Performance-based financing to increase utilization of maternal health services: Evidence from Burkina Faso.
Performance-based financing (PBF) programs are increasingly implemented in low and middle-income countries to improve health service quality and utilization. In April 2011, a PBF pilot program was launched in Boulsa, Leo and Titao districts in Burkina Faso with the objective of increasing the provision and quality of maternal health services. We evaluate the impact of this program using facility-level administrative data from the national health management information system (HMIS). Primary outcomes were the number of antenatal care visits, the proportion of antenatal care visits that occurred during the first trimester of pregnancy, the number of institutional deliveries and the number of postnatal care visits. To assess program impact we use a difference-in-differences approach, comparing changes in health service provision post-introduction with changes in matched comparison areas. All models were estimated using ordinary least squares (OLS) regression models with standard errors clustered at the facility level. On average, PBF facilities had 2.3 more antenatal care visits (95% CI [0.446-4.225]), 2.1 more deliveries (95% CI [0.034-4.069]) and 9.5 more postnatal care visits (95% CI [6.099, 12.903]) each month after the introduction of PBF. Compared to the service provision levels prior to the interventions, this implies a relative increase of 27.7 percent for ANC, of 9.2 percent for deliveries, and of 118.7 percent for postnatal care. Given the positive results observed during the pre-pilot period and the limited resources available in the health sector, the PBF program in Burkina Faso may be a low-cost, high impact intervention to improve maternal and child health.


G0S2 represses PI3K/mTOR signaling and increases sensitivity to PI3K/mTOR pathway inhibitors in breast cancer.
G0/G1 switch gene 2 (G0S2) is a direct retinoic acid target implicated in cancer biology and therapy based on frequent methylation-mediated silencing in diverse solid tumors. We recently reported that low G0S2 expression in breast cancer, particularly estrogen receptor-positive (ER+) breast cancer, correlates with increased rates of recurrence, indicating that G0S2 plays a role in breast cancer progression. However, the function(s) and mechanism(s) of G0S2 tumor suppression remain unclear. In order to determine potential mechanisms of G0S2 anti-oncogenic activity, we performed genome-wide expression analysis that revealed an enrichment of gene signatures related to PI3K/mTOR pathway activation in G0S2 null cells as compared to G0S2 wild-type cells. G0S2 null cells also exhibited a dramatic decreased sensitivity to PI3K/mTOR pathway inhibitors. Conversely, restoring G0S2 expression in human ER+ breast cancer cells decreased basal mTOR signaling and sensitized the cells to pharmacologic mTOR pathway inhibitors. Notably, we provide evidence here that the increase in recurrence seen with low G0S2 expression is especially prominent in patients who have undergone antiestrogen therapy. Further, ER+ breast cancer cells with restored G0S2 expression had a relative increased sensitivity to tamoxifen. These findings reveal that in breast cancer G0S2 functions as a tumor suppressor in part by repressing PI3K/mTOR activity, and that G0S2 enhances therapeutic responses to PI3K/mTOR inhibitors. Recent studies implicate hyperactivation of PI3K/mTOR signaling as promoting resistance to antiestrogen therapies in ER+ breast cancer. Our data establishes G0S2 as opposing this form of antiestrogen resistance. This promotes further investigation of the role of G0S2 as an antineoplastic breast cancer target and a biomarker for recurrence and therapy response.


Exploring novel strategies for AIDS protozoal pathogens: α-helix mimetics targeting a key allosteric protein-protein interaction in C. hominis TS-DHFR.
The bifunctional enzyme thymidylate synthase-dihydrofolate reductase (TS-DHFR) from the protozoal parasite Cryptosporidium hominis is a potential molecular target for the design of antiparasitic therapies for AIDS-related opportunistic infections. The enzyme exists as a homodimer with each monomer containing a unique swap domain known as a "crossover helix" that binds in a cleft on the adjacent DHFR active site. This crossover helix is absent in species containing monofunctional forms of DHFR such as human. An in-depth understanding of protein-protein interactions between the crossover helix and adjacent DHFR active site that might modulate enzyme integrity or function would allow for insights into rational design of species-specific allosteric inhibitors. Mutational analysis coupled with structural studies and biophysical and kinetic characterization of crossover helix mutants identifies this domain as essential for full enzyme stability and catalytic activity, and pinpoints these effects to distinct faces of the crossover helix important in protein-protein interactions. Moreover, targeting this helical protein interaction with α-helix mimetics of the crossover helix leads to selective inhibition and destabilization of the C. hominis TS-DHFR enzyme, thus validating this region as a new avenue to explore for species-specific inhibitor design.


Measuring reliability and validity of a newly developed stress instrument: Newly Diagnosed Breast Cancer Stress Scale.
To assess the reliability and validity of a developed instrument entitled Newly Diagnosed Breast Cancer Stress Scale. Distress, clinical anxiety and depression are evident in patients with cancer, leading to poor psychosocial and quality-of-life outcomes. Instrument development study with norm-referenced measurements. Content validity was determined by expert review. Cronbach's α was used to assess internal consistency reliability and product-moment correlations were conducted. Exploratory factor analysis measured validity of items using varimax rotation method. Criterion-related validity testing used the Perceived Stress Scale and the convergent validity test of construct validity used the Hospital Anxiety and Depression Scale. A total of 125 women pathologically diagnosed with breast cancer were interviewed on the day prior to initial breast surgery. After testing, the Newly Diagnosed Breast Cancer Stress Scale consisted of four main factors with 17 items with acceptable reliability and good validity, and its length and time to complete the questionnaire were appropriate. Internal consistency reliability of the scale was shown by Cronbach's α = 0·84, the criterion validity of Perceived Stress Scale-10 was r = 0·46 (p < 0·001), the convergent validity of Hospital Anxiety and Depression Scale-14 was r = 0·57 (p < 0·001) for anxiety and r = 0·35 (p < 0·001) for depression. The Newly Diagnosed Breast Cancer Stress Scale has acceptable reliability and good validity to measure stress in newly diagnosed patients with breast cancer. The Newly Diagnosed Breast Cancer Stress Scale can provide healthcare workers with an instrument to better identify stress levels in newly diagnosed breast cancer patients and provide valuable information when defining psychosocial care interventions.


Salvage Surgery for Recurrence after Radiotherapy for Squamous Cell Carcinoma of the Head and Neck.
Most studies that report on salvage surgery after primary radiotherapy for head and neck squamous cell carcinoma (HNSCC) are small and heterogeneous. Subsequently, some relevant questions remain unanswered. We specifically focused on (1) difference in prognosis per tumor subsite, corrected for disease stage, and (2) differences in prognosis after salvage surgery for local, regional, and locoregional recurrences. Retrospective analysis. Single-center study (2000-2016). Patients treated with salvage surgery for HNSCC recurrence after (chemo)radiotherapy. In total, 189 patients were included. Five-year overall survival (OS) was 33%, and median OS was 18 (95% confidence interval [CI], 11-26) months. Treatment-related mortality was 2%. Larynx carcinoma was associated with more favorable local (adjusted hazard ratio [HR] = 4.02; 95% CI, 1.46-11.10; P = .007) and locoregional control (adjusted HR = 5.34; 95% CI, 1.83-15.61; P = .002) than pharyngeal carcinoma. American Society of Anesthesiologists (ASA) score (≥3 vs 1-2: adjusted HR = 3.04; 95% CI, 1.17-7.91; P = .023), pT stage (3-4 vs 1-2: adjusted HR = 4.41; 95% CI, 1.65-11.82; P = .003), and salvage surgery for locoregional recurrences (locoregional vs local: adjusted HR = 3.81; 95% CI, 1.13-11.82; P = .021) were independent predictors for disease-free survival (DFS). Salvage surgery for larynx carcinoma, regardless of disease stage and other prognostic factors, results in more favorable loco(regional) control but not favorable DFS than pharyngeal carcinoma. The observed difference in DFS between salvage surgery for local and regional recurrences was not significant after correction for confounders. However, survival following salvage surgery for locoregional disease is significantly worse. For this subgroup, we propose to consider T status and comorbidity for clinical decision making, as high pT stage and ASA score are independent predictors for worse DFS.


Third-harmonic generation from arrays of sub-wavelength metal apertures.
We measure third-harmonic generation (THG) from arrays of sub-wavelength metal apertures in transmission using fundamental input at 800 nm. Samples with different aperture spacings, sizes, and shapes are used. Strong angular dependence of THG is observed, with maxima located at incidence angles corresponding to extraordinary optical transmission (EOT) for the fundamental. We demonstrate an anomalous scaling of TH intensity with aperture size, where at different EOT peaks, the TH may either increase or decrease with aperture size. The aperture shape is also shown to have a strong effect on TH output.


Ultrastructural characterization of SARS coronavirus.
Severe acute respiratory syndrome (SARS) was first described during a 2002-2003 global outbreak of severe pneumonia associated with human deaths and person-to-person disease transmission. The etiologic agent was initially identified as a coronavirus by thin-section electron microscopic examination of a virus isolate. Virions were spherical, 78 nm in mean diameter, and composed of a helical nucleocapsid within an envelope with surface projections. We show that infection with the SARS-associated coronavirus resulted in distinct ultrastructural features: double-membrane vesicles, nucleocapsid inclusions, and large granular areas of cytoplasm. These three structures and the coronavirus particles were shown to be positive for viral proteins and RNA by using ultrastructural immunogold and in situ hybridization assays. In addition, ultrastructural examination of a bronchiolar lavage specimen from a SARS patient showed numerous coronavirus-infected cells with features similar to those in infected culture cells. Electron microscopic studies were critical in identifying the etiologic agent of the SARS outbreak and in guiding subsequent laboratory and epidemiologic investigations.


Transcutaneous electrical nerve stimulation on acupoints relieves labor pain: a non-randomized controlled study.
To investigate the efficacy of transcutaneous electrical nerve stimulation (TENS) on four specific acupuncture points Hegu (LI4), Neiguan (PC6), Danshu (BL19) and Weishu (BL21) for reducing pain in labor. A total of 160 voluntary nulliparous women who were willing to receive TENS for analgesia were assigned to the treatment group after cervical dilation of more than 2 cm. Another 145 matched nullipara were recruited as the control group. Visual analogue scale (VAS) was used to assess the pain before and 0.5 h after the application of TENS. Then, VAS was assessed every one hour until delivery. Percentage of VAS score decreased by > 25% was the primary outcome, the delivery mode and neonatal outcome were measured as secondary outcomes. Adverse reactions were also recorded during TENS. The percentage of VAS score decreased by > 25% was 68.6% in the TENS treatment group. Maternal delivery mode and neonatal outcomes were not significantly different between the two groups. In addition, the incidence of postpartum hemorrhage in the TENS treatment group was less than the control group (P<0.05). There was no adverse reaction recorded with TENS on acupoints. As a novel and non-invasive approach, TENS on specific acupoints including Hegu (LI4), Neiguan (PC6), Danshu (BL19) and Weishu (BL21) was an effective method for analgesia in labor.


