Flexible mate choice when mates are rare and time is short.
Female mate choice is much more dynamic than we once thought. Mating decisions depend on both intrinsic and extrinsic factors, and these two may interact with one another. In this study, we investigate how responses to the social mating environment (extrinsic) change as individuals age (intrinsic). We first conducted a field survey to examine the extent of natural variation in mate availability in a population of threespine sticklebacks. We then manipulated the sex ratio in the laboratory to determine the impact of variation in mate availability on sexual signaling, competition, and mating decisions that are made throughout life. Field surveys revealed within season heterogeneity in mate availability across breeding sites, providing evidence for the variation necessary for the evolution of plastic preferences. In our laboratory study, males from both female-biased and male-biased treatments invested most in sexual signaling late in life, although they competed most early in life. Females became more responsive to courtship over time, and those experiencing female-biased, but not male-biased sex ratios, relaxed their mating decisions late in life. Our results suggest that social experience and age interact to affect sexual signaling and female mating decisions. Flexible behavior could mediate the potentially negative effects of environmental change on population viability, allowing reproductive success even when preferred mates are rare.


What makes a peer? Characteristics of certified peer recovery support specialists in an emergency department-based intervention.
Providing brief interventions by certified peer recovery support specialists (CPRSS) in the emergency department (ED) following a drug related visit is a promising method of service engagement and has garnered national attention. This study examines CPRSS's perceptions of the qualities that enable them to deliver interventions in the ED. We conducted qualitative interviews with 14 CPRSSs working in EDs. Interview topics included how the participants became involved with CPRSS work, experiences working in the ED, how the ED differs from other settings, and what interactions with patients look like. Interviews were digitally recorded, transcribed, and analyzed for emerging categories. Three categories were identified relating to CPRSS work: (1) how they approach peer work, (2) inherent qualities required to do the work, regardless of the setting, and (3) context-specific skills required to do the work in the ED. When describing their approach to this work, participants talked about CPRSS work as their life calling and their passion. Participants also identified certain qualities that all CPRSS workers possess, regardless of the setting, including the ability to build rapport, strong listening skills, and a shared lived experience. Lastly, participants identified how specific hard and soft skills help them to navigate organizational and structural challenges in the ED. The unique conditions of the ED and the required qualities of a CPRSS should be considered when implementing an ED-based intervention.


Cloning and heterologous production of Hiracin JM79, a Sec-dependent bacteriocin produced by Enterococcus hirae DCH5, in lactic acid bacteria and Pichia pastoris.
Hiracin JM79 (HirJM79), a Sec-dependent bacteriocin produced by Enterococcus hirae DCH5, was cloned and produced in Lactococcus lactis, Lactobacillus sakei, Enterococcus faecium, Enterococcus faecalis, and Pichia pastoris. For heterologous production of HirJM79 in lactic acid bacteria (LAB), the HirJM79 structural gene (hirJM79), with or without the HirJM79 immunity gene (hiriJM79), was cloned into the plasmid pMG36c under the control of the constitutive promoter P(32) and into the plasmid pNZ8048 under the control of the inducible P(NisA) promoter. For the production of HirJM79 in P. pastoris, the gene encoding the mature HirJM79 protein was cloned into the pPICZalphaA expression vector. The recombinant plasmids permitted the production of biologically active HirJM79 in the supernatants of L. lactis IL1403, L. lactis NZ9000, L. sakei Lb790, E. faecalis JH2-2, and P. pastoris X-33, the coproduction of HirJM79 and nisin A in L. lactis DPC5598, and the coproduction of HirJM79 and enterocin P in E. faecium L50/14-2. All recombinant LAB produced larger quantities of HirJM79 than E. hirae DCH5, although the antimicrobial activities of most transformants were lower than that predicted from their production of HirJM79. The synthesis, processing, and secretion of HirJM79 proceed efficiently in recombinant LAB strains and P. pastoris.


Electrical and optical characterization of atomically thin WS₂.
Atomically thin layers of materials, which are just a few atoms in thickness, present an attractive option for future electronic devices. Herein we characterize, optically and electronically, atomically thin tungsten disulphide (WS2), a layered semiconductor. We provide the distinctive Raman and photoluminescence signatures for single layers, and prepare field-effect transistors where atomically thin WS2 serves as the conductive channel. The transistors present mobilities μ = 10 cm(2) V(-1) s(-1) and exhibit ON/OFF ratios exceeding 100,000. Our results show that WS2 is an attractive option for applications in electronic and optoelectronic devices and pave the way for further studies in this two-dimensional material.


Unique Rhizosphere Micro-characteristics Facilitate Phytoextraction of Multiple Metals in Soil by the Hyperaccumulating Plant Sedum alfredii.
Understanding the strategies that the roots of hyperaccumulating plants use to extract heavy metals from soils is important for optimizing phytoremediation. The rhizosphere characteristics of Sedum alfredii, a hyperaccumulator, were investigated 6 months after it had been planted in weathered field soils contaminated with 5.8 μg of Cd g-1, 1985.1 μg of Zn g-1, 667.5 μg of Pb g-1, and 698.8 μg of Cu g-1. In contrast with the non-hyperaccumulating ecotype (NHE), the hyperaccumulating ecotype (HE) of S. alfredii was more tolerant to the metals, and higher levels of Cd and Zn accumulated. The HE was characterized by a unique rhizosphere, including extensive root systems, a reduced soil pH, a higher metal bioavailability, and increased rhizomicrobial activity. The bioavailability of metals was significantly correlated with the HE's unique bacterial communities (P < 0.005). The HE harbored abundant Streptomyces (9.43%, family Streptomycetaceae), Kribbella (1.08%, family Nocardioidaceae), and an unclassified genus (1.09%, family Nocardioidaceae) in its rhizosphere, a composition that differed from that of the NHE. PICRUSt analysis predicted high relative abundances of imputed functional profiles in the HE rhizosphere related to membrane transport and amino acid metabolism. This study reveals the rhizosphere characteristics, particularly the unique bacterial rhizobiome of a hyperaccumulator, that might provide a new approach to facilitating heavy metal phytoextraction.


Temporally and regionally disparate differences in plasmin activity by tranexamic acid.
A major complication associated with cardiac surgery is excessive and prolonged bleeding in the perioperative period. Improving coagulation by inhibiting fibrinolysis, primarily through inhibition of plasmin activity (PLact) with antifibrinolytics such as tranexamic acid (TXA), has been a pharmacological mainstay in cardiac surgical patients. Despite its almost ubiquitous use, the temporal and regional modulation of PLact profiles by TXA remains unexplored. Accordingly, we developed a fluorogenic-microdialysis system to measure in vivo dynamic changes in PLact after TXA administration in a large animal model. Pigs (25-35 kg) were randomly assigned to receive TXA (30 mg/kg, diluted into 50 mL normal saline; n = 9) or vehicle (50 mL normal saline; n = 7). Microdialysis probes were placed in the liver, myocardium, kidney, and quadriceps muscle compartments. The microdialysate infusion contained a validated plasmin-specific fluorogenic peptide. The fluorescence emission (standard fluorogenic units [SFU]) of the interstitial fluid collected from the microdialysis probes, which directly reflects PLact, was determined at steady-state baseline and 30, 60, 90, and 120 min after TXA/vehicle infusion. Plasma PLact was determined at the same time points using the same fluorogenic substrate approach. TXA reduced plasma PLact at 30 min after infusion by >110 SFU compared with vehicle values (P < 0.05). Specifically, there was a decrease in liver PLact at 90 and 120 min after TXA infusion of >150 SFU (P < 0.05) and 175 SFU (P < 0.05), respectively. The decrease in liver PLact occurred 60 min after the maximal decrease in plasma PLact. In contrast, kidney, heart, and quadriceps PLact transiently increased followed by an overall decrease at 120 min. Using a large animal model and in vivo microdialysis measurements of PLact, the unique findings from this study were 2-fold. First, TXA induced temporally distinct PLact profiles within the plasma and selected interstitial compartments. Second, TXA caused region-specific changes in PLact profiles. These temporal and regional differences in the effects of TXA may have important therapeutic considerations when managing fibrinolysis in the perioperative period.


Combined Administration of ASCs and BMP-12 Promotes an M2 Macrophage Phenotype and Enhances Tendon Healing.
Outcomes after intrasynovial tendon repair are highly variable. An intense inflammatory cascade followed by a delayed healing response can cause adhesion formation and repair-site failure that severely impair the function of repaired digits. No effective remedies exist to fully address these issues. Cell- and growth factor-based therapies have been shown to modulate inflammation and improve cell proliferation and matrix synthesis and therefore are promising treatment approaches for intrasynovial tendon repair. (1) Can autologous adipose-derived mesenchymal stromal cells (ASCs) and recombinant bone morphogenetic protein-12 (rBMP-12) be effectively delivered to an intrasynovial flexor tendon repair without adverse effects? (2) Do autologous ASCs modulate the inflammatory response after intrasynovial tendon injury and repair? (3) Does the combined application of autologous ASCs and rBMP-12 modulate the proliferative and remodeling responses after intrasynovial tendon injury and repair? Sixteen 1- to 2-year-old female canines were used in this study. Autologous ASC sheets, with and without rBMP-12, were applied to the surface of sutured flexor tendons. Fourteen days after repair, the effects of treatment were determined using quantitative PCR (six per group) for the expression of genes related to macrophage phenotype or inflammation (IL-4, CD163, VEGF, NOS2, IL-1B, and IFNG), cell proliferation (CCND1), and tendon formation (SCX, TNMD, COL1A1 and COL3A1). Proteomics analysis (four per group) was performed to examine changes in tendon protein abundances. CD146 immunostaining and hematoxylin and eosin staining (four per group) were used to detect tendon stem or progenitor cells and to semiquantitatively evaluate cellularity at the tendon repair; analyses were done blinded to group. Gross inspection and cell tracing showed that autologous ASCs and rBMP-12 were delivered to the flexor tendon repair site without the deleterious effects of adhesion and repair-site gap formation. Quantitative assessment of gene and protein expression showed effects of treatment: ASC-sheet treatment modulated the postrepair inflammatory response and facilitated healing by increasing regenerative M2 macrophages (M2 marker CD204, twofold of normal, p = 0.030), inflammatory inhibitor (prostaglandin reductase 1 [PTRG1], 1.6-fold of normal, p = 0.026), and proteins involved in tendon formation (periostin [POSTN], 1.9-fold of normal, p = 0.035). Consistently, semiquantitative and qualitative evaluations of repaired tissue showed that ASC-sheet treatment reduced mononuclear cell infiltration (12% less than nontreated tendons, p = 0.021) and introduced CD146+ stem or progenitor cells to the repair site. The combined administration of ASCs and rBMP-12 further stimulated M2 macrophages by increasing IL-4 (116-fold of normal, p = 0.002) and led to the increase of M2 effector matrix metalloproteinase-12 involved in matrix remodeling (twofold of normal, p = 0.016) and reduction of a negative regulator of angiogenesis and cell migration (StAR-related lipid transfer domain protein13 [STARD13]; 84% of normal, p = 0.000), thus facilitating the proliferative stage of tendon repair. ASCs and BMP-12 accelerated the progression of healing in the proliferative stage of tendon repair. The effects of ASCs and BMP-12 on tendon functional recovery should be evaluated in future studies. The cell sheet approach is an effective, biocompatible, and surgeon-friendly approach for cell and growth factor delivery during tendon repair. Combined application of ASCs and BMP-12 may accelerate intrasynovial tendon healing while suppressing the adverse inflammatory response.


