Constructing a validity argument for the Objective Structured Assessment of Technical Skills (OSATS): a systematic review of validity evidence.
In order to construct and evaluate the validity argument for the Objective Structured Assessment of Technical Skills (OSATS), based on Kane's framework, we conducted a systematic review. We searched MEDLINE, EMBASE, CINAHL, PsycINFO, ERIC, Web of Science, Scopus, and selected reference lists through February 2013. Working in duplicate, we selected original research articles in any language evaluating the OSATS as an assessment tool for any health professional. We iteratively and collaboratively extracted validity evidence from included articles to construct and evaluate the validity argument for varied uses of the OSATS. Twenty-nine articles met the inclusion criteria, all focussed on surgical technical skills assessment. We identified three intended uses for the OSATS, namely formative feedback, high-stakes assessment and program evaluation. Following Kane's framework, four inferences in the validity argument were examined (scoring, generalization, extrapolation, decision). For formative feedback and high-stakes assessment, there was reasonable evidence for scoring and extrapolation. However, for high-stakes assessment there was a dearth of evidence for generalization aside from inter-rater reliability data and an absence of evidence linking multi-station OSATS scores to performance in real clinical settings. For program evaluation, the OSATS validity argument was supported by reasonable generalization and extrapolation evidence. There was a complete lack of evidence regarding implications and decisions based on OSATS scores. In general, validity evidence supported the use of the OSATS for formative feedback. Research to provide support for decisions based on OSATS scores is required if the OSATS is to be used for higher-stakes decisions and program evaluation.


Quantum yields for oxygenic and anoxygenic photosynthesis in the cyanobacterium Oscillatoria limnetica.
A comparison of the quantum yield spectra of the oxygenic (H(2)O as the electron donor) with the anoxygenic (H(2)S as the electron donor) photosynthesis of the cyanobacterium, Oscillatoria limnetica reveals that anoxygenic photosynthesis is driven by photosystem I only. The highest quantum yields of the latter (maximum; 0.059 CO(2) molecules/quantum of absorbed light) were obtained with wavelengths which preferentially excite photosystem I (<550, >650) in which chlorophyll a and carotenoids are the major pigments. The addition of 3-(3,4-dichlorophenyl)-1,1-dimethylurea had no effect on anoxygenic photosynthesis, and no enhancement in quantum efficiency was observed by a superimposition of light preferentially exciting photosystem II.Oxygenic photosynthesis efficiently utilizes only a narrow range of the absorption spectrum (550-650 nm) where light is provided in excess to photosystem II via phycocyanin. The quantum yield (0.033 CO(2) molecules/quantum of absorbed light) is lower than the theoretical yield by a factor of 3, possibly due to inefficient light transfer from photosystem II to I. Thus, 3-fold enhancement of oxygenic photosynthesis by superimposition of photosystem I light, and low quantum yields for anoxygenic photosynthesis, were obtained in this region. These results are consonant with the suggestion that such a cyanobacterium represents an intermediate stage in phototrophic evolution.


Role of genital mycoplasmata and other bacteria in urolithiasis.
Urease-producing bacteria have been shown to affect the formation of infection stones by splitting urea into ammonia, bicarbonate and carbonate. An increase in alkaline pH results in urinary supersaturation of the ions. The increase in ammonia also causes injury to the urothelial glycosaminoglycan layer. Non-urease-producing bacteria have been speculated to form urinary stones. Midstream voided bladder urine and fractured stone nidus samples from 72 patients undergoing surgery for urolithiasis were cultured on specific media for genital mycoplasmata and on conventional media. Urine samples were obtained from a control group of 40 healthy subjects. Genital mycoplasmata and other bacteria were evaluated with regard to the composition of urinary stones. Compared with other origins of stones, the relation between isolation of Ureaplasma urealyticum and infection stone disease was statistically proven. Isolation of genital mycoplasmata was significantly higher in women than in men in the study group. The urinary stones comprised 84.7% calcium stones, 8.3% uric acid stones and 6.9% infection (magnesium ammonium phosphate) stones. Coagulase-negative Staphylococci, Escherichia coli, Corynebacterium spp., Enterobacterium spp. and U. urealyticum were cultured from stone samples. The results suggests that non-urease-producing bacteria, as well as urease-producing bacteria, may influence the formation of urinary stones.


Lifting-based invertible motion adaptive transform (LIMAT) framework for highly scalable video compression.
We propose a new framework for highly scalable video compression, using a lifting-based invertible motion adaptive transform (LIMAT). We use motion-compensated lifting steps to implement the temporal wavelet transform, which preserves invertibility, regardless of the motion model. By contrast, the invertibility requirement has restricted previous approaches to either block-based or global motion compensation. We show that the proposed framework effectively applies the temporal wavelet transform along a set of motion trajectories. An implementation demonstrates high coding gain from a finely embedded, scalable compressed bit-stream. Results also demonstrate the effectiveness of temporal wavelet kernels other than the simple Haar, and the benefits of complex motion modeling, using a deformable triangular mesh. These advances are either incompatible or difficult to achieve with previously proposed strategies for scalable video compression. Video sequences reconstructed at reduced frame-rates, from subsets of the compressed bit-stream, demonstrate the visually pleasing properties expected from low-pass filtering along the motion trajectories. The paper also describes a compact representation for the motion parameters, having motion overhead comparable to that of motion-compensated predictive coders. Our experimental results compare favorably to others reported in the literature, however, our principal objective is to motivate a new framework for highly scalable video compression.


Effect of endurance exercise training on Ca2+ calmodulin-dependent protein kinase II expression and signalling in skeletal muscle of humans.
Here the hypothesis that skeletal muscle Ca(2+)-calmodulin-dependent kinase II (CaMKII) expression and signalling would be modified by endurance training was tested. Eight healthy, young men completed 3 weeks of one-legged endurance exercise training with muscle samples taken from both legs before training and 15 h after the last exercise bout. Along with an approximately 40% increase in mitochondrial F(1)-ATP synthase expression, there was an approximately 1-fold increase in maximal CaMKII activity and CaMKII kinase isoform expression after training in the active leg only. Autonomous CaMKII activity and CaMKII autophosphorylation were increased to a similar extent. However, there was no change in alpha-CaMKII anchoring protein expression with training. Nor was there any change in expression or Thr(17) phosphorylation of the CaMKII substrate phospholamban with training. However, another CaMKII substrate, serum response factor (SRF), had an approximately 60% higher phosphorylation at Ser(103) after training, with no change in SRF expression. There were positive correlations between the increases in CaMKII expression and SRF phosphorylation as well as F(1)ATPase expression with training. After training, there was an increase in cyclic-AMP response element binding protein phosphorylation at Ser(133), but not expression, in muscle of both legs. Taken together, skeletal muscle CaMKII kinase isoform expression and SRF phosphorylation is higher with endurance-type exercise training, adaptations that are restricted to active muscle. This may contribute to greater Ca(2+) mediated regulation during exercise and the altered muscle phenotype with training.


The early development of head control in preterm infants.
This study documents the longitudinal development of head control in 104 infants born at 25-33 weeks gestation. Protective side turning of the head was found to have a developmental sequence of reducing spinal extension. In the 93 infants with normal motor outcome, individual differences in the rate of development correlated with caudo-cephalic muscle development (P less than 0.001, r = 0.5) but not with the length of extra-uterine experience. As a group, the 11 infants with later motor handicap showed a persistence of the early form of movement at 35-39 weeks post-menstrual age, without a significant correlation with the ratio of upper-lower limb muscle development. Head control, supine to sitting, in the infants with normal motor outcome showed variations in the rate of preterm development. The infants born at less than 31 weeks showed significantly higher scores at 33-35 weeks post-menstrual age than those born at 31-33 weeks (P less than 0.01). There was no difference at later ages. The spinal extension movement accompanying protective side turning of the head is age specific to the preterm infant. Individual rates of normal preterm development can be evaluated by longitudinal standardised examination. As a group, the infants with subsequent abnormal motor development showed delay at preterm age but this was not individually significant.


Membrane proteins of Pseudoalteromonas tunicata during the transition from planktonic to extracellular matrix-adherent state.
Pseudoalteromonas tunicata is a marine bacterium that was originally isolated from the surface of the tunicate Ciona intestinalis. Since C. intestinalis expresses extracellular matrix (ECM) and P. tunicata has a gene encoding a functional ECM-binding protein, we hypothesized that P. tunicata could adhere to this host via protein-ECM interactions and as a result change its membrane proteome. An in vitro adhesion assay was developed to show that P. tunicata adheres strongly to ECM. To further study the adhesion biology of P. tunicata, two-dimensional (2D) electrophoresis was used to explore the membrane-associated sub-proteome of P. tunicata during planktonic, adherent and non-adherent states. More than 30 proteins were resolved using blue native (BN)/SDS 2D PAGE, many of which were identified by mass spectrometry. BN/SDS PAGE also allowed the identification of several novel protein complexes, which indicate structural and functional relationships for these proteins and related proteins in several other organisms. A proteomic change associated with adhesion was identified by comparison of 2D gels from the three model states. Collectively, these studies explore the membrane proteome of P. tunicata during the transition from planktonic to ECM-adherent states.


Experiences with fistula repair surgery among women and families in Malawi.
Fistula treatment through surgery is reported to be successful in 80-90% of cases. Success in fistula repair has been defined by medical professionals in terms of clinical outcomes; beyond these definitions, it is important to understand how women perceive a positive clinical outcome and how it affects her family and home environment. This research was conducted in the Mangochi District of Malawi to answer these questions through interviews with women living with fistula and after surgical repair, as well as their partners and families. Over 104 interviews were conducted in June and October 2007. While eventually experiencing clinically successful surgical outcomes, women reported difficulty in seeking and receiving healthcare. Bureaucratic challenges were complicated by community misperceptions about the condition and fear of the healthcare system. Perspectives of women's families suggest that burdens and social disabilities caused by fistula extended beyond the individual to affect these family members. When women experienced surgical treatment, positive outcomes spread to her family and community. Positive experiences with the healthcare system turned women into advocates for healthcare in their communities. These findings illustrate that issues of obstetric fistula are not limited to individual women, but can dramatically affect their families, partners and communities.