Relationship between relative net vertical impulse and jump height in jump squats performed to various squat depths and with various loads.
The purpose of the current investigation was to determine the relationship between relative net vertical impulse (net vertical impulse (VI)) and jump height in the jump squat (JS) going to different squat depths and utilizing various loads. Ten males with two years of jumping experience participated in this investigation (Age: 21.8 ± 1.9 y; Height: 176.9 ± 5.2 cm; Body Mass: 79.0 ± 7.1 kg, 1RM: 131.8 ± 29.5 kg, 1RM/BM: 1.66 ± 0.27). Subjects performed a series of static jumps (SJS) and countermovement jumps (CMJJS) with various loads (Body Mass, 20% of 1RM, 40% of 1RM) in a randomized fashion to a depth of 0.15, 0.30, 0.45, 0.60, and 0.75 m and a self-selected depth. During the concentric phase of each JS, peak force (PF), peak power (PP), jump height (JH) and relative VI were recorded and analyzed. Increasing squat depth corresponded to a decrease in PF and an increase in JH, relative VI for both SJS and CMJJS during all loads. Across all squat depths and loading conditions relative VI was statistically significantly correlated to JH in the SJS (r = .8956, P < .0001, power = 1.000) and CMJJS (r = .6007, P < .0001, power = 1.000). Across all squat depths and loading conditions PF was statistically nonsignificantly correlated to JH in the SJS (r = -0.1010, P = .2095, power = 0.2401) and CMJJS (r = -0.0594, P = .4527, power = 0.1131). Across all squat depths and loading conditions peak power (PP) was significantly correlated with JH during both the SJS (r = .6605, P < .0001, power = 1.000) and the CMJJS (r = .6631, P < .0001, power = 1.000). PP was statistically significantly higher at BM in comparison with 20% of 1RM and 40% of 1RM in the SJS and CMJJS across all squat depths. Results indicate that relative VI and PP can be used to predict JS performance, regardless of squat depth and loading condition. However, relative VI may be the best predictor of JS performance with PF being the worst predictor of JS performance.


Biochemical markers of bone turnover, hip bone loss, and fracture in older men: the MrOS study.
We used data from the Osteoporotic Fractures in Men (MrOS) study to test the hypothesis that men with higher levels of bone turnover would have accelerated bone loss and an elevated risk of fracture. MrOS enrolled 5995 subjects >65 yr; hip BMD was measured at baseline and after a mean follow-up of 4.6 yr. Nonspine fractures were documented during a mean follow-up of 5.0 yr. Using fasting serum collected at baseline and stored at -190 degrees C, bone turnover measurements (type I collagen N-propeptide [PINP]; beta C-terminal cross-linked telopeptide of type I collagen [betaCTX]; and TRACP5b) were obtained on 384 men with nonspine fracture (including 72 hip fractures) and 947 men selected at random. Among randomly selected men, total hip bone loss was 0.5%/yr among those in the highest quartile of PINP (>44.3 ng/ml) and 0.3%/yr among those in the lower three quartiles (p = 0.01). Fracture risk was elevated among men in the highest quartile of PINP (hip fracture relative hazard = 2.13; 95% CI: 1.23, 3.68; nonspine relative hazard = 1.57, 95% CI: 1.21, 2.05) or betaCTX (hip fracture relative hazard = 1.76, 95 CI: 1.04, 2.98; nonspine relative hazard = 1.29, 95% CI: 0.99, 1.69) but not TRACP5b. Further adjustment for baseline hip BMD eliminated all associations between bone turnover and fracture. We conclude that higher levels of bone turnover are associated with greater hip bone loss in older men, but increased turnover is not independently associated with the risk of hip or nonspine fracture.


Thought Speed, Mood, and the Experience of Mental Motion.
This article presents a theoretical account relating thought speed to mood and psychological experience. Thought sequences that occur at a fast speed generally induce more positive affect than do those that occur slowly. Thought speed constitutes one aspect of mental motion. Another aspect involves thought variability, or the degree to which thoughts in a sequence either vary widely from or revolve closely around a theme. Thought sequences possessing more motion (occurring fast and varying widely) generally produce more positive affect than do sequences possessing little motion (occurring slowly and repetitively). When speed and variability oppose each other, such that one is low and the other is high, predictable psychological states also emerge. For example, whereas slow, repetitive thinking can prompt dejection, fast, repetitive thinking can prompt anxiety. This distinction is related to the fact that fast thinking involves greater actual and felt energy than slow thinking does. Effects of mental motion occur independent of the specific content of thought. Their consequences for mood and energy hold psychotherapeutic relevance.


Quantifying biases in marine-protected-area placement relative to abatable threats.
Marine protected areas (MPAs) are a critical defense against biodiversity loss in the world's oceans, but to realize near-term conservation benefits, they must be established where major threats to biodiversity occur and can be mitigated. We quantified the degree to which MPA establishment has targeted stoppable threats (i.e., threats that can be abated through effectively managed MPAs alone) by combining spatially explicit marine biodiversity threat data in 2008 and 2013 and information on the location and potential of MPAs to halt threats. We calculated an impact metric to determine whether countries are protecting proportionally more high- or low-threat ecoregions and compared observed values with random protected-area allocation. We found that protection covered <2% of ecoregions in national waters with high levels of abatable threat in 2013, which is ∼59% less protection in high-threat areas than if MPAs had been placed randomly. Relatively low-threat ecoregions had 6.3 times more strict protection (International Union for Conservation of Nature categories I-II) than high-threat ecoregions. Thirty-one ecoregions had high levels of stoppable threat but very low protection, which presents opportunities for MPAs to yield more significant near-term conservation benefits. The extent of the global MPA estate has increased, but the establishment of MPAs where they can reduce threats that are driving biodiversity loss is now urgently needed.


[Management of needed health care workers in primary care. Automating the calculation].
The Santa Coloma de Gramenet Primary Care Service has designed a new tool to standardize and automate the process of planning the number of needed health care workers. The tool is divided in two parts: a calculator, which gives guidance on the foreseeable risk depending on the activity and the health care workers' workload, and sentinel indicators; the main is the "welfare basic level", that is the percentage structure of visited patients and their delay at 2, 3 and 7 calendar days, assessing the impact on the care of the population. The results of its use in the summer of 2010 have demonstrated its efficiency by lowering the needed workers with respect to 2009, achieving a better distribution according to the workload and improving the economic management. Given that the necessary data are accessible through computerized databases and its simple use, we believe it to be exportable to other fields.


Training and evaluation of lumbar punctures in a VR-environment using a 6DOF haptic device.
A virtual reality system for the training of the lumbar puncture intervention is presented. We use a haptic device with six degrees of freedom (6DOF) to feedback forces that resist needle insertion and rotation. An improved haptic volume rendering approach is used to calculate the forces and an evaluation component has been developed to rate the success of virtual lumbar punctures to trace the training process of the user and to give feedback about failures.


High contrast modulation of plasmonic signals using nanoscale dual-frequency liquid crystals.
We have designed and simulated a dual-frequency liquid crystal (DFLC) based plasmonic signal modulator capable of achieving over 15 dB modulation depth. The voltage-controlled DFLC is combined with a groove and slit configuration and its operation is discussed. Using the finite-difference time domain (FDTD) method, simulations were conducted to discover the groove-slit separation distance that enabled a practically useful modulation depth for the two states of the DFLC. Moreover, we have shown that significant improvement in modulation depth can be achieved by addition of a second groove to the design structure. Additionally, a performance analysis indicates a switching energy on the order of femtojoules and a switching speed on the order of 100 microseconds. Results of this investigation can be useful for the future design, simulation, and fabrication of DFLC-based plasmonic signal modulating devices, which have application in electro-optical and all-optical information systems.


Highly potent half-sandwich iridium and ruthenium complexes as lysosome-targeted imaging and anticancer agents.
In this study, six half-sandwich luminescent iridium (Ir) and ruthenium (Ru) anticancer complexes bearing P^P-chelating ligands 1,2-bis(diphenylphosphino)benzene (dppbz) and 1,8-bis(diphenylphosphino)naphthalene (dppn) were synthesized and characterized via1H-NMR spectroscopy, 31P-NMR spectroscopy, mass spectrometry, elemental analysis and X-ray crystallography. All the complexes displayed more potent anticancer activity than cisplatin towards A549 lung cancer cells and HeLa cervical cancer cells, especially the most potent iridium complex Ir3, which was 73 times more potent than cisplatin against A549 cells. Different from cisplatin, no nucleobase adducts of Ir3 were detected. With the help of the self-luminescence of complex Ir3 and confocal microscopy, it was observed that Ir3 efficiently penetrated into the A549 cells via energy-dependent active transport, and specifically accumulated in lysosomes, affected the permeabilization of the lysosomal membranes and induced caspase-dependent cell death through lysosomal damage. Both apoptosis and autophagy of the A549 cells were observed. The reactive oxygen species (ROS) elevation, reduction of the mitochondrial membrane potential and cell cycle arrest at the G0/G1 phase also contributed to the observed cytotoxicity of Ir3. We demonstrate that these half-sandwich Ir and Ru anticancer complexes have different anticancer mechanism of action from that of cisplatin, which can be developed as potential multifunctional theranostic platforms that combine bioimaging and anticancer capabilities.


Advanced glycation end products in foods and a practical guide to their reduction in the diet.
Modern diets are largely heat-processed and as a result contain high levels of advanced glycation end products (AGEs). Dietary advanced glycation end products (dAGEs) are known to contribute to increased oxidant stress and inflammation, which are linked to the recent epidemics of diabetes and cardiovascular disease. This report significantly expands the available dAGE database, validates the dAGE testing methodology, compares cooking procedures and inhibitory agents on new dAGE formation, and introduces practical approaches for reducing dAGE consumption in daily life. Based on the findings, dry heat promotes new dAGE formation by >10- to 100-fold above the uncooked state across food categories. Animal-derived foods that are high in fat and protein are generally AGE-rich and prone to new AGE formation during cooking. In contrast, carbohydrate-rich foods such as vegetables, fruits, whole grains, and milk contain relatively few AGEs, even after cooking. The formation of new dAGEs during cooking was prevented by the AGE inhibitory compound aminoguanidine and significantly reduced by cooking with moist heat, using shorter cooking times, cooking at lower temperatures, and by use of acidic ingredients such as lemon juice or vinegar. The new dAGE database provides a valuable instrument for estimating dAGE intake and for guiding food choices to reduce dAGE intake.


