A statewide, prehospital emergency medical service selective patient spine immobilization protocol.
To evaluate the practices and outcomes associated with a statewide, emergency medical services (EMS) protocol for trauma patient spine assessment and selective patient immobilization. An EMS spine assessment protocol was instituted on July 1, 2002 for all EMS providers in the state of Maine. Spine immobilization decisions were prospectively collected with EMS encounter data. Prehospital patient data were linked to a statewide hospital database that included all patients treated for spine fracture during the 12-month period following the spine assessment protocol implementation. Incidence of spine fractures among EMS-assessed trauma patients and the correlation between EMS spine immobilization decisions and the presence of spine fractures-stable and unstable-were the primary investigational outcomes. There were 207,545 EMS encounters during the study period, including 31,885 transports to an emergency department for acute trauma-related illness. For this cohort, there were 12,988 (41%) patients transported with EMS spine immobilization. Linkage of EMS and hospital data revealed 154 acute spine fracture patients; 20 (13.0%) transported without EMS-reported spine immobilization interventions. This nonimmobilized group included 19 stable spine fractures and one unstable thoracic spine injury. The protocol sensitivity for immobilization of any acute spine fracture was 87.0% (95% confidence interval [CI], 81.7-92.3) with a negative predictive value of 99.9% (95% CI, 99.8-100). The use of this statewide EMS spine assessment protocol resulted in one nonimmobilized, unstable spine fracture patient in approximately 32,000 trauma encounters. Presence of the protocol affected a decision not to immobilize greater than half of all EMS-assessed trauma patients.


Urinary parabens and polyaromatic hydrocarbons independent of health conditions are associated with adult emotional support needs: USA NHANES, 2005-2008.
Everyone needs emotional support at some point in life, but the needs might not always be met. The present study was aimed to investigate the prevalence of unmet needs of emotional support in adults and to identify social, environmental and health attributes in a national and population-based setting in recent years. Data was retrieved from the US National Health and Nutrition Examination Surveys, 2005-2008, including demographics, blood pressure readings, self-reported emotional support needs in the last 12 months, self-reported ever health conditions and urinary environmental chemical concentrations. Statistical analyses included chi-square test, t test, survey-weighted logistic regression modeling and population attributable risk (PAR) estimation. Of 6733 American adults aged 40-80, 1273 (21.0 %) needed more emotional support in the past year. They tended to be aged 40-60, female, Mexican American, other Hispanic, education less than high school, or poverty income ratio 5+. People with higher levels of butyl paraben, ethyl paraben, methyl paraben, 1-hydroxynaphthalene, 2-hydroxynaphthalene, or 9-hydroxyfluorene (but not heavy metals, arsenic, phenols, phthalates, pesticides, or phytoestrogens) or historical diabetes, asthma, arthritis, stroke, thyroid disorder, chronic bronchitis, sleep complaint/disorder, or trouble seeing needed more emotional support. Significant risk associations from environmental chemicals mentioned above have remained after adjusting for historical health conditions as potential mediators. This is the first time examining prevalence of the unmet emotional support in adults and identifying the social, environmental and health attributes. Removal of parabens and polyaromatic hydrocarbons and increasing healthcare for people with health conditions to accommodate emotional support should be considered.


The SEPS1 G-105A polymorphism is associated with risk of spontaneous preterm birth in a Chinese population.
Inflammation plays an important role in the etiology and pathophysiology of spontaneous preterm birth (SPTB), and selenoprotein S (SEPS1) is involved in regulating the inflammatory response. Recently the G-105A promoter polymorphism in SEPS1 was shown to increase pro-inflammatory cytokine expression. We examined whether this functional polymorphism was related to the risk of SPTB in a Chinese population. We also examined the impact of premature rupture of membranes (PROM) on susceptibility to SPTB. The SEPS1 G-105A polymorphism was genotyped in 569 preterm singleton neonates and 673 term neonates by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. χ (2) tests and logistic regression analyses were used to calculate the odds ratios (ORs) and 95% confidence intervals (95% CIs). We observed that, compared with the GG genotype, -105A positive genotypes (GA + AA genotypes) were associated with significantly increased susceptibility to SPTB (adjusted OR, 1.87; 95% CI, 1.36-2.57; P<0.001). The -105A positive genotypes were also significantly associated with increased susceptibility to SPTB, both in the patients with PROM (adjusted OR, 2.65; 95% CI, 1.73-4.03; P<0.001) and in those without PROM (adjusted OR, 1.56; 95% CI, 1.09-2.24; P = 0.015). The -105A positive genotypes were also significantly associated with increased susceptibility to SPTB between extremely preterm neonates and controls (adjusted OR, 4.46; 95% CI, 1.86-10.73; P = 0.002) and between moderately preterm neonates and controls (adjusted OR, 1.76; 95% CI, 1.25-2.47; P = 0.001). Our findings suggest that the SEPS1 G-105A polymorphism contributes to the risk of developing SPTB in a Chinese population.