Quality-of-life assessment of fibroid treatment options and outcomes.
To obtain utilities (a unit of measure of a person's relative preferences for different health states compared with death or worst possible outcome) for uterine fibroids before and after treatment and to measure short-term utilities for the following uterine fibroid treatments: abdominal hysterectomy, magnetic resonance (MR) imaging-guided focused ultrasound surgery, and uterine artery embolization (UAE). This retrospective study was approved by the institutional review board and was HIPAA compliant. The waiting trade-off (WTO) method, a variation on the time trade-off (TTO) method, is used to obtain utilities for diagnostic procedures on the basis of the fact that people wait longer to avoid noxious tests and/or procedures. The WTO method provides short-term quality of life tolls in terms of quality-adjusted life-weeks by scaling wait times with pre- and posttreatment utilities. Utilities for uterine fibroids before and after treatment were obtained with the TTO method and a visual analog scale (VAS) by using a questionnaire administered by means of a phone interview. WTO wait times were adjusted for quality of life with VAS and TTO utilities and a transformation of VAS. Wait times were compared by using nonparametric tests. The study participants included 62 patients who had undergone abdominal hysterectomy, 74 who had undergone UAE, and 61 who had undergone MR imaging-guided focused ultrasound surgery. Quality of life increased with all treatments. The median WTO wait time was higher for hysterectomy (21.6 weeks) than for UAE or MR imaging-guided focused ultrasound surgery (14.1 weeks for both) (P < .05). Quality-adjusted life-week tolls were smaller when scaled according to TTO than when scaled according to VAS or transformation of VAS. Quality of life increased after all fibroid treatments. WTO is feasible for assessing the quality-adjusted morbidity of treatment procedures. http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.11100704/-/DC1.


Temporal and spatial differences in microbial composition during the manufacture of a continental-type cheese.
We sought to determine if the time, within a production day, that a cheese is manufactured has an influence on the microbial community present within that cheese. To facilitate this, 16S rRNA amplicon sequencing was used to elucidate the microbial community dynamics of brine-salted continental-type cheese in cheeses produced early and late in the production day. Differences in the microbial composition of the core and rind of the cheese were also investigated. Throughout ripening, it was apparent that cheeses produced late in the day had a more diverse microbial population than their early equivalents. Spatial variation between the cheese core and rind was also noted in that cheese rinds were initially found to have a more diverse microbial population but thereafter the opposite was the case. Interestingly, the genera Thermus, Pseudoalteromonas, and Bifidobacterium, not routinely associated with a continental-type cheese produced from pasteurized milk, were detected. The significance, if any, of the presence of these genera will require further attention. Ultimately, the use of high-throughput sequencing has facilitated a novel and detailed analysis of the temporal and spatial distribution of microbes in this complex cheese system and established that the period during a production cycle at which a cheese is manufactured can influence its microbial composition.


Granary trial of protein-enriched pea flour for the control of three stored-product insects in barley.
A granary trial was conducted to evaluate the efficacy of protein-enriched pea flour against three common stored-grain insects, Sitophilus oryzae (L.), Tribolium castaneum (Herbst), and Cryptolestes ferrugineus (Stephens). Six 30-t farm granaries were filled with approximately 11 t of barley. The barley was either not treated, treated with protein-enriched pea flour at 0.1% throughout the entire grain mass, or treated at 0.5% throughout the top half of the grain mass. Adult insects were released in screened boxes (two insects per kilogram barley for S. oryzae and T. castaneum 1.4 insects per kilogram barley for C. ferrugineus). Barley was sampled four times during the 70-d trial. The number and mortality of adults and emerged adults in the samples were noted. Four kinds of traps, flight, surface-pitfall, probe-pitfall, and sticky-bar, were placed at different locations in the granaries to estimate the movement of insects. The 0.1% protein-enriched pea flour treatment reduced adult numbers of S. oryzae by 93%, T. castaneum by 66%, and C. ferrugineus by 58%, and reduced the emerged adults by 87, 77, and 77%, respectively. Treating the top half of the barley with 0.5% protein-enriched pea flour had similar effects as treating the entire grain mass with 0.1% pea-protein flour. However, the top-half treatment failed to prevent insects from penetrating into the untreated lower layer. Differences between traps are discussed.


Outcome and Distal Access Patency in Subintimal Arterial Flossing with Antegrade-Retrograde Intervention for Chronic Total Occlusions in Lower Extremity Critical Limb Ischemia.
To report the outcome and distal access patency of the Subintimal Arterial Flossing with Antegrade-Retrograde Intervention (SAFARI) technique for chronic total occlusion (CTO) in critical limb ischemia (CLI). From January 2009 to June 2015, 220 SAFARI procedures were performed for 200 limbs in 191 patients (108 males [56.5%]; median age, 70 years old; range, 36 to 97 years old) with CLI (9.4% were Fontaine classification 3; and 90.6% were Fontaine classification 4). Distal access was obtained from the distal superficial femoral artery (n = 6), popliteal artery (n = 49), anterior tibial artery (n = 56), dorsalis pedis (n = 51), peroneal artery (n = 12), posterior tibial artery (n = 45), and lateral plantar artery (n = 1). Distal access hemostasis was obtained with internal balloon tamponade in 71.4% (n = 157). Outcome measurements were technical success, freedom from major amputation and complications. Preprocedural angiograms of clinically driven repeat interventions were reviewed in 73 cases for distal access patency. Technical success was achieved in 80.5% (n = 177). Reasons for technical failure include inability to obtain distal access (n = 3), cross the occlusion retrogradely (n = 16), re-enter the true lumen (n = 9), and achieve antegrade blood flow after the procedure (n = 15). Freedom from major amputation for technically successful procedures was 84.7%, 82.9%, and 81.9% at 6, 12, and 24 months, respectively. There were 3 cases of distal access bleeding with 1case that required coil embolization. The distal access remained patent in 80.8% of observable cases with repeated endovascular intervention. Distal retrograde arterial access (SAFARI) technique is safe and effective in the treatment of CTOs in the context of CLI, after failure of antegrade revascularization.


Three-month pegylated interferon-alpha-2a therapy for chronic hepatitis E virus infection in a haemodialysis patient.
Hepatitis E virus (HEV) can induce chronic hepatitis in immunosuppressed patients. There is no established treatment for HEV infection. Pegylated interferon-alpha-2a (Peg-IFN-alpha-2a) has been successfully used for treating HEV infection in liver transplant patients with chronic hepatitis. A kidney transplant patient with chronic HEV infection evolved to end-stage kidney disease and started haemodialysis. Three months after immunosuppressive therapy was stopped, HEV RNA was still detected both in serum and in stools. Before considering a retransplantation, we decided to initiate Peg-IFN-alpha-2a therapy to eradicate the virus. A 3-month course of Peg-IFN-alpha-2a was scheduled, and the latter was started at the weekly dose of 135 microg. Serum HEV RNA became negative by Week 3 of Peg-IFN-alpha-2a therapy, and remained negative until the last follow-up, i.e. 6 months after anti-viral therapy was stopped. Hence, we report the first known case of a 3-month course of Peg-IFN-alpha-2a inducing a sustained virological response in this HEV-positive and RNA-positive haemodialysis patient who had failed to be cleared of the virus after immunosuppressant withdrawal.


One-year outcome of a combination of weight loss therapies for subjects with type 2 diabetes: a randomized trial.
The purpose of this study was to evaluate the effects of a combination weight loss program using intermittent low-calorie diets, energy-controlled meal replacement products, and sibutramine on weight loss, diabetes control, and cardiovascular risk factors in overweight or obese subjects with type 2 diabetes. Overweight or obese individuals with type 2 diabetes treated with diet or oral medication were randomly assigned to either a standard therapy or combination therapy group. Both groups received a standardized program to facilitate weight loss. The combination therapy group also received 10-15 mg sibutramine daily, low-calorie diets using meal replacement products for 1 week every 2 months, and between low-calorie diet weeks, once daily use of meal replacement product and snack bars to replace one usual meal and snack. Primary outcome measures were changes in body weight, glycemic control, plasma lipids, blood pressure, pulse, and body composition at 1 year. At 1 year, combination therapy, compared with standard therapy, resulted in significantly more weight loss (-7.3 +/- 1.3 kg vs. -0.8 +/- 0.9 kg, P < 0.001) and reduction in HbA(1c) (-0.6 +/- 0.3 vs. 0.0 +/- 0.2%, P = 0.05). Combination therapy resulted in reduced requirement for diabetes medications and decreased fat mass and lean body mass. A 5-kg decrease in weight at 1 year was associated with a decrease of 0.4% in HbA(1c) (P = 0.006). Changes in fasting glucose, lipids, pulse, and blood pressure did not differ between groups. This combination weight loss program resulted in greater weight loss and improved diabetes control compared with a standard weight loss program in overweight or obese subjects with type 2 diabetes.


Synaptic change in the posterior cingulate gyrus in the progression of Alzheimer's disease.
Mild cognitive impairment (MCI) is considered to be an early stage in the progression of Alzheimer's disease (AD) providing an opportunity to investigate brain pathogenesis prior to the onset of dementia. Neuroimaging studies have identified the posterior cingulate gyrus (PostC) as a cortical region affected early in the onset of AD. This association cortex is involved in a variety of different cognitive tasks and is intimately connected with the hippocampal/entorhinal cortex region, a component of the medial temporal memory circuit that displays early AD pathology. We quantified the total number of synapses in lamina 3 of the PostC using unbiased stereology coupled with electron microscopy from short postmortem autopsy tissue harvested from cases at different stage of AD progression. Individuals in the early stages of AD showed a significant decline in synaptic numbers compared to individuals with no cognitive impairment (NCI). Subjects with MCI exhibited synaptic numbers that were between the AD and NCI cohorts. Adjacent tissue was evaluated for changes in both pre and postsynaptic proteins levels. Individuals with MCI demonstrated a significant loss in presynaptic markers synapsin-1 and synaptophysin and postsynaptic markers PSD-95 and SAP-97. Levels of [3H]PiB binding was significantly increased in MCI and AD and correlated strongly with levels of synaptic proteins. All synaptic markers showed a significant association with Mini-Mental Status Examination scores. These results support the idea that the PostC synaptic function is affected during the prodromal stage of the disease and may underlie some of the early clinical sequelae associated with AD.


