[Relationship between drinking, smoking, and dietary habits and the body mass index of Japanese alcoholic men].
Malnutrition and emaciation in alcoholics is associated with various alcoholism-related diseases, including Wernicke's encephalopathy, aero-digestive tract cancer, and serious metabolic disorders. We used a self-administered questionnaire survey for structured dietary habit screening to evaluate the dietary profiles of 467 Japanese alcoholic men aged 40 years or over and their relationship to body mass index (BMI). Their average daily ethanol consumption was 119 +/- 65 g (845 +/- 463 kcal). The survey showed that 50.5% of the subjects consumed three meals a day; 32.8%, two meals; 12.2%, one meal; and 4.5% rarely ate. The meals mainly consisted of carbohydrates and protein, with few vegetables. Daily alcohol consumption was inversely correlated with the frequency of meals, drinking milk, and consuming confectionery. The subjects who lived with their family (72.8%) consumed more meals than the subjects liv- ing alone. After excluding 22 subjects with leg edema or ascites, the average BMI was 21.3 +/- 3.2. The group with the lowest BMI values (<18.5) accounted for 19.3% of the subjects, and those with the highest BMI values (> or = 25) accounted for 11.5%. A multivariate stepwise logistic analysis showed that BMI increased 0.15 per 22 g ethanol consumed daily and decreased 0.03 per + 10 cigarettes smoked daily, 0.43 per decrease by one in daily frequency of meals, and 0.54 per category (daily, occasionally, rarely, seldom) of milk consumption. The likelihood of a low BMI <18.5 was significantly and independently associated with smoking [OR (95%CI) =1.24 (1.02-1.51) per +10 cigarettes] and with intake of seafood [0.62 (0.41-0.94) per +1 category], milk [1.52 (1.16-2.00) per +1 category] and green and yellow vegetables [1.52 (1.05-2.21) per +1 category]. Intervention in regard to diet as well as drinking is important to preventing malnutrition and emaciation in alcoholics.


A Wearable System for Continuous Monitoring and Assessment of Speech, Gait, and Cognitive Decline for Early Diagnosis of ADRD.
Early detection of cognitive decline is essential to study mild cognitive impairment and Alzheimer's Disease in order to develop targeted interventions and prevent or stop the progression of dementia. This requires continuous and longitudinal assessment and tracking of the related physiological and behavioral changes during daily life. In this paper, we present a low cost and low power wearable system custom designed to track the trends in speech, gait, and cognitive stress while also considering the important human factor needs such as privacy and compliance. In the form factors of a wristband and waist-patch, this multimodal, multi-sensor system measures inertial signals, sound, heart rate, electrodermal activity and pulse transit time. A total power consumption of 2.6 mW without any duty cycling allows for more than 3 weeks of run time between charges when 1500 mAh batteries are used.Clinical Relevance- Much earlier detection of Alzheimer's disease and related dementias may be possible by continuous monitoring of physiological and behavioral state using application specific wearable sensors during the activities of daily life.


A-kinase anchoring protein 79/150 coordinates α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor sensitization in sensory neurons.
Changes in sensory afferent activity contribute to the transition from acute to chronic pain. However, it is unlikely that a single sensory receptor is entirely responsible for persistent pain. It is more probable that extended changes to multiple receptor proteins expressed by afferent neurons support persistent pain. A-Kinase Anchoring Protein 79/150 (AKAP) is an intracellular scaffolding protein expressed in sensory neurons that spatially and temporally coordinates signaling events. Since AKAP scaffolds biochemical modifications of multiple TRP receptors linked to pain phenotypes, we probed for other ionotropic receptors that may be mediated by AKAP and contribute to persistent pain. Here, we identify a role for AKAP modulation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid Receptor (AMPA-R) functionality in sensory neurons. Pharmacological manipulation of distinct AMPA-R subunits significantly reduces persistent mechanical hypersensitivity observed during hyperalgesic priming. Stimulation of both protein kinases C and A (PKC, PKA, respectively) modulate AMPA-R subunit GluR1 and GluR2 phosphorylation and surface expression in an AKAP-dependent manner in primary cultures of DRG neurons. Furthermore, AKAP knock out reduces sensitized AMPA-R responsivity in DRG neurons. Collectively, these data indicate that AKAP scaffolds AMPA-R subunit organization in DRG neurons that may contribute to the transition from acute-to-chronic pain.


Midline granuloma.
A 34-year-old woman had a granulomatous ulceration of the nose that responded to radiation therapy. The limitation of the disease to the nose and the histologic findings were consistent with a diagnosis of midline granuloma, Stewart type. The relationship of midline granuloma to Wegener's granulomatosis is reviewed. In view of the uniform mortality that accompanies untreated midline granuloma, a correct diagnosis must be made so that radiation therapy can be promptly instituted.


First familial limb-girdle muscular dystrophy 2L in China: Clinical, imaging, pathological, and genetic features.
Limb-girdle muscular dystrophy 2L (LGMD2L) is mainly characterized by late adult onset, atrophy of proximal muscles, chronic progressive and asymmetric weakness, accompanied by increased creatine kinase (CK) levels, dystrophic pathological changes and electromyography showing myogenic damage. To date, familial LGMD2L was reported in European countries and had not been reported in China.A careful investigation of the clinical manifestations, muscle performance imaging, biopsy, and target next-generation sequencing (NGS) technology was utilized to identify pathogenic genetic variants in a 4-generation pedigree that includes 6 affected individuals.The results revealed mild-to-moderate hypertrophy of bilateral gastrocnemii and slight weakness and atrophy in the proximal muscles of the lower limbs, with obviously increased serum creatine kinase levels. The symptoms were more serious in the male proband but were also observed in females. Obvious and symmetric atrophy and fat infiltration of posterior segments of the thigh was evident in muscle magnetic resonance imaging (MRI). The pathological changes included a small amount of atrophic and hypertrophic fibers, scattered necrotizing fibers, a small number of increased nuclei, inward migration, mild proliferation of interstitial connective tissue, and no inflammatory cell infiltration. The pathogenic allele was a c.220C > T mutation in the anoctamin 5 (ANO5) gene.The LGMD2L family was characterized by mild chronic myopathy and bilateral gastrocnemius hypertrophy with obviously increased CK levels. Pathological changes included atrophy of fibers with interstitial connective tissues hyperplasia. The pathogenic allele was a c.220C> T mutation in the ANO5 gene.


Involvement of Penicillium digitatum PdSUT1 in fungicide sensitivity and virulence during citrus fruit infection.
A putative sucrose transporter PdSUT1 included in the same clade that Sut1p from Schizosaccharomyces pombe was identified in Penicillium digitatum, the major citrus postharvest pathogen. PdSUT1 gene was characterized using target gene disruption and gene overexpression. The ΔPdSUT1 mutants generated by gene elimination showed reduction in fungal virulence during citrus fruit infection assayed in mature fruit at 20°C. However, the overexpression mutants did not increased disease severity neither in the mutants coming from a high virulent nor from a low virulent P. digitatum progenitor strains. Moreover, fungicide sensitivity was affected in the deletant mutants but not in the overexpression transformants. The expression analysis of several genes involved in fungicide resistance showed an intensification of MFS transporters and a decrease of sterol demethylases transcriptional abundance in the ΔPdSUT1 mutants compare to the parental wild type strain. PdSUT1 appear not to be directly involved in fungicide resistance although can affect the gene expression of fungicide related genes. These results indicate that PdSUT1 contribute to P. digitatum fungal virulence and influence fungicide sensitivity through carbohydrate uptake and MFS transporters gene activation.


Assessing the sensitivity of egg yolk antibody testing for detecting Salmonella enteritidis infections in laying hens.
The identification of infected commercial poultry flocks has become a pivotal component of efforts to reduce the incidence of egg-associated transmission of Salmonella enteritidis to humans. To assess the sensitivity with which testing for specific antibodies in egg yolks can be applied to detect S. enteritidis infection in laying chickens, groups of hens were orally inoculated with either 10(3), 10(5), or 10(7) cfu of a phage type 13a strain of S. enteritidis. Eggs from these hens were collected for 4 wk after inoculation and yolk samples were tested for antibodies to S. enteritidis flagella by ELISA. All hens that were inoculated with 10(7) cfu of S. enteritidis were detected as infected by the egg yolk ELISA when eggs were tested individually, as were up to 66 and 35% of hens inoculated with 10(5) or 10(3) cfu, respectively. Even when yolks from infected hens were diluted 1:10 in yolk from uninfected hens, specific antibodies could still be found in eggs from 31% of hens given 10(7) cfu of S. enteritidis and 13% of hens given 10(3) cfu. These results demonstrate that egg yolk antibody testing can provide a highly sensitive indication of prior exposure to S. enteritidis, and should accordingly be useful for verifying the effectiveness of programs designed to reduce the incidence of S. enteritidis infection in poultry.


Interventions that effectively target Anopheles funestus mosquitoes could significantly improve control of persistent malaria transmission in south-eastern Tanzania.
Malaria is transmitted by many Anopheles species whose proportionate contributions vary across settings. We re-assessed the roles of Anopheles arabiensis and Anopheles funestus, and examined potential benefits of species-specific interventions in an area in south-eastern Tanzania, where malaria transmission persists, four years after mass distribution of long-lasting insecticide-treated nets (LLINs). Monthly mosquito sampling was done in randomly selected households in three villages using CDC light traps and back-pack aspirators, between January-2015 and January-2016, four years after the last mass distribution of LLINs in 2011. Multiplex polymerase chain reaction (PCR) was used to identify members of An. funestus and Anopheles gambiae complexes. Enzyme-linked immunosorbent assay (ELISA) was used to detect Plasmodium sporozoites in mosquito salivary glands, and to identify sources of mosquito blood meals. WHO susceptibility assays were done on wild caught female An. funestus s.l, and physiological ages approximated by examining mosquito ovaries for parity. A total of 20,135 An. arabiensis and 4,759 An. funestus were collected. The An. funestus group consisted of 76.6% An. funestus s.s, 2.9% An. rivulorum, 7.1% An. leesoni, and 13.4% unamplified samples. Of all mosquitoes positive for Plasmodium, 82.6% were An. funestus s.s, 14.0% were An. arabiensis and 3.4% were An. rivulorum. An. funestus and An. arabiensis contributed 86.21% and 13.79% respectively, of annual entomological inoculation rate (EIR). An. arabiensis fed on humans (73.4%), cattle (22.0%), dogs (3.1%) and chicken (1.5%), but An. funestus fed exclusively on humans. The An. funestus populations were 100% susceptible to organophosphates, pirimiphos methyl and malathion, but resistant to permethrin (10.5% mortality), deltamethrin (18.7%), lambda-cyhalothrin (18.7%) and DDT (26.2%), and had reduced susceptibility to bendiocarb (95%) and propoxur (90.1%). Parity rate was higher in An. funestus (65.8%) than An. arabiensis (44.1%). Though An. arabiensis is still the most abundant vector species here, the remaining malaria transmission is predominantly mediated by An. funestus, possibly due to high insecticide resistance and high survival probabilities. Interventions that effectively target An. funestus mosquitoes could therefore significantly improve control of persistent malaria transmission in south-eastern Tanzania.