Carboxyhemoglobin levels in Kenyan children with Plasmodium falciparum malaria.
Heme oxygenase (HO) is thought to be induced in severe malaria, but the pathophysiologic consequences have not been examined. It is induced by hemolysis, oxidative stress, and inflammation. It degrades heme, producing carbon monoxide (CO), which causes elevated levels of carboxyhemoglobin (COHb). In a prospective study of 1,520 children admitted to a Kenyan district hospital, COHb levels were no higher in children with malaria than with other infections. The COHb levels in children with severe malarial anemia were higher than in other children with malaria, but significantly lower than in children with other causes of severe anemia such as sickle cell disease. Levels of COHb were not significantly higher in children with cerebral malaria or in those dying of malaria. These results do not support a systemic increase in HO activity in malaria compared with other infectious diseases, but the roles of HO and CO in malaria require further study.


Unheard Voices: African American Fathers Speak about their Parenting Practices.
Researchers have called for qualitative investigations into African American fathers' parenting practices that consider their social context and identify specific practices. Such investigations can inform the way we conceptualize African American fathers' parenting practices, which can in turn contribute to prevention interventions with at-risk youth. We conducted semi-structured, qualitative interviews about parenting with 30 self-identified, African American, biological fathers of pre-adolescent sons at-risk for developing aggressive behaviors, depressive symptoms, or both. Fathers provided descriptions of their parenting practices, which were at times influenced by their environmental context, fathers' residential status, and masculine ideologies. Our systematic analysis revealed four related themes that emerged from the data: managing emotions, encouragement, discipline, and monitoring. Of particular note, fathers in the current sample emphasized the importance of teaching their sons to manage difficult emotions, largely utilized language consistent with male ideologies (i.e., encouragement rather than love or nurturance), and engaged in high levels of monitoring and discipline in response to perceived environmental challenges and the developmental needs of their sons. The findings provide deeper insight into the parenting practices of African American fathers who are largely understudied, and often misunderstood. Further, these findings highlight considerations that may have important implications for father-focused prevention interventions that support African American fathers, youth, and families.


Identification and characterization of expressed retrotransposons in the genome of the Paracoccidioides species complex.
Species from the Paracoccidioides complex are thermally dimorphic fungi and the causative agents of paracoccidioidomycosis, a deep fungal infection that is the most prevalent systemic mycosis in Latin America and represents the most important cause of death in immunocompetent individuals with systemic mycosis in Brazil. We previously described the identification of eight new families of DNA transposons in Paracoccidioides genomes. In this work, we aimed to identify potentially active retrotransposons in Paracoccidioides genomes. We identified five different retrotransposon families (four LTR-like and one LINE-like element) in the genomes of three Paracoccidioides isolates. Retrotransposons were present in all of the genomes analyzed. P. brasiliensis and P. lutzii species harbored the same retrotransposon lineages but differed in their copy numbers. In the Pb01, Pb03 and Pb18 genomes, the number of LTR retrotransposons was higher than the number of LINE-like elements, and the LINE-like element RtPc5 was transcribed in Paracoccidioides lutzii (Pb01) but could not be detected in P. brasiliensis (Pb03 and Pb18) by semi-quantitative RT-PCR. Five new potentially active retrotransposons have been identified in the genomic assemblies of the Paracoccidioides species complex using a combined computational and experimental approach. The distribution across the two known species, P. brasiliensis and P. lutzii, and phylogenetics analysis indicate that these elements could have been acquired before speciation occurred. The presence of active retrotransposons in the genome may have implications regarding the evolution and genetic diversification of the Paracoccidioides genus.


Nonlinear resonances and antiresonances of a forced sonic vacuum.
We consider a harmonically driven acoustic medium in the form of a (finite length) highly nonlinear granular crystal with an amplitude- and frequency-dependent boundary drive. Despite the absence of a linear spectrum in the system, we identify resonant periodic propagation whereby the crystal responds at integer multiples of the drive period and observe that this can lead to local maxima of transmitted force at its fixed boundary. In addition, we identify and discuss minima of the transmitted force ("antiresonances") between these resonances. Representative one-parameter complex bifurcation diagrams involve period doublings and Neimark-Sacker bifurcations as well as multiple isolas (e.g., of period-3, -4, or -5 solutions entrained by the forcing). We combine them in a more detailed, two-parameter bifurcation diagram describing the stability of such responses to both frequency and amplitude variations of the drive. This picture supports a notion of a (purely) "nonlinear spectrum" in a system which allows no sound wave propagation (due to zero sound speed: the so-called sonic vacuum). We rationalize this behavior in terms of purely nonlinear building blocks: apparent traveling and standing nonlinear waves.


Connexin-36 gap junctions mediate electrical coupling between ventral tegmental area GABA neurons.
Communication between neurons in the mammalian brain is primarily through chemical synapses; however, evidence is accumulating in support of electrical synaptic transmission between some neuronal types in the mature nervous system. The authors have recently demonstrated that the gap junction (GJ) blocker quinidine suppresses stimulus-induced and dopamine-evoked coupling of gamma amino butyric acid (GABA) neurons in the ventral tegmental area (VTA) of mature rats (Stobbs et al., 2004). The aim of this study was to evaluate the role of connexin-36 (Cx36) GJs in mediating electrical coupling between VTA GABA neurons in P50-80 rats in vivo and P25-50 rats in vitro. Single stimulation of the internal capsule (IC) evoked VTA GABA neuron spike couplets in mature rats when activated antidromically, and multiple poststimulus spike discharges (PSDs) when activated with brief high-frequency stimulation of the IC (ICPSDs). The Cx36 GJ blocker mefloquine (30 mg/kg) suppressed VTA GABA neuron ICPSDs in mature freely behaving rats. VTA GABA neurons recorded via whole-cell patch clamp in the midbrain slice preparation of P25-50 rats showed robust expression of Cx36 transcripts when tested with single-cell quantitative reverse transcription polymerase chain reaction. In P50-80 rats, Cx36 protein immunoreactivity was evident in the VTA and surrounding structures. Dye-coupling between VTA neurons was observed following Neurobiotin labeling of VTA GABA neurons, as well as with the fluorochrome Alexa Fluor 488 using real-time video fluorescent microscopy. Thus, mature VTA GABA neurons appear to be connected by electrical synapses via Cx36 GJs, whose coupling is enhanced by corticotegmental input and by dopamine.


Protocol of the European Registry on the management of Helicobacter pylori infection (Hp-EuReg).
Helicobacter pylori selectively infects the human stomach, being the most prevalent chronic infection in the world. H pylori presence causes chronic gastritis in 100% of infected patients and is the major cause of relevant diseases such as atrophic gastritis, peptic ulcer disease, and gastric cancer; it is for this reason that from a public health standpoint, it is considered a high-impact pathogen, responsible of a significant morbidity and mortality. Nowadays, there are consensus and clinical guidelines regarding the infection management at a European level and in most of European countries, but no data have shown the level of implementation of these recommendations. The high costs that this infection carries both socially and to the health system require the continuous and systematic assessment of the diagnostic and treatment strategies, as well as the accessibility to diagnostic methods and most efficient drugs. To register the diagnosis, management strategies, and treatment of H pylori-infected adult patients in the Digestive Services outpatient clinics throughout Europe. Noninterventionist prospective multicentre international Registry promoted by the European Helicobacter and Microbiota Study Group. National Coordinators will select recruiting gastroenterologists in their country that will register the H pylori-related routine clinical practice consultations they receive in an electronic case report form (e-CRF) provided by AEG-REDCap. Variables retrieved will include clinical, diagnostic, treatment, eradication confirmation, and outcome data. The database will allow researchers to perform specific subanalyses after approval by the Scientific Committee of the study.


Developing a smoking cessation program for Turkish-speaking migrants in Switzerland: novel findings and promising effects.
Recent studies show that smoking prevalence in the Turkish-speaking migrant population in Switzerland is substantially higher than in the general population. A specific group treatment for Turkish-speaking migrants was developed and tested in order to provide the migrant population with equal access to smoking cessation programs and to improve the migration-sensitive quality of such programs by sociocultural targeting. The evaluation of the program included quantitative (questionnaires t1 and t2 and follow-up by telephone) and qualitative methods (participant observation and semi-structured interviews). The results showed that 37.7% of the 61 participants were smoke free at the 12-month follow-up. The factors of being in a partnership and using nicotine replacement products during the program were positively associated with successful cessation. We also demonstrated the importance of "strong ties" (strong relationships between participants) and the sensitivity of the program to sociocultural (e.g., social aspects of smoking in Turkish culture, which were addressed in relapse prevention), socioeconomic (e.g., low financial resources, which were addressed by providing the course for free), and migration-specific (e.g., underdeveloped access to smoking cessation programs, which was addressed using outreach strategy for recruiting) issues. Overall, the smoking cessation program was successfully tested and is now becoming implemented as a regular service of the Swiss Public Health Program for Tobacco Prevention (by the Swiss Association for Smoking Prevention).


Regeneration of neural crest derivatives in the Xenopus tadpole tail.
After amputation of the Xenopus tadpole tail, a functionally competent new tail is regenerated. It contains spinal cord, notochord and muscle, each of which has previously been shown to derive from the corresponding tissue in the stump. The regeneration of the neural crest derivatives has not previously been examined and is described in this paper. Labelling of the spinal cord by electroporation, or by orthotopic grafting of transgenic tissue expressing GFP, shows that no cells emigrate from the spinal cord in the course of regeneration. There is very limited regeneration of the spinal ganglia, but new neurons as well as fibre tracts do appear in the regenerated spinal cord and the regenerated tail also contains abundant peripheral innervation.The regenerated tail contains a normal density of melanophores. Cell labelling experiments show that melanophores do not arise from the spinal cord during regeneration, nor from the mesenchymal tissues of the skin, but they do arise by activation and proliferation of pre-existing melanophore precursors. If tails are prepared lacking melanophores, then the regenerates also lack them. On regeneration there is no induction of a new neural crest similar to that seen in embryonic development. However there is some regeneration of neural crest derivatives. Abundant melanophores are regenerated from unpigmented precursors, and, although spinal ganglia are not regenerated, sufficient sensory systems are produced to enable essential functions to continue.