Endoscopic ultrasound guided gastroenterostomy: Technical details updates, clinical outcomes, and adverse events.
Endoscopic ultrasound-guided gastroenterostomy (EUS-GE) has been transformed from an innovative technique, into a viable alternative to enteral stenting and surgical gastrointestinal anastomosis for patients with gastric outlet obstruction. Even EUS-GE guided ERCP and EUS-guided gastrointestinal anastomosis for the treatment of afferent loop syndrome have been performed, giving patients more less invasive options. However, EUS-GE is still a technically challenging procedure. In order to improve EUS-GE, several techniques have been reported to improve the technical details. With EUS-GE widely performed, more data about EUS-GE's clinical outcomes have been reported. The aim of the current review is to describe technical details updates, clinical outcomes, and adverse events of EUS-GE.


Wound Healing Complications Following Guided Bone Regeneration for Ridge Augmentation: A Systematic Review and Meta-Analysis.
The rate of developing soft tissue complications that accompany guided bone regeneration (GBR) procedures varies widely, from 0% to 45%. The present review was conducted to investigate the rate for resorbable versus nonresorbable membranes and the timing of soft tissue complications. Electronic and manual literature searches were conducted by two independent reviewers using several databases, including MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Cochrane Oral Health Group Trials Register, for articles published through July 2015, with no language restriction. Articles were included if they were clinical trials aimed at demonstrating the incidence of soft tissue complications following GBR procedures. Overall, 21 and 15 articles were included in the qualitative and quantitative synthesis, respectively. The weighted complication rate of the overall soft tissue complications, including membrane exposure, soft tissue dehiscence, and acute infection/abscess, into the calculation was 16.8% (95% CI = 10.6% to 25.4%). When considering the complication rate based on membrane type used, resorbable membrane was associated with a weighted complication rate of 18.3% (95% CI: 10.4% to 30.4%) and nonresorbable membrane with a rate of 17.6% (95% CI: 10.0% to 29.3%). Moreover, soft tissue lesions were reported as early as 1 week and as late as 6 months based on the included studies. Soft tissue complications after GBR are common (16.8%). Membrane type did not appear to significantly affect the complication rate, based on the limited number of data retrieved in this study. Technique sensitivity (ie, soft tissue management) may still be regarded as the main component to avoid soft tissue complications and, hence, to influence the success of bone regenerative therapy.


Ecological Entomology: How Is Gibson's Framework Useful?
To date, numerous studies have demonstrated the fundamental role played by optic flow in the control of goal-directed displacement tasks in insects. Optic flow was first introduced by Gibson as part of their ecological approach to perception and action. While this theoretical approach (as a whole) has been demonstrated to be particularly suitable for the study of goal-directed displacements in humans, its usefulness in carrying out entomological field studies remains to be established. In this review we would like to demonstrate that the ecological approach to perception and action could be relevant for the entomologist community in their future investigations. This approach could provide a conceptual and methodological framework for the community in order to: (i) take a critical look at the research carried out to date, (ii) develop rigorous and innovative experimental protocols, and (iii) define scientific issues that push the boundaries of the current scientific field. After a concise literature review about the perceptual control of displacement in insects, we will present the framework proposed by Gibson and suggest its added value for carrying out research in the field of behavioral ecology in insects.


Pre-surgery exercise and post-operative physical function of people undergoing knee replacement surgery: A systematic review and meta-analysis of randomized controlled trials.
To summarize the evidence regarding the effectiveness and dose-response characteristics of pre-operative exercise programmes on post-operative physical function following total knee arthroplasty. CINAHL, Cochrane Library, PubMed, SPORTDiscus and EMBASE. Randomized controlled trials were eligible if they provided full description of physiological stress (i.e. mode, frequency, intensity and duration). Data extraction and evaluation were performed by one reviewer. Methodological quality of the selected studies was assessed using the Physiotherapy Evidence Database scale. Twelve candidate studies were identified, but only 3 papers satisfied all inclusion criteria: 2 studies evaluated the effect of resistance training and 1 trial investigated proprioceptive training. The latter study elicited significantly enhanced post-operative gains in function for indices of standing balance (overall stability index: Hedges' g = -1; anteroposterior stability index: Hedges' g = -1.15; 6 weeks post-surgery). Results of meta-analysis based on the findings of 2 studies showed that, compared with controls, prehabilitative exercise involving resistance training offered no additional gains in isometric quadriceps muscle strength at 6 and 12 weeks post-operatively. Despite a potential for efficacy of exercise-based conditioning, this review highlights the scarcity of robust dose-response evidence to guide the formulation of total knee arthroplasty prehabilitation effectively.


MCP-1 deficiency reduces susceptibility to atherosclerosis in mice that overexpress human apolipoprotein B.
The earliest recognizable atherosclerotic lesions are fatty streaks composed of lipid-laden macrophages (foam cells). Circulating monocytes are the precursors of these foam cells, but the molecular mechanisms that govern macrophage trafficking through the vessel wall are poorly understood. Monocyte chemoattractant protein-1 (MCP-1), a member of the chemokine (chemotactic cytokine) family, is a potent monocyte agonist that is upregulated by oxidized lipids. Recent studies in hypercholesterolemic mice lacking apo E or the low-density lipoprotein receptor have suggested a role for MCP-1 in monocyte recruitment to early atherosclerotic lesions. To determine if MCP-1 is critically involved in atherogenesis in the setting of elevated physiological plasma cholesterol levels, we deleted the MCP-1 gene in transgenic mice expressing human apo B. Here we report that the absence of MCP-1 provides dramatic protection from macrophage recruitment and atherosclerotic lesion formation in apo B transgenic mice, without altering lipoprotein metabolism. Taken together with the results of earlier studies, these data provide compelling evidence that MCP-1 plays a critical role in the initiation of atherosclerosis.


On-line exit dose profile measurements by a diode linear array.
The possibility of using a commercial diode linear array (BMS Schuster Inc.) in on-line portal dosimetry has been investigated. The system is composed of 88 equispaced diodes (distance between diodes, 0.5 cm; detection area, 2.5 x 2.5 mm2). The ability to measure exit dose profiles has been demonstrated by comparing relative exit dose profiles measured by an ionization chamber (NE 2571) with 'portal' profiles measured by the diode array on a number of homogeneous and inhomogeneous phantoms in 6 MV x-ray beams (from a Clinac Varian 6/100). The influence of the variation of the scattered radiation at the exit level with respect to the detector level has been discussed and investigated by varying the air gap (from 0 to 80 cm for a homogeneous phantom and from 0 to 25 cm for inhomogeneous phantoms) as well as the field width. A good agreement (maximum difference 3.8%; 2.5% when the array was positioned in contact with the phantoms) between 'portal' profiles and exit dose profiles in both homogeneous and inhomogeneous phantoms has been found if the array-phantom distance is kept below 7.5 cm. Results indicate that the system should be suitable for applications in transit dosimetry.


p38{alpha} MAP kinase controls IL-17 synthesis in vogt-koyanagi-harada syndrome and experimental autoimmune uveitis.
PURPOSE. Interleukin (IL)-17, which is responsible for the initial influx of leukocytes into the target tissue, was recently described as the main cytokine involved in autoimmune diseases. Vogt-Koyanagi-Harada (VKH) syndrome is a significant cause of noninfectious blindness in the world. Herein the authors aimed at unraveling the involvement of IL-17 in VKH and in experimental autoimmune uveitis, focusing on the signaling pathways involved in IL-17 synthesis. METHODS. Mice were immunized with 161-180 peptide and pertussis toxin. Draining lymph node cells, harvested 21 days after immunization, were cultured in the presence or absence of p38alpha mitogen-activated protein kinase (MAPK) inhibitor (SB203580) and assayed for cytokine production and quantification of CD4(+)IL-17(+) cells. Mice received intraocular injections of SB203580, and disease severity was evaluated by histologic examination of the enucleated eyes at day 21. CD4(+) lymphocytes from MSK-1/2-deficient mice, human CD4(+) cells silenced with MSK1 siRNA, or peripheral blood mononuclear cells (PBMCs) from VKH patients were cultured in the presence or absence of p38alpha MAPK inhibitor and then assayed for IL-17, IFN-gamma, and IL-4 production. RESULTS. The inhibition of p38alpha MAPK fully blocked the synthesis of IL-17 by PBMCs from VKH patients and lymphocytes from EAU mice. The absence of the msk1/2 gene resulted in failure to produce IL-17 by murine and human lymphocytes. Interestingly, intraocular injections of SB203580 in EAU mice did not suppress development of the disease. CONCLUSIONS. These data show that p38alpha MAPK-MSK1/2 is involved in the control of IL-17 synthesis by CD4(+) T cells and that inhibition of p38alpha MAPK in vitro suppresses IL-17 synthesis but that inhibition of this kinase in vivo did not protect from EAU.


Electrophoretic studies of serum gamma-glutamyl transferase from patients with hepatoma.
Activities and isoenzyme patterns of gamma-glutamyl transferase (GGT) were studied in serum samples from fifteen Bantu males suffering from primary hepatoma; the results were compared with those obtained from normal samples. Enzyme activities were significantly higher in hepatoma patients than in controls. Results with Cellogel electrophoresis and the fluorescent substrate gamma-L-glutamine-7-amido-4-methylcoumarin were reproducible; two major bands of activity were observed in normal serum and three bands in hepatoma serum. The additional band seen in hepatoma serum was also detected in serum from patients with certain other disorders. With polyacrylamide gel electrophoresis using either gamma-L-glutamyl-alpha-naphthylamide or gamma-L-glutamyl-p-nitroanilide as substrates, results were inconsistent and difficult to interpret since there was a lack of specificity for GGT.