Use of virtual reality in improving poststroke neglect: Promising neuropsychological and neurophysiological findings from a case study.
After experiencing a stroke in the right hemisphere, almost 50% of patients show unilateral spatial neglect (USN). Virtual Reality technologies offer impressive opportunities for both the rehabilitation and assessment of different cognitive deficits, including USN. A 57-year-old woman, affected by subarachnoid hemorrhage presented a severe left hemiparesis with severe cognitive and behavioral alterations, including temporal and spatial disorientation, reduction of attention and memory process, slowing ideation, USN, and depression of mood. She underwent two different rehabilitation trainings, including standard cognitive training (SCT) in addition to semi-immersive virtual training with her shadow (S-IVT_s) and SCT in addition to a Semi- immersive virtual training, without her shadow (S-IVT). The patient was assessed before and after each of the two different trainings, by using a specific psychometric battery and the event related potential, P300. Only at the end of the use of the S-IVT, we observed a significant improvement in the motor and cognitive function, with regard to USN. SCT in addition to S-IVT with Bts-Nirvana System may be a promising approach in improving attention process, spatial cognition, and mood in patients with post stroke USN, as also demonstrated by the electrophysiological parameters.


Reconstruction of multiple gastric electrical wave fronts using potential-based inverse methods.
One approach for non-invasively characterizing gastric electrical activity, commonly used in the field of electrocardiography, involves solving an inverse problem whereby electrical potentials on the stomach surface are directly reconstructed from dense potential measurements on the skin surface. To investigate this problem, an anatomically realistic torso model and an electrical stomach model were used to simulate potentials on stomach and skin surfaces arising from normal gastric electrical activity. The effectiveness of the Greensite-Tikhonov or the Tikhonov inverse methods were compared under the presence of 10% Gaussian noise with either 84 or 204 body surface electrodes. The stability and accuracy of the Greensite-Tikhonov method were further investigated by introducing varying levels of Gaussian signal noise or by increasing or decreasing the size of the stomach by 10%. Results showed that the reconstructed solutions were able to represent the presence of propagating multiple wave fronts and the Greensite-Tikhonov method with 204 electrodes performed best (correlation coefficients of activation time: 90%; pacemaker localization error: 3 cm). The Greensite-Tikhonov method was stable with Gaussian noise levels up to 20% and 10% change in stomach size. The use of 204 rather than 84 body surface electrodes improved the performance; however, for all investigated cases, the Greensite-Tikhonov method outperformed the Tikhonov method.


Effective screening of medium-assisted van der Waals interactions between embedded particles.
The effect of an implicit medium on dispersive interactions of particle pairs is discussed, and simple expressions for the correction relative to vacuum are derived. We show that a single point Gauss quadrature leads to the intuitive result that the vacuum van der Waals C6-coefficient is screened by the permittivity squared of the environment evaluated near to the resonance frequencies of the interacting particles. This approximation should be particularly relevant if the medium is transparent at these frequencies. In this manuscript, we provide simple models and sets of parameters for commonly used solvents, atoms, and small molecules.


Changes in the immune landscape of TNBC after neoadjuvant chemotherapy: correlation with relapse.
Patients with high-risk, triple negative breast cancer (TNBC) often receive neoadjuvant chemotherapy (NAC) alone or with immunotherapy. Various single-cell and spatially resolved techniques have demonstrated heterogeneity in the phenotype and distribution of macrophages and T cells in this form of breast cancer. Furthermore, recent studies in mice have implicated immune cells in perivascular (PV) areas of tumors in the regulation of metastasis and anti-tumor immunity. However, little is known of how the latter change during NAC in human TNBC or their impact on subsequent relapse, or the likely efficacy of immunotherapy given with or after NAC. We have used multiplex immunofluorescence and AI-based image analysis to compare the immune landscape in untreated and NAC-treated human TNBCs. We quantified changes in the phenotype, distribution and intercellular contacts of subsets of tumor-associated macrophages (TAMs), CD4+ and CD8+ T cells, and regulatory T cells (Tregs) in PV and non-PV various areas of the stroma and tumor cell islands. These were compared in tumors from patients who had either developed metastases or were disease-free (DF) after a three-year follow up period. In tumors from patients who remained DF after NAC, there was a marked increase in stromal CD163+ TAMs, especially those expressing the negative checkpoint regulator, T-cell immunoglobulin and mucin domain 3 (TIM-3). Whereas CD4+ T cells preferentially located to PV areas in the stroma of both untreated and NAC-treated tumors, specific subsets of TAMs and Tregs only did so only after NAC. Distinct subsets of CD4+ and CD8+ T cells formed PV clusters with CD163+ TAMs and Tregs. These were retained after NAC. Quantification of stromal TIM-3+CD163+ TAMs in tumor residues after NAC may represent a new way of identifying patients at high risk of relapse. PV clustering of immune cells is highly likely to regulate the activation and function of T cells, and thus the efficacy of T cell-based immunotherapies administered with or after NAC.


Using contraceptives to delay first birth: a qualitative study of individual, community and health provider perceptions in southern Tanzania.
Young adolescents and unmarried women in low and middle income countries face challenges in accessing family planning services. One factor likely to limit contraceptive use is the attitude and opinion of local stakeholders such as community leaders and health workers. Much of the existing evidence on this topic focuses on women who have already started childbearing. Using primary qualitative data, we explored individual, community and health provider's perceptions about using modern contraceptives to delay the first birth in a high fertility setting. A descriptive qualitative study was conducted in Tandahimba district in southern Tanzania between December 2014 and March 2015. We conducted 8 focus group discussions with men and women and 25 in-depth interviews (18 with women, 4 with family planning service providers and 3 with district-level staff). Participants were purposively sampled. Data transcripts were managed and coded using Nvivo 11 software and we employed a thematic framework analysis. Three main themes emerged about using modern contraceptives to delay first birth: (1) the social and biological status of the woman (2) the type of contraceptive and (3) non-alignment among national policies for adolescents. Use of modern contraceptives to delay first birth was widely acceptable for women who were students, young, unmarried and women in unstable marriage. But long-acting reversible methods such as implants and intrauterine devices were perceived as inappropriate methods for delaying first birth, partly because of fears around delayed return to fecundity, discontinuation once woman's marital status changes and permanently limiting future fertility. The support for use of modern contraceptives to delay a first pregnancy was not unanimous. A small number of participants from both rural and urban areas did not approve the use of contraceptive methods before the birth of a first baby at all, not even for students. There was lack of clarity and consistency on the definition of 'young' and that had direct implications for access, autonomy in decision-making, confidentiality and consent for young people. Women who wish to delay their first birth face challenges related to restrictions by age and method imposed by stakeholders in accessing and provision of modern contraceptives. There is a need for a clearly communicated policy on minimum age and appropriate method choice for delayers of first birth.


Association Between Allergies and Psychiatric Disorders in Patients Undergoing Invasive Procedures.
Associations between allergies and psychiatric disorders have been reported in the context of depression and suicide; psychiatric disorders may affect pain perception. To investigate the relationship of allergies with psychiatric disorders and pain perception in the context of invasive procedures, specifically during tunneled hemodialysis catheter placement. We identified 89 patients (51 men, 38 women), mean age 66 years (range: 23-96), who underwent tunneled hemodialysis catheter placement (1/2014-2/2015), recording numeric rating scale pain scores, medications, psychiatric history, allergies, and smoking status. Of 89 patients, 47 patients had no allergies, and 42 had ≥1 allergy. Patients with allergies were more likely to have a pre-existing psychiatric disorder compared to those without allergies, odds ratio 2.6 (95% CI: 1.0-6.8). Having allergies did not affect procedural sedation or postprocedural pain scores. Multiple logistic regression with age, sex, smoking, presence of allergies, psychiatric history, inpatient/outpatient status, procedure time, and procedural sedation administration as inputs and postprocedural pain as the outcome showed that the only independent predictor was receiving procedural sedation (P = 0.005). Findings corroborate anecdotal reports of allergies as a marker for psychiatric history. However, having allergies was not associated with increased pain or need for more sedation. Further studies could prospectively assess whether allergies and psychiatric disorders affect patient/doctor perceptions beyond pain during invasive procedures.


Exploring the Potential of Plant Bioactive Compounds against Male Infertility: An In Silico and In Vivo Study.
Infertility is a well-recognized multifactorial problem affecting the majority of people who struggle with infertility issues. In recent times, among infertility cases, the male factor has acquired importance, and now it contributes to approximately half of the infertility cases because of different abnormalities. In the current study, we used natural phytochemicals as potential drug-lead compounds to target different receptor proteins that are involved in the onset of male infertility. A set of 210 plant phytochemicals were docked counter to active site residues of sex hormone-binding globulin, a disintegrin and metalloproteinase 17, and DNase I as receptor proteins. On the basis of binding scores and molecular dynamics simulation, the phytochemicals tricin, quercetin, malvidin, rhamnetin, isorhamnetin, gallic acid, kaempferol, esculin, robinetin, and okanin were found to be the potential drug candidates to treat male infertility. Molecular dynamics simulation showed tricin as a strong inhibitor of all selected receptor proteins because the ligand-protein complexes remained stabilized during the entire simulation time of 100 ns. Further, an in vivo study was designed to evaluate the effect of tricin in male rats with nicotine-induced infertility. It was explored that a high dose of tricin significantly reduced the levels of alanine transaminase, aspartate transaminase, urea, creatinine, cholesterol, triglyceride, and low-density lipoprotein and raised the level of high-density lipoprotein in intoxicated male rats. A high dose of tricin also increased the reproductive hormones (i.e., testosterone, luteinizing hormone, follicle-stimulating hormone, and prolactin) and reduced the level of DHEA-SO4. The phytochemical (tricin, 10 mg/kg body weight) also showed significant improvement in the histo-architecture after nicotine intoxication in rats. From the current study, it is concluded that the phytochemical tricin could serve as a potential drug candidate to cure male infertility.