Systematic analysis of inflammation and pain pathways in a mouse model of gout.
Gout is a prevalent and painful inflammatory arthritis, and its global burden continues to rise. Intense pain induced by gout attacks is a major complication of gout. However, systematic studies of gout inflammation and pain are lacking. Using a monosodium urate (MSU) crystal-induced gout model, we performed genome-wide transcriptome analysis of the inflamed ankle joint, dorsal root ganglion (DRG), and spinal cord of gouty mice. Our results revealed important transcriptional changes, including highly elevated inflammation and broad activation of immune pathways in both the joint and the nervous system, in gouty mice. Integrated analysis showed that there was a remarkable overlap between our RNAseq and human genome-wide association study (GWAS) of gout; for example, the risk gene, stanniocalcin-1 (STC1) showed significant upregulation in all three tissues. Interestingly, when compared to the transcriptomes of human osteoarthritis (OA) and rheumatoid arthritis (RA) joint tissues, we identified significant upregulation of cAMP/cyclic nucleotide-mediated signaling shared between gouty mice and human OA with high knee pain, which may provide excellent drug targets to relieve gout pain. Furthermore, we investigated the common and distinct transcriptomic features of gouty, inflammatory pain, and neuropathic pain mouse models in their DRG and spinal cord tissues. Moreover, we discovered distinct sets of genes with significant differential alternative splicing or differential transcript usage in each tissue, which were largely not detected by conventional differential gene expression analysis approaches. Based on these results, our study provided a more accurate and comprehensive depiction of transcriptomic alterations related to gout inflammation and pain.


Dichotomous effects of VEGF-A on adipose tissue dysfunction.
Obese fat pads are frequently undervascularized and hypoxic, leading to increased fibrosis, inflammation, and ultimately insulin resistance. We hypothesized that VEGF-A-induced stimulation of angiogenesis enables sustained and sufficient oxygen and nutrient exchange during fat mass expansion, thereby improving adipose tissue function. Using a doxycycline (Dox)-inducible adipocyte-specific VEGF-A overexpression model, we demonstrate that the local up-regulation of VEGF-A in adipocytes improves vascularization and causes a "browning" of white adipose tissue (AT), with massive up-regulation of UCP1 and PGC1α. This is associated with an increase in energy expenditure and resistance to high fat diet-mediated metabolic insults. Similarly, inhibition of VEGF-A-induced activation of VEGFR2 during the early phase of high fat diet-induced weight gain, causes aggravated systemic insulin resistance. However, the same VEGF-A-VEGFR2 blockade in ob/ob mice leads to a reduced body-weight gain, an improvement in insulin sensitivity, a decrease in inflammatory factors, and increased incidence of adipocyte death. The consequences of modulation of angiogenic activity are therefore context dependent. Proangiogenic activity during adipose tissue expansion is beneficial, associated with potent protective effects on metabolism, whereas antiangiogenic action in the context of preexisting adipose tissue dysfunction leads to improvements in metabolism, an effect likely mediated by the ablation of dysfunctional proinflammatory adipocytes.


Synthesis and antimycobacterial activity of 4-[5-(substituted phenyl)-4, 5-dihydro-3-isoxazolyl]-2-methylphenols.
Compounds based on the isoxazoline moiety were screened for their antimycobacterial activity in vitro against Mycobacterium tuberculosis H37R (MTB), and INH (isoniazid) resistant Mycobacterium tuberculosis (INHR-MTB) using the agar dilution method and bactec 460. Among the synthesized compounds, 4-[5-(4-bromophenyl)-4,5-dihydro-3-isoxazolyl]-2-methylphenol (4l) was found to be the most active agent against MTB and INHR-MTB with minimum inhibitory concentration of 0.62 microM. When compared to INH, compound (4l) was 1.12 fold and 3.0 fold more active against MTB and INHR-MTB, respectively.


High risk behavior related to HIV transmission among recently diagnosed TB patients in Jakarta.
This study investigated the demographic and high risk behavior characteristics among recently diagnosed pulmonary tuberculosis patients aged 18-40 years old in Jakarta, Indonesia. Three hundred and four participants were recruited voluntarily from two general hospitals. Among the study population, 38.5% were unemployed, 69.7% were in low socio-economic condition, and 69.7% had a high school or higher level of education. About 8% had received a transfusion, 0.3% were intravenous drug users (IVDU) and had sex with other IVDU's no males admitted to being homosexual, 3.2% of males were bisexual, 20.1% (35.5% of males, 4% of females) engaged in extramarital heterosexual intercourse, and 3.6% (7.1% of males) had one or more sexually transmitted diseases (STD). We found very strong associations between gender and extramarital heterosexual activity (p < 0.001, prevalence odds ratio (POR 13.11), between occupation and extramarital heterosexual activity (p < 0.001, POR 3.84), and between extramarital heterosexual contact and a history of an STD (p < 0.001, POR 20.86). High risk activities were common among these TB patients, especially among males. These results suggests that the necessary social conditions for transmission of HIV are common in Jakarta.


Low disease risk and penetrance in Leber hereditary optic neuropathy.
The risk of Leber hereditary optic neuropathy (LHON) has largely been extrapolated from disease cohorts, which underestimate the population prevalence of pathogenic primary LHON variants as a result of incomplete disease penetrance. Understanding the true population prevalence of primary LHON variants, alongside the rate of clinical disease, provides a better understanding of disease risk and variant penetrance. We identified pathogenic primary LHON variants in whole-genome sequencing data of a well-characterized population-based control cohort and found that the prevalence is far greater than previously estimated, as it occurs in approximately 1 in 800 individuals. Accordingly, we were able to more accurately estimate population risk and disease penetrance in LHON variant carriers, validating our findings by using other large control datasets. These findings will inform accurate counseling in relation to the risk of vision loss in LHON variant carriers and disease manifestation in their family. This Matters Arising paper is in response to Lopez Sanchez et al. (2021), published in The American Journal of Human Genetics. See also the response by Mackey et al. (2022), published in this issue.


Activated GTPase movement on an RNA scaffold drives co-translational protein targeting.
Approximately one-third of the proteome is initially destined for the eukaryotic endoplasmic reticulum or the bacterial plasma membrane. The proper localization of these proteins is mediated by a universally conserved protein-targeting machinery, the signal recognition particle (SRP), which recognizes ribosomes carrying signal sequences and, through interactions with the SRP receptor, delivers them to the protein-translocation machinery on the target membrane. The SRP is an ancient ribonucleoprotein particle containing an essential, elongated SRP RNA for which precise functions have remained elusive. Here we used single-molecule fluorescence microscopy to show that the Escherichia coli SRP-SRP receptor GTPase complex, after initial assembly at the tetraloop end of SRP RNA, travels over 100 Å to the distal end of this RNA, where rapid GTP hydrolysis occurs. This movement is negatively regulated by the translating ribosome and, at a later stage, positively regulated by the SecYEG translocon, providing an attractive mechanism for ensuring the productive exchange of the targeting and translocation machineries at the ribosome exit site with high spatial and temporal accuracy. Our results show that large RNAs can act as molecular scaffolds that enable the easy exchange of distinct factors and precise timing of molecular events in a complex cellular process; this concept may be extended to similar phenomena in other ribonucleoprotein complexes.


Frequency of occurrence of medication discrepancies and associated risk factors in cases of acute hospital admission.
Medication discrepancies are a common occurrence following hospital admission and carry the potential for causing harm. However, little is known about the potential risk factors involved in medication discrepancies. The objective of this study was to determine how frequently medication discrepancies occur and their associated risk factors, in patients hospitalized via the emergency department of the Spaarne Gasthuis Hospital, located in The Netherlands. This retrospective observational study examines 832 hospital admissions which took place between April 1st and June 30th, 2015. Medication reconciliation was performed within 24 hours of admission and medication discrepancies were registered. The primary outcome recorded in the study was the proportion of patients experiencing one or more medication discrepancies, as verified by the physician. As a secondary outcome, the association between these discrepancies and pre-specified variables was analyzed using univariate and multivariate logistic regression. At least one medication discrepancy was found to have occurred with 97 of the 832 patients (11.7%), the most common discrepancies involving incorrect drug dose (44.9%) and omission of medication (36.4%). In the univariate analysis, age (OR=1.03 [95% CI 1.02:1.04] p<0.001) and number of pre-admission medications taken (OR=1.13 [95%CI 1.09:1.17] p<0.001) were revealed to be significantly associated with the risk of medication discrepancies. Sex, type of medical specialty, and surgical versus non-surgical specialty were found not to be significantly associated with discrepancies. In the multivariate analysis, both the number of pre-admission medications (OR=1.10 [95%CI 1.06:1.15] p<0.001) and age (OR=1.02 [95%CI 1.01:1.03] p=0.004) were independently associated with the risk of medication discrepancy. Of the total number of patients, 11.7% experienced one or more medication discrepancies following admission to the hospital. Elderly patients taking multiple drugs were found to be particularly at risk.


Unveiling the immune system ageing in single-cell resolution.
This writing serves as a commentary on the findings presented in the original manuscript by Yang et al. in 2023, published in the Journal of Leukocyte Biology (JLB). This commentary first summarizes the spatial-temporal dynamics of regulatory T-cells (T-reg) derived from mice (Tabula Muris Senis) of different ages (3M, 18M, and 24M) at different anatomical niches like lymph nodes and bone marrow. We also reported possible combinations of receptor-ligand interactions among T follicular regulatory cells (Tfr), T follicular helper cells (Tfr), and Germinal Centre (GC) B-cells, such as Calmodulin/Fas axis and PSGL-1/L-selectin axis. Then, we have elaborated on the significance of understanding aging T-reg, and have offered some possible future research directions for Yang et al., contributing to a critical analysis of their recent study. Building upon these foundations, further investigations and studies can be conducted to delve deeper into the mechanisms by which T-reg influence health upon aging, potentially unveiling novel therapeutic targets to ameliorate age-related pathogenicity.


