion characteristics and birefringence of fluorinated polyimide film. A 40-wavelength device is designed by use of the proposed technique for a working wavelength of 1550 nm and a wavelength interval of 0.8 nm. The device exhibited a 1-dB passband of 0.5 nm and a 3-dB passband of 0.8 nm, and output wavelength fluctuation due to polarization effects of less than 0.08 nm.


Dietary supplementation with a combination of alpha-lipoic acid, acetyl-L-carnitine, glycerophosphocoline, docosahexaenoic acid, and phosphatidylserine reduces oxidative damage to murine brain and improves cognitive performance.
Alzheimer disease has a complex etiology composed of nutritional and genetic risk factors and predispositions. Moreover, genetic risk factors for cognitive decline may remain latent pending age-related decline in nutrition, suggesting the potential importance of early nutritional intervention, including preventative approaches. We hypothesized that a combination of multiple nutritional additives may be able to provide neuroprotection. We demonstrate herein that dietary supplementation with a mixture of ALA, ALCAR, GPC, DHA, and PS reduced reactive oxygen species in normal mice by 57% and prevented the increase in reactive oxygen species normally observed in mice lacking murine ApoE when maintained on a vitamin-free, iron-enriched, oxidative-challenge diet. We further demonstrate that supplementation with these agents prevented the marked cognitive decline otherwise observed in normal mice maintained on this challenge diet. These findings add to the growing body of research indicating that key dietary supplementation may delay the progression of age-related cognitive decline.


Young women's perspectives on cervical cancer prevention in Appalachian Kentucky.
Human papillomavirus (HPV) vaccination coupled with routine Papanicolaou (Pap) tests can prevent pervasive HPV infections causing cervical cancer. However, both HPV vaccination rates and Pap testing rates in Appalachian Kentucky are lower among all age groups than the rest of the United States. We recruited 19 young women residing in Appalachian Kentucky from university-based and rural clinical settings for group and individual interviews. After considering an integrated behavioral framework, we illustrate these women's perspectives by detailing five themes, including (a) experiential beliefs pose barriers to performing behaviors, (b) three vaccine doses complicate vaccination intention, (c) women have misunderstandings about HPV and the HPV vaccination function, (d) normative influences cue action (and inaction), and (e) specific environmental and contextual barriers exist to performing cervical cancer prevention behaviors in Appalachian Kentucky. These findings related to cervical cancer prevention in Appalachian Kentucky have implications for health-message design and clinical practice.


Integrated analysis identities Rho GTPases related molecular map in patients with gastric carcinoma.
The intricate involvement of Rho GTPases in a multitude of human malignancies and their diverse array of biological functions has garnered substantial attention within the scientific community. However, their expression pattern and potential role in gastric cancer (GC) remain unclear. In this study, we successfully identified two distinct subtypes associated with Rho GTPase-related gene (RGG) through consensus clustering analysis, which exhibited significant disparities in overall survival and the tumor microenvironment. Subsequently, an extensively validated risk model termed RGGscore was meticulously constructed to prognosticate the outcomes of GC patients. This model was further assessed and validated using an external cohort. Notably, the high RGGscore group was indicative of a poorer prognosis. Univariate and multivariate Cox regression analyses unveiled the RGGscore as an autonomous prognostic indicator for GC patients. Subsequent external validation, utilizing two cohorts of patients who underwent immunotherapy, demonstrated a significant correlation between a low RGGscore and improved response to immunotherapy. Additionally, the expression levels of three genes associated with RGGscore were examined using qRT-PCR. Taken together, a pioneering RGGscore model has been successfully established, showcasing its potential efficacy in offering valuable therapeutic guidance for GC.


Socioeconomic status and risk of hemorrhage during warfarin therapy for atrial fibrillation: A population-based study.
Among patients taking warfarin, lower socioeconomic status is associated with poorer control of anticoagulation. However, the extent to which socioeconomic status influences the risk of hemorrhage is unknown. We examined the extent to which socioeconomic status influences the risk of hemorrhage in older individuals newly commencing warfarin therapy for atrial fibrillation. We conducted a population-based cohort study of individuals 66 years or older with atrial fibrillation who commenced warfarin therapy between April 1, 1997, and November 30th 2011, in Ontario, Canada. We used neighborhood-level income quintiles as a measure of socioeconomic status. The primary outcome was an emergency department visit or hospitalization for hemorrhage, and the secondary outcome was fatal hemorrhage. We studied 166,742 older patients with atrial fibrillation who commenced warfarin therapy. Of these, 16,371 (9.8%) were hospitalized for hemorrhage during a median follow-up of 369 (interquartile range 102-865) days. After multivariable adjustment using Cox proportional hazards regression, we found that those in the lowest-income quintile faced an increased risk of hospitalization for hemorrhage relative to those in the highest quintile (adjusted hazard ratio 1.18, 95% CI 1.12-1.23). Similarly, the risk of fatal hemorrhage (n = 1,802) was increased in the lowest-income relative to the highest-income quintile (adjusted hazard ratio 1.28, 95% CI 1.11-1.48). Among older individuals receiving warfarin therapy for atrial fibrillation, lower socioeconomic status is a risk factor for hemorrhage and hemorrhage-related mortality. This factor should be carefully considered when initiating and monitoring warfarin therapy.