Refractory recurrent thymoma successfully treated with long-acting somatostatin analogue and prednisolone.
The patient was 54-year-old woman diagnosed as recurrent invasive thymoma (type B3; WHO classification). Although partial response was obtained by systemic chemotherapy (PAC: cisplatin, doxorubicin, cyclophosphamide), the tumor started to become enlarged after cessation of chemotherapy. Combined treatment of octreotide and prednisolone was administrated because various chemotherapies, including PAC, were not effective. After seven months, the tumor size was markedly decreased. The combination of octreotide and prednisolone should be considered as one of the choices of treatment in patients with recurrent thymoma.


[Glutoxim in the complex treatment of tuberculosis].
Results of Glutoxim investigation are presented. Glutoxim is the the drug of the new class--thiopoietins. It is considered to be immunorehabilitator as it modulates intracellular process of thiols metabolism, initiates cytokins system, activates phagocytosis etc. Results of the glutoxim administration at the 42 patients with tuberculosis using traditional treatment regimes are presented. Results of the randomized study at the patients with severe disseminated drug-sensitive and drug-resistant pulmonary tuberculosis demonstrated high efficacy of the glutoxim and its good tolerability. Glutoxim administration allowed to shorten the period of tuberculosis intoxication signs disappearance, to shorten the period of sputum negativation and shortened the period of pulmonary inflammation reverse process. Glutoxim application was specially favorable at the patients with severe tuberculosis complicated by viral or medicamental hepatitis.


Pacemakers in patients with familial dysautonomia--a review of experience with 20 patients.
Familial dysautonomia (FD) is a genetic disease associated with a high incidence of sudden death. If fatal bradyarrhythmia is an etiological factor then the incidence of sudden death should decrease after pacemaker placement. Retrospective review of 596 registered FD patients revealed that 22 FD patients (3.7%) had pacemakers placed between December 1984 and June 2003. Clinical and electrocardiographic indications for placement and demographic data were assessed for 20 of the 22 patients (10 males, 10 females, ages 4 to 48 years). Two patients were excluded because of insufficient data. Prior to pacemaker placement, presenting symptoms were syncope and cardiac arrest, 16/20 (80%) and 6/20 (30 %), respectively. Asystole was the most frequent electrocardiographic finding and was documented in 17/20 patients (85 %). Other electrocardiographic abnormalities included bradycardia, AV block, prolonged QTc and prolonged JTc. The average duration of pacemaker utilization was 5.7 years (range 5 months to 14.5 years). Complications included infection (1 patient) and wire migration (2 patients). In the one patient with infection, the pacemaker was permanently removed. This patient then experienced multiple syncopal episodes and death. There were 7 other deaths. Three deaths occurred suddenly without preceding events, and 4 patients had non-cardiac causes of death. None of these 7 deceased patients had recurrence of syncope after pacemaker placement. In the 12 surviving patients, 6 had recurrence of syncope but none had cardiac arrest. Pacemaker placement may protect FD patients from fatal bradyarrhythmia and may decrease the incidence of syncope. However, data are limited and prospective analysis is needed.


Allo-SCT for myelofibrosis: reversing the chronic phase in the JAK inhibitor era?
At present, allo-SCT is the only curative treatment for patients with myelofibrosis (MF). Unfortunately, a significant proportion of candidate patients are considered transplant ineligible due to their poor general condition and advanced age at the time of diagnosis. The approval of the first JAK inhibitor, ruxolitinib, for patients with advanced MF in 2011 has had a qualified impact on the treatment algorithm. The drug affords substantial improvement in MF-associated symptoms and splenomegaly but no major effect on the natural history. There has, therefore, been considerable support for assessing the drug's candidacy in the peritransplant period. The drug's precise impact on clinical outcome following allo-SCT is currently not known; nor are the drug's long-term efficacy and safety known. Considering the rarity of MF and the small proportion of patients who undergo allo-SCT, well designed collaborative efforts are required. In order to address some of the principal challenges, an expert panel of laboratory and clinical experts in this field was established, and an independent workshop held during the 54th American Society of Hematology Annual Meeting in New Orleans, USA on 6 December 2013, and the European Hematology Association's Annual Meeting in Milan, Italy on 13 June 2014. This document summarizes the results of these efforts.


An emotion-induced retrograde amnesia in humans is amygdala- and beta-adrenergic-dependent.
The influence of emotion on human memory is associated with two contradictory effects in the form of either emotion-induced enhancements or decrements in memory. In a series of experiments involving single word presentation, we show that enhanced memory for emotional words is strongly coupled to decrements in memory for items preceding the emotional stimulus, an effect that is more pronounced in women. These memory effects would appear to depend on a common neurobiological substrate, in that enhancements and decrements are reversed by propranolol, a beta-adrenergic antagonist, and abolished by selective bilateral amygdala damage. Thus, our findings suggest that amygdala-dependent beta-adrenergic modulation of episodic encoding has costs as well as benefits.


Unobserved Population Heterogeneity and Dynamics of Health Disparities.
A growing body of literature has reported widening educational health disparities across birth cohorts or time periods in the United States, but has paid little attention to the implication of mortality selection on the cohort trend in health disparities. This study investigates how changes in the variance of unobserved frailty over time may complicate the interpretation of cohort trends in health disparities and life expectancy. We use the microsimulation method to test the effect of mortality selection and further propose a counterfactual simulation procedure to estimate its contribution. Data used in the simulations are based on Panel Studies of Income Dynamics 1968-2013, National Health and Nutrition Examination Survey data 1999-2012, and National Health Interview Survey data 1986-2011. Simulation shows that mortality selection may generate seemingly contradictory trends in health disparities and life expectancy across birth cohorts at the group and individual level. Life expectancy can change even when individual mortality curve is fixed. In the absence of a change in the causal effect of education on mortality at the individual level, an educational life expectancy gap can change across cohorts as a result of the change in frailty variance. Empirical analysis shows that mortality selection accounts for a sizeable amount of contribution to the widening educational life expectancy gap from the 1950s to 1960s birth cohorts in the United States. We demonstrate mortality selection can complicate the cohort trend in health disparities and life expectancy and propose a counterfactual simulation method to evaluate its contribution.


Glutathione as a mediator of cartilage oxidative stress resistance and resilience during aging and osteoarthritis.
Purpose: An underlying cause of osteoarthritis (OA) is the inability of chondrocytes to maintain homeostasis in response to changing stress conditions. The purpose of this article was to review and experimentally evaluate oxidative stress resistance and resilience concepts in cartilage using glutathione redox homeostasis as an example. This framework may help identify novel approaches for promoting chondrocyte homeostasis during aging and obesity.Materials and Methods: Changes in glutathione content and redox ratio were evaluated in three models of chondrocyte stress: (1) age- and tissue-specific changes in joint tissues of 10 and 30-month old F344BN rats, including ex vivo patella culture experiments to evaluate N-acetylcysteine dependent resistance to interleukin-1beta; (2) effect of different durations and patterns of cyclic compressive loading in bovine cartilage on glutathione stress resistance and resilience pathways; (3) time-dependent changes in GSH:GSSG in primary chondrocytes from wild-type and Sirt3 deficient mice challenged with the pro-oxidant menadione.Results: Glutathione was more abundant in cartilage than meniscus or infrapatellar fat pad, although cartilage was also more susceptible to age-related glutathione oxidation. Glutathione redox homeostasis was sensitive to the duration of compressive loading such that load-induced oxidation required unloaded periods to recover and increase total antioxidant capacity. Exposure to a pro-oxidant stress enhanced stress resistance by increasing glutathione content and GSH:GSSG ratio, especially in Sirt3 deficient cells. However, the rate of recovery, a marker of resilience, was delayed without Sirt3.Conclusions: OA-related models of cartilage stress reveal multiple mechanisms by which glutathione provides oxidative stress resistance and resilience.


Rods and cones contain antigenically distinctive S-antigens.
S-antigen (48 kDa protein or arrestin) is known to be present in rod photoreceptors. Its localization in cones is less clear with several conflicting reports among various species examined. This study employed three different anti-S-antigen antibodies (a48K, a polyclonal antiserum and two monoclonal antibodies, MAb A9-C6 and MAb 5c6.47) and examined their localization in rods and cones of human and cat retinas. To identify the respective cone types, an enzyme histochemical technique for carbonic anhydrase (CA) was employed to distinguish blue cones (CA-negative) from red or green cones (CA-positive). S-antigen localization was then examined by immunocytochemical staining of adjacent sections. In human retinas, a similar labeling pattern was seen with both a48K and MAb A9-C6, i.e., the rods and blue-sensitive cones were strongly positive, whereas the red- or green-sensitive cones showed little immunoreactivity. All human photoreceptors showed reactivity to MAb 5c6.47. In the cat retina, only CA-positive cones could be found. As in the human retina, both rods and cones of the cat were positive for MAb 5c6.47. A difference from the labeling pattern in human retina was noted for the other S-antigen antibodies; a48K labeled rods and all of the cones, whereas MAb A9-C6 reacted strongly with the rods but showed no cone staining. These results suggest that both rods and cones contain S-antigen but that they are antigenically distinctive.