The real risk of splenectomy after discharge home following nonoperative management of blunt splenic injury.
The postdischarge natural history of nonoperative blunt splenic injury (BSI) has not been adequately elucidated. As a result, outpatient management is poorly defined. Population-based outpatient data would provide clinicians with an estimate of baseline risk of postdischarge splenectomy after nonoperative management of BSI. The purpose of this study was to analyze, using population-based data, the 180-day risk of splenectomy in a clinically relevant sample. A statewide Hospital Discharge Data System containing patient level data was used to construct a prospective cohort of persons 18 or older with nonoperatively managed BSI admitted to any hospital in the state from 2000 to 2005 and discharged home. Re-admission for splenectomy within 180 days from the original injury date was analyzed. Four thousand one hundred three persons with BSI were admitted from 2000 to 2005. Two thousand nine hundred seventy-one (72.4%) were managed nonoperatively. One thousand nine hundred thirty-two (47.1%) were discharged. Twenty-seven of 1,932 were re-admitted for splenectomy within 180 days. Median time from injury to re-admission for splenectomy was 8 days (range, 3-146). The 180-day risk of splenectomy was 1.4% after nonoperative management and discharge home. Nonoperative management of BSI results in a 180-day risk of re-admission for splenectomy of 1.4% for persons discharged home. A majority of splenectomies occur within 8 days. Explicit patient education and close follow-up are necessary.


The dual impact of coxsackie and adenovirus receptor expression on human prostate cancer gene therapy.
In a recent paper, we reported a significant difference in coxsackie and adenovirus receptor (CAR) from several human bladder cancer cell lines that correlated with their sensitivities to adenoviral infection (Y. Li, R-C. Pong, J. M. Bergelson, M. C. Hall, A. I. Sagalowsky, C-P. Tseng, Z. Wang, and J. T. Hsieh, Cancer Res., 59: 325-330, 1999). In human prostate cancer, CAR protein is down-regulated in the highly tumorigenic PC3 cell line, which suggests that, in addition to its function as a viral receptor, CAR may have a pathophysiological role in prostate cancer progression. In this paper, we document that CAR does not merely enhance the viral sensitivity of prostate cancer cells but also acts as a tumor inhibitor for androgen-independent prostate cancer cells. Our data indicate that CAR is a potential therapeutic agent for increasing the efficacy of prostate cancer therapy.


Cardiac Myosin Promotes Thrombin Generation and Coagulation In Vitro and In Vivo.
Cardiac myosin (CM) is structurally similar to skeletal muscle myosin, which has procoagulant activity. Here, we evaluated CM's ex vivo, in vivo, and in vitro activities related to hemostasis and thrombosis. Approach and Results: Perfusion of fresh human blood over CM-coated surfaces caused thrombus formation and fibrin deposition. Addition of CM to blood passing over collagen-coated surfaces enhanced fibrin formation. In a murine ischemia/reperfusion injury model, exogenous CM, when administered intravenously, augmented myocardial infarction and troponin I release. In hemophilia A mice, intravenously administered CM reduced tail-cut-initiated bleeding. These data provide proof of concept for CM's in vivo procoagulant properties. In vitro studies clarified some mechanisms for CM's procoagulant properties. Thrombin generation assays showed that CM, like skeletal muscle myosin, enhanced thrombin generation in human platelet-rich and platelet-poor plasmas and also in mixtures of purified factors Xa, Va, and prothrombin. Binding studies showed that CM, like skeletal muscle myosin, directly binds factor Xa, supporting the concept that the CM surface is a site for prothrombinase assembly. In tPA (tissue-type plasminogen activator)-induced plasma clot lysis assays, CM was antifibrinolytic due to robust CM-dependent thrombin generation that enhanced activation of TAFI (thrombin activatable fibrinolysis inhibitor). CM in vitro is procoagulant and prothrombotic. CM in vivo can augment myocardial damage and can be prohemostatic in the presence of bleeding. CM's procoagulant and antifibrinolytic activities likely involve, at least in part, its ability to bind factor Xa and enhance thrombin generation. Future work is needed to clarify CM's pathophysiology and its mechanistic influences on hemostasis or thrombosis.


Tumorigenic poxviruses: analysis of viral DNA sequences implicated in the tumorigenicity of Shope fibroma virus and malignant rabbit virus.
The DNA sequence has been determined for a 7-kb region within the terminal inverted repeats (TIR) of Shope fibroma virus (SFV), a poxvirus which induces benign fibromas in rabbits. This region of the SFV TIR, which flanks the junction of the TIR with the unique internal sequences of the viral genome, had previously been shown to be also present in the genome of malignant rabbit virus (MRV), a hybrid poxvirus derived from a recombination event between SFV and a related leporipoxvirus, myxoma. Unlike SFV, the recombinant MRV induces an invasive profile of tumors in infected rabbits, but the capacity to induce proliferant fibromas appears to have been derived from SFV. These SFV DNA sequences have been analyzed and their genetic organization shows a unique tandem arrangement of three large open reading frames (ORFs) which share considerable homology with each other. Very short spacer sequences are present between the majority of ORFs, all of which are transcribed toward the terminal hairpins of SFV. Unusual dyad symmetries flank two of the most closely related ORFs and evidence is presented that one SFV ORF (T9-L) which maps precisely at the TIR/unique sequence boundary was truncated during transposition to the left terminus from a progenitor copy (T9-R) at the right terminus. The origin of these putative viral genes is considered in light of the recent observation (C. Upton and G. McFadden, 1986, Mol. Cell. Biol. 6, 265-276) that a subset of this region of the SFV genome is closely related to, and may have been originally derived from, an endogenous covalently closed circular plasmid species detected in uninfected rabbit cells.


The Swedish translation and cross-cultural adaptation of the Functional Assessment of Chronic Illness Therapy - Cervical Dysplasia (FACIT-CD): linguistic validity and reliability of the Swedish version.
Cervical dysplasia is a precancerous condition, which has been shown to create anxiety in women. To be able to investigate these women's health-related quality of life, a disease-specific instrument is required. There does not seem to be a Swedish version of an instrument to screen for this specific disease. Therefore, this study aims to translate and cross-culturally adapt the Functional Assessment of Chronic Illness Therapy - Cervical Dysplasia (FACIT-CD) into a Swedish context and evaluate its linguistic validity and reliability. The Functional Assessment of Chronic Illness Therapy (FACIT) translation methodology was used, which consists of several steps including pilot testing of the FACIT-CD instrument through cognitive debriefing interviews. Ten women diagnosed with cervical dysplasia participated in the cognitive debriefing interviews. The internal consistency reliability of the Swedish FACIT-CD was estimated by Cronbach's alpha coefficient. Homogeneity of the items was evaluated by corrected item-total correlations. The sample consists of 34 women who were diagnosed with cervical dysplasia. The translation and cross-cultural adaptation went smoothly without any problems for the majority of the items. The cognitive debriefing interviews indicated that the Swedish FACIT-CD consists of relevant items, is easy to understand and complete, and has unambiguous and comprehensive response categories. The translation and cross-cultural adaptation resulted in a Swedish FACIT-CD, which is conceptually and semantically equivalent to the English version and linguistically valid. The total scale of the Swedish FACIT-CD exhibited good internal consistency reliability with a Cronbach's alpha coefficient of 0.84, and all of the subscales exhibited acceptable value between 0.71 and 0.81 except the Relationships subscale, which had a value of 0.67. Finally, all but four items exceeded the acceptable level for the corrected item-total correlations of ≥ 0.20. The Swedish FACIT-CD is conceptually and semantically equivalent to the English version and linguistically valid; further, it exhibits good internal consistency reliability.


Prevalence of disability among the major cities in Australia 2012 with geographical representation of distribution in Western Australia.
The aim of this study was to use a novel approach to geographically model the relationship between socio-economic disadvantage and prevalence of profound and severe disability. This study used national census data and the survey of disability, ageing and carers data to geographically model the relationship between socio-economic disadvantage and prevalence of profound and severe disability. The results in this study show that there were more people living in the least disadvantaged areas (wealthiest) when compared to the most disadvantaged (poorest) areas. Whereas for people with a disability as the relative socio-economic disadvantage of the area increased, the number of people reporting any disability also increased, with the highest number coming from the most disadvantaged areas. The maps show a significant distribution with fewer cases of disability in metropolitan areas and relatively higher number in the rural area along with the higher proportion of people with disability living in the relatively more disadvantaged areas. Socio-economic profile is one of the key factors influencing the various aspects of health and hence should hold an important place during policy making. Policy should be formulated and implemented to help reduce the inequality by either directly aiming at the most disadvantaged group or by trying to bridge the gap between them. SO WHAT?: This paper provides a geographic visualisation of the distribution of people with profound and severe disability to help identify priority areas with high prevalence of disability.


The Mechanism of Programmed Aging: The Way to Create a Real Remedy for Senescence.
Accumulation of various damages is considered the primary cause of aging throughout the history of gerontology. No progress has been made in extending animal lifespan under the guidance of this concept. This concept denies the existence of longevity genes, but it has been experimentally shown that manipulating genes that affect cell division rates can increase the maximum lifespan of animals. These methods of prolonging life are unsuitable for humans because of dangerous side effects, but they undoubtedly indicate the programmed nature of aging. The objective was to understand the mechanism of programmed aging to determine how to solve the problem of longevity. Fundamental research has already explored key details relating to the mechanism of programmed aging, but they are scattered across different fields of knowledge. The way was to recognize and combine them into a uniform mechanism. Only a decrease in bioenergetics is under direct genetic control. This causes many different harmful processes that serve as the execution mechanism of the aging program. The aging rate and, therefore, lifespan are determined by the rate of cell proliferation and the magnitude of the decrease in bioenergetics per cell division in critical tissues. The mechanism of programmed aging points the way to achieving an unlimited healthy life; it is necessary to develop a means for managing bioenergetics. It has already been substantially studied by molecular biologists and is now waiting for researchers from gerontology.