Monitoring and evaluation of blood pressure changes with a home healthcare system.
We investigated changes in blood pressure with exercise, including walking and ergometer training, sleep, and body weight. Blood pressure was monitored over a period of about 1 year in 61 subjects in Osaka, Japan. The morning systolic blood pressures were analyzed using multivariate regression analysis, and the correlations between systolic blood pressure and the above parameters were determined. The systolic blood pressure distribution was classified into improved, stable, and ingravescence groups. In the improved group, exercise intensity and total calories were important factors controlling the systolic blood pressure. More than 300 kcal per day was needed to improve the systolic blood pressure. In the stable and ingravescence groups, body weight control was also an important factor in maintaining blood pressure. An increase of 1 kg in body weight was associated with systolic blood pressure increases of 3 and 6 mm Hg in the stable and ingravescence groups, respectively. The long-term repeated use of home blood pressure testing may be a good self-care strategy for monitoring daily health.


CHARM, a gender equity and family planning intervention for men and couples in rural India: protocol for the cluster randomized controlled trial evaluation.
Globally, 41% of all pregnancies are unintended, increasing risk for unsafe abortion, miscarriage and maternal and child morbidities and mortality. One in four pregnancies in India (3.3 million pregnancies, annually) are unintended; 2/3 of these occur in the context of no modern contraceptive use. In addition, no contraceptive use until desired number and sex composition of children is achieved remains a norm in India. Research shows that globally and in India, the youngest and most newly married wives are least likely to use contraception and most likely to report husband's exclusive family planning decision-making control, suggesting that male engagement and family planning support is important for this group. Thus, the Counseling Husbands to Achieve Reproductive Health and Marital Equity (CHARM) intervention was developed in recognition of the need for more male engagement family planning models that include gender equity counseling and focus on spacing contraception use in rural India. For this study, a multi-session intervention delivered to men but inclusive of their wives was developed and evaluated as a two-armed cluster randomized controlled design study conducted across 50 mapped clusters in rural Maharashtra, India. Eligible rural young husbands and their wives (N = 1081) participated in a three session gender-equity focused family planning program delivered to the men (Sessions 1 and 2) and their wives (Session 3) by village health providers in rural India. Survey assessments were conducted at baseline and 9&18 month follow-ups with eligible men and their wives, and pregnancy tests were obtained from wives at baseline and 18-month follow-up. Additional in-depth understanding of how intervention impact occurred was assessed via in-depth interviews at 18 month follow-up with VHPs and a subsample of couples (n = 50, 2 couples per intervention cluster). Process evaluation was conducted to collect feedback from husbands, wives, and VHPs on program quality and to ascertain whether program elements were implemented according to curriculum protocols. Fidelity to intervention protocol was assessed via review of clinical records. All study procedures were completed in February 2015. Findings from this work offer important contributions to the growing field of male engagement in family planning, globally. ClinicalTrial.gov, NCT01593943.


Smartphone Ownership and Interest in Mobile Health Technologies for Self-care Among Patients With Chronic Heart Failure: Cross-sectional Survey Study.
Heart failure (HF) is a highly prevalent chronic condition that places a substantial burden on patients, families, and health care systems worldwide. Recent advances in mobile health (mHealth) technologies offer great opportunities for supporting many aspects of HF self-care. There is a need to better understand patients' adoption of and interest in using mHealth for self-monitoring and management of HF symptoms. The purpose of this study is to assess smartphone ownership and patient attitudes toward using mHealth technologies for HF self-care in a predominantly minority population in an urban clinical setting. We conducted a cross-sectional survey of adult outpatients (aged ≥18 years) at an academic outpatient HF clinic in the Midwest. The survey comprised 34 questions assessing patient demographics, ownership of smartphones and other mHealth devices, frequently used smartphone features, use of mHealth apps, and interest in using mHealth technologies for vital sign and HF symptom self-monitoring and management. A total of 144 patients were approached, of which 100 (69.4%) participated in the study (63/100, 63% women). The participants had a mean age of 61.3 (SD 12.25) years and were predominantly Black or African American (61/100, 61%) and Hispanic or Latino (18/100, 18%). Almost all participants (93/100, 93%) owned a cell phone. The share of patients who owned a smartphone was 68% (68/100). Racial and ethnic minorities that identified as Black or African American or Hispanic or Latino reported higher smartphone ownership rates compared with White patients with HF (45/61, 74% Black or African American and 11/18, 61% Hispanic or Latino vs 9/17, 53% White). There was a moderate and statistically significant association between smartphone ownership and age (Cramér V [ΦC]=0.35; P<.001), education (ΦC=0.29; P=.001), and employment status (ΦC=0.3; P=.01). The most common smartphone features used by the participants were SMS text messaging (51/68, 75%), internet browsing (43/68, 63%), and mobile apps (41/68, 60%). The use of mHealth apps and wearable activity trackers (eg, Fitbits) for self-monitoring of HF-related parameters was low (15/68, 22% and 15/100, 15%, respectively). The most popular HF-related self-care measures participants would like to monitor using mHealth technologies were physical activity (46/68, 68%), blood pressure (44/68, 65%), and medication use (40/68, 59%). Most patients with HF have smartphones and are interested in using commercial mHealth apps and connected health devices to self-monitor their condition. Thus, there is a great opportunity to capitalize on the high smartphone ownership among racial and ethnic minority patients to increase reach and enhance HF self-management through mHealth interventions.


Transcriptomics Reveals Host-Dependent Differences of Polysaccharides Biosynthesis in Cynomorium songaricum.
Cynomorium songaricum is a root holoparasitic herb that is mainly hosted in the roots of Nitraria roborowskii and Nitraria sibirica distributed in the arid desert and saline-alkaline regions. The stem of C. songaricum is widely used as a traditional Chinese medicine and applied in anti-viral, anti-obesity and anti-diabetes, which largely rely on the bioactive components including: polysaccharides, flavonoids and triterpenes. Although the differences in growth characteristics of C. songaricum between N. roborowskii and N. sibirica have been reported, the difference of the two hosts on growth and polysaccharides biosynthesis in C. songaricum as well as regulation mechanism are not limited. Here, the physiological characteristics and transcriptome of C. songaricum host in N. roborowskii (CR) and N. sibirica (CS) were conducted. The results showed that the fresh weight, soluble sugar content and antioxidant capacity on a per stem basis exhibited a 3.3-, 3.0- and 2.1-fold increase in CR compared to CS. A total of 16,921 differentially expressed genes (DEGs) were observed in CR versus CS, with 2573 characterized genes, 1725 up-regulated and 848 down-regulated. Based on biological functions, 50 DEGs were associated with polysaccharides and starch metabolism as well as their transport. The expression levels of the selected 37 genes were validated by qRT-PCR and almost consistent with their Reads Per kb per Million values. These findings would provide useful references for improving the yield and quality of C. songaricum.


[The evaluation of an incentive system for the primary care professionals of Mallorca].
To describe the assessment made by Mallorca's primary care professionals of the economic incentives system set up in 1994 and find their opinions of financial incentives and other motivating mechanisms. A descriptive, crossover study. Primary care in Mallorca (INSALUD of the Balearics). All the health professionals and ancillary workers (554) of Mallorca's 24 Health Centres. A self-filled questionnaire was used as a measuring instrument. There was a 74% reply rate. Their assessment of the incentives system used was that the distribution of the incentives was unjust and a cause of tension. However, expectations as to the amount received had been met to a reasonable extent. Self-management was a stronger motivating force than incentives (48.4% vs 13.6%). The incentives system used displayed certain faults (in distribution and the work atmosphere generated). However, decentralization was shown to be a powerful motivating force. Monitoring professionals' expectations and the fulfillment of them should be integrated into management habits.


[Biochemical mechanisms of skeletal muscle adaptation to increased activity].
The adaptation changes caused by the systematic muscular activity relate to morphology and functional properties of the muscular fibre subcellular structures, content and state of substrates and enzymes. There occurs not only an increase in the activity of enzymes but also a change in the ratio of the activities in polyenzymic systems. The increase in the enzymes activity is based on the substrate induction and derepression of the enzymes synthesis as well as changes in the isoenzymic spectra, sensitivity of the enzymic systems to hormones. All these changes are specific and determined by the functional profile of the muscles and character of the muscular activity. The energy supply of the adaptive synthesis of structural and enzymatic proteins, phospholipids and a more intensified synthesis of different substrates (glycogen, phosphocreatine) is based on regular changes occurring at rest determined by muscular activity and providing for a higher energy production during this period. Development and stabilization of the adaptation biochemical changes is under control of the chemical self-regulation of the metabolic cycles, neuro-trophic--somatic and sympathetic as well as of the endocrine regulation. At the different stages of adaptation its biochemical mechanisms have definite differences.


Are confusional arousals pathological?
The objective of this study was to determine the extent that confusional arousals (CAs) are associated with mental disorders and psychotropic medications. Cross-sectional study conducted with a representative sample of 19,136 noninstitutionalized individuals of the US general population aged 18 years or older. The study was performed using the Sleep-EVAL expert system and investigated sleeping habits; health; and sleep, mental, and medical conditions (DSM-IV-TR, ICSD-II, ICD-10). A total of 15.2% (95% confidence interval 14.6%-15.8%) (n=2,421) of the sample reported episodes of CAs in the previous year; 8.6% had complete or partial amnesia of the episodes and 14.8% had CAs and nocturnal wandering episodes. Eighty-four percent of CAs were associated with sleep/mental disorders or psychotropic drugs. Sleep disorders were present for 70.8% of CAs. Individuals with a circadian rhythm sleep disorder or a long sleep duration (≥9 hours) were at higher risk of CAs. Mental disorders were observed in 37.4% of CAs. The highest odds were observed in individuals with bipolar disorders or panic disorder. Use of psychotropic medication was reported by 31.3% of CAs: mainly antidepressant medications. After eliminating possible causes and associated conditions, only 0.9% of the sample had CA disorder. CAs are highly prevalent in the general population. They are often reported allegedly as a consequence of the treatment of sleep disorders. For the majority of subjects experiencing CAs, no medications were used, but among those who were using medications, antidepressants were most common. Sleep and/or mental disorders were important factors for CAs independent of the use of any medication.