Confinement of Skyrmions in Nanoscale FeGe Device-like Structures.
Skyrmion-based devices have been proposed as a promising solution for low-energy data storage. These devices include racetrack or logic structures and require skyrmions to be confined in regions with dimensions comparable to the size of a single skyrmion. Here we examine skyrmions in FeGe device shapes using Lorentz transmission electron microscopy to reveal the consequences of skyrmion confinement in a device-like structure. Dumbbell-shaped elements were created by focused ion beam milling to provide regions where single skyrmions are confined adjacent to areas containing a skyrmion lattice. Simple block shapes of equivalent dimensions were also prepared to allow a direct comparison with skyrmion formation in a less complex, yet still confined, device geometry. The impact of applying a magnetic field and varying the temperature on the formation of skyrmions within the shapes was examined. This revealed that it is not just confinement within a small device structure that controls the position and number of skyrmions but that a complex device geometry changes the skyrmion behavior, including allowing skyrmions to form at lower applied magnetic fields than in simple shapes. The impact of edges in complex shapes is observed to be significant in changing the behavior of the magnetic textures formed. This could allow methods to be developed to control both the position and number of skyrmions within device structures.


Computerized screening of children congenital heart diseases.
In this paper, we propose a method for automated screening of congenital heart diseases in children through heart sound analysis techniques. Our method relies on categorizing the pathological murmurs based on the heart sections initiating them. We show that these pathelogical murmur categories can be identified by examining the heart sound energy over specific frequency bands, which we call, Arash-Bands. To specify the Arash-Band for a category, we evaluate the energy of the heart sound over all possible frequency bands. The Arash-Band is the frequency band that provides the lowest error in clustering the instances of that category against the normal ones. The energy content of the Arash-Bands for different categories constitue a feature vector that is suitable for classification using a neural network. In order to train, and to evaluate the performance of the proposed method, we use a training data-bank, as well as a test data-bank, collectively consisting of ninety samples (normal and abnormal). Our results show that in more than 94% of cases, our method correctly identifies children with congenital heart diseases. This percentage improves to 100%, when we use the Jack-Knife validation method over all the 90 samples.


Infrared surface temperature monitoring in the postoperative management of free tissue transfers.
Early identification of failing free flaps may allow for potential intervention and flap salvage. The predictive ability of flap temperature monitoring has been previously questioned. The present study investigated the ability of an infrared surface temperature monitoring device to detect trends in flap temperature and correlation with anastomotic thrombosis and flap failure. Postoperative measurement of surface temperature was obtained in 47 microvascular free flaps. Differences in temperature between survival and failure groups were evaluated for statistical significance using Student's t test (P<0.05). In addition, a single variable analysis was performed on 30 different flap characteristics to evaluate their prediction of flap failure. In total, eight flaps failed. Five of these were re-explored, of which one was salvaged. The three other flaps died a progressive death secondary to presumed thrombosis of the microcirculation despite adequate Doppler signals. Temperatures of the flap failure group during the last 24 h yielded a mean difference of 2 degrees C (3.56 degrees F) compared with surviving flaps (P<0.05). The temperature of the failing flaps began to decline at the eighth postoperative hour. Single variable analysis identified prior radiation to be a predictor of flap failure. A surface temperature measurement device provides reproducible digital readings without physical contact with the flap. Technical difficulties encountered in previous research with implantable or surface contact temperature probes are obviated with this noncontact technique. Flap temperature monitoring revealed a trend in temperature that correlates with anastomotic thrombosis and eventual flap failure.


Classification of protein-protein association rates based on biophysical informatics.
Proteins form various complexes to carry out their versatile functions in cells. The dynamic properties of protein complex formation are mainly characterized by the association rates which measures how fast these complexes can be formed. It was experimentally observed that the association rates span an extremely wide range with over ten orders of magnitudes. Identification of association rates within this spectrum for specific protein complexes is therefore essential for us to understand their functional roles. To tackle this problem, we integrate physics-based coarse-grained simulations into a neural-network-based classification model to estimate the range of association rates for protein complexes in a large-scale benchmark set. The cross-validation results show that, when an optimal threshold was selected, we can reach the best performance with specificity, precision, sensitivity and overall accuracy all higher than 70%. The quality of our cross-validation data has also been testified by further statistical analysis. Additionally, given an independent testing set, we can successfully predict the group of association rates for eight protein complexes out of ten. Finally, the analysis of failed cases suggests the future implementation of conformational dynamics into simulation can further improve model. In summary, this study demonstrated that a new modeling framework that combines biophysical simulations with bioinformatics approaches is able to identify protein-protein interactions with low association rates from those with higher association rates. This method thereby can serve as a useful addition to a collection of existing experimental approaches that measure biomolecular recognition.


Peripheral blood mitochondrial DNA copy number is associated with prostate cancer risk and tumor burden.
Alterations of mitochondrial DNA (mtDNA) have been associated with the risk of a number of human cancers; however, the relationship between mtDNA copy number in peripheral blood leukocytes (PBLs) and the risk of prostate cancer (PCa) has not been investigated. In a case-control study of 196 PCa patients and 196 age-paired healthy controls in a Chinese Han population, the association between mtDNA copy number in PBLs and PCa risk was evaluated. The relative mtDNA copy number was measured using quantitative real-time PCR; samples from three cases and two controls could not be assayed, leaving 193 cases and 194 controls for analysis. PCa patients had significantly higher mtDNA copy numbers than controls (medians 0.91 and 0.82, respectively; P<0.001). Dichotomized at the median value of mtDNA copy number in the controls, high mtDNA copy number was significantly associated with an increased risk of PCa (adjusted odds ratio= 1.85, 95% confidence interval: 1.21-2.83). A significant dose-response relationship was observed between mtDNA copy number and risk of PCa in quartile analysis (Ptrend = 0.011). Clinicopathological analysis showed that high mtDNA copy numbers in PCa patients were significantly associated with high Gleason score and advanced tumor stage, but not serum prostate-specific antigen level (P = 0.002, 0.012 and 0.544, respectively). These findings of the present study indicate that increased mtDNA copy number in PBLs is significantly associated with an increased risk of PCa and may be a reflection of tumor burden.