The Cutting Edge of Headache Surgery: A Systematic Review on the Value of Extracranial Surgery in the Treatment of Chronic Headache.
Migraine is a debilitating neurologic condition, with a large socioeconomic impact. There is a subgroup of patients that does not adequately respond to pharmacologic management and may have underlying neuralgia. Surgical decompression of extracranial sensory nerves has been proposed as an alternative therapy. The aim of this article is to review the evidence for the surgical treatment of neuralgias. A systematic review was conducted to study the efficacy of decompression of extracranial sensory nerves as a treatment for neuralgia. Clinical studies were included that studied patients, aged 18 years or older, diagnosed with any definition of headache and were treated with extracranial nerve decompression surgery. Outcome parameters included intensity (on a 10-point scale), duration (in days), and frequency (of headaches per month). Thirty-eight articles were found describing extracranial nerve decompression in patients with headaches. Postoperative decrease in headache intensity ranged from 2 to 8.2, reduction of duration ranged from 0.04 to 1.04 days, and reduction in frequency ranged between 4 and 14.8 headaches per month. Total elimination of symptoms was achieved in 8.3 to 83 percent of cases. A detailed summary of the outcome of single-site decompression is described. Statistical pooling and therefore meta-analysis was not possible, because of articles having the same surgeon and an overlapping patient database. Nerve decompression surgery is an effective way of treating headaches in a specific population of patients with neuralgia. Although a meta-analysis of the current data was not possible, the extracranial decompression of peripheral head and neck sensory nerves has a high success rate.


Downregulation of proteins involved in the endoplasmic reticulum stress response and Nrf2-ARE signaling in lymphoblastoid cells of spinocerebellar ataxia type 17.
Spinocerebellar ataxia type 17 (SCA17) is caused by CAG repeat expansion in the TATA-box binding protein gene. Studies of several polyglutamine (polyQ) expansion diseases have suggested that the expanded polyQ proteins misfold and induce oxidative stress to contribute to cell death. Substantial deficits in peripheral tissues including lymphocytes have been shown and these peripheral abnormalities could also be found in neurons possessing polyQ disease proteins. In this study, we used a lymphoblastoid cell model to investigate the functional implication of SCA17 expanded alleles and assess the potential therapeutic strategies that may ameliorate the effects of expanded polyQ. Proteomics studies of patient/control pairs including two-dimensional (2-D) gel electrophoresis, mass spectrometry and immunoblotting were conducted. A total of 8 proteins with reduced expression changes greater than 1.3-fold were identified, including previously reported HSPA5 and HSPA8. Among 6 proteins further semi-quantified by immunoblotting and real-time PCR, the reduced expression of HYOU1, PDIA3, P4HB, NQO1 and HMOX1 was confirmed. Treatment with resveratrol and genipin up-regulated NQO1 and HMOX1 expression and reduced oxidative stress in patients' lymphoblastoid cells. The results illustrate downregulation of proteins involved in the endoplasmic reticulum stress response (HYOU1, HSPA5, PDIA3, and P4HB) and Nrf2-ARE signaling (NQO1 and HMOX1) in SCA17 lymphoblastoid cells. Compounds increasing anti-oxidative activity such as resveratrol and genipin may serve as a potential therapeutic strategy for SCA17.


Post-Traumatic Tremor and Thalamic Deep Brain Stimulation: Evidence for Use of Diffusion Tensor Imaging.
Deep brain stimulation (DBS) is a well-established treatment to reduce tremor, notably in Parkinson disease. DBS may also be effective in post-traumatic tremor, one of the most common movement disorders caused by head injury. However, the cohorts of patients often have multiple lesions that may impact the outcome depending on which fiber tracts are affected. A 20-year-old man presented after road traffic accident with severe closed head injury and polytrauma. Computed tomography scan showed left frontal and basal ganglia hemorrhagic contusions and intraventricular hemorrhage. A disabling tremor evolved in step with motor recovery. Despite high-intensity signals in the intended thalamic target, a visual analysis of the preoperative diffusion tensor imaging revealed preservation of connectivity of the intended target, ventralis oralis posterior thalamic nucleus (VOP). This was confirmed by the postoperative tractography study presented here. DBS of the VOP/zona incerta was performed. Six months postimplant, marked improvement of action (postural, kinetic, and intention) tremor was achieved. We demonstrated a strong connectivity between the VOP and the superior frontal gyrus containing the premotor cortex and other central brain areas responsible for movement control. In spite of an existing lesion in the target, the preservation of these tracts may be relevant to the improvement of the patient's symptoms by DBS.


Low cholesterol levels in children predict impulsivity in young adulthood.
Severe behavioural issues such as impulsive action and suicide have since long been associated with low levels of cholesterol. While it is known that cholesterol plays a role in neural development and hence low levels of serum lipids could have long-term effects on behaviour, no longitudinal studies showed the association of serum lipids levels with impulsivity. We aimed to examine the prognostic properties of serum lipid levels during childhood and adolescence on measures of impulsivity during early adulthood in a representative birth cohort sample. We have investigated whether serum lipid levels measured at 9, 15, 18 and 25 years of age have an association with impulsivity in 25 years old young adults. This analysis was based on data of the birth cohort representative samples of the Estonian Children Personality Behaviour and Health Study (original n = 1238). Impulsivity was self-reported with the Adaptive and Maladaptive Impulsivity Scale. Total and low-density lipoprotein (LDL) cholesterol measured in boys aged 9, 15 and 18 years predicted disinhibition and thoughtlessness in 25-year-old young adults. High scores of disinhibition were associated with low total and LDL cholesterol levels in males but, while less consistently, with high total and LDL cholesterol levels in females. Cross-sectional analysis did not result in systematic outcomes. Serum lipid levels could have an impact on the development of Maladaptive Impulsivity starting from an early age. This effect of cholesterol continues throughout adolescence into young adulthood.


Human immunodeficiency virus type 1 drug resistance in a subset of mothers and their infants receiving antiretroviral treatment in Ouagadougou, Burkina Faso.
The emergence of HIV-1 drug resistance (HIVDR) is a public health problem that affects women and children. Local data of HIVDR is critical to improving their care and treatment. So, we investigated HIVDR in mothers and infants receiving antiretroviral therapy (ART) at Saint Camille Hospital of Ouagadougou, Burkina Faso. This study included 50 mothers and 50 infants on ART. CD4 and HIV-1 viral load were determined using FACSCount and Abbott m2000rt respectively. HIVDR was determined in patients with virologic failure using ViroSeq HIV-1 Genotyping System kit on the 3130 Genetic Analyzer. The median age was 37.28 years in mothers and 1.58 year in infants. Sequencing of samples showed subtypes CRF02_AG (55.56%), CRF06_cpx (33.33%) and G (11.11%). M184V was the most frequent and was associated with highlevel resistance to 3TC, FTC, and ABC. Other mutations such as T215F/Y, D67N/E, K70R, and K219Q were associated with intermediate resistance to TDF, AZT, and 3TC. No mutation to LPV/r was detected among mothers and infants. The findings of HIVDR in some mothers and infants suggested the change of treatment for these persons.


Decomposition of Mediterranean Dietary Pattern on Successful Aging, Among Older Adults: A Combined Analysis of Two Epidemiological Studies.
Objective: To investigate the association of Mediterranean food group consumption with successful aging (SA), among people more than 50 years old. Method: Dietary habits, as well as several bio-clinical characteristics of the Greek participants enrolled in the ATTICA (n = 1,128 men and women from Athens metropolitan area) and the MEDIS (n = 2,221 men and women from selected Greek islands) cohort studies were investigated in relation to SA; SA was measured using a validated 10-scale index. Results: Multivariate discriminant food group analysis revealed that legumes consumption, followed by vegetables, cereals, and poultry were associated with higher levels of SA index (explained variability: 7.9%), mainly among islanders, but not among mainland participants. Further analysis revealed that alcohol consumption was positively associated with SA for mainlanders (ATTICA study) but inversely for islanders (MEDIS study; all p's < .05). Conclusion: The differential and hierarchical effect of various foods on SA and the diet-environmental interaction revealed in the present work may help health professionals to better understand the role of diet on SA, and to prioritize the nutritional needs of older people for better quality of life.


A genome-wide screen identifies the evolutionarily conserved KEOPS complex as a telomere regulator.
Telomere capping is the essential function of telomeres. To identify new genes involved in telomere capping, we carried out a genome-wide screen in Saccharomyces cerevisiae for suppressors of cdc13-1, an allele of the telomere-capping protein Cdc13. We report the identification of five novel suppressors, including the previously uncharacterized gene YML036W, which we name CGI121. Cgi121 is part of a conserved protein complex -- the KEOPS complex -- containing the protein kinase Bud32, the putative peptidase Kae1, and the uncharacterized protein Gon7. Deletion of CGI121 suppresses cdc13-1 via the dramatic reduction in ssDNA levels that accumulate in cdc13-1 cgi121 mutants. Deletion of BUD32 or other KEOPS components leads to short telomeres and a failure to add telomeres de novo to DNA double-strand breaks. Our results therefore indicate that the KEOPS complex promotes both telomere uncapping and telomere elongation.


Combined Aerobic and Resistance Exercise Training Reduces Circulating Apolipoprotein J Levels and Improves Insulin Resistance in Postmenopausal Diabetic Women.
Circulating apolipoprotein J (ApoJ) is closely associated with insulin resistance; however, the effect of exercise on circulating ApoJ levels and the association of ApoJ with metabolic indices remain unknown. Here, we investigated whether a combined exercise can alter the circulating ApoJ level, and whether these changes are associated with metabolic indices in patients with type 2 diabetes mellitus. Postmenopausal women with type 2 diabetes mellitus were randomly assigned into either an exercise (EXE, n=30) or control (CON, n=15) group. Participants in the EXE group were enrolled in a 12-week program consisting of a combination of aerobic and resistance exercises. At baseline, 4, 8, and 12 weeks, body composition and metabolic parameters including homeostatic model assessment of insulin resistance (HOMA-IR) and serum ApoJ levels were assessed. In the EXE group, ApoJ levels decreased 26.3% and 19.4%, relative to baseline, at 8 and 12 weeks, respectively. Between-group differences were significant at 8 and 12 weeks (P<0.05 and P<0.001, respectively). In the EXE group, 12 weeks of exercise resulted in significant decreases in body weight, percent body fat, and HOMA-IR indices. Concurrently, weight-adjusted appendicular skeletal muscle mass (ASM/wt) was increased in the EXE group compared with the CON group. Importantly, changes in the ApoJ level were significantly correlated with changes in ASM/wt. Exercise training resulted in a significant decrease in the circulating ApoJ level, with changes in ApoJ associated with an improvement in some insulin resistance indices. These data suggest that circulating ApoJ may be a useful metabolic marker for assessing the effects of exercise on insulin resistance.