Ultrasonographic assessment of human skeletal muscle size.
The measurement of human muscle size is essential when assessing the effects of training, disuse and ageing. The considered 'gold standard' for cross-sectional area measurements of muscle size is magnetic resonance imaging (MRI). However, MRI is costly and often inaccessible. The aim of the present study was to test the reproducibility and validity of a more accessible alternative method using ultrasonography (ULT). We examined the cross-sectional areas in the vastus lateralis muscle of six individuals. Axial-plane ULT scans were taken at given levels along the entire muscle length. The ULT scanning was repeated on different days (reliability) and validated against MRI-based measurements. Mean intraclass correlation coefficients were 0.998 for the reliability of ULT and 0.999 for the validity of ULT against MRI. The coefficient of variation values for cross-sectional area measurements assessed by six different experimenters were 2.1% and 0.8% for images obtained with ULT and MRI, respectively. The ULT method is a valid and reliable alternative tool for assessing cross-sectional areas of large individual human muscles. The present findings justify the application of the ULT method for the detection of changes throughout large muscles in response to training, disuse or as a consequence of sarcopenia.


Combination chemotherapy of hepatocellular cancer. Comparison of adriamycin + VM 26 + 5-fluorouracil with mAMSA + VM 26 + 5-fluorouracil.
Forty-seven patients with hepatocellular cancer were treated in a randomised trial comparing adriamycin + VM 26 + 5-Fluorouracil (5-FU) to mAMSA + VM 26 + 5-FU. Thirteen patients had a partial response to treatment (28%) and another 6 (13%) showed disease stabilisation. There were no significant differences in the response rates between the two treatment regimens. Patients who responded to treatment showed significant prolongation of survival (48 weeks) when compared to non-responders (5 weeks).


Promoting Equity, Diversity, and Inclusion in Medicine: A Comprehensive Toolkit for Change in Radiology.
This toolkit presents a comprehensive framework for a toolkit intended to increase equity, diversity, and inclusion (EDI) within the medical field and recommendations. We advocate for clear, comprehensive definitions and interpretations of fundamental EDI terms, laying the groundwork necessary for initiating and maintaining EDI initiatives. Furthermore, we offer a systematic approach to establishing EDI committees within medical departments, accentuating the pivotal role these committees play as they drive and steer EDI strategies. This toolkit also explores strategies tailored for the recruitment of a diverse workforce. This includes integral aspects such as developing inclusive job advertisements, implementing balanced search methods for candidates, conducting unbiased appraisals of applications, and structuring diverse hiring committees. The emphasis on these strategies not only augments the diversity within medical institutions but also sets the stage for a more holistic approach to healthcare delivery. Therefore, by adopting the recommended strategies and guidelines outlined in this framework, medical institutions and specifically radiology departments can foster an environment that embodies inclusivity and equity, thereby enhancing the quality of patient care and overall health outcomes.


Psychopathology and young people with Down's syndrome: childhood predictors and adult outcome of disorder.
There is a scarcity of follow-up studies into adult life of psychiatric disorder in young people with intellectual disability. The key aims of the present study were: (1) to determine the outcome of psychopathology present in childhood in individuals with Down's syndrome (DS); and (2) to look at childhood predictors of adult psychiatric disorder. Fifty-two young people with DS were identified from a sample of 193 subjects examined in childhood and adolescence for psychiatric and behaviour disorder. These young adults were interviewed for the presence of psychiatric disorder. No significant relationship was found between childhood mental disorder and psychiatric disorder in adult life for those individuals with DS. Early childhood factors of psychiatric disorder, challenging behaviour and family environment, except social background, did not predict adult psychopathology in young people with DS. Childhood disorder in individuals with DS has a good early prognosis with little evidence of continuity of the disorder into adult life.


Beyond One's Attitude Toward the Self: The Role of Social Anxiety in Self-Stigma Among Individuals With Schizophrenia.
Self-stigma is associated with a variety of negative self-perceptions among people coping with schizophrenia, as well as with different aspects of social behaviors. We explored the associations between self-compassion, self-esteem, social anxiety, and self-stigma among people coping with schizophrenia. The baseline data of 56 adults with schizophrenia who were enrolled in a Metacognitive Reflection and Insight Therapy trial were used. Participants filled out self-report questionnaires measuring self-compassion, self-esteem, social anxiety, and self-stigma. Self-esteem and self-compassion were negatively correlated with self-stigma and social anxiety. Self-compassion was not found to contribute beyond self-esteem to the prediction of self-stigma. Importantly, self-esteem and social anxiety were found to mediate the effects of self-compassion on self-stigma. Thus, it seems that social variables, in addition to self-variables, may lead to the formation of self-stigma among people with schizophrenia. Therefore, alongside addressing self-esteem and self-compassion, integrating therapeutic elements related to coping with social anxiety into interventions would seem to be an important factor in reducing self-stigma among people with serious mental illness.


A colorimetric sensor array for detection and discrimination of antioxidants based on Ag nanoshell deposition on gold nanoparticle surfaces.
There is growing interest in developing a high-performance sensor array for detection and discrimination of antioxidants owing to their widespread use and essential role in the human body. The present work unveils a novel colorimetric sensor array for colorimetric discrimination of antioxidants based on the red, green, and blue alteration (ΔRGB) pattern recognition. In this sensor array, three concentrations of AgNO3 were used as sensing elements, and gold nanoparticles (AuNPs) were employed as a colorimetric probe. In the presence of antioxidants, the sensor array produces unique colorimetric response patterns for the discrimination of these antioxidants due to different reactivities between three different concentrations of AgNO3 and each antioxidant, leading to deposition of different quantities of Ag nanoshells on the surface of AuNPs, enabling an excellent discrimination of six antioxidants (catechin, epigallocatechin 3-gallate, epicatechin, epigallocatechin, epicatechin 3-gallate, and gallocatechin) at a 20 nM level, when linear discriminant analysis (LDA), hierarchical cluster analysis (HCA), centroid diagram, spidergram, and color contour profiles were smartly combined. Furthermore, different concentrations of antioxidants and binary antioxidant mixtures, even ternary mixtures, could also be discriminated with this sensor array. Finally, the sensor array was successfully used for the discrimination of antioxidants in serum samples, demonstrating its potential applications in the diagnosis of antioxidant-related diseases.


Patterns of human oral yeast species distribution on Hainan Island in China.
Infections by yeast strains of the genus Candida are among the most prevalent fungal infections of humans. These yeasts are common residents of the oral mucosa and other body surfaces. Since most yeast infections are due to endogenous strains and that species of Candida differ in virulence properties and in intrinsic susceptibilities to antifungal drugs, understanding the human commensal yeast flora can help designing effective treatment and prevention strategies against yeast infections. Here, we report the patterns of yeast species distributions in the oral cavities of 1,799 people from Hainan Island in southern China. Based on sequence information at the fungal barcode locus ITS regions, 368 of the 415 obtained oral yeast strains were identified as belonging to 26 yeast species, while the remaining 47 strains all showed significant sequence divergence to the currently described species. The four most common yeast species were C. albicans (42 %), C. tropicalis (20 %), C. glabrata (5.5 %), and C. parapsilosis (4.1 %) and 10 of the 26 yeast species were represented by only one strain each. Our analyses identified that the gender of hosts and ethnical background showed no contribution to oral yeast species distributions. However, the health status, place of birth, current residency, and the age of hosts all showed significant contributions to the distributions of the four dominant yeast species. We compared our results with those reported previously and discussed the potential mechanisms for the observed differences in oral yeast species distributions.


Association of Postpartum Smoking Relapse With Breastfeeding and Body Mass Index.
This study aimed to determine the relationship between smoking relapse and breastfeeding and body mass index in the postpartum period. This descriptive, cross-sectional study was conducted between November 2016 and November 2017 in the polyclinic for children's health and common illnesses at a university hospital in eastern Turkey. One hundred eleven women who met the inclusion criteria constituted the sample of the study. The data were evaluated using the analyses of percentage, arithmetic mean, standard deviation, independent-samples t test, analysis of variance, and multiple linear regression. In the study, the week of pregnancy period when the women quit smoking was 8.19 ± 5.17, and the week of postpartum smoking relapse was 8.47 ± 11.76. Furthermore, 72.1% of the women stated that they wanted to quit smoking permanently. The study determined that the status of wanting to quit smoking permanently, the status of smoking while breastfeeding, and gained weight during the last gestation are important predictors of postpartum smoking relapse. Knowledge on the characteristics of the women who started smoking again in the postpartum period is important for helping women who have quitted smoking in pregnancy but who are prone to relapse as a risk group by health care personnel.


Bacterial biofilms in a 'genes-to-ecosystems' context.
In ecology, there is an increasing amount of research dedicated to understanding how intraspecific genetic diversity can extend beyond the population level to influence the assembly of communities and the functioning of ecosystems. In this issue of Molecular Ecology, Koh et al. (2012) take this exploration to a new level using bacterial biofilms and protozoan grazers. They show that there is heritable variation in the phenotypes of different variants of biofilms of Serratia marcescens and that these strains display complementarity when combined in a diverse assemblage. Mixtures of variants were significantly more resistant to protozoan grazing than either wild-type or variant biofilms grown in monocultures. While similar biodiversity effects of genotype mixtures have been observed in other systems, Koh et al. (2012) link phenotype variation of the biofilms to a single nucleotide polymorphism in one regulatory gene. Importantly, the authors demonstrate that minimal changes in a genotype can result in substantial shifts in interspecific ecological interactions.


Urinary tract infections, bacterial resistance and immunological status: a cross sectional study in pregnant and non-pregnant women at Mbouda Ad-Lucem Hospital.
Urinary tract infections (UTI) are frequently encountered medical complications of pregnancy. This study was aimed at analyzing the bacterial resistance in urogenital tract as well as the immunological profile amongst pregnant and non-pregnant women at Mbouda Ad-Lucem Hospital, Western Region of Cameroon. A cross-sectional study was carried out from December 2015 to May 2016 at Mbouda Ad-Lucem hospital on 104 pregnant women and 24 non-pregnant women. The midstream urine from participants was analysed for the presence, isolation and identification of the uro-pathogens, using selective and specific bacterial culture media. An antibiotic susceptibility tests was carried out using disk diffusion method. Blood samples were collected for C-reactive protein (CRP) dosage, CD4 and CD8 lymphocytes count. Out of 128 participants in this study, a high prevalence of uro-pathogens and resistance strains was observed. The most prevalent urinary tract pathogens were Staphylococcus sp. with 45% and 38.89% respectively in pregnant and non-pregnant women. Staphylococcus sp. showed resistance to Amoxicillin (AMO; 55.56%) and Chloramphenicol (CHL; 100%) respectively in pregnant and non-pregnant women. Pregnant women had a significantly high average of granulocytes (p=0.009), monocytes (P=0.001), high ratio of CD4/CD8 (p< 0.0001) and significantly low CD8 lymphocytes (p< 0.0001) average compared to non-pregnant women. This study outlines high prevalence of Staphylococcus sp as the main urinary tract infectious pathogen in women at Mbouda Ad-Lucem hospital. It prevalence was accompanied with resistance to the routine antibiotics treatment, and a pronounced lymphocytosis and monocytosis.