Purification and characterization of NAD:Penicillamine ADP transferase from Bacillus sphaericus. A novel NAD-dependent enzyme catalyzing phosphoramide bond formation.
A strain of Bacillus sphaericus isolated from a local soil sample has been found to use beta,beta-dimethyl-DL-cysteine (DL-penicillamine) as the sole nitrogen source. Crude cell extract of the bacterium showed potent penicillamine-consuming activity only in the presence of NAD, which, however, was not used as an electron acceptor. Characterization of reaction products revealed that penicillamine was derivatized to a phosphoramide adduct with the ADP moiety of NAD, whereas the nicotinamide-ribose group was released and hydrolyzed spontaneously to ribose and nicotinamide. The phosphoramide product, ADP-penicillamine, caused potent product inhibition on the purified enzyme, and adenylate deaminase was found to be effective in converting the inhibitory product into inosine-diphosphate-penicillamine and thereby maintained the catalysis for several hours. The novel enzyme, termed as NAD:penicillamine ADP transferase, showed a single band on SDS-polyacrylamide gel electrophoresis with a mass of approximately 42 kDa. The native enzyme was monomeric. The enzyme showed high substrate specificity to NAD (Km = 13.0 mM) and L-penicillamine (Km = 6.5 mM); other nucleotides such as NADP, NAD(P)H, AMP, ADP, and ADP-ribose did not substitute for NAD, and L-valine, L-cysteine, L-homocysteine, L-cystine, L-leucine, and L-isoleucine did not serve as the substrate. Kinetic studies suggested an Ordered Bi Bi mechanism, with NAD as the first substrate to bind and ADP-L-penicillamine as the last product released. The novel NAD-dependent enzyme may catalyze the first step in penicillamine degradation in the strain of B. sphaericus.


[Decompression sickness of the spinal cord. Results of early and of late treatment].
The treatment of 20 scuba divers with decompression sickness of the spinal cord between 1969 and 1984 is reported. Seven patients presented with mild sensomotor impairments, 13 patients were paraplegic and some suffered from additional impairments to the arms. In 12 of the divers the accident that occurred in a Swiss lake and recompression was initiated with a latency of a few hours. These early treatments were successful in 11 patients. The neurologic symptoms already improved during recompression even in the 7 patients who were paraplegic. In a paraplegic woman early treatment failed, but her condition improved under subsequent hyperbaric oxygen treatment. In 9 patients late treatment after an interval of 48 to 192 hours, consisting of repeated hyperbaric oxygen exposures, was performed. 3 patients with mild neurologic disturbances improved completely. 6 patients were paraplegic. In 5 of these early treatment was without success. On 3 occasions, however, early treatment was not started before 15 to 24 hours after the dive. All 6 paraplegic patients improved considerably during late treatment. 8 of the 9 patients undergoing hyperbaric oxygen treatment had been transported by air with slightly reduced cabin pressure from the foreign country to Zurich. No deterioration of neurologic symptoms was observed during air transport.


Disseminated Tuberculosis Associated With Adalimumab Therapy.
Therapeutic blockade of tumour necrosis factor alpha (anti-TNF-α) is the mainstay treatment of several rheumatologic diseases. They are unfrequently associated with opportunistic infections and latent tuberculosis (TB) screening is paramount before immunosuppression. A 62-year-old man with psoriatic arthritis was under treatment with adalimumab for over 5 years. The screening for latent tuberculosis infection (LTBI) prior to the start of immunosuppression was negative, and a subsequent interferon gamma release assay 4 years later was also negative. He presented in the emergency department complaining of asthenia, anorexia, fever, night sweats and weight loss for over 5 months. He also complained of memory loss, despite his normal cognitive and neurological examination. After an exhaustive workup, he was diagnosed with a disseminated tuberculosis (cerebral, pulmonary and peritoneal) and treated accordingly. TB diagnosis remains challenging in certain situations. Latent TB screening tests may lack sensitivity and immunosuppressive therapy increases the risk of disseminated infection. We discuss the workup and management of a central nervous system disseminated TB related to adalimumab therapy.


The host response to smallpox: analysis of the gene expression program in peripheral blood cells in a nonhuman primate model.
Smallpox has played an unparalleled role in human history and remains a significant potential threat to public health. Despite the historical significance of this disease, we know little about the underlying pathophysiology or the virulence mechanisms of the causative agent, variola virus. To improve our understanding of variola pathogenesis and variola-host interactions, we examined the molecular and cellular features of hemorrhagic smallpox in cynomolgus macaques. We used cDNA microarrays to analyze host gene expression patterns in sequential blood samples from each of 22 infected animals. Variola infection elicited striking and temporally coordinated patterns of gene expression in peripheral blood. Of particular interest were features that appear to represent an IFN response, cell proliferation, immunoglobulin gene expression, viral dose-dependent gene expression patterns, and viral modulation of the host immune response. The virtual absence of a tumor necrosis factor alpha/NF-kappaB-activated transcriptional program in the face of an overwhelming systemic infection suggests that variola gene products may ablate this response. These results provide a detailed picture of the host transcriptional response during smallpox infection, and may help guide the development of diagnostic, therapeutic, and prophylactic strategies.


Polymyxin B selectively inhibits insulin effects on transport in isolated muscle.
Polymyxin B (PMB), a cyclic decapeptide antibiotic, inhibits the hypoglycemic effect of insulin in vivo. To elucidate the mechanism of PMB action, we have studied its effect in vitro on insulin-stimulated pathways in the mouse skeletal muscle. PMB, added to the incubation mixture, specifically inhibited insulin-stimulated 2-deoxyglucose transport and alpha-aminoisobutyric acid uptake in the isolated soleus muscle but did not affect the basal rates of transport (measured in the absence of insulin). PMB did not alter insulin binding and hexokinase activity. PMB effect was observed at all deoxyglucose concentrations tested, and PMB was also able to inhibit vanadate-stimulated glucose transport. By contrast, insulin activation of glycogen synthase was not prevented by PMB. Basal and maximally insulin-stimulated insulin receptor tyrosine kinase activity, tested in a cell-free system, was similar for both autophosphorylation and phosphorylation of exogenous substrates in the absence or in the presence of PMB. Furthermore, the insulin sensitivity of the kinase was increased in the presence of PMB. Our results suggest that the anti-insulin effect of PMB observed in vivo is due to an inhibition of insulin-stimulated glucose transport in the skeletal muscle perhaps through a specific blockade of the insulin-induced translocation of the glucose carriers.


Mini review roles of the bZIP gene family in rice.
The basic leucine zipper (bZIP) genes encode transcription factors involved in the regulation of various biological processes. Similar to WRKY, basic helix-loop-helix, and several other groups of proteins, the bZIP proteins form a superfamily of transcription factors that mediate plant stress responses. In this review, we present the roles of bZIP proteins in multiple biological processes that include pathogen defense; responses to abiotic stresses; seed development and germination; senescence; and responses to salicylic, jasmonic, and abscisic acids in rice. We also examined the characteristics of the bZIP proteins and their genetic composition. To ascertain the evolutionary changes in and functions of this supergene family, we performed an exhaustive comparison among the 89 rice bZIP genes that were previously described and those more recently listed in the MSU Rice Genome Annotation Project Database using a Hidden Markov Model. We excluded 3 genes from the list, resulting in a total of 86 bZIP genes in japonica rice.


Reducing HIV stigma among healthcare providers in India using a partly tablet-administered intervention: the DriSti trial.
HIV stigma has long been recognized as a significant barrier in the worldwide fight against HIV. Across cultures, stigma has been shown to cause psychological distress and act as a barrier to engagement in care. Health professionals can serve as a crucial source of HIV stigma, with drivers that include fears and transmission misconceptions and pre-existing negative attitudes towards marginalized groups. To increase their impact, stigma reduction interventions need to be scalable and sustainable as well as adaptable to different cultural contexts. The DriSti intervention was designed to meet these needs through an easily adaptable, mostly tablet-administered, interactive intervention delivered to ward staff (n = 1,557) and nursing students (n = 1,625) in 62 Indian institutions, using a cRCT design, with wait-list controls. Six-month outcome analyses, showed significant reductions in misconceptions (p < .001) and worry about acquiring HIV at work (p < .001). Intervention participants also reported significantly greater reductions in endorsement of coercive policies (p < .001) and in the number of situations in which they intended to discriminate against PLWH (p < .001) than control participants. This brief, scaleable intervention could be adapted for similar populations in the region, using different mHealth platforms and thus has important implications for current global stigma reduction initiatives and training curricula.


Localization of Evi-2 to chromosome 11: linkage to other proto-oncogene and growth factor loci using interspecific backcross mice.
A common site of ecotropic murine leukemia virus integration designated Evi-2 (ecotropic viral integration site-2) has been identified in BXH-2 myeloid tumors. As part of experiments to determine whether Evi-2 identified a new proto-oncogene locus involved in myeloid disease, we determined its chromosomal location. We mapped Evi-2 to mouse Chromosome 11 using standard recombinant inbred strain and genetic backcross analysis. We then determined the location of Evi-2 relative to other proto-oncogene and growth factor loci located on Chromosome 11 by interspecific backcross analysis. The loci included in this study were the proto-oncogene loci, Erbb, Erba, and Rel, as well as, Il-3 (interleukin-3), Csfgm (granulocyte-macrophage colony stimulating factor), and Trp53-1 (transforming protein p53). All loci except Erbb had been previously mapped to Chromosome 11 with the use of somatic cell hybrids and consequently their positions on Chromosome 11 were not known. One proto-oncogene, Erbb-2 (analogous to the neu proto-oncogene), and one growth factor locus, Csfg (granulocyte colony-stimulating factor), which had not been mapped in the mouse were also localized on Chromosome 11 using the interspecific backcross mice. Recombination between Evi-2 and all proto-oncogene and growth factor loci was demonstrated, suggesting that Evi-2 may ultimately identify a new proto-oncogene involved in myeloid disease. This study revealed a number of interesting conserved linkage groups common to mouse and man.