Physiologic Effects from Using Tight- and Loose-Fitting Powered Air-Purifying Respirators on Inhaled Gases, Peak Pressures, and Inhalation Temperatures During Rest and Exercise.
The goal of this investigation was to evaluate the physiologic stresses of powered air-purifying respirators (PAPRs) used by workers in many industries (e.g., health care, automobile repair, public safety, building trades, etc.) during rest and three levels of energy expenditure. Twelve men and twelve women wore one tight-fitting and three loose-fitting PAPRs at rest (REST) and while walking for four minutes at oxygen consumption (V̇O2) rates of 1.0 l·min-1(LOW), 2.0 l·min-1 (MODERATE), and 3.0 l·min-1 or maximum (HIGH). Minimum inhaled carbon dioxide concentration (FICO2), maximum inhaled oxygen concentration (FIO2), peak inhalation pressure, and end inhalation temperature were measured continuously breath-by-breath. Repeated measures analysis of variance found that neither the main effect of gender, nor any interactions involving gender were significant. The highest minimum FICO2 among PAPRs occurred for MODERATE and HIGH energy expenditures while wearing the loose-fitting PAPR with the largest dead space. The lowest maximum FIO2 was observed during HIGH intensity energy expenditure also for the loose-fitting PAPR with the largest dead space. Among all PAPR models, peak inhalation pressures were negative at V̇O2 > LOW, suggesting that peak inhalation flow was greater than blower flow. Results using the variables reported here suggest that PAPRs used at various levels of energy expenditure may be tolerated among healthy workers. Further research is needed to determine the source of supplemented air when inhalation flow exceeds blower flow.


Nanoplatform-based optical contrast enhancement in epithelial tissues: quantitative analysis via Monte Carlo simulations and implications on precancer diagnostics.
This paper presents a comprehensive computational analysis of the spectral optical response of epithelial tissues labeled with gold nanoparticles. Monte Carlo modeling is employed to simulate nanoparticle-induced changes in reflectance signals and to assess whether labeling can generate sufficient exogenous contrast that can better pinpoint precancer progression. Simulation results suggest that the observed contrast profile is highly dependent on a series of factors including the labeling scheme, optical sensor geometry, and wavelength. It is evident, however, that selection of an optimal labeling and sensing strategy can lead to a significant enhancement of the inherent positive or negative contrast and can improve the diagnostic potential of optical measurements.


Levothyroxine therapy and serum free thyroxine and free triiodothyronine concentrations.
Although the normal thyroid gland secretes both levothyroxine (L-T4) and levotriiodothyronine (L-T3), normalization of serum TSH with L-T4-replacement therapy alone in hypothyroidism is generally believed to result in a normal serum L-T3 and to reflect a euthyroid state. However several recent studies suggest that this may not be the case. Accordingly, the relationship between serum free L-T4 and free L-T3 was examined in 20 normal individuals (group A) and in 53 patients with chronic autoimmune thyroiditis, 18 with normal TSH on no L-T4-replacement (group B), and 35 with normal TSH on L-T4-replacement therapy for hypothyroidism (group C). Data were analyzed by applying a one-way analysis of variance with correction for multiple comparisons. Serum TSH values were very similar among the 3 groups. In groups A and B, mean serum free T4 and free T3 were very similar. In group C, the mean free T4 (16+/-2 pmol/l) was significantly higher than the values in groups A (14+/-1) and B (14+/-2) (p<0.001) and the mean free T3 lower (4.0+/-0.5 pmol/l vs 4.2+/-0.5, NS and 4.4+/-0.5, p<0.02). Consequently, the mean molar ratio of free T4 to free T3 was significantly higher in group C than the ratios in groups A and B (p<0.0001), despite very similar TSH values. These findings indicate that in hypothyroid patients L-T4-replacement, that is sufficient to maintain a normal serum TSH, is accompanied by a serum free T4 that is higher than that in untreated euthyroid patients or normal individuals and may not result in an appropriately normal serum free T3 concentration.


A putative regulatory genetic locus modulates virulence in the pathogen Leptospira interrogans.
Limited research has been conducted on the role of transcriptional regulators in relation to virulence in Leptospira interrogans, the etiological agent of leptospirosis. Here, we identify an L. interrogans locus that encodes a sensor protein, an anti-sigma factor antagonist, and two genes encoding proteins of unknown function. Transposon insertion into the gene encoding the sensor protein led to dampened transcription of the other 3 genes in this locus. This lb139 insertion mutant (the lb139(-) mutant) displayed attenuated virulence in the hamster model of infection and reduced motility in vitro. Whole-transcriptome analyses using RNA sequencing revealed the downregulation of 115 genes and the upregulation of 28 genes, with an overrepresentation of gene products functioning in motility and signal transduction and numerous gene products with unknown functions, predicted to be localized to the extracellular space. Another significant finding encompassed suppressed expression of the majority of the genes previously demonstrated to be upregulated at physiological osmolarity, including the sphingomyelinase C precursor Sph2 and LigB. We provide insight into a possible requirement for transcriptional regulation as it relates to leptospiral virulence and suggest various biological processes that are affected due to the loss of native expression of this genetic locus.


The effects of intravenous cimetidine and metoclopramide on gastric pH and volume in outpatients.
To evaluate and compare the preinduction effects of intravenously (IV) administered cimetidine alone and combined with metoclopramide on gastric contents and postoperative nausea and vomiting in outpatients undergoing elective surgery. Patients were allocated randomly to 4 groups with 20 patients in each group. Ambulatory surgery at a university-affiliated city hospital. Eighty patients undergoing elective gynecologic or orthopedic procedures were studied. Outpatients in Group 1 and inpatients in Group 2 served as controls. Outpatients in Group 3 received 300 mg of cimetidine, and outpatients in Group 4 received 300 mg of cimetidine and 10 mg of metoclopramide. All drugs were administered IV as an infusion over a 15-minute period, 30 to 45 minutes prior to induction of anesthesia. After induction of general anesthesia and endotracheal intubation, stomach contents were retrieved and volume and pH measured. Group 1 outpatients had a large residual gastric volume of 29.2 +/- 15.9 ml, with a very low pH of 2.32 +/- 1.23 and 15% frequency of postoperative vomiting. These patients are at high risk of developing significant pneumonitis in the event of the aspiration of gastric contents. The combination of cimetidine and metoclopramide in Group 4 provided the optimal, or safest, condition--i.e., high gastric pH [6.15 +/- 0.71 (p less than 0.005)] and low gastric volume [11.6 +/- 7.37 ml (p less than 0.001)], with no postoperative vomiting. The combination of cimetidine and metoclopramide given to ambulatory patients during the preinductive phase may prevent severe pulmonary consequences should aspiration occur and is more effective in this regard than cimetidine alone.


A single-nucleotide-polymorphism real-time PCR assay for genotyping of Mycobacterium tuberculosis complex in peri-urban Kampala.
Accurate and high-throughput genotyping of Mycobacterium tuberculosis complex (MTBC) may be important for understanding the epidemiology and pathogenesis of tuberculosis (TB). In this study, we report the development of a LightCycler® real-time PCR single-nucleotide-polymorphism (LRPS) assay for the rapid determination of MTBC lineages/sublineages in minimally processed sputum samples from TB patients. Genotyping analysis of 70 MTBC strains was performed using the Long Sequence Polymorphism-PCR (LSP-PCR) technique and the LRPS assay in parallel. For targeted sequencing, 9 MTBC isolates (three isolates per MTBC lineage) were analyzed for lineage-specific single nucleotide polymorphisms (SNPs) in the following three genes to verify LRPS results: Rv004c for MTB Uganda family, Rv2962 for MTB lineage 4, and Rv0129c for MTB lineage 3. The MTBC lineages present in 300 smear-positive sputum samples were then determined by the validated LRPS method without prior culturing. The LSP-PCR and LRPS assays produced consistent genotyping data for all 70 MTBC strains; however, the LSP-PCR assay was 10-fold less sensitive than the LRPS method and required higher DNA concentrations to successfully characterize the MTBC lineage of certain samples. Targeted sequencing of genes containing lineage-specific SNPs was 100 % concordant with the genotyping results and provided further validation of the LRPS assay. Of the 300 sputum samples analyzed, 58 % contained MTBC from the MTBC-Uganda family, 27 % from the MTBC lineage 4 (excluding MTBC Uganda family), 13 % from the MTBC lineage 3, and the remaining 2 % were of indeterminate lineage. The LRPS assay is a sensitive, high-throughput technique with potential application to routine genotyping of MTBC in sputum samples from TB patients.


Full-length genomes of 16 hepatitis C virus genotype 1 isolates representing subtypes 1c, 1d, 1e, 1g, 1h, 1i, 1j and 1k, and two new subtypes 1m and 1n, and four unclassified variants reveal ancestral relationships among subtypes.
We characterized the full-length genomes of 16 distinct hepatitis C virus genotype 1 (HCV-1) isolates. Among them, four represented the first full-length genomes for subtypes 1d (QC103), 1i (QC181), 1j (QC329) and 1k (QC82), and another four corresponded to subtypes 1c (QC165), 1g (QC78), 1h (QC156) and 1e (QC172). Both QC196 and QC87 were assigned into a new subtype 1m, and QC113 and QC74 into another new subtype 1n. The remaining four (QC60, QC316, QC152 and QC180) did not classify among the established subtypes and corresponded to four new lineages. Subtypes 1j, 1k, 1m, 1n and the unclassified isolate QC60 were identified in Haitian immigrants. In the updated HCV nomenclature of 2005, a total of 12 subtypes of HCV-1 were designated. Including the data from the present study, all but subtype 1f now have their full-length genomes defined. Further analysis of partial NS5B sequences available in GenBank denoted a total of 21 unclassified lineages, indicating the taxonomic complexity of HCV-1. Among them, six have had their full-length genomes characterized. Based on the available full-length genome sequences, a timescale phylogenetic tree was reconstructed which estimated important time points in the evolution of HCV-1. It revealed that subtype 1a diverged from its nearest relatives 135 years ago and subtype 1b diverged from its nearest relatives 112 years ago. When subtypes 1a, 1j, 1k, 1m, 1n and six close relatives (all but one from Haitian immigrants) were considered as a whole, the divergence time was 176 years ago. This diversification was concurrent with the time period when the transatlantic slave trade was active. When taking all the HCV-1 isolates as a single lineage, the divergence time was 326 years ago. This analysis suggested the existence of a recent common ancestor for subtype 1a and the Haitian variants; a co-origin for subtypes 1b, 1i and 1d was also implied.