Clinical results of unconventional fractionation radiotherapy in central nervous system tumors.
Malignant brain tumors (primary and metastatic) are apparently resistant to most therapeutic efforts. Several randomized trials have provided evidence supporting the efficacy of radiation therapy. Attempts at improving the results of external beam radiotherapy include altered fractionation, radiation sensitizers and concomitant chemotherapy. In low-grade gliomas, all clinical studies with radiotherapy have employed conventional dose fractionation regimens. In high-grade gliomas, hypofractionation schedules represent effective palliative regimens in poor prognosis subsets of patients; short-term survival in these patients has not allowed to evaluate late toxicity. In tumors arising within the central nervous system, hyperfractionated irradiation exploits the differences in repair capacity between tumour and late responding normal tissues. It may allow for higher total dose and may result in increased tumor cell kill. Accelerated radiotherapy may reduce the repopulation of tumor cells between fractions. It may potentially improve tumor control for a given dose level, provided that there is no increase in late normal tissue injury. In supratentorial malignant gliomas, superiority of accelerated hyperfractionated over conventionally fractionated schedules was observed in a randomized trial; however, the gain in survival was less than 6 months. At present no other randomized trial supports the preferential choice for altered fractionation irradiation. Also in pediatric brainstem tumors there are no data to confirm the routine use of hyperfractionated irradiation, and significant late sequelae have been reported in the few long-term survivors. Shorter treatment courses with accelerated hyperfractionated radiotherapy may represent a useful alternative to conventional irradiation for the palliation of brain metastases. Different considerations have been proposed to explain this gap between theory and clinical data. Patients included in dose/effect studies are not stratified by prognostic factors and other treatment-related parameters. This observation precludes any definite conclusion about the relative role of conventional and of altered fractionation. New approaches are currently in progress. More prolonged radiation treatments, up to higher total doses, could delay time to tumor progression and improve survival in good prognosis subsets of patients; altered fractionation may be an effective therapeutic tool to achieve this goal.


[Physiological control and pharmacological inhibition of digestive secretions].
The pharmacological treatment of alimentary tract fistulas was for a long time limited to the use of atropine and related substances. More recently H2 blockers, pirenzepine, omeprazole and loperamide have been used. It is likely that in the coming years specific and long acting derivatives of somatostatin and enkephalins inhibiting digestive secretions will be synthetized.


Metformin increases APP expression and processing via oxidative stress, mitochondrial dysfunction and NF-κB activation: Use of insulin to attenuate metformin's effect.
Clinical and experimental biomedical studies have shown Type 2 diabetes mellitus (T2DM) to be a risk factor for the development of Alzheimer's disease (AD). This study demonstrates the effect of metformin, a therapeutic biguanide administered for T2DM therapy, on β-amyloid precursor protein (APP) metabolism in in vitro, ex vivo and in vivo models. Furthermore, the protective role of insulin against metformin is also demonstrated. In LAN5 neuroblastoma cells, metformin increases APP and presenilin levels, proteins involved in AD. Overexpression of APP and presenilin 1 (Pres 1) increases APP cleavage and intracellular accumulation of β-amyloid peptide (Aβ), which, in turn, promotes aggregation of Aβ. In the experimental conditions utilized the drug causes oxidative stress, mitochondrial damage, decrease of Hexokinase-II levels and cytochrome C release, all of which lead to cell death. Several changes in oxidative stress-related genes following metformin treatment were detected by PCR arrays specific for the oxidative stress pathway. These effects of metformin were found to be antagonized by the addition of insulin, which reduced Aβ levels, oxidative stress, mitochondrial dysfunction and cell death. Similarly, antioxidant molecules, such as ferulic acid and curcumin, are able to revert metformin's effect. Comparable results were obtained using peripheral blood mononuclear cells. Finally, the involvement of NF-κB transcription factor in regulating APP and Pres 1 expression was investigated. Upon metformin treatment, NF-κB is activated and translocates from the cytoplasm to the nucleus, where it induces increased APP and Pres 1 transcription. The use of Bay11-7085 inhibitor suppressed the effect of metformin on APP and Pres 1 expression.


The first single particle analysis Map Challenge: A summary of the assessments.
The recent successes of cryo-electron microscopy fostered great expectation of solving many new and previously recalcitrant biomolecular structures. However, it also brings with it the danger of compromising the validity of the outcomes if not done properly. The Map Challenge is a first step in assessing the state of the art and to shape future developments in data processing. The organizers presented seven cases for single particle reconstruction, and 27 members of the community responded with 66 submissions. Seven groups analyzed these submissions, resulting in several assessment reports, summarized here. We devised a range of analyses to evaluate the submitted maps, including visual impressions, Fourier shell correlation, pairwise similarity and interpretation through modeling. Unfortunately, we did not find strong trends. We ascribe this to the complexity of the challenge, dealing with multiple cases, software packages and processing approaches. This puts the user in the spotlight, where his/her choices becomes the determinant of map quality. The future focus should therefore be on promulgating best practices and encapsulating these in the software. Such practices include adherence to validation principles, most notably the processing of independent sets, proper resolution-limited alignment, appropriate masking and map sharpening. We consider the Map Challenge to be a highly valuable exercise that should be repeated frequently or on an ongoing basis.


Correlated and decoupled evolution of adult and larval body size in frogs.
The majority of animal species have complex life cycles, in which larval stages may have very different morphologies and ecologies relative to adults. Anurans (frogs) provide a particularly striking example. However, the extent to which larval and adult morphologies (e.g. body size) are correlated among species has not been broadly tested in any major group. Recent studies have suggested that larval and adult morphology are evolutionarily decoupled in frogs, but focused within families and did not compare the evolution of body sizes. Here, we test for correlated evolution of adult and larval body size across 542 species from 42 families, including most families with a tadpole stage. We find strong phylogenetic signal in larval and adult body sizes, and find that both traits are significantly and positively related across frogs. However, this relationship varies dramatically among clades, from strongly positive to weakly negative. Furthermore, rates of evolution for both variables are largely decoupled among clades. Thus, some clades have high rates of adult body-size evolution but low rates in tadpole body size (and vice versa). Overall, we show for the first time that body sizes are generally related between adult and larval stages across a major group, even as evolutionary rates of larval and adult size are largely decoupled among species and clades.


Cell therapy of pseudarthrosis.
To assess the safety and efficiency of cell therapy for pseudarthrosis. Implant of the bone marrow aspirate was compared to mononuclear cells purified extemporaneously using the Sepax(®) equipment. Six patients with nonunion of the tibia or femur were treated. Four received a percutaneous infusion of autologous bone marrow aspirated from the iliac crest, and two received autologous bone marrow mononuclear cells separated from the aspirate with the Sepax(®). The primary fixation method was unchanged, and the nonunion focus was not exposed. Physical examination and radiographies were performed 2, 4 and 6 months after the treatment by the same physician. After consolidation of the fracture the satisfaction of the patients was estimated using the adapted QALY scale. No complications occurred as a result of the referred procedures. Bone consolidation was obtained in all cases within 3 to 24 weeks. The degree of patient satisfaction before and after bone consolidation was assessed, with the average value increasing from two to nine (p=0.0156). We conclude that the proposed method is effective and safe for the treatment of nonunion of long bones regardless of the stabilization method used. Level of Evidence II, Prospective Comparative Study.


Perceived social support in African American breast cancer patients: Predictors and effects.
Social support plays an important role in quality of life and health outcomes after breast cancer diagnosis and treatment. To examine changes in perceived social support in African American women during the two years following a new breast cancer diagnosis. This secondary analysis uses data collected from 2009 to 2015 from 227 newly diagnosed, African American women with breast cancer (mean age 56 [SD = 10], 59% household income < $25,000; 28% married/partnered, 72% early stage) participating in a randomized controlled trial testing the effects of a video-communication intervention on quality-of-life and follow-up care. Participants, all of whom received treatment in one metropolitan area of the Midwestern United States, completed five telephone interviews over 2-year follow-up; demographic, psychosocial, quality of life, and clinical data were collected. Growth curve models were used to examine change in perceived social support (measured by the Medical Outcomes Study Social Support Survey) as well as correlates of baseline levels of social support and predictors of change in individuals' social support. Additional analyses examined whether change in social support over the first year affected depressive symptoms (Center for Epidemiologic Studies Depression Scale) and general health perceptions (RAND SF-36 subscale) at two years. Being married, reporting greater spirituality, and reporting fewer depressive symptoms at baseline were significantly associated with higher initial levels of perceived social support. Women whose social support declined during the first year after diagnosis reported more severe depressive symptoms and worse general health perceptions at two years. Clinicians should periodically assess perceived social support among African American women with breast cancer to help find support resources for those who have low initial social support and for those whose support declines in the first year after diagnosis.


Severe neck scarring: A consequence of fractional CO2 laser resurfacing.
Fractional CO2 laser resurfacing using aggressive treatment parameters may result in adverse effects comparable to those of fully ablative CO2 laser resurfacing. A 45-year-old female underwent fractional CO2 laser treatment of the neck. She contacted the author for treatment of the marked erythema, swelling, and perceived skin tightness that resulted from the resurfacing procedure. This case report describes how the author treated these complications, provides a plausible explanation for why they occurred, and recommends treatment modifications to minimize the risk of their occurrence.


New Volvovirus Isolates from Acheta domesticus (Japan) and Gryllus assimilis (United States).
A novel circular single-stranded DNA (ssDNA) virus, volvovirus, from the house cricket has been described recently. Here, we report the isolation of volvoviruses from Acheta domesticus in Japan and Gryllus assimilis in the United States. These Acheta domesticus volvovirus (AdVVV) isolates have genomes of 2,517 and 2,516 nucleotides (nt) and 4 large open reading frames (ORFs).