Consideration of patient age and life expectancy in implantable cardioverter-defibrillator referral.
Primary prevention implantable cardioverter-defibrillator (ICD) guidelines recommend device consideration for at-risk patients with a life expectancy of greater than 1 year regardless of age. We sought to assess the influence of patient age and prognosis on ICD referral. A survey was mailed to a random, national sample of 3,000 physicians in the specialties of cardiology, family medicine, and internal medicine. Participants were asked focused questions regarding patient age, life expectancy, and ICD referral. The overall response rate was 64%. More than one quarter of physicians (n = 386 [27%], 95% CI 25%-30%) withhold primary prevention ICD referral solely because of patient age. Life expectancy is not considered by 23% (n = 324, 95% CI 20%-25%) of physicians before referral, whereas 13% (n = 144, 95% CI 11%-15%) refer patients with a prognosis of less than 1 year. Providers who refer patients for ICD implantation with a life expectancy of less than 1 year are less likely to be cardiologists (odds ratio [OR] 0.50, 95% CI 0.32-0.79, P = .003), are less often affiliated with a teaching hospital (OR 0.62, 95% CI 0.41-0.94, P = .025), and have a greater number of years in practice (OR 1.25 for each 10 years in practice, 95% CI 1.03-1.51, P = .026). Only a minority (n = 315 [22%], 95% CI 20%-24%) of physicians use a life expectancy threshold of 1 year to guide ICD referral. Physicians frequently withhold ICD referral because of patient age. The referral of patients with a prognosis of less than 1 year or without consideration of life expectancy is common.


Nucleus accumbens core single cell ensembles bidirectionally respond to experienced versus observed aversive events.
Empathy is the ability to adopt others' sensory and emotional states and is an evolutionarily conserved trait among mammals. In rodents, empathy manifests itself as social modulation of aversive stimuli such as acknowledging and acting on conspecifics' distress. The neuronal network underlying social transmission of information is known to overlap with the brain regions that mediate behavioral responses to aversive and rewarding stimuli. In this study, we recorded single cell activity patterns of nucleus accumbens (NAc) core neurons using in vivo optical imaging of calcium transients via miniature scopes. This cutting-edge imaging methodology not only allows us to record activity patterns of individual neurons but also lets us longitudinally follow these individual neurons across time and different behavioral states. Using this approach, we identified NAc core single cell ensembles that respond to experienced and/or observed aversive stimuli. Our results showed that experienced and observed aversive stimuli evoke NAc core ensemble activity that is largely positive, with a smaller subset of negative responses. The size of the NAc single cell ensemble response was greater for experienced aversive stimuli compared to observed aversive events. Our results also revealed a subpopulation within the NAc core single cell ensembles that show a bidirectional response to experienced aversive stimuli versus observed aversive stimuli (i.e., negative response to experienced and positive response to observed). These results suggest that the NAc plays a role in differentiating somatosensory experience from social observation of aversion at a single cell level. This has important implications for psychopathologies where social information processing is maladaptive, such as autism spectrum disorders.


Graphite felts modified by vertical two-dimensional WO3 nanowall arrays: high-performance electrode materials for cerium-based redox flow batteries.
Cerium-based redox flow batteries (RFBs) are very attractive for highly efficient energy storage applications with industrial-scale storage capacity. However, the development of active, stable, and earth-abundant catalysts for cerium redox reactions with sluggish kinetics remains a major challenge. Herein, for the first time, two-dimensional (2D) nanostructured architectures were used to design and fabricate efficient and stable electrocatalysts from earth-abundant components toward the Ce(iv)/Ce(iii) redox reaction. A novel WO3/GF hybrid architecture (WGF) built from WO3 nanowall arrays (NWAs) anchored on graphite felt (GF) surfaces was prepared for cerium-based RFBs. This unique hybrid exhibits superior electrocatalytic performance since the vertical nanowall arrays display open and ordered structures that ensure full exposure of the active sites toward electrolytes, which allows direct and full contact of every nanowall with the electrolyte. As an electrode for cerium redox reactions, this WGF electrode exhibits a 42.1% and 32.0% increase in energy efficiency as compared with that of pristine GF and acid-treated GF at a high charge/discharge rate of 30 mA cm-2. Moreover, the long-term cycling performance confirms the superior durability of the as-prepared WGF. This study suggests that the use of 2D nanostructures combined with vertical array microstructures is a promising strategy for efficient electrocatalysts toward cerium redox reactions with scale-up potential.


The efficacy of a working memory training in substance use patients: A randomized double-blind placebo-controlled clinical trial.
Substance use disorder patients show impairments in working memory (WM) functioning. Previous findings indicate that a WM training results in improvements of working memory capacity (WMC) and in decreased clinical symptoms in a range of mental disorders, including alcohol use disorder. The aim of the current study is to investigate the efficacy of a 24-session WM training in addition to treatment as usual on craving, WMC, substance use, impulsivity, attention bias, and psychopathology using a randomized double-blind placebo-controlled trial. Inpatients (n = 180) diagnosed with an alcohol, cocaine, or cannabis use disorder were included. Although the WM training resulted in better scores on the trained tasks in both groups, the placebo training resulted in a better or equal WMC compared to the experimental training, as measured with two nontrained transfer tasks. The WM training had no effect on craving, substance use, impulsivity, attention bias, and psychopathology. Overall, we did not find evidence for the efficacy of WM training on WMC or clinical symptoms as compared to a placebo training in a population of substance use disorder patients. Future research needs to investigate further whether WMC is an important factor that is associated with substance-abuse-related behavior, and whether working memory training could be useful in substance use disorders.


Looking back at five decades of embryo technology in practice.
This paper covers developments from International Embryo Technology Society (IETS) meetings over the past 50years. The IETS was officially 'born' at a meeting in Denver, Colorado on Sunday 26 May 1974. There have been 51 IETS meetings (the first was in May 1974), and the first conference at which papers were presented was in 1975. The name of the IETS was changed from International Embryo Transfer Society to International Embryo Technology Society in 2016. The annual IETS conferences are held once a year in January. Embryo technology advanced from the laborious and slow techniques of surgical recovery and transfer of bovine embryos to non-surgical recovery and transfer in many species. Cryopreservation of embryos was initially a slow process that met with only moderate technical success before the development of technology that resulted in high embryo survival rates. The polymerase chain reaction was used to determine the sex of embryos following laminar flow cytology, which came into use to separate X- and Y-bearing spermatozoa. IVF has grown to become widely used, and several factors make it more useful than superovulation and embryo recovery/transfer. Perhaps the most important tool of all was the system that allowed the genetic 'mapping' of the genomic sequence of Bos taurus cattle. Charting key DNA differences by scientists, 'haplotypes' are now used routinely to identify animals with desirable traits of economic importance, discover new genetic disorders, and track carrier status of genotyped animals. Future technology is discussed.


Effects of food on cortisol and mood in vulnerable subjects under controllable and uncontrollable stress.
The aim of this study was to investigate whether in stress-prone subjects, carbohydrate-rich, protein-poor food (CR/PP) diminished depressive mood and a cortisol response under controllable as well as uncontrollable laboratory stress. Twenty-two subjects with high stress proneness (HS) and 23 subjects with low stress proneness (LS) participated in a controllable- and uncontrollable-stress experiment during either a CR/PP or protein-rich, carbohydrate-poor (PR/CP) diet. Both controllable and uncontrollable laboratory stress significantly increased pulse rate and skin conductance in HS and LS subjects, whereas uncontrollable stress increased feelings of depression, anger, tension, and fatigue and decreased feelings of vigor. Only in HS subjects, a cortisol response and feelings of depression became lower under the CR/PP diet condition, irrespective of the controllability of the laboratory stressor, suggesting an increased ability to cope with stress. Because the CR/PP diet compared with the PR/CP diet previously has been found to cause a 42% increase in plasma tryptophan/SigmaLNAA, seen as an indirect measure of increases in brain serotonin levels, the present results suggest that an enhanced serotonin function in HS subjects may be involved.


Risk factors for men's lifetime perpetration of physical violence against intimate partners: results from the international men and gender equality survey (IMAGES) in eight countries.
This paper examines men's lifetime physical intimate partner violence (IPV) perpetration across eight low- and middle-income countries to better understand key risk factors that interventions can target in order to promote gender equality and reduce IPV. We use data from men (n = 7806) that were collected as part of the International Men and Gender Equality Survey (IMAGES) in Bosnia and Herzegovina, Brazil, Chile, Croatia, Democratic Republic of Congo (DRC), India, Mexico, and Rwanda. Results show that there is wide variation across countries for lifetime self-reported physical violence perpetration (range: 17% in Mexico to 45% in DRC), men's support for equal roles for men and women, and acceptability of violence against women. Across the sample, 31% of men report having perpetrated physical violence against a partner in their lifetime. In multivariate analyses examining risk factors for men ever perpetrating physical violence against a partner, witnessing parental violence was the strongest risk factor, reinforcing previous research suggesting the inter-generational transmission of violence. Additionally, having been involved in fights not specifically with an intimate partner, permissive attitudes towards violence against women, having inequitable gender attitudes, and older age were associated with a higher likelihood of ever perpetrating physical IPV. In separate analyses for each country, we found different patterns of risk factors in countries with high perpetration compared to countries with low perpetration. Findings are interpreted to identify key knowledge gaps and directions for future research, public policies, evaluation, and programming.


Highly conductive ribbons prepared by stick-slip assembly of organosoluble gold nanoparticles.
Precisely positioning and assembling nanoparticles (NPs) into hierarchical nanostructures is opening opportunities in a wide variety of applications. Many techniques employed to produce hierarchical micrometer and nanoscale structures are limited by complex fabrication of templates and difficulties with scalability. Here we describe the fabrication and characterization of conductive nanoparticle ribbons prepared from surfactant-free organosoluble gold nanoparticles (Au NPs). We used a flow-coating technique in a controlled, stick-slip assembly to regulate the deposition of Au NPs into densely packed, multilayered structures. This affords centimeter-scale long, high-resolution Au NP ribbons with precise periodic spacing in a rapid manner, up to 2 orders-of-magnitude finer and faster than previously reported methods. These Au NP ribbons exhibit linear ohmic response, with conductivity that varies by changing the binding headgroup of the ligands. Controlling NP percolation during sintering (e.g., by adding polymer to retard rapid NP coalescence) enables the formation of highly conductive ribbons, similar to thermally sintered conductive adhesives. Hierarchical, conductive Au NP ribbons represent a promising platform to enable opportunities in sensing, optoelectronics, and electromechanical devices.