Impediments and catalysts to task-shifting psychotherapeutic interventions for adolescents with PTSD: perspectives of multi-stakeholders.
This qualitative study was nested within a randomized controlled trial (RCT) where two psychotherapeutic interventions (supportive counselling and prolonged exposure for adolescents) were provided by supervised nurses (who served as 'nurse counsellors') to adolescents with PTSD in school settings. This paper describes the perspectives of nurse counsellors (NCs) and school liaisons (SLs). SLs were teachers or administrative personnel at the schools who coordinated the study visits of participants with the NCs. We focus on the impediments and catalysts to and recommendations for treatment implementation. NCs (n = 3) and SLs (n = 3) who participated in the RCT during 2014 were purposively recruited by telephone and participated in face-to-face semi-structured in-depth interviews that were recorded and doubly transcribed. Thematic content analysis was applied using Atlas.ti software to identify emerging themes. This paper describes the impediments and catalysts to provide psychotherapy by task-shifting in a community setting across three sub-themes: personal, community, and collaborative care. Although nurses were initially resistant to supervision it was central to personally coping with complex interventions, managing traumatic content, and working apart from a multi-disciplinary team. Delivering the interventions in the community presented multiple logistical impediments (e.g. transport, communication, venue suitability) which required creative solutions. In light of resource shortages, networking is central to effective delivery and uptake of the interventions. Collaboration between government departments of health and education may have a major impact on providing school-based psychotherapy through task-shifting. Impediments to implementation are not insurmountable. This article provides recommendations to maximize the success of task-shifting interventions should they be rolled out.


Development of first- and second-language vocabulary knowledge among language-minority children: evidence from single language and conceptual scores.
This study evaluated the development of vocabulary knowledge over the course of two academic years, beginning in preschool, in a large sample (N = 944) of language-minority children using scores from single-language vocabulary assessments and conceptual scores. Results indicated that although children began the study with higher raw scores for Spanish vocabulary knowledge than for English vocabulary knowledge, this was reversed by the end of the first year of the study. Similarly, at the beginning of the study unique Spanish vocabulary scores were larger than unique English or shared Spanish-English vocabulary scores; however, by the end of the first year of the study children's shared Spanish-English vocabulary scores were larger than unique English vocabulary scores, which were larger than unique Spanish vocabulary scores. These trends continued through the second year of the study. These results suggest that conceptual scoring is a useful assessment technique for children with limited exposure to their second language. Implications for assessment and instruction are discussed.


Inhibition of bacterial growth and biofilm production by constituents from Hypericum spp.
Biofilm embedded bacterial pathogens such as Staphylococcus spp., Escherichia coli, Pseudomonas aeruginosa, and Acinetobacter baumannii are difficult to eradicate and are major sources of bacterial infections. New drugs are needed to combat these pathogens. Hypericum is a plant genus that contains species known to have antimicrobial properties. However, the specific constituents responsible for the antimicrobial properties are not entirely known, nor have most compounds been tested as inhibitors of biofilm development. The investigation presented here tested seven secondary metabolites isolated from the species Hypericum densiflorum, Hypericum ellipticum, Hypericum prolificum, and Hypericum punctatum as inhibitors of bacterial growth and biofilm production. Assays were conducted against Staphylococcus epidermidis, Staphylococcus aureus, clinical methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, Escherichia coli, and Acinetobacter baumannii. Five of the seven compounds demonstrated growth inhibition against the Gram-positive bacteria with minimum inhibitory concentrations (MIC) ranging from 1.95 µg/mL to 7.81 µg/mL. Four of the secondary metabolites inhibited biofilm production by certain Gram-positive strains at sub-MIC concentrations.


The immunoreactivity of systemic antibodies to Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis in adult periodontitis.
Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis secrete several potent virulence factors and are known to be two of the major periodontal pathogens. In the present case-control study, the systemic immunoreactivity to A. actinomycetemcomitans exotoxins, cytolethal distending toxin (Cdt) and leukotoxin was analyzed in adult subjects with periodontitis and in periodontally healthy controls. Furthermore, systemic immunoreactivity to P. gingivalis was analyzed in these subjects. Reactivity to the A. actinomycetemcomitans toxins was determined in bioassays that quantified neutralizing antibodies, and P. gingivalis antibodies were detected by enzyme-linked immunosorbent assay (ELISA). The results showed a significantly enhanced immunoreactivity to P. gingivalis in the subjects with periodontitis, while the reactivity to A. actinomycetemcomitans leukotoxin showed no significant difference between patients and controls. However, combined immunoreactivity to leukotoxin and Cdt was more prevalent in the subjects with periodontitis than in the controls. In addition, immunoreactivity to leukotoxin correlated to periodontitis in men but not in women. In conclusion, data from the present study indicate that immunoreactivity to P. gingivalis is frequent in adult periodontitis, while the role of A. actinomycetemcomitans seems to be more complex and depends on gender of the infected subject as well as the virulence of the bacteria.


Modulation of glucocorticoids by the serotonin transporter polymorphism: A narrative review.
The biological background and consequences of serotonin transporter polymorphism-glucocorticoid relationship in individual differences in stress reactivity has been a major interest in neuropsychiatry research. Individual differences in glucocorticoid release have long been implicated in vulnerability to stress-related psychopathologies, like depression and anxiety in various species. Yet, it is largely elusive to what extent results from non-human primates and rodents translate to human findings. Based on our structured, comprehensive and non-hypothesis driven overview of this topic, we conclude that although gene-environment interaction studies have highlighted the importance of serotonin transporter polymorphism in modulating glucocorticoid release, there is compelling evidence that age, gender and ethnicity are significant factors too contributing to the equation. We conclude too that the way early life events modulate an individual's stress reactivity as a function of serotonin transporter polymorphism is comparable between species. These data provide a rationale for the design of new, prospective translational studies into sex-specific gene-environment interactions across the lifespan with the goal of improving preventative efforts and optimizing (personalized) treatment in stress-related psychopathologies.


Clinical features of late-onset pseudotumor cerebri fulfilling the modified dandy criteria.
To characterize the clinical features of patients with pseudotumor cerebri (PTC) fulfilling the Modified Dandy Criteria who were diagnosed at or after the age of 44 years. We reviewed the medical records between 1987 and 1999 of 14 patients at a single institution who were diagnosed as having PTC at 44 years of age or older according to the Modified Dandy Criteria: neurologic manifestations attributable to generalized increased intracranial pressure, elevated cerebrospinal fluid pressure with normal cerebrospinal fluid composition demonstrated by lumbar puncture, and normal or small ventricles demonstrated by neuroimaging. We documented presenting symptoms and signs, significant medical conditions, and visual field follow-up. There were nine women and five men. Nine patients (64%) were obese. Five patients (36%) were asymptomatic. None presented with headache alone. Four patients (29%) had an identifiable cause of intracranial hypertension, including two with transverse sinus thrombosis, one with severe chronic obstructive pulmonary disease and cor pulmonale, and one with corticosteroid withdrawal after prolonged administration. During a median follow-up of 2 years of 12 patients, visual fields remained stable in 8, improved in 3, and worsened in 1. In comparison with patients who have idiopathic intracranial hypertension, our small series of 14 patients diagnosed after the age of 44 years were more often men, were less often obese, were less symptomatic, and had identifiable causes of intracranial hypertension in a substantial minority (29%). The visual prognosis in this age group is generally good. Because the nonidiopathic causes of PTC would be overlooked by adhering to the Modified Dandy Criteria, we propose a modification that excludes patients who have dural venous sinus disease demonstrated on magnetic resonance imaging and those who may be exposed to medications or toxins or have systemic disorders that are known to increase intracranial pressure.


A dominant role for the methyl-CpG-binding protein Mbd2 in controlling Th2 induction by dendritic cells.
Dendritic cells (DCs) direct CD4(+) T-cell differentiation into diverse helper (Th) subsets that are required for protection against varied infections. However, the mechanisms used by DCs to promote Th2 responses, which are important both for immunity to helminth infection and in allergic disease, are currently poorly understood. We demonstrate a key role for the protein methyl-CpG-binding domain-2 (Mbd2), which links DNA methylation to repressive chromatin structure, in regulating expression of a range of genes that are associated with optimal DC activation and function. In the absence of Mbd2, DCs display reduced phenotypic activation and a markedly impaired capacity to initiate Th2 immunity against helminths or allergens. These data identify an epigenetic mechanism that is central to the activation of CD4(+) T-cell responses by DCs, particularly in Th2 settings, and reveal methyl-CpG-binding proteins and the genes under their control as possible therapeutic targets for type-2 inflammation.


Hopping approach towards exciton dissociation in conjugated polymers.
By employing random walk an analytic theory for the dissociation of singlet excitons in a random organic solid, for instance, a conjugated polymer, has been developed. At variance of conventional three-dimensional Onsager theory, it is assumed that an exciton with finite lifetime can first transfer endothermically an electron to an adjacent site, thereby generating a charge transfer state whose energy is above the energy of that of the initial exciton. In a second step the latter can fully dissociate in accordance with Onsager's concept Brownian motion. The results indicate that, depending of the energy required for the first jump, the first jump contributes significantly to the field dependence of the dissociation yield. Disorder weakens the temperature dependence of the yield dramatically and precludes extracting information on the exciton binding energy from it.


EFFECT OF BOLUS SIZE ON DEGLUTITION AND ESOPHAGEAL TRANSIT IN HEALTHY DOGS.
Contrast videofluoroscopy is the gold standard procedure for evaluating dysphagia in humans, but quantitative measures vary depending on bolus size and consistency. We hypothesized that quantitative measures made during videofluoroscopy of swallowing in dogs would differ between bolus sizes and consistencies. Ten healthy adult dogs were enrolled a prospective, crossover experimental study and underwent contrast videofluoroscopy while swallowing liquid (5, 10, and 15 ml) and canned food (3, 8, and 12 g) boluses. Maximum pharyngeal contraction occurred significantly later with medium solid boluses than with medium liquid boluses, with a mean difference of 0.021 s (adjusted P = 0.042). Upper esophageal sphincter opening occurred significantly earlier with large solid boluses than with medium solid boluses, with a mean difference of 0.018 s (adjusted P = 0.025). Thoracic esophageal transit time was significantly longer with small solid boluses than with small liquid boluses, with a mean difference of 0.68 s (adjusted P = 0.004). Odds of primary esophageal peristalsis occurring were significantly (18.5 times) higher with large solid vs. large liquid boluses (adjusted P = 0.031). No other statistical comparisons reached significance. Based on these results, we recommend a standardized approach to videofluoscopy in dogs with determination of quantitative measures using medium liquid and soft food boluses to minimize effects of size. Furthermore, we conclude that measurements made on liquid swallows should not be directly compared to measurements made on soft food boluses.