Precise Tuning of Cortical Contractility Regulates Cell Shape during Cytokinesis.
The mechanical properties of the actin cortex regulate shape changes during cell division, cell migration, and tissue morphogenesis. We show that modulation of myosin II (MII) filament composition allows tuning of surface tension at the cortex to maintain cell shape during cytokinesis. Our results reveal that MIIA generates cortex tension, while MIIB acts as a stabilizing motor and its inclusion in MII hetero-filaments reduces cortex tension. Tension generation by MIIA drives faster cleavage furrow ingression and bleb formation. We also show distinct roles for the motor and tail domains of MIIB in maintaining cytokinetic fidelity. Maintenance of cortical stability by the motor domain of MIIB safeguards against shape instability-induced chromosome missegregation, while its tail domain mediates cortical localization at the terminal stages of cytokinesis to mediate cell abscission. Because most non-muscle contractile systems are cortical, this tuning mechanism will likely be applicable to numerous processes driven by myosin-II contractility.


Accuracy of Birth Certificate Data for Classifying Preterm Birth.
Classifying preterm birth as spontaneous or indicated is critical both for clinical care and research, yet the accuracy of classification based on different data sources is unclear. We examined the accuracy of preterm birth classification as spontaneous or indicated based on birth certificate data. This is a retrospective cohort study of 123 birth certificates from preterm births in Missouri. Correct classification of spontaneous or indicated preterm birth subtype was based on multi-provider (RN, MFM Fellow, MFM attending) consensus after full medical record review. A categorisation algorithm based on clinical data available in the birth certificate was designed a priori and classification was performed by a single investigator according to the algorithm. Accuracy of birth certificate classification as spontaneous or indicated was compared to the consensus classification. Errors in misclassification were explored. Classification based on birth certificates was correct for 66% of preterm births. Most errors in classification by birth certificate occurred in classifying a birth as spontaneous when it was in fact indicated. The vast majority of errors occurred when preterm rupture of membranes (≥12 h) was checked on the birth certificate causing classification as spontaneous when there was a maternal or fetal indication for delivery. Birth certificate classification overestimated spontaneous preterm birth and underestimated indicated preterm birth compared to classification performed from medical record review. Revisions to birth certificate clinical data would allow more accurate population level surveillance of preterm birth subtypes.


Natural regulation of immunity to minor histocompatibility antigens.
MHC-matched hemopoietic stem cell transplantation is commonly used for the treatment of some forms of leukemia. Conditioning regimens before transplant act to reduce the burden of leukemic cells and the graft-vs-leukemia (GvL) effect can eliminate residual disease. The GvL effect results largely from the recognition of minor histocompatibility Ags by donor T cells on recipient tissues. These Ags are generally widely expressed and also provoke graft-vs-host (GvH) disease. Manipulation of immunity to promote GvL while curtailing GvH would greatly improve clinical outcome. To develop strategies that may achieve this, the parameters which control immunity to minor histocompatibility Ags need to be defined. In this study, we have analyzed responses to the mouse HY minor histocompatibility Ag using hemopoietic cell and skin grafts as surrogate GvL and GvH targets, respectively. We show that natural regulation of CD8 T cell responses to HY operates at multiple levels. First, CD4 T cell help is required for primary CD8 responses directed at hemopoietic cells. However, although CD4 T cells of H2(k) mouse strains recognize HY, they provide ineffective help associated with a proportion of recipients developing tolerance. This was further investigated using TCR-transgenic mice which revealed H2(k)-restricted HY-specific CD4 T cells are highly susceptible to regulation by CD25(+) regulatory T cells which expand in tolerant recipients. A second level of regulation, operating in the context of skin grafts, involves direct inhibition of CD8 T cell responses by CD94/NKG2 engagement of the nonclassical MHC class I molecule Qa1.


Combining motivational and volitional interventions to promote exercise participation: protection motivation theory and implementation intentions.
This study compared a motivational intervention based on protection motivation theory (PMT, Rogers, 1975, 1983) with the same motivational intervention augmented by a volitional intervention based on implementation intentions (Gollwitzer, 1993). The study had a longitudinal design, involving three waves of data collection over a 2-week period, incorporating an experimental manipulation of PMT variables at Time 1 and a volitional, implementation intention intervention at Time 2. Participants (N=248) were randomly allocated to a control group or one of two intervention groups. Cognitions and exercise behaviour were measured at three time-points over a 2-week period. The motivational intervention significantly increased threat and coping appraisal and intentions to engage in exercise but did not bring about a significant increase in subsequent exercise behaviour. In contrast, the combined protection motivation theory/implementation intention intervention had a dramatic effect on subsequent exercise behaviour. This volitional intervention did not influence behavioural intention or any other motivational variables. It is concluded that supplementing PMT with implementation intentions strengthens the ability of the model to explain behaviour. This has implications for health education programmes, which should aim to increase both participants' motivation and their volition.


Convergence of IPMK and LKB1-AMPK signaling pathways on metformin action.
Metformin is a biguanide drug that is widely prescribed for type 2 diabetes. Metformin suppresses hepatic gluconeogenesis and increases fatty acid oxidation. Although studies have suggested that metformin acts, at least in part, via activation of the liver kinase B1 (LKB1)/AMP-activated protein kinase (AMPK) pathway, the specific molecular mechanisms underlying metformin's regulation of glucose and lipid metabolism have not been well delineated. Recently, we have shown that inositol polyphosphate multikinase (IPMK) plays an important role in cellular energy metabolism and glucose-mediated AMPK regulation. Here we investigated the role of IPMK in metformin-induced AMPK activation. We observed that metformin-mediated activation of AMPK was impaired in the absence of IPMK. Overexpression of wild-type IPMK was sufficient to restore LKB1-AMPK activation by either metformin or AICAR in IPMK(-/-) murine embryonic fibroblast cells, suggesting that IPMK may act as an upstream regulator of LKB1-AMPK signaling in response to metformin. Moreover, this regulation was mediated by protein-protein interaction between IPMK and LKB1 as a dominant-negative peptide, which abrogates this interaction, attenuated metformin's ability to activate AMPK. Our data demonstrate that IPMK plays an important role in LKB1/AMPK signaling and may be targeted for treatment of metabolic diseases.


Adipocyte-derived monocyte chemotactic protein-1 (MCP-1) promotes prostate cancer progression through the induction of MMP-2 activity.
Obesity is known to be associated with prostate cancer development and progression, but the detailed mechanism is not clear. Monocyte chemotactic protein-1 (MCP-1) is secreted from cancer cells, stromal cells, and adipocytes, and it is involved in prostate cancer progression. Here we investigated the biological role of MCP-1 secreted from adipocytes for prostate cancer cells. Human pre-adipocytes (HPAds) were cultured and differentiated to mature adipocytes. Conditioned medium (CM) from HPAd cells was obtained using phenol red-free RPMI1640 medium. We performed a cytokine membrane array analysis to detect cytokines in the CM. To characterize the physiological function of MCP-1 in the CM, we performed an MTT-assay, a wound-healing and invasion assay with anti-MCP-1 antibody using three prostate cancer cell lines: DU145, LNCaP, and PC-3. Matrix metalloproteinase (MMP)-2 and MMP-9 activities were evaluated by gelatin zymography. A qPCR and Western blotting were used to examine the mRNA and protein expression levels of MMP-2. The cytokine membrane array of the CM showed a strong signal of MCP-1compared to the control medium, and we thus focused our attention on MCP-1 in the CM. The CM up-regulated the cancer cell proliferation, and the neutralization by anti-MCP-1 antibody inhibited the proliferative effect of the prostate cancer cell lines. The CM greatly increased the invasive activity in the prostate cancer cell lines, and anti-MCP-1 antibody decreased the invasiveness. Gelatin zymography revealed that the CM markedly enhanced the enzymatic activity of MMP-2, and anti-MCP-1 antibody down-regulated its effect. MMP-2 mRNA expression was undetected and the MMP-2 protein level was unchanged between the control medium and CM in DU145 cells. MCP-1 from adipocytes enhances the growth and invasion activity of prostate cancer cells. The inhibition of MCP-1 derived from adipocytes might be an effective treatment for prostate cancer.


The efficacy of Shugan Jianpi Zhixie therapy for diarrhea-predominant irritable bowel syndrome: a meta-analysis of randomized, double-blind, placebo-controlled trials.
Shugan Jianpi Zhixie therapy (SJZT) has been widely used to treat diarrhea-predominant irritable bowel syndrome (IBS-D), but the results are still controversial. A meta-analysis of randomized, double-blind, placebo-controlled trials was performed to assess the efficacy and tolerability of SJZT for IBS-D. The MEDLINE, EMBASE, Cochrane Library, the China National Knowledge Infrastructure database, the Chinese Biomedical Literature database and the Wanfang database were searched up to June 2014 with no language restrictions. Summary estimates, including 95% confidence intervals (CI), were calculated for global symptom improvement, abdominal pain improvement, and Symptom Severity Scale (BSS) score. Seven trials (N=954) were included. The overall risk of bias assessment was low. SJZT showed significant improvement for global symptom compared to placebo (RR 1.61; 95% CI 1.24, 2.10; P =0.0004; therapeutic gain = 33.0%; number needed to treat (NNT) = 3.0). SJZT was significantly more likely to reduce overall BSS score (SMD -0.67; 95% CI -0.94, -0.40; P < 0.00001) and improve abdominal pain (RR 4.34; 95% CI 2.64, 7.14; P < 0.00001) than placebo. The adverse events of SJZT were no different from those of placebo. This meta-analysis suggests that SJZT is an effective and safe therapy option for patients with IBS-D. However, due to the high clinical heterogeneity and small sample size of the included trials, further standardized preparation, large-scale and rigorously designed trials are needed.


Selection and acquisition of audiovisual materials by health professionals.
Audiovisual (AV) materials are widely used in the education of health professionals, and health science educators are usually the people who select audiovisual teaching materials. However, little is known about the selection process and there are few parameters that can be used for guidance. No previous research was uncovered that documented the selection/acquisition of materials by users. This paper reports a survey of health science educators and resource consultants at forty-five academic health centers in the United States, on their experiences in identifying, selecting, and using AV materials. The results provide a baseline of information on which future research can build.