Functional neuroimaging provides evidence of anomalous cerebral laterality in adults with Klinefelter's syndrome.
This study aimed to characterize cerebral perfusion in men with Klinefelter's syndrome, known to present specific deficits in language, using (99m)Tc- hexamethylpropylene-amine-oxime scintigraphy and Talairach normalization. While a perfusion asymmetry toward the left hemisphere was found in controls, perfusion was mostly symmetrical in Klinefelter patients in the upper temporal and lower parietal areas. Scores on verbal tests were inversely correlated with perfusion changes, providing neurobiological substrate of anomalous cerebral laterality.


TMPRSS2 and COVID-19: Serendipity or Opportunity for Intervention?
TMPRSS2 is both the most frequently altered gene in primary prostate cancer and a critical factor enabling cellular infection by coronaviruses, including SARS-CoV-2. The modulation of its expression by sex steroids could contribute to the male predominance of severe infections, and given that TMPRSS2 has no known indispensable functions, and inhibitors are available, it is an appealing target for prevention or treatment of respiratory viral infections.


Interleukin-4 modulates cholinergic neural control of mouse small intestinal longitudinal muscle.
Interleukin-4 contributes to expulsion of certain gastrointestinal parasites and causes intestinal mucosal mastocytosis. Because mast cell-derived mediators are spasmogenic, potentially causing parasitic expulsion, we investigated the effect of interleukin-4 on smooth muscle and the mast cell and mediator dependency of this effect. BALB/c, mast cell-deficient W/Wv mice, 5-lipoxygenase-efficient mice, and their littermate controls were injected with interleukin-4-anti-interleukin-4 antibody complexes that chronically increase serum interleukin-4 levels. Mid-small intestinal segments, hung longitudinally in organ baths, were stimulated electrically or by agonists. The cholinergic response to electrical field stimulation was significantly increased by interleukin-4 treatment in BALB/c but not W/Wv mice. The enhanced cholinergic contraction was not due to increased acetylcholine responsiveness but was dependent on leukotriene D4, since it was reversed by leukotriene D4 receptor antagonism, and not observed in 5-lipoxygenase knock-out mice. Leukotriene D4 responsiveness was unaffected by interleukin-4 treatment. We conclude that interleukin-4 amplifies cholinergic excitation through a mast cell and leukotriene D4-dependent mechanism.


Reconsidering against medical advice discharges: embracing patient-centeredness to promote high quality care and a renewed research agenda.
Hospital discharges against medical advice (AMA) are common, costly, stigmatizing to patients, and are associated with excess morbidity and mortality. Achieving better quality care for patients discharged AMA has been limited both by the sparse research illuminating how best to care for this challenging patient population, as well as a lack of standards regarding this clinical practice. This paper will review elements of the AMA literature and highlight the gaps, including the predictors of AMA discharge, challenges to high quality informed consent in AMA discharges, problematic aspects of AMA discharge forms, and the stigma associated with patients discharged AMA. These gaps in the evidence base collectively limit the ability to adequately and completely address AMA discharges and improve health care quality. This paper will recommend future directions to answer remaining questions for the field, and offer guidance for providing ethically sound and high quality care for the affected population. Applying the widely accepted principles of patient-centered care and shared decision making to AMA discharges offers the opportunity to improve quality of care and promote ethical health care practice.


Implementation of postpartum intrauterine device (PPIUD) services across 10 districts in Malawi.
Malawi has a high maternal mortality and unmet need for family planning, which could be reduced by improving access to postpartum intrauterine device (PPIUD) insertion. Our objective is to describe the implementation of PPIUD services by 4 local organizations at 14 government health services across 10 districts in Malawi. This program was a collaborative effort between the Malawi Ministry of Health's Reproductive Health Directorate and 4 supporting organizations. Training, educational, and monitoring and evaluation materials for PPIUD insertion were developed between December 2013 and April 2014. Each organization was then responsible for PPIUD community sensitization, provider training, and tracking of PPIUD insertions (via PPIUD register books) at their targeted health facilities. Community sensitization activities included Open Day campaigns, which were organized by local leaders to sensitize their communities, and Population Weekends, which were organized by religious leaders to target their congregations. Community sensitization activities, provider trainings, and mentoring occurred from January 2014 to June 2015, and monitoring and evaluation continued until December 2016 at some sites. One national Radio Discussion Panel with religious leaders was broadcast, 20 Open Day campaigns and 2 Population Weekends were held, 429 providers were trained during 27 trainings, and 249 PPIUD insertions occurred. PPIUD can be safely offered in Malawi. However, the biggest challenge with program implementation was with encouraging providers to take the extra time and effort to insert an IUD within 48 hours of delivery. In addition, frequent rotation of trained labour ward staff to other clinical areas hindered the program's sustainability since new trainings had to be held whenever staff members were rotated. Further research should be done to determine the best strategies to motivate busy providers to insert PPIUD, and PPIUD should be integrated into both medical and nursing curriculums to reduce the number of postgraduate trainings required to sustain PPIUD services.


Confessions of a Reluctant Caregiver Palliative Educational Program: Using Readers' Theater to Teach End-of-Life Communication in Undergraduate Medical Education.
End-of-life care can be stressful for patients, caregivers, and providers. Caregivers often experience high levels of burden from caregiving duties such as performing medical tasks, communicating with providers, and making decisions. Similarly, many physicians feel unprepared to provide end-of-life care or communicate with patients and families about sensitive issues associated with death and dying. Physicians often attribute their lack of preparation to inadequate training in medical school. Previous research suggests that drama-based learning opportunities are valuable supplements to existing end-of-life curricula. The current study evaluates the success of the Confessions of a Reluctant Caregiver Palliative Educational Program - a drama-based educational program that depicts patient and caregiver experiences. A total of 477 osteopathic medical students participated in the program, which includes viewing a play, engaging in a facilitated post-performance talkback session, and completing an evaluation survey. The results suggest the program is a valuable learning experience that is positively associated with important facets of experiential learning using narratives such as perceived realism, increased reflection, strong emotions, and increased comfort with difficult behaviors. The program offers a safe environment for medical students to identify, understand, and process the sensitive and complex issues associated with end-of-life care. Moreover, the play offers insight into the often-overlooked experiences of family caregivers who are at risk of experiencing high caregiver burden while managing health-related communication and decision-making.


Global transcriptomic analysis in avocado nursery trees reveals differential gene expression during asymptomatic infection by avocado sunblotch viroid (ASBVd).
Avocado sunblotch viroid (ASBVd) is the type species of the family Avsunviroidae and the causal agent of avocado sunblotch disease. The disease is characterised by the presence of chlorotic lesions on avocado fruit, leaves and/or stems. Infected trees may remain without chlorosis for extended periods of time, though distorted growth and reduced yield has been observed in these cases. The molecular effects of ASBVd on avocado, and members of the Avsunviroidae on their respective hosts in general, remain poorly understood. Host global transcriptomic studies within the family Pospiviroidae have identified several host pathways that are affected during these plant-pathogen interactions. In this study, we used RNA sequencing to investigate host gene expression in asymptomatic avocado nursery trees infected with ASBVd. Transcriptome data showed that 631 genes were differentially expressed, 63 % of which were upregulated during infection. Plant defence responses, phytohormone networks, gene expression pathways, secondary metabolism, cellular transport as well as protein modification and degradation were all significantly affected by ASBVd infection. This work represents the first global gene expression study of ASBVd-infected avocado, and the transcriptional reprogramming observed during this asymptomatic infection improves our understanding of the molecular interactions underlying broader avsunviroid-host interactions.


Insulin resistance in polycystic ovary syndrome: progress and paradoxes.
Over the past 20 years, it has been clearly documented that 1) polycystic ovary syndrome (PCOS) has major metabolic sequelae related to insulin resistance and 2) insulin resistance plays an important role in the pathogenesis of the reproductive abnormalities of the disorder. Women with PCOS are at significantly increased risk of developing type 2 diabetes mellitus (DM). Studies in isolated adipocytes and in cultured skin fibroblasts from PCOS women have demonstrated intrinsic postbinding defects in insulin-mediated glucose metabolism. In fibroblasts, the mitogenic pathway of insulin action is intact, consistent with a selective defect in insulin signaling. While PCOS skeletal muscle is resistant to insulin in vivo, cultured muscle cells have normal insulin sensitivity, consistent with a major role of extrinsic factors in producing insulin resistance in this tissue. Excessive serine phosphorylation of the insulin receptor or downstream signaling proteins may be involved in the pathogenesis of insulin resistance in PCOS. The putative serine kinase is extrinsic to the insulin receptor but its identity is unknown. The explanations for tissue-specific and signaling pathway-specific differences in insulin action in PCOS are unknown but may involve differential roles of insulin receptor substrate (IRS)-1 and IRS-2 in insulin signal transduction.


Biosynthesis and characterization with antimicrobial activity of TiO2 nanoparticles using probiotic Bifidobacterium bifidum.
Bifidobacterium selectively colonizes the infants' intestinal tract, and the relevant coliform bacteria in adults are particularly beneficial because of their enhanced capability to prevent pathogens of gastro intestine by direct antimicrobial action and relieve infection, which led to their intensification, the antibacterial activities of titanium nanoparticles producing by some bacteria, makes them attractive as a new agent against pathogenic bacteria. In our present study, we used a probiotic bacteria Bifidobacterium bifidum which was isolated from the commercial market capsule to produce TiO2 nanoparticles and study the biologically characterized nanoparticle using various techniques like Scanning Electron Microscopic (SEM), atomic force microscopy (AFM), and study its antimicrobial activity against a bacteria isolated from the stool of patients suffering from acute diarrhea. The results showed that the morphological characteristics of nanoparticles were found to have a spherical shape and mean size of 81 nm by AFM while scanning electron microscope viewed as an oval shape with anatase form synthesized by B. bifidum. TiO2-NP synthesized by B. bifidum had an inhibitory effect against P. aeruginosa, A. baumanii, K. pneumonia at a concentration 16 mg/ml and 32 mg/ml towards E. coli and S. typhi, the minimum inhibitory concentration (MIC) against pathogenic bacteria isolated from acute diarrhea included Pseudomonas aeruginosa, Acinetobacter baumanii, Klebsiella pneumonia, E.coli and salmonella typhi was utilized to determine the antibacterial impact of the synthesized TIO2 nanoparticles. Our biologically synthesized titanium nanoparticles were effective against all the tested pathogenic bacteria at various degrees and had a probable role in significantly greater antimicrobial efficacy against all isolates under study. This trial may have considerable significance for the prevention of antibiotic resistance associated diarrhea in hospitals.