Reawakening the cellular death program in neoplasia through the therapeutic blockade of IAP function.
Recent studies have shown that members of the inhibitor of apoptosis (IAP) protein family are highly expressed in several classes of cancer. The primary implication of these findings is that the elevated expression of IAPs is not coincidental but actually participates in oncogenesis by helping to allow the malignant cell to avoid apoptotic cell death. This concept, together with the discovery of several IAP-regulatory proteins that use a conserved mode of action, has stimulated a major effort by many research groups to devise IAP-targeting strategies as a means of developing novel antineoplastic drugs. In this Review, we consider the evidence both for and against the IAPs being valid therapeutic targets, and we describe the types of strategies being used to neutralize their functions.


Risk of subsequent disabling or fatal stroke in patients with transient ischaemic attack or minor ischaemic stroke: an international, prospective cohort study.
Patients who have had a transient ischaemic attack or minor stroke have an increased risk of cardiovascular events for the following 5 years. We aimed to assess 5-year functional outcomes in patients with transient ischaemic attack or minor ischaemic stroke and to determine the factors associated with long-term disability. We analysed data from patients in TIAregistry.org, an international, prospective, observational registry of patients with transient ischaemic attack or minor ischaemic stroke from 61 specialised centres in 21 countries. Patients aged 18 years or older who had a transient ischaemic attack or minor stroke within the previous 7 days between May 30, 2009, and Dec 30, 2011, with a baseline modified Rankin scale (mRS) score of 0-1, and who had been followed up for 5 years, were eligible for inclusion in this study. We evaluated whether existing comorbidities and stroke recurrence, categorised as disabling (mRS score of >1, including death) or non-disabling (mRS score of 0-1), at 5 years after baseline, were associated with poor functional outcome (defined as an mRS score of >1). We used multivariable generalised equation models for factors associated with poor functional outcome at 5 years and multivariable cause-specific Cox hazard regression models in case of stroke recurrence. Between May 30, 2009, and Dec 30, 2011, 3847 eligible patients were included in the study, 3105 (80·7%) of whom had an mRS evaluation at 5 years of follow-up. Median follow-up duration was 5·00 years (IQR 4·78-5·00). 710 (22·9%) of 3105 patients had an mRS score greater than 1 at 5 years. Factors associated with poor functional outcome at 5 years were older age (per 10-year increase, odds ratio [OR] 2·18, 95% CI 1·93-2·46; p<0·0001), diabetes of any type (1·45, 1·18-1·78; p=0·0001), history of stroke or transient ischaemic attack before the qualifying event (1·74, 1·37-2·22; p<0·0001), hypertension (1·38, 1·00-1·92; p=0·050), atrial fibrillation or flutter (1·52, 1·04-1·94; p=0·030), congestive heart failure (1·73, 1·22-2·46; p=0·0024), valvular disease (2·47, 1·70-3·58; p<0·0001), stroke as qualifying event (1·31, 1·09-1·57; p=0·0037), history of peripheral artery disease (1·98, 1·28-3·07; p=0·0023), history of coronary artery disease (1·32, 1·00-1·74; p=0·049), intracranial haemorrhage during follow up (4·94, 1·91-12·78; p=0·0013), and living alone (1·32, 1·10-1·59; p=0·0031). Regular physical activity before the index event was associated with reduced risk of poor functional outcome (OR 0·52, 95% CI 0·42-0·66; p<0·0001). 345 recurrent strokes had occurred at 5 years of follow-up, 141 (40·9%) of which were disabling or fatal. Stroke recurrence increased the risk of having a disability at 5 years (OR 3·52, 95% CI 2·37-5·22; p<0·0001). Recurrent disabling or fatal strokes were independently associated with older age (per 10-year increase, hazard ratio [HR] 1·61, 95% CI 1·35-1·92; p<0·0001), diabetes of any type (2·23, 1·56-3·17; p<0·0001), National Institutes of Health Stroke Scale score of greater than 5 at discharge (5·11, 2·15-12·13; p=0·0013), history of coronary artery disease (1·76, 1·17-2·65; p=0·0063), history of stroke or transient ischaemic attack before the qualifying event (1·54, 1·03-2·29; p=0·035), congestive heart failure (1·86, 1·01-3·47; p=0·044), stroke as qualifying event (1·73, 1·22-2·45; p=0·0024), mRS score of greater than 1 at discharge (2·48, 1·27-4·87; p=0·0083), and intracranial haemorrhage during follow-up (17·15, 9·95-27·43; p<0·0001). Regular physical activity before the index event was associated with reduced risk of recurrent disabling stroke at 5 years (HR 0·56, 95% CI 0·31-0·99; p=0·046), and 5-year disability without recurrent stroke (0·61, 0·47-0·79; p=0·0001). We found a substantial burden of disability (mRS score of >1) at 5 years after transient ischaemic attack or minor ischemic stroke, and most predictors of this disability were modifiable risk factors. Patients who did regular physical exercise before the index event had a significantly reduced risk of disability at 5 years compared with patients who did no exercise. AstraZeneca, Sanofi, Bristol Myers Squibb, SOS Attaque Cérébrale Association.


Gram-negative bacillary community acquired meningitis is not a rare entity in last two decades.
The aim of this short note is to assess gram-negative bacillary community acquired meningitis (CBM) and nosocomial meningitis (NM) within 17 years nationwide survey. All cases of gram-negative bacillary CBM within 1990-2007 were assessed in national database of 372 patients with bacterial meningitis: 69 of gram-negative cases were nosocomial and 24 of gram-negative meningitis cases were CBM. Those 24 cases were compared with all CBM (201 cases) for risk factors and outcome. Among nosocomial gram-negative pathogens, A. baumannii in 23 cases, Ps. aeruginosa in 15 cases and Enterobacteriaceae in 31 cases were isolated. Among CBM, in 13 cases Enterobacteriaceae (Escherichia coli 6, Klebsiella pneumoniae 3, Proteus mirabilis 2, Enterobacter cloacae 2), in 5 cases Ps. aeruginosa and in 6 cases Acinetobacter baumannii were isolated from cerebrospinal fluid (CSF). The only significant risk factor for CBM due to gram-negative bacilli was neonatal age (12.5% vs. 3.5%, p=0.04) as underlying disease. However, mortality among gram-negative bacillary meningitis was significantly higher (12.4% vs. 37.5%, p=0.001) in comparison to other meningitis.


Glue ear: the new dyslexia?
Several factors have led to the current epidemic of surgery for glue ear in children, including the widespread introduction of audiometry; greater recognition of the presence of fluid in the middle ear by general practitioners; the availability of more otolaryngologists; and technical advances such as the availability of antibiotics to treat postoperative infections and of flanged tympanostomy tubes (grommets). The need of surgeons to fill the vacuum caused by the decline in the number of adenotonsillectomies, and the fact that a diagnosis of glue ear legitimises the continued use of these operations, may also have contributed to the increase. Finally, glue ear may provide parents with a medical explanation of their children's poor educational performance, as the term dyslexia did in the past. The high social and public costs of this operation demand a reappraisal of its increasing use.


Aging and arteriosclerosis. I. Development of myointimal hyperplasia after endothelial injury.
Old Fischer 344 rats are more susceptible to vascular lesions after arterial endothelial injury than are young animals. Thus, 20-26-mo-old Fischer 344 rats developed greater and more persistent intimal proliferative lesions than did 2-5-mo-old rats after aortic endothelial denudation. 3 d after deendothelialization, intimal thickness was increased two-fold in both old and young animals. However, 14 d after endothelial injury, intimal thickness had increased nearly five times in old animals, but had regressed to normal in young animals. Intimal thickness of young aortic grafts transplanted into young recipients did not differ significantly from adjacent host aorta or autotransplanted aortic segments 6 wk after surgery. In contrast, intimal thickness of old grafts transplanted into young recipients was eight times greater than adjacent young host aorta 6 wk after surgery. The density of cell nuclei in the intima of old grafts was also much greater than that in young grafts. Thus, in two experimental models of vascular injury, old rats have consistently had greater myointimal hyperplasia than young rats. The increased proliferative response of aortic smooth muscle cells after vascular injury of old animals may contribute to the increased prevalence of vascular disease with age.


Come together over me: Cells that form the dermatocranium and chondrocranium in mice.
Most bone develops either by intramembranous ossification where bone forms within a soft connective tissue, or by endochondral ossification by way of a cartilage anlagen or model. Bones of the skull can form endochondrally or intramembranously or represent a combination of the two types of ossification. Contrary to the classical definition of intramembranous ossification, we have previously described a tight temporo-spatial relationship between cranial cartilages and dermal bone formation and proposed a mechanistic relationship between chondrocranial cartilage and dermal bone. Here, we further investigate this relationship through an analysis of how cells organize to form cranial cartilages and dermal bone. Using Wnt1-Cre2 and Mesp1-Cre transgenic mice, we determine the derivation of cells that comprise cranial cartilages from either cranial neural crest (CNC) or paraxial mesoderm (PM). We confirm a previously determined CNC-PM boundary that runs through the hypophyseal fenestra in the cartilaginous braincase floor and identify four additional CNC-PM boundaries in the chondrocranial lateral wall, including a boundary that runs along the basal and apical ends of the hypochiasmatic cartilage. Based on the knowledge that as osteoblasts differentiate from CNC- and PM-derived mesenchyme, the differentiating cells express the transcription factor genes RUNX2 and osterix (OSX), we created a new transgenic mouse line called R2Tom. R2Tom mice carry a tdTomato reporter gene joined with an evolutionarily well-conserved enhancer sequence of RUNX2. R2Tom mice crossed with Osx-GFP mice yield R2Tom;Osx-GFP double transgenic mice in which various stages of osteoblasts and their precursors are detected with different fluorescent reporters. We use the R2Tom;Osx-GFP mice, new data on the cell derivation of cranial cartilages, histology, immunohistochemistry, and detailed morphological observations combined with data from other investigators to summarize the differentiation of cranial mesenchyme as it forms condensations that become chondrocranial cartilages and associated dermal bones of the lateral cranial wall. These data advance our previous findings of a tendency of cranial cartilage and dermal bone development to vary jointly in a coordinated manner, promoting a role for cranial cartilages in intramembranous bone formation.