Charge Order and Superconductivity in Underdoped YBa_{2}Cu_{3}O_{7-δ} under Pressure.
In underdoped cuprates, an incommensurate charge density wave (CDW) order is known to coexist with superconductivity. A dip in T_{c} at the hole doping level where the CDW is strongest (n_{p}≃0.12) suggests that CDW order may suppress superconductivity. We investigate the interplay of charge order with superconductivity in underdoped YBa_{2}Cu_{3}O_{7-δ} by measuring the temperature dependence of the Hall coefficient R_{H}(T) at high magnetic field and at high hydrostatic pressure. We find that, although pressure increases T_{c} by up to 10 K at 2.6 GPa, it has very little effect on R_{H}(T). This suggests that pressure, at these levels, only weakly affects the CDW and that the increase in T_{c} with pressure cannot be attributed to a suppression of the CDW. We argue, therefore, that the dip in T_{c} at n_{p}≃0.12 at ambient pressure is probably not caused by the CDW formation.


Addressing Challenges of Macrocyclic Conformational Sampling in Polar and Apolar Solvents: Lessons for Chameleonicity.
We evaluated a workflow to reliably sample the conformational space of a set of 47 peptidic macrocycles. Starting from SMILES strings, we use accelerated molecular dynamics simulations to overcome high energy barriers, in particular, the cis-trans isomerization of peptide bonds. We find that our approach performs very well in polar solvents like water and dimethyl sulfoxide. Interestingly, the protonation state of a secondary amine in the ring only slightly influences the conformational ensembles of our test systems. For several of the macrocycles, determining the conformational distribution in chloroform turns out to be considerably more challenging. Especially, the choice of partial charges crucially influences the ensembles in chloroform. We address these challenges by modifying initial structures and the choice of partial charges. Our results suggest that special care has to be taken to understand the configurational distribution in apolar solvents, which is a key step toward a reliable prediction of membrane permeation of macrocycles and their chameleonic properties.


[Recovery of the dog myocardial contractile function in the diastolic period].
Isolated canine heart has an expressed ability for autoregulation of mechanical restitution irrespective of the influence of neurohumoral factors and Frank-Starling law on the work of the heart. Mechanical restitution of canine heart in diastolic period starts after the end of mechanical refractory period of the heart and develops exponentially. The higher the heart rhythm the faster the speed of mechanical restitution. The higher the heart rhythm the shorter the mechanical refractory period. Mechanical refractory period of the heart is longer than bioelectrical refractory period.


Cutaneous larva migrans infection in the pediatric foot. A review and two case reports.
Cutaneous larva migrans is the result of infestation of human skin by helminth larvae, which burrow through the epidermis. This route of infestation makes the foot a typical site for origination of this infection. Children, who frequently play barefoot in locations where the most common of the helminth larvae, the dog and cat hookworms, are endemic, are at particular risk for this disorder. This article reviews the differential diagnosis of cutaneous larva migrans and current concepts in management. Two cases of related children who presented to their pediatricians with this condition are reported.


Hypnosis principles and applications: an adjunct to health care.
Hypnosis has existed since the beginning of humankind, and is a part of everyday life. It is a valuable addition to the methods and techniques available to all health care providers, as well as a safe and uncomplicated method used to enhance patient health care. It is simply a state of complete physical and mental relaxation which produces an altered state of consciousness acceptable to suggestions. It is characterized by an increased ability to produce desirable changes in habit patterns, motivation, self-image, lifestyle, and personal health.


Rapid detection of food-borne Salmonella contamination using IMBs-qPCR method based on pagC gene.
Detection of Salmonella is very important to minimize the food safety risk. In this study, the recombinant PagC protein and PagC antibody were prepared and coupled with immunomagnetic beads (IMBs) to capture Salmonella cells from pork and milk samples. And then the SYBR Green qualitative PCR was developed to detect the pathogenic Salmonella. The results showed that the PagC polyclonal antiserum is of good specificity and the capture rate of 0.1mg IMBs for Salmonella tended to be stable at the range of 70-74% corresponding to the concentrations between 101 and 104CFU/mL. The method developed demonstrated high specificity for the positive Salmonella samples when compared to non-specific DNA samples, such as Escherichia coli, Staphylococcus aureus, Yersinia enterocolitica, and Yersinia pseudotuberculosis. The limit of detection of this assay was 18CFU/mL. Detection and quantitative enumeration of Salmonella in samples of pork or milk shows good recoveries of 54.34% and 52.07%. In conclusion, the polyclonal antibody of recombinant PagC protein is effective to capture Salmonella from detected samples. The developed pagC antibody IMBs-qPCR method showed efficiency, sensitivity and specificity for 30 Salmonella detection, enabling detection within 10h, which is a promising rapid method to detect Salmonella in emergency.


Extending conceptual DFT to include additional variables: oriented external electric field.
The extension of the E = E[N, v] functional for exploring chemical reactivity in a conceptual DFT context to include external electric fields is discussed. Concentrating on the case of a homogeneous field the corresponding response functions are identified and integrated, together with the conventional response functions such as permanent dipole moment and polarizability, in an extended response function tree associated with the E = E[N, v, ε] functional. In a case study on the dihalogens F2, Cl2, Br2, I2 the sensitivity of condensed atomic charges (∂q/∂ε) is linked to the polarizability of the halogen atoms. The non-integrated (∂ρ(r)/∂ε) response function, directly related to the field induced density change, is at the basis of these features. It reveals symmetry breaking for a perpendicular field, not detectable in its atom condensed counterpart, and accounts for the induced dipole moment directly related to the molecular polarizability. The much higher sensitivity of the electronic chemical potential/electronegativity as compared to the chemical hardness is highlighted. The response of the condensed Fukui functions to a parallel electric field increases when going down in the periodic table and is interpreted in terms of the extension of the outer contours in the non-condensed Fukui function. In the case of a perpendicular field the (∂f(r)/∂ε) response function hints at stereoselectivity with a preferential side of attack which is not retrieved in its condensed form. In an application the nucleophilic attack on the carbonyl group in H2CO is discussed. Similar to the dihalogens, stereoselectivity is displayed in the Fukui function for nucleophilic attack (f+) in the case of a perpendicular electric field, and opposite to the one that would arise based on the induced density. Disentangling the expression for the evolution of the Fukui function in the presence of an electric field reveals that this difference can be traced back to local differences in the polarization or induced density between the anionic and the neutral system. This difference may be exploited, e.g. for an appropriately substituted H2CO, to generate enantioselectivity.


Meta-analysis and sensitivity analysis for multi-arm trials with selection bias.
Multi-arm trials meta-analysis is a methodology used in combining evidence based on a synthesis of different types of comparisons from all possible similar studies and to draw inferences about the effectiveness of multiple compared-treatments. Studies with statistically significant results are potentially more likely to be submitted and selected than studies with non-significant results; this leads to false-positive results. In meta-analysis, combining only the identified selected studies uncritically may lead to an incorrect, usually over-optimistic conclusion. This problem is known asbiselection bias. In this paper, we first define a random-effect meta-analysis model for multi-arm trials by allowing for heterogeneity among studies. This general model is based on a normal approximation for empirical log-odds ratio. We then address the problem of publication bias by using a sensitivity analysis and by defining a selection model to the available data of a meta-analysis. This method allows for different amounts of selection bias and helps to investigate how sensitive the main interest parameter is when compared with the estimates of the standard model. Throughout the paper, we use binary data from Antiplatelet therapy in maintaining vascular patency of patients to illustrate the methods.


Fasting improves static apnea performance in elite divers without enhanced risk of syncope.
In competitive apnea divers, the nutritional demands may be essentially different from those of, for example, endurance athletes, where energy resources need to be maximised for successful performance. In competitive apnea, the goal is instead to limit metabolism, as the length of the sustainable apneic period will depend to a great extent on minimising oxygen consumption. Many but not all elite divers fast before performing static apnea in competition. This may increase oxygen consumption as mainly lipid stores are metabolised but could also have beneficial effects on apneic duration. Our aim was to determine the effect of over-night fasting on apnea performance. Six female and seven male divers performed a series of three apneas after eating and fasting, respectively. The series consisted of two 2-min apneas spaced by 3 min rest and, after 5 min rest, one maximal effort apnea. Apneas were performed at supine rest and preceded by normal respiration and maximal inspiration. Mean (± SD) time since eating was 13 h (± 2 h 43 min) for the fasting and 1 h 34 min (± 33 min) for the eating condition (P < 0.001). Mean blood glucose was 5.1 (± 0.4) mmol/L after fasting and 5.9 (± 0.7) mmol/L after eating (P<0.01). Lung volumes were similar in both conditions (NS). For the 2-min apneas, nadir SaO2 during fasting was 95 (± 1)% and 92 (± 2)% (P < 0.001) on eating and ETCO2 was lower in the fasting condition (P < 0.01) while heart rate (HR) during apnea was 74 (± 10) bpm for fasting and 80 (± 10) bpm for eating conditions (P < 0.01). Maximal apnea durations were 4 min 41 s (± 43 s) during fasting and 3 min 51 s (± 37 s) after eating (P < 0.001), and time without respiratory contractions was 31 s (25%) longer after fasting (P < 0.01). At maximal apnea termination, SaO2 and ETCO2 were similar in both conditions (NS) and apneic HR was 63 (± 9) bpm for fasting and 70 (± 10) bpm for eating (P < 0.01). The 22% longer apnea duration after fasting with analogous end apnea SaO2 levels suggests that fasting is beneficial for static apnea performance in elite divers, likely via metabolism-limiting mechanisms. The oxygen-conserving effect of the more pronounced diving response and possibly other metabolism-limiting mechanisms related to fasting apparently outweigh the enhanced oxygen consumption caused by lipid metabolism.


Defective viral genomes: critical danger signals of viral infections.
Viruses efficiently block the host antiviral response in order to replicate and spread before host intervention. The mechanism initiating antiviral immunity during stealth viral replication is unknown, but recent data demonstrate that defective viral genomes generated at peak virus replication are critical for this process in vivo. This article summarizes the supporting evidence and highlights gaps in our understanding of the mechanisms and impact of immunostimulatory defective viral genomes generated during natural infections.