Continuous practice quality improvement initiative for communication of critical findings in neuroradiology.
The authors examined faculty's compliance with a hospital-approved neuroradiology critical findings (CFs) policy, which requires urgent verbal communication with the clinical team when 17 specific critical pathologies are identified. During June 2011 to July 2013, 50 random neuroradiology reports were sampled monthly for the presence of CFs and appropriate action. Faculty were provided ongoing feedback, and at the end of 2 years, the medical records for cases with noncommunicated CFs were reviewed to identify potential adverse outcomes. Of the 1200 reviewed reports, 195 (16.3%) had and 1005 (83.8%) did not have a CF. A total of 176 of 195 (90.3%) cases with CFs were communicated, and compliance increased from 77.4% to 85.6% (P = .027) since the monthly sampling was instituted; 1 of 19 (5.3%) noncommunicated CFs resulted in a potential adverse event. The ongoing monthly feedback resulted in improved faculty compliance with the CF policy. However, a small number of cases with CFs are still not being communicated.


Heparin-induced thrombocytopenia in critically ill patients.
Critically ill patients commonly evince thrombocytopenia, either evident on admission to the intensive care unit (ICU) or that develops during their stay. Heparin-induced thrombocytopenia (HIT) explains thrombocytopenia in only approximately 1/100 critically ill patients; also, only 1 or 2 in 10 ICU patients with a positive PF4-dependent enzyme immunoassay has "true" HIT. Thus, there is major potential for overdiagnosis of HIT in the ICU. A recent study showing that dalteparin is associated with a reduced frequency of HIT indicates that critically ill patients too can benefit from the HIT-reducing potential of this low molecular weight heparin preparation.


Antiplatelet therapy for preventing stroke in patients with non-valvular atrial fibrillation and no previous history of stroke or transient ischemic attacks.
Atrial fibrillation (AF) carries an increased risk of stroke; antiplatelet agents are proven effective for stroke prevention in other settings. The objective of this review was to determine the efficacy and safety of antiplatelet therapy for prevention of stroke in patients with chronic non-valvular AF. We searched the Cochrane Stroke Group Specialised Register of Trials, MEDLINE database (June 1999), and the database of the Antithrombotic Trialists Collaboration, as well as reference lists of relevant articles. All randomized trials comparing antiplatelet therapies to placebo in patients with non-valvular AF and no history of transient ischemic attack (TIA) or stroke. Trials for inclusion were independently selected by two reviewers who also extracted each outcome and double-checked the data. The Peto method was used for combining odds ratios. All analysis were, as far as possible, "intention-to-treat". Since the published results of two trials included 3-8% of participants with prior stroke or TIA, unpublished results excluding these participants were obtained from the Atrial Fibrillation Investigators. Among 1680 participants without prior stroke/TIA, randomized to aspirin (N = 838) or placebo in two trials, aspirin was associated with nonsignificantly lower risks of ischemic stroke (OR = 0.71, CI 95% 0. 46 - 1.10), all stroke (OR = 0.70, CI 95% 0.45 - 1.08) all disabling/fatal stroke (OR =0.88, CI 95% 0.48 - 1.58) and the constellation of stroke, MI or vascular death (OR = 0.76, CI 95% 0. 54 - 1.05 ). Considering all randomized participants including those with prior stroke or TIA, reductions in these events by aspirin were consistently smaller and marginally statistically significant: ischemic stroke (OR = 0.77, CI 95% 0.60-1.00), all stroke (OR = 0.76, CI 95% 0.61 - 0.93), all disabling/fatal stroke (OR = 0.87, CI 95% 0.64 - 1.19) and the combined outcome (OR = 0.79, CI 95% 0.64 - 0. 99). No increase in major hemorrhage was seen, but the number of hemorrhagic events was small. Considering all randomized data, aspirin modestly (by about 20%) reduces stroke and major vascular events in nonvalvular AF. For primary prevention among AF patients with an average stroke rate of 4.5%/year, about 10 strokes would be prevented yearly for every 1000 given aspirin.


Inhibition of the erbB-2 tyrosine kinase receptor in breast cancer cells by phosphoromonothioate and phosphorodithioate antisense oligonucleotides.
Antisense activity against erbB-2 of a variety of sulfur-modified oligonucleotides was examined in a breast cancer cell line which overexpresses this oncogene. Using a 15 base anti-erbB-2 sequence previously shown to be effective, various backbone configurations containing phosphoromonothioate or phosphorodithioate linkages were evaluated for antisense activity by a two-color flow cytometric assay. This sequence was effective in inhibiting the production of erbB-2 protein when it was configured as a monothioate at each linkage and as an alternating dithioate/phosphodiester. Both of these compounds were also able to specifically inhibit erbB-2 mRNA expression, indicative of RNase H-mediated activity. The same sequence protected by either three dithioate or three monothioate linkages at each end was ineffective as an antisense reagent, suggesting that endonuclease activity is a significant determinant of the stability of oligonucleotides. Finally, the erbB-2 sequence target was shifted in an effort to improve antisense activity. A new lead sequence was identified that was significantly more effective in inhibiting erbB-2 protein levels and retained activity at lower concentrations.


Prediction of shot success for basketball free throws: visual search strategy.
In ball games, players have to pay close attention to visual information in order to predict the movements of both the opponents and the ball. Previous studies have indicated that players primarily utilise cues concerning the ball and opponents' body motion. The information acquired must be effective for observing players to select the subsequent action. The present study evaluated the effects of changes in the video replay speed on the spatial visual search strategy and ability to predict free throw success. We compared eye movements made while observing a basketball free throw by novices and experienced basketball players. Correct response rates were close to chance (50%) at all video speeds for the novices. The correct response rate of experienced players was significantly above chance (and significantly above that of the novices) at the normal speed, but was not different from chance at both slow and fast speeds. Experienced players gazed more on the lower part of the player's body when viewing a normal speed video than the novices. The players likely detected critical visual information to predict shot success by properly moving their gaze according to the shooter's movements. This pattern did not change when the video speed was decreased, but changed when it was increased. These findings suggest that temporal information is important for predicting action outcomes and that such outcomes are sensitive to video speed.


Intraruminal rehydration of ovine fetuses.
During oral rehydration of adult mammals, oropharyngeal stimulation, the act of swallowing, and/or gastric factors contribute to a rapid decrease in plasma arginine vasopressin (AVP) that precedes plasma osmolality changes. To determine whether similar mechanisms are present in the developing fetus, six chronically prepared ovine fetuses were rehydrated with intraruminal (IR) distilled water infusions (1 ml.kg-1.min-1 for 60 min) after 43 +/- 3 h of maternal water deprivation. In response to maternal dehydration, significant increases were noted in maternal and fetal mean plasma osmolalities, sodium and AVP concentrations, and fetal urine osmolality. As estimated by hematocrit, fetal intravascular volume decreased by 11%. Fetal rehydration via IR distilled water infusion evoked a significant decrease in fetal plasma osmolality but no change in urine osmolality. Unexpectedly, fetal arterial blood pressure increased and arterial PO2 decreased while fetal hematocrit indicated a further 7% decrease in intravascular volume after the IR infusion. There was a nonsignificant trend toward increased fetal glomerular filtration rate, urine volume, and plasma AVP concentrations. Identical IR water infusions to five euhydrated fetuses resulted in significant decreases in fetal plasma osmolality and increases in glomerular filtration rate, urine flow, and osmolar excretion. The euhydrated fetuses also exhibited significant increases in mean arterial blood pressure and hematocrit and decreased fetal arterial PO2. These results indicate that IR water does not suppress AVP secretion in the dehydrated ovine fetus. Rather, both euhydrated and dehydrated fetuses exhibit an idiosyncratic vasoconstrictive response to IR water.


Clade-specific virulence patterns of Mycobacterium tuberculosis complex strains in human primary macrophages and aerogenically infected mice.
In infection experiments with genetically distinct Mycobacterium tuberculosis complex (MTBC) strains, we identified clade-specific virulence patterns in human primary macrophages and in mice infected by the aerosol route, both reflecting relevant model systems. Exclusively human-adapted M. tuberculosis lineages, also termed clade I, comprising "modern" lineages, such as Beijing and Euro-American Haarlem strains, showed a significantly enhanced capability to grow compared to that of clade II strains, which include "ancient" lineages, such as, e.g., East African Indian or M. africanum strains. However, a simple correlation of inflammatory response profiles with strain virulence was not apparent. Overall, our data reveal three different pathogenic profiles: (i) strains of the Beijing lineage are characterized by low uptake, low cytokine induction, and a high replicative potential, (ii) strains of the Haarlem lineage by high uptake, high cytokine induction, and high growth rates, and (iii) EAI strains by low uptake, low cytokine induction, and a low replicative potential. Our findings have significant implications for our understanding of host-pathogen interaction and factors that modulate the outcomes of infections. Future studies addressing the underlying mechanisms and clinical implications need to take into account the diversity of both the pathogen and the host. Clinical strains of the Mycobacterium tuberculosis complex (MTBC) are genetically more diverse than previously anticipated. Our analysis of mycobacterial growth characteristics in primary human macrophages and aerogenically infected mice shows that the MTBC genetic differences translate into pathogenic differences in the interaction with the host. Our study reveals for the first time that "TB is not TB," if put in plain terms. We are convinced that it is very unlikely that a single molecular mechanism may explain the observed effects. Our study refutes the hypothesis that there is a simple correlation between cytokine induction as a single functional parameter of host interaction and mycobacterial virulence. Instead, careful consideration of strain- and lineage-specific characteristics must guide our attempts to decipher what determines the pathological potential and thus the outcomes of infection with MTBC, one of the most important human pathogens.


Integrating the multiple dimensions of genomic and epigenomic landscapes of cancer.
Advances in high-throughput, genome-wide profiling technologies have allowed for an unprecedented view of the cancer genome landscape. Specifically, high-density microarrays and sequencing-based strategies have been widely utilized to identify genetic (such as gene dosage, allelic status, and mutations in gene sequence) and epigenetic (such as DNA methylation, histone modification, and microRNA) aberrations in cancer. Although the application of these profiling technologies in unidimensional analyses has been instrumental in cancer gene discovery, genes affected by low-frequency events are often overlooked. The integrative approach of analyzing parallel dimensions has enabled the identification of (a) genes that are often disrupted by multiple mechanisms but at low frequencies by any one mechanism and (b) pathways that are often disrupted at multiple components but at low frequencies at individual components. These benefits of using an integrative approach illustrate the concept that the whole is greater than the sum of its parts. As efforts have now turned toward parallel and integrative multidimensional approaches for studying the cancer genome landscape in hopes of obtaining a more insightful understanding of the key genes and pathways driving cancer cells, this review describes key findings disseminating from such high-throughput, integrative analyses, including contributions to our understanding of causative genetic events in cancer cell biology.