Effects of ketone bodies on insulin release and islet-cell metabolism in the rat.
Ketone bodies promote insulin secretion from isolated rat pancreatic islets in the presence of 5 mM-glucose, but are ineffective in its absence. At concentrations of 10 mM or less, the relative abilities of the ketone bodies to potentiate release are in the order D-3-hydroxybutyrate greater than DL-3-hydroxybutyrate greater than acetoacetate. The response curve relating insulin release to D-3-hydroxybutyrate concentration displays a threshold at 1 mM and a maximum at 10 mM. D-3-Hydroxybutyrate (5 mM, but not 10 mM) promotes insulin secretion in the presence of 5 mM concentrations of both L-arginine and DL-glyceraldehyde, but not with L-leucine, L-alanine, L-glutamate or 4-methyl-2-oxopentanoate. The oxidation rates of the exogenous ketone bodies do not correlate well with their capacities to promote insulin release. Moreover, the oxidation of 5 mM-D-3-hydroxybutyrate can be inhibited by 25% with methylmalonate (10 mM) without any diminution of release. The potentiation with D-3-hydroxybutyrate occurs without an observable increase in total islet cyclic AMP. However, a small net efflux matches the relative abilities of the ketone bodies to promote insulin release. With islets from 48 h-starved animals the insulin response is both diminished and less sensitive than in fed animals, since insulin secretion is not significantly raised until a threshold of 5 mM-D-3-hydroxybutyrate is reached. These results suggest that, in the rat at least, there should be a reappraisal of the physiological role of ketone bodies in the promotion of insulin release.


miR-21 Might be Involved in Breast Cancer Promotion and Invasion Rather than in Initial Events of Breast Cancer Development.
Breast cancer (BC) is a heterogeneous disease that develops into a large number of varied phenotypes. One of the features used in its classification and therapy selection is invasiveness. MicroRNA-21 (miR-21) is considered to be an important element of BC invasiveness, and miR-21 levels are frequently increased in different tumor types compared with normal tissue, including the breast. Experimental and literature research has highlighted that miR-21 was always significantly elevated in every study that included invasive breast carcinomas compared with healthy breast tissue. The main goal of this research was to specify the predominant role of miR-21 in the different phases of BC pathogenesis, i.e. whether it was involved in the early (initiation), later (promotion), or late (propagation, progression) phases. Our second goal was to explain the roles of miR-21 targets in BC by an in silico approach and literature review, and to associate the importance of miR-21 with particular phases of BC pathogenesis through the action of its target genes. Analysis has shown that changes in miR-21 levels might be important for the later and/or late phases of breast cancerogenesis rather than for the initial early phases. Targets of miR-21 (TIMP3, PDCD4, PTEN, TPM1 and RECK) are also primarily involved in BC promotion and progression, especially invasion, angiogenesis and metastasis. miR-21 expression levels could perhaps be used in conjunction with the standard diagnostic parameters as an indicator of BC presence, and to indicate a phenotype likely to show early invasion/metastasis detection and poor prognosis.


Changes in mitochondrial adenine nucleotides and in permeability transition in two models of rat liver regeneration.
Although enhanced phosphorylative activity can be a requisite for later DNA synthesis during liver regeneration (LR), mitochondrial generation of reactive oxygen species could lead to altered mitochondrial membrane permeability during the prereplicative phase of LR. Therefore, the role of mitochondrial permeability transition (MPT) was evaluated during rat LR, induced by either partial hepatectomy (PH) or after CCl(4) administration. Parameters indicative of mitochondrial function and membrane potentials, those of oxidative stress, and in vivo changes of the intramitochondrial pool of adenine nucleotides were determined. Twelve hours after PH, mitochondrial oxidative and phosphorylative activities and adenosine diphosphate (ADP) content were increased, reaching a maximal peak at 24 hours after surgery (maximal DNA synthesis). Parameters suggestive of oxidant stress were enhanced, but mitochondrial volume and membrane electrical potential remained unaltered. Interestingly, moderate mitochondrial swelling and depolarization were found at later post-PH times (72 hours). In CCl(4)-treated animals, it was found that an active liver cell necrosis delayed mitotic activity and mitochondrial uncoupled respiration. Starting 12 hours after CCl(4) intoxication, a drastic increase of inorganic phosphate occurred within swollen and strongly depolarized mitochondria, suggesting changes in the MPT. Despite expression of messenger RNA (mRNA) for mitochondrial transcription, factor A showed a similar time course in both experimental models. The so-called augmenter liver regeneration was found significantly elevated only in PH rats. In conclusion, onset of MPT could be associated with cell necrosis and inflammation after CCl(4) treatment, whereas this mitochondrial event could constitute a putative effector mechanism, through which growth or inflammatory factors inhibiting cell proliferation could initiate LR termination.


Phenobarbital treatment and major depressive disorder in children with epilepsy.
The prevalence and severity of psychopathology in 15 epileptic patients treated with phenobarbital and 24 patients treated with carbamazepine were compared. The groups were similar across a wide range of demographic, seizure-related, and family-environmental variables. Patients treated with phenobarbital, when compared with those treated with carbamazepine, showed a much higher prevalence of major depressive disorder (40% v 4%, P = .02), and suicidal ideation (47% v 4%, P = .005) as determined by semistructured psychiatric interviews. The differential prevalence of depression between medication groups was only noted in those with a family history of a major affective disorder among first-degree relatives. Family discord and number of stressful life events were also associated with depression in this cohort. Patients treated with phenobarbital should be closely monitored for depression, and alternative treatments should probably be sought for patients with newly diagnoses epilepsy and a personal or family history of an affective disorder. The clinical and research implications of these findings are discussed.


ICTV Virus Taxonomy Profile: Arenaviridae 2023.
Arenaviridae is a family for ambisense RNA viruses with genomes of about 10.5 kb that infect mammals, snakes, and fish. The arenavirid genome consists of two or three single-stranded RNA segments and encodes a nucleoprotein (NP), a glycoprotein (GP) and a large (L) protein containing RNA-directed RNA polymerase (RdRP) domains; some arenavirids encode a zinc-binding protein (Z). This is a summary of the International Committee on Taxonomy of Viruses (ICTV) report on the family Arenaviridae, which is available at www.ictv.global/report/arenaviridae.


Functions, diversity, and evolution of traumatic mating.
Copulation can involve the wounding of the mating partner by specialised devices. This type of mating, which we term traumatic mating, has been regarded as exceptional. Its prevalence, however, has not been compared across taxa, nor have its functions and putative evolutionary pathways. A categorisation has been lacking to date. We here show that traumatic mating is a widespread and diverse phenomenon that likely evolved via several pathways. Its putative functions include: (i) anchorage during mating; (ii) stimulation of short-term female reproductive investment; (iii) male paternity advantages; and (iv) enhanced fertilisation efficiency in transitions to internal fertilisation. Both natural and sexual selection have likely contributed to the parallel evolution of traumatic intromittent organs in phylogenetically distant taxa. These organs are sometimes remarkably similar in shape and often, but not always, inject sperm. The target sites of trauma infliction and the nature of secretions delivered alongside sperm are thus far poorly studied, but data on both are needed to elucidate the function of traumatic mating. The few existing studies that explicitly quantify fitness impacts of traumatic mating indicate that this strategy may often be costly to the party being wounded. However, a comprehensive approach to assess overall investments and returns for both sexes is a major target for future work. Finally, for the first time, we corroborate quantitatively the hypothesis that traumatic mating evolved relatively more often among hermaphroditic than among gonochoric taxa.


Cesarean delivery in Shantou, China: a retrospective analysis of 1922 women.
In China the cesarean section rate increased significantly during the past four decades. This study examined the frequency and indications of cesarean birth in Shantou, a southern city in China. An analysis was conducted of the medical records of 1922 women who had cesarean deliveries at Shantou City 2nd People's Hospital between January 1990 and December 1997. The medical records of 10,490 women who gave birth during this period were examined. The average rate of cesarean delivery during the 8-year period was 19.4 +/- 2.3 percent (means +/- standard error). From 1990 to 1997 the cesarean delivery rates ranged from 11.05 to 29.9 percent, respectively, although during this period the total annual number of deliveries decreased significantly from 1683 to 951. The rates of the most common indications per 100 women for cesarean delivery were failure to progress (23%), premature rupture of membranes (20%), fetal distress (19.4%), breech presentation (18.1%), uterine scar (14.6%), and prolonged pregnancy (11.3%). The cesarean delivery rate in Shantou, China, has increased steadily and significantly between 1990 and 1997, despite a decrease in the total number of births during the same period. This study showed that on an individual basis vaginal delivery was often possible and reduction of the cesarean delivery rate could be achieved safely by paying greater heed to appropriate indications.


Ranolazine-induced myopathy in a patient on chronic statin therapy.
We present a case demonstrating clinical, electrophysiological, serological, and radiological evidence of a myopathy induced by ranolazine, in a patient otherwise asymptomatic on chronic statin therapy. The patient developed proximal weakness, serum creatine kinase levels of 1875 U/L, electromyography with muscle membrane instability and small short-duration motor unit potentials, and magnetic resonance imaging evidence of muscle edema. The manifestations began within one week of initiation of ranolazine and improved within days after discontinuation. Ranolazine is a weak inhibitor of CYP3A4 known to increase the serum level of simvastatin and its active metabolite 2-fold. We postulate that the addition of ranolazine to a medical regimen that included atorvastatin induced a myoncecrotic myopathy.


Childhood meningitis caused by enterococci and viridans streptococci.
Selected clinical and laboratory parameters were studied respectively in patients with meningitis caused by enterococci and viridans streptococci in an academic children's hospital. During a nine-year period (1981-1989), enterococci or viridans streptococci were isolated from the cerobrospinal fluid (CSF) of 48 patients. In nine of these 48 patients, enterococci or viridans streptococci were the causative agents of meningitis. These nine children constituted 2.0% of 450 patients with bacterial meningitis in this period. All nine children suffered from underlying diseases; neurosurgical procedures were performed in six of these patients, of whom four had ventricular drains. A head trauma preceded the development of meningitis in another patient. Drainage of the lacrimal duct was associated with the development of meningitis in another patients. One child concurrently suffered from severe gastroenteritis. CSF leukocyte count and CSF protein levels were moderately elevated, whereas CSF glucose levels were either slightly decreased or within the normal range. Meningitis due to enterococci or viridans streptococci is seen predominantly in children under the age of one year. Predisposing factors, including neurosurgical procedures, head trauma and severe gastroenteritis, are usually present in these patients. The prognosis for recovery is generally good.