Dramatic increases in obesity and overweight prevalence and body mass index among ethnic-immigrant and social class groups in the United States, 1976-2008.
This study examined trends in US obesity and overweight prevalence and body mass index (BMI) among 30 immigrant groups, stratified by race/ethnicity and length of immigration, and among detailed education, occupation, and income/poverty groups from 1976 to 2008. Using 1976-2008 National Health Interview Surveys, differentials in obesity, overweight, and BMI, based on self-reported height and weight, were analyzed by using disparity indices, logistic, and linear regression. The obesity prevalence for the US population aged ≥18 tripled from 8.7% in 1976 to 27.4% in 2008. Overweight prevalence increased from 36.9% in 1976 to 62.0% in 2008. During 1991-2008, obesity prevalence for US-born adults increased from 13.9 to 28.7%, while prevalence for immigrants increased from 9.5 to 20.7%. While immigrants in each ethnic group and time period had lower obesity and overweight prevalence and BMI than the US-born, immigrants' risk of obesity and overweight increased with increasing duration of residence. In 2003-2008, obesity prevalence ranged from 2.3% for recent Chinese immigrants to 31-39% for American Indians, US-born blacks, Mexicans, and Puerto Ricans, and long-term Mexican and Puerto Rican immigrants. Between 1976 and 2008, the obesity prevalence more than quadrupled for those with a college education or sales occupation. Although higher prevalence was observed for lower education, income, and occupation levels in each period, socioeconomic gradients in obesity and overweight decreased over time because of more rapid increases in prevalence among higher socioeconomic groups. Continued immigrant and socioeconomic disparities in prevalence will likely have substantial impacts on future obesity trends in the US.


Is there a role for airway clearance techniques in chronic obstructive pulmonary disease?
Chronic cough and sputum production are common features of chronic obstructive pulmonary disease (COPD) and have a significant impact on exacerbation frequency and quality of life. Despite this, techniques to assist with removal of sputum from the airway do not have a well-defined role in COPD management. Clinical trials of airway clearance techniques (ACTs) in COPD have shown mixed results with little evidence of long-term benefit. However many studies have failed to account for the heterogeneity of COPD lung disease, particularly with regard to the presence of bronchiectasis. Analysis of short-term studies suggests that there may be a cohort of patients who will benefit from prescription of a sputum clearance regimen. This review proposes a physiological rationale for the use of ACTs in COPD, taking into consideration the presence of bronchiectasis, the amount of sputum produced, the degree of airflow obstruction and the presence of decreased lung elastic recoil. The selection of an optimal ACT for individuals with COPD should take into account its effects on lung vloumes, expiratory flow and dynamic airway compression. Care should be taken to avoid airway collapse during forced expirations in patients with reduced lung recoil pressure; positive expiratory pressure therapy or autogenic drainage may prove effective in this patient group. The acceptability of ACTs to patients should also be considered, especially where long-term adherence is required. Future research should focus on more appropriate matching of the physiological effects of individual ACTs to the pathophysiology of lung disease in COPD.


Prostate Cancer Working Group report.
The incidence of prostate cancer, while still lower than in Western nations, is increasing rapidly in Asian countries due to a more westernized lifestyle. Prostate cancer mortality is declining in the USA, where most prostate cancers are diagnosed in the early stage. In contrast, the mortality rates of prostate cancer in Asian countries are expected to continue to increase, because the percentage of advanced-stage prostate cancers remains high. Therefore, early detection by prostate-specific antigen screening and a comprehensive strategy for cancer prevention are essential for Asian people. The exposure rate of prostate-specific antigen screening is very low in Asian countries. Increased prostate-specific antigen screening may reduce the mortality rate. The stances regarding population screening differ among countries. Urological associations should promote population screening. Reliable data from Asian countries are needed. The prostate cancer incidence is low in Asian countries, perhaps due to high soy consumption. Isoflavones may prevent prostate cancer in Asian countries, but that is not yet clear. A large, multinational study in Asia is needed to clarify whether or not isoflavone consumption shows efficacy in preventing prostate cancer. Clinical data suggest that hormonal therapy is more effective in Asians than in Westerners. Clinical guidelines should consider including hormonal therapy as one of the options for the treatment of localized prostate cancer. At the same time, effort should be made to decrease the adverse effects of each treatment. Collaborative studies on the treatment of prostate cancer should be carried out among Asian countries.


Sleep and autonomic nervous system changes - enhanced cardiac sympathetic modulations during sleep in permanent night shift nurses.
Disturbed sleep is the most common problem among the many health-related effects of shift work, with shift workers clearly having higher rates of cardiac disorders. However, the possible mechanism underlying the related health effects of shift work has yet to be examined. Consequently, this study aimed to explore the influence of long-term night shift work on the sleep patterns of nurses and their cardiac autonomic nervous system during sleep. Our sample comprised ten permanent night shift and ten regular morning shift nurses. Nurses slept in their dormitory where they were allowed to sleep and wake spontaneously. All sleep parameters were digitized using an ambulatory polysomnographic recorder. Using sleep patterns and heart rate variability, the day- and nighttime sleep of permanent night shift nurses were compared with the nighttime sleep of regular morning shift nurses. Compared with the nighttime sleep of regular morning shift nurses, the pattern of daytime sleep of permanent night shift nurses showed significantly lower sleep onset latency. Permanent night shift nurses' daytime sleep also had greater proportions of Stage 3 and 4 (deep sleep), and arousal index than recorded during their nighttime sleep. Both the low frequency and low to high frequency ratio of the nighttime sleep of night shift nurses were significantly higher during periods of non-rapid eye movement (NREM) sleep than the nighttime sleep of morning shift workers. In addition, the electroencephalography delta-power of the nighttime sleep of night shift nurses was significantly lower during the first NREM episode sleep than those of both the daytime sleep of night shift workers and the nighttime sleep of morning shift nurses. Permanent night shift nurses have higher sympathetic activity during nighttime sleep than regular morning shift nurses. Night shift working may have effects on the sleeping patterns of nurses in the long run, inducing higher cardiac sympathetic regulation.


Modulation of proteasomal activity required for the generation of a cytotoxic T lymphocyte-defined peptide derived from the tumor antigen MAGE-3.
We have analyzed the presentation of human histocompatability leukocyte antigen-A*0201-associated tumor peptide antigen MAGE-3271-279 by melanoma cells. We show that specific cytotoxic T lymphocyte (CTL)-recognizing cells transfected with a minigene encoding the preprocessed fragment MAGE-3271-279 failed to recognize cells expressing the full length MAGE-3 protein. Digestion of synthetic peptides extended at the NH2 or COOH terminus of MAGE-3271-279 with purified human proteasome revealed that the generation of the COOH terminus of the antigenic peptide was impaired. Surprisingly, addition of lactacystin to purified proteasome, though partially inhibitory, resulted in the generation of the antigenic peptide. Furthermore, treatment of melanoma cells expressing the MAGE-3 protein with lactacystin resulted in efficient lysis by MAGE-3271-279-specific CTL. We therefore postulate that the generation of antigenic peptides by the proteasome in cells can be modulated by the selective inhibition of certain of its enzymaticactivities.


[Scientific production trajectory of the São Paulo Federal University Post-Graduate Program in Nursing Services Management].
This article describes the scientific production trajectory of the Post-Graduate Program in Nursing Services Management at São Paulo Federal University based on the analysis of monographies produced by the students over the last 10 years. The study aimed at identifying subjects and objectives and to delineate research lines of these studies, 113 monographs were analyzed. The verification of the simple and relative frequency of the studied variables and the thematic classification according to the theoretical referential on this subject showed that at the beginning the studies did not considered the area of course extent but gradually they began to reach it with emphasis in " Human Resources" , which was accelerated with the establishment of a research group with the focus in the sub-specialty " nursing management" .


Phase 1 study of the histone deacetylase inhibitor vorinostat (suberoylanilide hydroxamic acid [SAHA]) in patients with advanced leukemias and myelodysplastic syndromes.
Vorinostat (suberoylanilide hydroxamic acid, SAHA) is a histone deacetylase inhibitor active clinically in cutaneous T-cell lymphoma and preclinically in leukemia. A phase 1 study was conducted to evaluate the safety and activity of oral vorinostat 100 to 300 mg twice or thrice daily for 14 days followed by 1-week rest. Patients with relapsed or refractory leukemias or myelodysplastic syndromes (MDS) and untreated patients who were not candidates for chemotherapy were eligible. Of 41 patients, 31 had acute myeloid leukemia (AML), 4 chronic lymphocytic leukemia, 3 MDS, 2 acute lymphoblastic leukemia, and 1 chronic myelocytic leukemia. The maximum tolerated dose (MTD) was 200 mg twice daily or 250 mg thrice daily. Dose-limiting toxicities were fatigue, nausea, vomiting, and diarrhea. Common drug-related adverse experiences were diarrhea, nausea, fatigue, and anorexia and were mild/moderate in severity. Grade 3/4 drug-related adverse experiences included fatigue (27%), thrombocytopenia (12%), and diarrhea (10%). There were no drug-related deaths; 7 patients had hematologic improvement response, including 2 complete responses and 2 complete responses with incomplete blood count recovery (all with AML treated at/below MTD). Increased histone acetylation was observed at all doses. Antioxidant gene expression may confer vorinostat resistance. Further evaluation of vorinostat in AML/MDS is warranted.


Quantum limits of super-resolution of optical sparse objects via sparsity constraint.
Sparsity constraint is a priori knowledge of the signal, which means that in some properly chosen basis only a small percentage of the total number of the signal components is nonzero. Sparsity constraint has been used in signal and image processing for a long time. Recent publications have shown that the Sparsity constraint can be used to achieve super-resolution of optical sparse objects beyond the diffraction limit. In this paper we present the quantum theory which establishes the quantum limits of super-resolution for the sparse objects. The key idea of our paper is to use the discrete prolate spheroidal sequences (DPSS) as the sensing basis. We demonstrate both analytically and numerically that this sensing basis gives superior performance of super-resolution over the Fourier basis conventionally used for sensing of sparse signals. The explanation of this phenomenon is in the fact that the DPSS are the eigenfunctions of the optical imaging system while the Fourier basis are not. We investigate the role of the quantum fluctuations of the light illuminating the object, in the performance of reconstruction algorithm. This analysis allows us to formulate the criteria for stable reconstruction of sparse objects with super-resolution. Our results imply that sparsity of the object is not the only parameter which describes super-resolution achievable via sparsity constraint.