Hydrocephalus in achondroplasia: efficacy of endoscopic third ventriculostomy.
Ventriculoperitoneal shunts (VPSs) for hydrocephalus in patients with achondroplasia are known to have a higher failure rate than in other hydrocephalus populations. However, the etiology of hydrocephalus in this group is considered "communicating," and, therefore, potentially not amenable to endoscopic third ventriculostomy (ETV). ETV has, nonetheless, been reported to be successful in a small number of patients with achondroplasia. The authors aimed to investigate the long-term results of ETV in this population. Patients with achondroplasia who had undergone surgical treatment for hydrocephalus (ETV or VPS placement) were identified. In patients who had undergone ETV, medical records and neuroimages were reviewed to determine ventricular volumes and frontal and occipital horn ratios (FOHRs) pre- and postoperatively, as well as the incidence of surgical complications and reoperation. Patients who underwent VPS placement were included for historical comparison, and their medical records were reviewed for basic demographic information as well as the incidence of surgical complications and reoperation. Of 114 pediatric patients with achondroplasia referred for neurosurgical consultation, 19 (17%) were treated for hydrocephalus; 10 patients underwent ETV only, 7 patients underwent VPS placement only, and 2 patients had a VPS placed followed by ETV. In patients treated with ETV, ventricular volume and FOHRs were normal, if measured at birth, and increased significantly until the time of the ETV. After ETV, all patients demonstrated significant and sustained decreases in ventricular measurements with surveillance up to 15 years. There was a statistically significant difference in rates of repeat CSF surgery between the ETV and VPS cohorts (0/12 vs 7/9, p < 0.001). ETV was efficacious, safe, and durable in the treatment of hydrocephalus in patients with achondroplasia. Although many studies have indicated that hydrocephalus in these patients is "communicating," a subset may develop an "obstructive" component that is progressive and responsive to ETV.


Structure and reactivity of a seven-coordinate ruthenium acylperoxo complex.
The use of metal-acylperoxo complexes as oxidants has been little explored. Herein we report the synthesis and characterization of the first seven-coordinate Ru-acylperoxo complex, [RuIV(bdpm)(pic)2(mCPBA)]+ (H2bdpm = [2,2'-bipyridine]-6,6'-diylbis(diphenylmethanol); pic = 4-picoline; HmCPBA = m-chloroperbenzoic acid). This complex is a highly reactive oxidant for C-H bond activation and O-atom transfer reactions.


CD47 in the tumor microenvironment limits cooperation between antitumor T-cell immunity and radiotherapy.
Although significant advances in radiotherapy have increased its effectiveness in many cancer settings, general strategies to widen the therapeutic window between normal tissue toxicity and malignant tumor destruction would still offer great value. CD47 blockade has been found to confer radioprotection to normal tissues while enhancing tumor radiosensitivity. Here, we report that CD47 blockade directly enhances tumor immunosurveillance by CD8(+) T cells. Combining CD47 blockade with irradiation did not affect fibrosarcoma growth in T cell-deficient mice, whereas adoptive transfer of tumor-specific CD8(+) T cells restored combinatorial efficacy. Furthermore, ablation of CD8(+) T cells abolished radiotherapeutic response in immunocompetent syngeneic hosts. CD47 blockade in either target cells or effector cells was sufficient to enhance antigen-dependent CD8(+) CTL-mediated tumor cell killing in vitro. In CD47-deficient syngeneic hosts, engrafted B16 melanomas were 50% more sensitive to irradiation, establishing that CD47 expression in the microenvironment was sufficient to limit tumor radiosensitivity. Mechanistic investigations revealed increased tumor infiltration by cytotoxic CD8(+) T cells in a CD47-deficient microenvironment, with an associated increase in T cell-dependent intratumoral expression of granzyme B. Correspondingly, an inverse correlation between CD8(+) T-cell infiltration and CD47 expression was observed in human melanomas. Our findings establish that blocking CD47 in the context of radiotherapy enhances antitumor immunity by directly stimulating CD8(+) cytotoxic T cells, with the potential to increase curative responses.


Palliative care in adolescents and young adults with cancer.
Adolescents and young adults (AYA) with advanced or terminal cancer have distinctive medical and psychosocial needs that may not have been adequately provided by either pediatric or adult palliative care services. A discussion group, as part of a larger workshop on AYA with cancer, was held in Toronto on March 11-13, 2010;117:-. Recommendations were as follows: Develop a specific AYA screening tool designed to detect increased anxiety or new symptoms and to initiate discussion about palliative or symptom care; Set Canadian standards for palliative care in AYA patients. These standards should be included in hospital accreditation; Involve the palliative/symptom care team early in the disease trajectory to help manage clinically important symptoms that may not be associated with imminent death; Establish specific AYA multidisciplinary palliative care teams throughout Canada that are flexible and can work in both pediatric and adult facilities, and are able to work in a "virtual" environment to support patients being cared for at home; Improve physical facilities in hospices and hospitals to meet the distinctive needs of terminally ill AYA patients; Enhance support for palliative care at home by: changing legislation to improve Compassionate Care Benefits and developing "virtual palliative care support teams". Adequate provision of AYA palliative care and symptom management services will likely confer notable benefits to AYA patients and their families, and is likely to be cost saving to the tax payer by avoiding prolonged hospitalization and promoting easier return to work for the families and caregivers.


A national COVID-19 quarantine survey and its impact on the Italian sports community: Implications and recommendations.
The outbreak of the 2019 coronavirus disease (COVID-19) created an international public health emergency, challenging the psychological resilience of the general population. Regarding this matter, a web-based survey was performed. Data were collected from the following 1,668 self-selected volunteers: 800 athletes (28.30 ± 10.93 years old); 558 coaches (36.91 ± 11.93 years old); and 310 sports managers (42.07 ± 13.38 years old). To assess the level of psychological stress, an Impact of the Event Scale-Revised (IES-R) questionnaire was used. The results indicated that 34.4% of the participants who were interviewed were affected by subjective distress while 26.4% rated their psychological impact from the sports activity interruption as severe. Separated one-way analysis of variance (ANOVA) tests showed significant differences in the IES-R total score (TS), indicating that the level of stress in terms of gender revealed that women were more stressed than men (p = 0.000), for "sports roles" in which the manager and coaches were more stressed than the athletes (p < 0.05), and "type of sport" in which fitness and individual athletes were more stressed than team athletes (p < 0.01). The middle-level athletes showed significantly more hyperarousal levels than high-level athletes (p = 0.012). The results of this survey may raise awareness of this problem and help athletic associations to have appropriate guidelines in order to better sustain their memberships and organize an optimal resumption of their sports activities. Along these lines, social interactions, which are typical of team sports, are crucial to warrant resilience and psychological health. The athletes by managing independently the new rules and measures, thanks to a clear communication, could improve their adaptive stress reaction.


Compassion Satisfaction, Burnout, and Secondary Traumatic Stress Among Nursing Staff at an Academic Medical Center: A Cross-Sectional Analysis.
Although several studies have recently described compassion satisfaction (CS), burnout (BO), and secondary traumatic stress (STS) in nurses, few to date have examined these issues across nursing specialties. Such examination is needed to inform future nursing-subspecialty tailored interventions. To examine (1) differences in CS, BO, and STS across nursing specialties and (2) differences associated with demographic, work-related, and behavioral factors among nurses. A secondary analysis of survey responses from nurses (N = 350) at an academic medical center. Demographic, behavioral, work-related, and professional quality of life variables were analyzed using hierarchical regression analyses. CS, BO, and STS scores significantly varied across specialties with emergency nurses experiencing significantly elevated rates of BO and STS, and lowest rates of CS; scores were also differentially associated with demographic, work-related, behavioral, and workplace violence variables. Key differences in CS, BO, and STS by nursing specialty suggests the importance of tailoring BO and STS mitigative interventions. BO and STS risk factors should be assessed in nurses (e.g., behavioral health problems and poor sleep quality) and specialty-specific interventions (e.g., reducing workplace violence exposure in emergency settings) may be considered to improve CS while reducing BO and STS among nurses.


Multifaceted intervention to improve diagnosis and treatment of osteoporosis in patients with recent wrist fracture: a randomized controlled trial.
Older patients who experience a fragility fracture are at high risk of future fractures but are rarely tested or treated for osteoporosis. We developed a multifaceted intervention directed at older patients with wrist fractures (in the form of telephone-based education) and their physicians (in the form of guidelines endorsed by opinion leaders, supported by reminders) to improve the quality of osteoporosis care. In a randomized controlled trial with blinded ascertainment of outcomes, we compared our intervention with usual care (provision of printed educational materials to patients). Eligible patients were those older than 50 years of age who had experienced a wrist fracture and were seen in emergency departments and fracture clinics; we excluded those who were already being treated for osteoporosis. The primary outcome was bisphosphonate treatment within 6 months after the fracture. Secondary outcomes included bone mineral density testing, "appropriate care" (consisting of bone mineral density testing with treatment if bone mass was low) and quality of life. We screened 795 patients for eligibility and randomly assigned 272 to the intervention (137 patients) or control (135 patients) group. The median age was 60 years; 210 (77%) of the subjects were women, and 130 (48%) reported a previous fracture as an adult. Six months after the fracture, 30 (22%) of the intervention patients, as compared with 10 (7%) of the control patients, were receiving bisphosphonate therapy for osteoporosis (adjusted relative risk [RR] 2.6, 95% confidence interval [CI] 1.3-5.1, p = 0.008). Intervention patients were more likely than control patients to undergo bone mineral density testing (71/137 [52%] v. 24/135 [18%]; adjusted RR 2.8, 95% CI 1.9-4.2, p < 0.001) and to receive appropriate care (52/137 [38%] v. 15/135 [11%]; adjusted RR 3.1, 95% CI 1.8-5.3, p < 0.001). There were no differences between the groups in other outcomes. One patient died, and 4 others experienced recurrent fracture. A multifaceted intervention directed at high-risk patients and their physicians substantially increased rates of testing and treatment for osteoporosis. Nevertheless, more than half of the patients in the intervention group were not receiving appropriate care 6 months after their fracture, which suggests that additional strategies should be explored. (ClinicalTrials.gov trial register no. NCT00152321.).