The CERAB technique: tips, tricks and results.
In this article we wanted to present an overview of the latest study results, in vitro and in vivo, of the Covered Endovascular Reconstruction of the Aortic Bifurcation or CERAB technique and the C-CERAB or Chimney CERAB for the endovascular treatment of either extensive occlusive aortoiliac or iuxtarenal disease with preservation of visceral arteries; in combination with tips and tricks to facilitate recanalization and revascularization. A review was performed of the literature of the last 5 years regarding the endovascular treatment of aortoiliac and iuxtarenal TASC II C& D lesions with covered balloon expandable stents. Furthermore we did a retrospective analysis of our most special techniques to achieve a successful interventional recanalization of these challenging lesions. Both the in vitro and the in vivo studies pointed out that there exists an important benefit of the CERAB configuration with excellent patency rates at one and two years in combination with very low mortality and morbidity, when compared to other techniques. Also the C-CERAB variant seems to be a feasible and safe option; 100% technical success; to deal with iuxtarenal or extensive aortic occlusive disease together with the safeguarding of visceral arteries. The CERAB and C-CERAB techniques may change the treatment algorithm of extensive aortoiliac occlusive disease in the near future and appears to be a safe and feasible alternative with promising results, together with a more anatomical and physiological reconstruction of the aortic bifurcation, being a valid alternative for surgery and/or kissing stents. A few critical issues still need to be solved, such as cost-effectiveness, patient selection, fine-tuning of the technique and defining the optimal medical support.


Facilitating reproductive choices: the impact of health services on the experiences of young women with breast cancer.
Chemotherapy and hormone treatments carry significant implications on the fertility of young women with breast cancer. Increasingly, nulliparous women experience fertility dilemmas due to rising survival rates and pregnancy delay. This qualitative study investigated women's responses to being told that treatments affected their fertility and how their interactions with health services impacted on their experiences. Twenty-four women under 40 years participated in three focus groups using a flexible interview structure. Data were analysed using content analysis and participants subsequently member checked the themes generated. The priority for most women was survival, although women without children were more willing to take risks. Many women felt that pregnancy after breast cancer and methods of egg harvesting carried a significant risk to survival and fears appeared to be increased by conflicting advice from health professionals. Overall, the women felt the cancer, its treatment options and the health service itself had each robbed them of choice. Hence, with hindsight, many said they would have welcomed an open and honest discussion with a fertility expert to maximise their options. Young women with breast cancer face complex decisions regarding their fertility and treatment options. Survival remains the priority for the majority of women. Although there is a paucity of evidence concerning many fertility issues, it is essential that available options and any potential risks are discussed in a coherent, objective fashion. Early referral to specialist fertility services that provide clear, cohesive advice can aid informed decision making.


[The key role of calcium in the mechanism of deprivational potentiation of population responses in hippocampal CA1 neurons].
We investigated a role of calcium in the mechanisms of deprivational potentiation (DeP) of the popspikes amplitude of CA1 neurons that was induced in consequence of long (60 min) interruption of rare test stimulation (0.05 Hz) of Schaffer collaterals in rat hippocampal slices. There are two phases of deprivational potentiation that have presumably different genesis: short-term initial "peak" (about 12 min) and long-term "plateau" (more than 1 h). The presence of the membrane permeable Ca2+ chelator (BAPTA-AM) in the solution, or decrease of [Ca2+](out), or depletion of intracellular Ca2+ stores (in the presence of thapsigargin/cyclopiazonic acid) led to reduction of the short-term and to suppression of the long-term phases of DeP. Thus the key role of calcium in the DeP induction mechanisms and participation of two main sources (the extracellular environment and the intracellular Ca2+ stores) was demonstrated.


Reliable genotypic tropism tests for the major HIV-1 subtypes.
Over the past decade antiretroviral drugs have dramatically improved the prognosis for HIV-1 infected individuals, yet achieving better access to vulnerable populations remains a challenge. The principal obstacle to the CCR5-antagonist, maraviroc, from being more widely used in anti-HIV-1 therapy regimens is that the pre-treatment genotypic "tropism tests" to determine virus susceptibility to maraviroc have been developed primarily for HIV-1 subtype B strains, which account for only 10% of infections worldwide. We therefore developed PhenoSeq, a suite of HIV-1 genotypic tropism assays that are highly sensitive and specific for establishing the tropism of HIV-1 subtypes A, B, C, D and circulating recombinant forms of subtypes AE and AG, which together account for 95% of HIV-1 infections worldwide. The PhenoSeq platform will inform the appropriate use of maraviroc and future CCR5 blocking drugs in regions of the world where non-B HIV-1 predominates, which are burdened the most by the HIV-1 pandemic.


Increasing the Sustainability of Biocatalytic Processes.
The number of industrial processes which include one or more enzyme-mediated step is growing rapidly, together with our understanding of how biocatalysts can be adapted to efficiently perform chemical reactions, often only remotely related to their natural reactivity. While enzymes as naturally biodegradable molecules are the most sustainable approach to catalysis, a more global vision of the overall sustainability of enzymatic process must be considered. Here an insight of how sustainability can be further improved when enzymes are immobilized on solid supports is discussed.


An easy method for detection of nasopharyngeal carriage of multiple Streptococcus pneumoniae serotypes.
In this paper, a simplified method for detection of pneumococcal carriage and for revealing the presence of several serotypes in a nasopharyngeal sample is evaluated. Enrichment broth was used for transportation and for the initial culturing of samples. All specimens were examined directly by the capsular reaction test for the presence of any of the 91 known pneumococcal serotypes. Sub-culturing on blood agar was used for isolation of the pneumococcal strains detected in the primary broth culture. A total of 693 nasopharyngeal swabs were obtained among children, their parents and employees in day care centres. Pneumococci were observed in 363 samples and 36 of these (9.9%) contained more than one serotype (multiple carriages). Two persons carried 3 different serotypes simultaneously. A significant increase in the positive sampling rate (5.8%) was achieved by using the simplified method compared to conventional streaking of the swabs directly on blood agar (p<0.0001).


Health-care provider screening for tobacco smoking and advice to quit - 17 countries, 2008-2011.
Tobacco use is the leading cause of preventable mortality in the world. Article 14 of the World Health Organization (WHO) Framework Convention on Tobacco Control (FCTC) states that countries should promote cessation of tobacco use and adequate treatment for tobacco dependence. Health-care providers asking all patients about their tobacco use and advising tobacco users to quit are evidence-based strategies that increase tobacco abstinence. This report examines the proportion of tobacco smokers in 17 countries responding to the Global Adult Tobacco Survey (GATS) who saw a health-care provider in the past year and who reported that a health-care provider asked them about smoking and advised them to quit. Respondents were tobacco smokers aged ≥15 years surveyed during 2008-2011 in Bangladesh, Brazil, China, Egypt, India, Indonesia, Malaysia, Mexico, Philippines, Poland, Romania, Russia, Thailand, Turkey, Ukraine, Uruguay, and Vietnam. The proportion of smokers who had visited a health-care provider during the previous 12 months ranged from 21.6% in Egypt to 62.3% in Poland. Among these, the proportion reporting that a health-care provider asked if they smoked ranged from 34.9% in Vietnam to 82.1% in Romania. Among those screened for tobacco use, those who reported their health-care providers advised them to quit ranged from 17.3% in Mexico to 67.3% in Romania. In most countries, persons aged ≥45 years were more likely to report being screened and advised to quit than were persons aged ≤24 years. Health-care providers should identify smokers and provide advice and assistance in quitting at each visit as an adjunct to effective community interventions (e.g., increased price of tobacco products; smoke-free policies, mass media campaigns, and tobacco quitlines).


Plasma exchange and glucocorticoid dosing in the treatment of anti-neutrophil cytoplasm antibody associated vasculitis (PEXIVAS): protocol for a randomized controlled trial.
Granulomatosis with polyangiitis (GPA, Wegener's) and microscopic polyangiitis (MPA) are small vessel vasculitides collectively referred to as anti-neutrophil cytoplasm antibody-associated vasculitis (AAV). AAV is associated with high rates of morbidity and mortality due to uncontrolled disease and treatment toxicity. Small randomized trials suggest adjunctive plasma exchange may improve disease control, while observational evidence suggests that current oral glucocorticoid doses are associated with severe infections in patients with AAV. A randomized study of both plasma exchange and glucocorticoids is required to evaluate plasma exchange and oral glucocorticoid dosing in patients with AAV. PEXIVAS is a two-by-two factorial randomized trial evaluating adjunctive plasma exchange and two oral glucocorticoid regimens in severe AAV. Five hundred patients are being randomized at centers across Europe, North America, Asia, and Australasia to receive plasma exchange or no plasma exchange, and to receive standard or reduced oral glucocorticoid dosing. All patients receive immunosuppression with either cyclophosphamide or rituximab. The primary outcome is the time to the composite of all-cause mortality and end-stage renal disease.PEXIVAS is funded by the National Institute of Health Research (UK), the Food and Drug Administration (USA), the National Institutes of Health (USA), the Canadian Institute of Health Research (Canada), the National Health and Medical Research Council (Australia), and Assistance Publique (France). Additional in-kind supplies for plasma exchange are provided by industry partners (TerumoBCT, Gambro Australia, and Fresenius Australia). This is the largest trial in AAV undertaken to date. PEXIVAS will inform the future standard of care for patients with severe AAV. The cooperation between investigators, funding agencies, and industry provides a model for conducting studies in rare diseases. Current Controlled Trials: (ISRCTN07757494) and clinicaltrials.gov: (NCT00987389).


Peptidyltransferase activity of ribosomes and a ribosome precursor from a mutant of Escherichia coli.
Escherichia coli strain 15-28 is a mutant with a defect in ribosome synthesis that caused the accumulation of ribonucleoprotein ('47S') particles during exponential growth. These particles are precursors to 50S ribosomes that lack three ribosomal proteins. Peptidyltransferase activity and binding at the peptidyl site of the peptidyltransferase centre are greatly decreased in 47S particles. Both these activities are lower in the 50S and 70S ribosomes of strain 15-28 than in its parent. Unusual assembly of the larger ribosomal subunit in strain 15-28 may produce completed ribosomes with diminished biological activity.