Challenged and changed: Quiet ego and posttraumatic growth in mothers raising children with autism spectrum disorder.
Posttraumatic growth theory posits that when life circumstances are perceived as stressful, secondary appraisal processes can be recruited in ways to facilitate both coping efforts and personal growth. Using a mixed-methods approach, we found mothers' most challenging experiences involved child behavior (e.g. aggression, communication, and social issues) and psychosocial impacts (e.g. lack of social support, perceived judgment of others, perceived loss, and personal distress). Descriptions of most rewarding experiences reflect posttraumatic growth frameworks including constructive perceptions about themselves, life, and their relationships as well as evidence for what Maercker and Zoellner call illusory types of posttraumatic growth. Quantitative data were subjected to a hierarchical regression analysis for self-reported posttraumatic growth and included mothers' demographics, child functioning, and psychosocial measures. As predicted, posttraumatic growth was positively associated with social support from mothers' most important network member and quiet ego characteristics, a type of eudaimonic motivation. Contrary to expectation, neither autism spectrum disorder-related rumination nor time since diagnosis (or their interaction) was associated with posttraumatic growth. Discussion focuses on the practical implications of our findings that posttraumatic growth-related coping includes both constructive and illusory forms and the importance of social support and eudaimonic motivation in facilitating positive forms of secondary coping.


Knowledge, attitudes, and behaviours towards schizophrenia, bipolar disorder, and autism: a pilot study.
Lack of knowledge and discriminatory attitudes and behaviours towards individuals with mental disorders is a worldwide problem but may be particularly damaging for young people. This pilot study examined knowledge, attitudes and behaviours towards schizophrenia, bipolar disorder and autism within a large sample of adults in Ireland, a country with the youngest population in Europe, in order to better understand public views on these groups. In a correlational, cross-sectional design, 307 adults in Ireland over the age of 18 completed a questionnaire over Google Forms examining knowledge, attitudes and behaviours towards schizophrenia, bipolar disorder and autism. Responses to questions specifically relating to each diagnosis were compared using trimmed mean ANOVA to examine whether responses to questions differed depending on diagnosis. Results indicate varied knowledge, attitudes and behaviours towards these groups, but a majority believe it should be a research priority. ANOVA and post hoc tests revealed significant differences in knowledge, attitudes and behaviours towards each of schizophrenia, bipolar disorder, and autism (p < 0.005), and reported attitudes and behaviours towards schizophrenia were more negative than either bipolar disorder or autism. A majority of participants (54.8%) felt not informed enough about mental health by the media. In our Irish sample, type and level of stigma varies according to mental health diagnosis. Our sample also report feeling inadequately informed about mental health by the media. Thus future policy and campaigns could consider targeting individual mental health diagnoses, with a focus on increasing familiarity and knowledge.


S1P1 bridges mechanotransduction and angiogenesis during vascular development.
Mechanisms of stabilization of the vascular plexus and the role of mechanotransduction in this process are not well understood. In this issue of Developmental Cell, Jung et al. (2012) and Gaengel et al. (2012) describe the ligand-sensitive and mechanosensitive functions of an important vascular G protein-coupled receptor, S1P1.


Sphingosine-1-Phosphate Lyase Deficient Cells as a Tool to Study Protein Lipid Interactions.
Cell membranes contain hundreds to thousands of individual lipid species that are of structural importance but also specifically interact with proteins. Due to their highly controlled synthesis and role in signaling events sphingolipids are an intensely studied class of lipids. In order to investigate their metabolism and to study proteins interacting with sphingolipids, metabolic labeling based on photoactivatable sphingoid bases is the most straightforward approach. In order to monitor protein-lipid-crosslink products, sphingosine derivatives containing a reporter moiety, such as a radiolabel or a clickable group, are used. In normal cells, degradation of sphingoid bases via action of the checkpoint enzyme sphingosine-1-phosphate lyase occurs at position C2-C3 of the sphingoid base and channels the resulting hexadecenal into the glycerolipid biosynthesis pathway. In case the functionalized sphingosine looses the reporter moiety during its degradation, specificity towards sphingolipid labeling is maintained. In case degradation of a sphingosine derivative does not remove either the photoactivatable or reporter group from the resulting hexadecenal, specificity towards sphingolipid labeling can be achieved by blocking sphingosine-1-phosphate lyase activity and thus preventing sphingosine derivatives to be channeled into the sphingolipid-to-glycerolipid metabolic pathway. Here we report an approach using clustered, regularly interspaced, short palindromic repeats (CRISPR)-associated nuclease Cas9 to create a sphingosine-1-phosphate lyase (SGPL1) HeLa knockout cell line to disrupt the sphingolipid-to-glycerolipid metabolic pathway. We found that the lipid and protein compositions as well as sphingolipid metabolism of SGPL1 knock-out HeLa cells only show little adaptations, which validates these cells as model systems to study transient protein-sphingolipid interactions.


A longitudinal study of hymenal development from 3 to 9 years of age.
To document hymenal characteristics associated with normal development in girls between 3 and 9 years of age. The hymens of 93 children without a history of sexual abuse were examined and photographed at 3 and 5 years of age; 80 children were reexamined at 7 and 61 at 9 years of age. Hymenal features recorded included periurethral and vestibular bands, notches, transections, longitudinal intravaginal ridges, external ridges, mounds, and tags. Transhymenal diameters were measured as well as the tissue at 3, 6, and 9 o'clock positions. Changes in hymenal measurements over time were analyzed using the general estimating equation approach to repeated measures. Crescentic configuration became more common as the children aged (P <.01). The number of mounds and intravaginal ridges observed per child as well as the size of the transhymenal diameter increased as the sample aged. The mean amount of tissue at the 6 o'clock position significantly changed over time (P <.01). However, no significant changes were observed in the number of tags, periurethral or vestibular bands, notches, external ridges, or amount of tissue present at the 3 or 9 o'clock position. Few changes occur in the morphologic features of the hymen between 3 and 9 years of age.


Agriculture's impact on microbial diversity and associated fluxes of carbon dioxide and methane.
Agriculture has marked impacts on the production of carbon dioxide (CO(2)) and consumption of methane (CH(4)) by microbial communities in upland soils-Earth's largest biological sink for atmospheric CH(4). To determine whether the diversity of microbes that catalyze the flux of these greenhouse gases is related to the magnitude and stability of these ecosystem-level processes, we conducted molecular surveys of CH(4)-oxidizing bacteria (methanotrophs) and total bacterial diversity across a range of land uses and measured the in situ flux of CH(4) and CO(2) at a site in the upper United States Midwest. Conversion of native lands to row-crop agriculture led to a sevenfold reduction in CH(4) consumption and a proportionate decrease in methanotroph diversity. Sites with the greatest stability in CH(4) consumption harbored the most methanotroph diversity. In fields abandoned from agriculture, the rate of CH(4) consumption increased with time along with the diversity of methanotrophs. Conversely, estimates of total bacterial diversity in soil were not related to the rate or stability of CO(2) emission. These combined results are consistent with the expectation that microbial diversity is a better predictor of the magnitude and stability of processes catalyzed by organisms with highly specialized metabolisms, like CH(4) oxidation, as compared with processes driven by widely distributed metabolic processes, like CO(2) production in heterotrophs. The data also suggest that managing lands to conserve or restore methanotroph diversity could mitigate the atmospheric concentrations of this potent greenhouse gas.


What are the significant turning demands of match play of an English Premier League soccer team?
This study aimed to compare the significant turning demands of English Premier League soccer match play relative to playing position using LiDAR technology. Turning data were collected from an English Premier League soccer team (2020-2021 season; 18 fixtures) using a Sportlight® LiDAR tracking system. Turns were tracked during match play, sub-categorised by entry speed (<3.0, 3.0-5.5, 5.5-7.0 and >7.0 m/s) and turning angle (Low: 20-59°; Medium: 60-119°; High: 120-180°). Turning metric frequencies were compared between playing positions (centre backs, full-backs, central midfielders, wide midfielders, and central forwards). On average, per match, central midfielders performed more total turns (~38 vs ~18-27), turns with entry speeds <3.0 (~15 vs ~7-10) and 3.0-5.5 m/s (~21 vs ~8-15) and low (~4 vs ~1-2), medium (~10 vs ~3-6) and high angled turns (~24 vs ~12-18) compared to all other playing positions (p ≤ 0.001, d = 0.96-2.74). Approximately, 90% of turns during matches were performed with entry speeds <5.5 m/s and ~63-70% were high angled turns. This study provides unique insights into the turning demands of English Premier League soccer matches , which can be used to inform position-specific physical preparation strategies, turning testing battery selection, agility drill construction, and rehabilitation and return to play standards.


Facility and home based HIV Counseling and Testing: a comparative analysis of uptake of services by rural communities in southwestern Uganda.
In Uganda, public human immunodeficiency virus (HIV) Voluntary Counseling and Testing (VCT) services are mainly provided through the facility based model, although the home based approach is being promoted as a strategy for improving access to VCT. However the uptake of VCT varies according to service delivery model and is influenced by a number of factors. The aim of this study therefore, was to compare predictors for uptake of facility and home based VCT in a rural context. A longitudinal study with cross-sectional investigative phases was conducted at two sites (Rugando and Kabingo) in southwestern Uganda between November 2007 (baseline) and March 2008 (follow up). During the baseline visit, facility based VCT was offered at the main health centre in Rugando while home based VCT was offered at the household level in Kabingo and a mixed survey questionnaire administered to the respondents. The results presented in this paper are derived from only the baseline data. Nine hundred ninety four (994) respondents were interviewed, of whom 500 received facility based VCT in Rugando and 494 home based VCT in Kabingo during the baseline visit. The respondents had a mean age of 32.2 years (SD 10.9) and were mainly female (68 percent). Clients who received facility based VCT were less likely to be residents of the more rural households (adjusted Odds Ratio (aOR)=0.14, 95% CI 0.07, 0.22). The clients who received home based VCT were less likely to report having an STI symptom (aOR=0.63, 95% CI 0.46, 0.86), and more likely to be worried about discrimination if they contracted AIDS (aOR=1.78, 95% CI 1.22, 2.61). The uptake of VCT provided through either the facility or home based models is influenced by client characteristics such as proximity to service delivery points, HIV related symptoms, and fear of discrimination in rural Uganda. Interventions that seek to improve uptake of VCT should provide potential clients with both facility and home based VCT options within a given setting. The clients are then able to select a model for VCT that best fits their characteristics. This is likely to have positive implications for both service coverage and uptake by different sub-groups within particular communities.