[Diagnosis and treatment of complicated and recurrent traumatic strictures of the urethral canal].
In 40 patients, the treatment for traumatic stricture of the urethra lasted 3 and more years. In complex examination, the short urethral stricture was revealed in 10, long one--in 30 patients. Stricture of the membraniform portion of the urethra was diagnosed in 28, prostatic one--in 10, spongiform one--in 2 patients; changes in the prostate and seminal vesicles were revealed in 36. At operation, the scars of the narrowed urethra were excised en-block with the cicatricially changed prostate up to the neck of the urinary bladder, it was anastomosed to the unchanged portion of the urethra. Drainage was accomplished via the urethra by means of the Foley catheter and suprapubic drain. In all the patients, the independent uresis was restored.


Affected Others Responsivity to Gambling Harm: An International Taxonomy of Consumer-Derived Behaviour Change Techniques.
Affected others impacted by someone else's gambling utilise numerous behaviour change strategies to minimise gambling-related harm but knowledge on what these strategies are and how they are implemented is limited. This study aimed to develop a comprehensive data-driven taxonomy of the types of self-help strategies used by affected others, and to categorize these into high-level behaviour change techniques (BCTs). Two taxonomies were developed using an inductive and deductive approach which was applied to a dataset of online sources and organised into the Rubicon model of action phases. These taxonomies were family-focused (how to reduce the impact of gambling harm on families) and gambler-focused (how to support the gambler in behaviour change). In total, 329 online sources containing 3536 different strategies were identified. The family-focused classification contained 16 BCTs, and the most frequent were professional support, financial management and planned consequences. The gambler-focused classification contained 11 BCTs, and the most frequent were feedback on behaviours, professional support and financial management. The majority of family- and gambler-focused BCTs fell under the actional phase of the Rubicon model. Grounded in lived experience, the findings highlight the need for intervention and resource development that includes a wide range of specific techniques that affected others can utilise.


No Evidence of Apoptotic Response of the Potato Psyllid Bactericera cockerelli to "Candidatus Liberibacter solanacearum" at the Gut Interface.
"Candidatus Liberibacter solanacearum" is a pathogen transmitted by the potato psyllid Bactericera cockerelli (Šulc) (Hemiptera: Triozidae) in a persistent manner. In this study, we investigated the molecular interaction between "Ca. Liberibacter solanacearum" and the potato psyllid at the gut interface. Specifically, we focused on the apoptotic response of potato psyllids to the infection by two "Ca. Liberibacter solanacearum" haplotypes, LsoA and LsoB. To this end, we first quantified and localized "Ca. Liberibacter solanacearum" in the gut of adult psyllids. We then evaluated the existence of an apoptotic response in the insect gut using microscopy analyses to visualize the nuclei and the actin cytoskeleton of the gut cells and DNA fragmentation analyses by agarose gel electrophoresis. We also performed annexin V cell death assays to detect apoptosis. Finally, we annotated apoptosis-related genes from the potato psyllid transcriptome and evaluated their expression in response to "Ca. Liberibacter solanacearum" infection. The results showed no cellular markers of apoptosis despite the large amount of "Ca. Liberibacter solanacearum" present in the psyllid gut. In addition, only three genes potentially involved in apoptosis were regulated in the psyllid gut in response to "Ca. Liberibacter solanacearum": the apoptosis-inducing factor AIF3 was downregulated in LsoA-infected psyllids, while the inhibitor of apoptosis IAPP5 was downregulated and IAP6 was upregulated in LsoB-infected psyllids. Overall, no evidence of apoptosis was observed in the gut of potato psyllid adults in response to either "Ca. Liberibacter solanacearum" haplotype. This study represents a first step toward understanding the interactions between "Ca. Liberibacter solanacearum" and the potato psyllid, which is crucial to developing approaches to disrupt their transmission.


Expression of a provirus of human T cell leukaemia virus type I by DNA transfection.
We isolated the full length provirus of human T cell leukaemia virus type I (HTLV-I) from MT-2, a lymphoid cell line producing HTLV-I. In three non-lymphoid cell lines (COS7, human osteosarcoma HOS cells, and HeLa) this provirus expressed a trans-acting activity after co-transfection with a recombinant plasmid carrying a bacterial chloramphenicol acetyltransferase gene under the control of a long terminal repeat of HTLV-I provirus. The trans-acting protein p40 was detected by immunoprecipitation in transfected HOS cells. Structural proteins of HTLV-I, the gag and env products, were also formed and processed in the same manner as observed in MT-2 cells. In transfected HeLa cells, the p40 protein was mainly localized in the nucleus, while other structural proteins were detected in the cytoplasm and/or the membrane by indirect immunofluorescence. Syncytium formation was observed in HeLa cells after transfection. These results demonstrated that non-lymphoid cells could produce the major proteins of HTLV-I after DNA transfection of the cloned provirus.


Solution structure of a repeated unit of the ABA-1 nematode polyprotein allergen of Ascaris reveals a novel fold and two discrete lipid-binding sites.
Nematode polyprotein allergens (NPAs) are an unusual class of lipid-binding proteins found only in nematodes. They are synthesized as large, tandemly repetitive polyproteins that are post-translationally cleaved into multiple copies of small lipid binding proteins with virtually identical fatty acid and retinol (Vitamin A)-binding characteristics. They are probably central to transport and distribution of small hydrophobic compounds between the tissues of nematodes, and may play key roles in nutrient scavenging, immunomodulation, and IgE antibody-based responses in infection. In some species the repeating units are diverse in amino acid sequence, but, in ascarid and filarial nematodes, many of the units are identical or near-identical. ABA-1A is the most common repeating unit of the NPA of Ascaris suum, and is closely similar to that of Ascaris lumbricoides, the large intestinal roundworm of humans. Immune responses to NPAs have been associated with naturally-acquired resistance to infection in humans, and the immune repertoire to them is under strict genetic control. The solution structure of ABA-1A was determined by protein nuclear magnetic resonance spectroscopy. The protein adopts a novel seven-helical fold comprising a long central helix that participates in two hollow four-helical bundles on either side. Discrete hydrophobic ligand-binding pockets are found in the N-terminal and C-terminal bundles, and the amino acid sidechains affected by ligand (fatty acid) binding were identified. Recombinant ABA-1A contains tightly-bound ligand(s) of bacterial culture origin in one of its binding sites. This is the first mature, post-translationally processed, unit of a naturally-occurring tandemly-repetitive polyprotein to be structurally characterized from any source, and it belongs to a new structural class. NPAs have no counterparts in vertebrates, so represent potential targets for drug or immunological intervention. The nature of the (as yet) unidentified bacterial ligand(s) may be pertinent to this, as will our characterization of the unusual binding sites.


Oviposition preference and life-history parameters of Callosobruchus maculatus (Coleoptera: Chrysomelidae) on different soybean (Glycine max) cultivars.
Callosobruchus maculatus (F.) (Coleoptera: Chrysomelidae) is one of the most destructive pests of stored legume seeds in many regions of the world. Evaluation of varietal resistance of host seeds to C. maculatus infestation can be useful in preventing severe damage. We studied the susceptibility and resistance of eight conventional soybean cultivars (Caspian, Kosar, L17, Nekador, Sari, Tapour, Williams and Zane) based on the oviposition preference (choice and no-choice tests) and population growth parameters of the pest. Compared with other cultivars tested, oviposition preference of C. maculatus was the lowest on Nekador. The developmental time of C. maculatus differed from 40.34 days on Nekador to 48.35 days on L17, and was negatively correlated with the seed protein content. Other performance measures of C. maculatus did not match the oviposition preference. Immature survival and female longevity were highest on Caspian. The intrinsic rate of increase (rm ) was higher on Tapour, Nekador and Caspian than on Zane, Williams, and Kosar. A positive correlation was observed between the rm value of the pest and moisture content of the cultivars. Cluster analysis showed that cvs Nekador, Sari, Tapour, and Caspian were relatively susceptible, and cvs Kosar, Zane, Williams and L17 were partially resistant to this pest. Protein and moisture contents of soybean cultivars play an important role in the development and population growth of C. maculatus, and these traits could be used to develop safe and effective management strategies for this pest on stored soybean seeds. © 2022 Society of Chemical Industry.


Implementing dynamic daylight spectra with light-emitting diodes.
Algorithms for selecting LEDs to imitate a group of daylight spectra, instead of fixed-spectrum lighting, are based on minimizing two indices. The first index related to the LEDs only is minimized for determining LED candidates. Minimizing the second index obtained by applying the daylight spectra to the candidates achieves a minimax solution. The sum of the second indices of the daylight spectra can be well approximated by that of the average spectrum of the daylight spectra and is treated as a target spectrum for the LED selection. A pruning process is followed to delete redundant LEDs.


[Effects of Cd2+ on seedling growth and phytohormone contents of Glycine max].
A laboratory incubation experiment was conducted to study the effects of different Cd2+ concentrations on seedling growth and phytohormone contents of Glycine max through determining some physiological and biochemical indexes. The results showed as follows: (1) Different Cd2+ concentrations inhibited the synthesis of indoleacetic acid (IAA) and gibberellins (GA3) in roots and stimulated the synthesis of zeatin (Z) and abscisic acid (ABA) not only in roots but also in aerial parts of Glycine Max. Cd2+ stimulated the synthesis of IAA and GA3 in aerial parts at lower concentrations, but inhibited the synthesis of IAA and GA3 at higher concentrations. (2) Cd2+ stress for 84h increased the root vitality and the contents of chlorophyll a and b, but no significant difference was found in carotinoid contents compared with the control. (3) Cd2+ stress decreased POD activities and MAD contents atlower concentrations and increased POD activities and MAD contents at higher concentrations. With increasing Cd2+ concentrations, this increase became significant gradually. (4) Cd2+ stress with lower concentrations stimulated the physiological activity of Glycine max seedling in a short time. When Cd2+ concentration was 0.50 mg/L, the root vitality, IAA and GA3 contents of Glycine max were the highest, and POD activity was the lowest.


SESAM mode-locked Yb:CaGdAlO4 thin disk laser with 62 fs pulse generation.
We present a semiconductor saturable absorber mirror (SESAM) mode-locked thin disk laser (TDL) based on Yb:CaGdAlO(4) (Yb:CALGO) generating 62 fs pulses, which is the shortest pulse duration achieved from mode-locked TDLs to date. The oscillator operates at a repetition rate of 65 MHz and delivers 5.1 W of average output power. The short pulse duration of our TDL in combination with the high intracavity peak power of 44 MW makes this oscillator attractive for intracavity table-top extreme nonlinear optics applications such as high harmonic generation and vacuum ultraviolet frequency comb generation. The current average power was limited by the quality of the Yb:CALGO disk. However, power scaling of Yb:CALGO TDLs to the multi-10-W range with short pulse durations (<100 fs) appears feasible in the near future by using thinner disks of better quality and further optimized SESAMs.


Effect of nano-sized, elemental selenium supplement on the proteome of chicken liver.
The nano-sized (100-500 nm) selenium has higher bioavailability and relatively lower toxicity compared to other selenium forms. The objective of the present study was to compare liver proteome profiles of broiler chicken fed with control diet without Se supplementation and diet supplemented with nano-Se with 4.25 mg/kg DM. Differential proteome analyses were performed by two-dimensional gel electrophoresis (2D-PAGE) followed by tryptic digestion and protein identification by liquid chromatography-mass spectrometry (LC-MS). Seven hundred and eight spots were detected, and 18 protein spots showed significant difference in their intensity (p < 0.05) between the two groups. In response to nano-Se supplementation, the expression of 8 proteins was higher, and 5 proteins were lower in nano-Se supplemented group compared to control group. The functions of the differentially expressed proteins indicate that the high dose of selenium supplementation induced a dietary stress. Selenium supplementation may influence the metabolism of fatty acids and carbohydrates and antioxidant system, and increase the quantity of cytoskeletal actin and the expression of actin regulatory protein as well.


Deficiency of endogenous acute phase serum amyloid A does not affect atherosclerotic lesions in apolipoprotein E-deficient mice.
Although elevated plasma concentrations of serum amyloid A (SAA) are associated strongly with increased risk for atherosclerotic cardiovascular disease in humans, the role of SAA in the pathogenesis of lesion formation remains obscure. Our goal was to determine the impact of SAA deficiency on atherosclerosis in hypercholesterolemic mice. Apolipoprotein E-deficient (apoE(-/-)) mice, either wild type or deficient in both major acute phase SAA isoforms, SAA1.1 and SAA2.1, were fed a normal rodent diet for 50 weeks. Female mice, but not male apoE-/- mice deficient in SAA1.1 and SAA2.1, had a modest increase (22%; P≤0.05) in plasma cholesterol concentrations and a 53% increase in adipose mass compared with apoE-/- mice expressing SAA1.1 and SAA2.1 that did not affect the plasma cytokine levels or the expression of adipose tissue inflammatory markers. SAA deficiency did not affect lipoprotein cholesterol distributions or plasma triglyceride concentrations in either male or female mice. Atherosclerotic lesion areas measured on the intimal surfaces of the arch, thoracic, and abdominal regions were not significantly different between apoE-/- mice deficient in SAA1.1 and SAA2.1 and apoE-/- mice expressing SAA1.1 and SAA2.1 in either sex. To accelerate lesion formation, mice were fed a Western diet for 12 weeks. SAA deficiency had effect neither on diet-induced alterations in plasma cholesterol, triglyceride, or cytokine concentrations nor on aortic atherosclerotic lesion areas in either male or female mice. In addition, SAA deficiency in male mice had no effect on lesion areas or macrophage accumulation in the aortic roots. The absence of endogenous SAA1.1 and 2.1 does not affect atherosclerotic lipid deposition in apolipoprotein E-deficient mice fed either normal or Western diets.


Models of shared care for the management of psychotic disorder after first diagnosis in Ontario.
To describe the provision of care for young people following first diagnosis of psychotic disorder. Retrospective cohort study using health administrative data. Ontario. People aged 14 to 35 years with a first diagnosis of nonaffective psychotic disorder in Ontario between 2005 and 2015 (N=39,449). Models of care, defined by psychosis-related service contacts with primary care physicians and psychiatrists during the 2 years after first diagnosis of psychotic disorder. During the 2-year follow-up period, 29% of the cohort received only primary care, 30% received only psychiatric care, and 32% received both primary and psychiatric care (shared care). Among the shared care group, 72% received care predominantly from psychiatrists, 20% received care predominantly from primary care physicians, and 9% received approximately equal care from psychiatry and primary care. Variation in patient and physician characteristics was observed across the different models of care. One in 3 young people with psychotic disorder received shared care during the 2-year period after first diagnosis. The findings highlight opportunities for increasing collaboration between primary care physicians and psychiatrists to enhance the quality of care for those with early psychosis.


Recommendations for the management of the haematological and onco-haematological aspects of Gaucher disease.
Current knowledge of the haematological and onco-haematological complications of type 1 Gaucher disease has been reviewed with the aim of identifying best clinical practice for treatment and disease management. It was concluded that: (i) Awareness of typical patterns of cytopenia can help clinicians distinguish haematological co-morbidities. (ii) Red blood cell studies and complete iron metabolism evaluation at baseline are recommended. (iii) Haemoglobin levels defining anaemia should be raised and used in Gaucher disease treatment and monitoring. (iv) Surgeons should be aware of potential bleeding complications during surgery in Gaucher patients. The higher incidence of multiple myeloma in Gaucher disease suggests that Gaucher patients should have their immunoglobulin profile determined at diagnosis and monitored every 2 years (patients <50 years) or every year (patients >50 years). If monoclonal gammopathy of undetermined significance (MGUS) is found, general MGUS guidelines should be followed. Future studies should focus on the utility of early treatment to prevent immunoglobulin abnormalities and multiple myeloma.


[Poisons and antidotes according to Gunyetü'l Muhassilin and an 18th century Ottoman pamphlet].
This study deals with the chapter on poisons (Sümum) of Gunyetü'l-Muhassilin, a translation, and a pamphlet on antidotes called Panzehir, by Ahmed Sani, one of the most prominent figures of the Ottoman physicians. As a foreword, the terminology related with the subject; and an introduction to the Islamic medical theory, the basis of the subject, is discussed. The main topics on poisons are; protection against and treatment of poisons; being poisoned by the sting of insects, snakes etc. and diseases such as rabies, as a result of bites of animals and their treatment; treatment of poisoned suppuration; insecticide drugs and measures; and common drugs against all kinds of poisons. Immunization and nutrition with respect to being poisoned; and preventive measures against insects; and mineral and organic antidotes are also discussed. The classification of diseases and treatment ase evaluated on the humoral theory basis. The treatment of insect poisoning is viewed from the perspective of its symptoms. The pamphlet named Panzehir is about a special antidote, the bezoar stone. This antidote is divided into two, of the mineral and the animal origin and the uses of the bezoar are discussed. A vocabulary is added to help readers to understand the terminology.


The S2 gene nucleotide sequences of prototype strains of the three reovirus serotypes: characterization of reovirus core protein sigma 2.
The S2 gene nucleotide sequences of prototype strains of the three reovirus serotypes were determined to gain insight into the structure and function of the S2 translation product, virion core protein sigma 2. The S2 sequences of the type 1 Lang, type 2 Jones, and type 3 Dearing strains are 1,331 nucleotides in length and contain a single large open reading frame that could encode a protein of 418 amino acids, corresponding to sigma 2. The deduced sigma 2 amino acid sequences of these strains are very conserved, being identical at 94% of the sequence positions. Predictions of sigma 2 secondary structure and hydrophobicity suggest that the protein has a two-domain structure. A larger domain is suggested to be formed from the amino-terminal three-fourths of sigma 2 sequence, which is separated from a smaller carboxy-terminal domain by a turn-rich hinge region. The carboxy-terminal domain includes sequences that are more hydrophilic than those in the rest of the protein and contains sequences which are predicted to form an alpha-helix. A region of striking similarity was found between amino acids 354 and 374 of sigma 2 and amino acids 1008 and 1031 of the beta subunit of the Escherichia coli DNA-dependent RNA polymerase. We suggest that the regions with similar sequence in sigma 2 and the beta subunit form amphipathic alpha-helices which may play a related role in the function of each protein. We have also performed experiments to further characterize the double-stranded RNA-binding activity of sigma 2 and found that the capacity to bind double-stranded RNA is a property of the sigma 2 protein of prototype strains and of the S2 mutant tsC447.


Sustained attractiveness and natural youthful appearance by upper lip rejuvenation : Minimally invasive procedures to combat facial aging.
Facial aging is a complex process individualized by interaction with exogenous and endogenous factors. The upper lip is one of the facial components by which facial attractiveness is defined. Upper lip aging is significantly influenced by maxillary bone and teeth. Aging of the cutaneous part can be aggravated by solar radiation and smoking. We provide a review about minimally invasive techniques for correction of aging signs of the upper lip with a tailored approach to patient's characteristics. The treatment is based upon use of fillers, laser, and minor surgery.


Limited evidence for third-party affiliation during development in wild chimpanzees (Pan troglodytes schweinfurthii).
Examining the ontogeny of conflict-mitigating behaviours in our closest living relatives is an important component of understanding the evolutionary origins of cooperation in our species. In this study, we used 26 years of data to investigate the emergence of third-party affiliation (TPA), defined as affiliative contact given to recipients of aggression by uninvolved bystanders (regardless of initiation), in wild immature eastern chimpanzees (Pan troglodytes schweinfurthii) of Gombe National Park, Tanzania. We also characterized TPA by mothers in the same dataset as an adult benchmark for interpreting immature TPA patterns. In summary, we found that immatures did not express TPA as measured by grooming between the ages of 1.5 and 12.0 years, and that there was limited evidence that immatures expressed TPA via play. We also found that mothers did express TPA to offspring, although mothers did not show TPA towards non-offspring. Cases of TPA by mothers to other adults were too few to analyse separately. These results contrast with findings from captive studies which found that chimpanzees as young as 6 years of age demonstrated TPA. We argue that within-species variation in the expression of TPA, both in immatures and adulthood, provides evidence that the conflict management behaviours of young chimpanzees may be heavily influenced by social, ecological and demographic factors.