The effectiveness of lifestyle triple P in the Netherlands: a randomized controlled trial.
Lifestyle Triple P is a general parenting intervention which focuses on preventing further excessive weight gain in overweight and obese children. The objective of the current study was to assess the effectiveness of the Lifestyle Triple P intervention in the Netherlands. We used a parallel randomized controlled design to test the effectiveness of the intervention. In total, 86 child-parent triads (children 4-8 years old, overweight or obese) were recruited and randomly assigned (allocation ratio 1:1) to the Lifestyle Triple P intervention or the control condition. Parents in the intervention condition received a 14-week intervention consisting of ten 90-minute group sessions and four individual telephone sessions. Primary outcome measure was the children's body composition (BMI z-scores, waist circumference and skinfolds). The research assistant who performed the measurements was blinded for group assignment. Secondary outcome measures were the children's dietary behavior and physical activity level, parenting practices, parental feeding style, parenting style, and parental self-efficacy. Outcome measures were assessed at baseline and 4 months (short-term) and 12 months (long-term) after baseline. Multilevel multiple regression analyses were conducted to determine the effect of the intervention on primary and secondary outcome measures. No intervention effects were found on children's body composition. Analyses of secondary outcomes showed positive short-term intervention effects on children's soft-drink consumption and parental responsibility regarding physical activity, encouragement to eat, psychological control, and efficacy and satisfaction with parenting. Longer-term intervention effects were found on parent's report of children's time spent on sedentary behavior and playing outside, parental monitoring food intake, and responsibility regarding nutrition. Although the Lifestyle Triple P intervention showed positive effects on some parent reported child behaviors and parenting measures, no effects were visible on children's body composition or objectively measured physical activity. Several adjustments of the intervention content are recommended, for example including a booster session. Nederlands Trial Register NTR 2555.


Dermatofibrosarcoma Protuberans: An Immunomarker Study of 57 Cases That Included Putative Mesenchymal Stem Cell Markers.
Dermatofibrosarcoma protuberans (DFSP) is a low-grade fibroblastic sarcoma with a superficial location that has been suggested to potentially be a type of mesenchymal stem cell tumor. We studied the expression of various immunomarkers, including putative stem cell markers, in a series of 57 DFSPs including variants, and 12 dermatofibromas (DFs). CD105, a mesenchymal stem cell marker, was weakly expressed in 24 DFSPs, whereas other stem cell markers, including CD133, ALK-1, and Oct3/4, were completely negative in all samples. The expression rates of CD105 and CD34 were significantly higher in DFSP (42% and 93%) than in DF (0% and 17%), and CD10 and D2-40 were significantly lower in DFSP (40% and 3.5%) than in DF (100% and 33%), respectively. CD99, CD117, PDGFB, and PDGFRβ expression was comparable between the groups. CD105 mesenchymal cells were not observed in non-neoplastic dermis. In summary, we did not obtain sufficient immunohistochemical evidence to support the DFSP as a cutaneous mesenchymal stem cell tumor. CD34 alone was the most consistent marker of DFSP, irrespective of its variants. Because CD34 non-neoplastic mesenchymal cells were distributed in a location similar to that of DFSP, we suggest that DFSP might have originated from CD34 mesenchymal cells in the dermis.


[Promoting nursing competitiveness: introduction to the digital divide].
Increasingly sophisticated information technology (IT) has widened the gap (the so-called "digital divide") between those with effective access to IT resources and those without. Problems related to the digital divide exist in every country. In addition to level of familiarity with technology, the divide can also be influenced by factors of race, gender, age, education, economic status and area of residence. The digital divide may be ameliorated through technology innovations in terms of access to information, information application and information literacy. As IT is an increasingly significant component of modern healthcare, it may be expected that the "width" of the potential gap widens as IT applications increase in sophistication. Nursing professionals must keep abreast of advancing technologies in order to narrow the digital divide. To cope with this challenge, nursing professionals should enhance their understanding of new technologies beyond what is taught in formal education curricula. This knowledge enhancement may be attained through self learning or on-the-job training in nursing informatics. Content could cover hospital information system (IS) usage, security, applications and web access. This will improve the ability of nursing staff to face the current IT challenge.


Association between Neuropathic Pain and Depression: Focusing on the Transcranial Magnetic Stimulation As a Promising Treatment Approach.
Neuropathic pain (NP) affects approximately 7% of the general population and is often accompanied by depressive symptoms with up to 85% of NP patients are suffering from comorbid depression (CD). The noninvasive neuromodulation technique of transcranial magnetic stimulation (TMS) is an established proven clinically effective nonpharmacological treatment for depression, and considered a highly promising option also for reducing the burden of NP by relieving pain perception and increasing patients' quality of life. In this article, we systematically review the various clinical protocols used in TMS treatments in patients suffering from NP and comorbid depression. Using Scopus, Elsevier, and PubMed databases, our keyword search identified 639 articles, of which 22 were selected for detailed analysis based on the inclusion criteria and in consideration of the heterogeneous study design of the majority of small trials. We evaluated the clinical efficacy in NP and comorbid depression, in relation to various TMS protocol parameters including coil type, target brain area, locus of increased evoked motor potential, amplitude of stimulation, duration of session, number of sessions per day/month, as well as inter-session-intervals, number and frequency of trains, and number and frequency of pulses. The most effective TMS protocols for treating comorbid NP and depression, as marked by decreased pain and depression scores proved to entail figure-of-8 coils targeting the primary motor area (M1), and applying at least ten daily rTMS sessions using high frequency stimulation (10-20 Hz) with a sub threshold intensity of 80-90% RMT and a total number of pulses of at least 1500 per session. Performing an additional maintenance phase after the acute treatment phase may strengthen and prolong the therapeutic effects of rTMS. Our database analysis suggests that a specific combination of TMS parameters is most effective for treating NP and comorbid depression. Although results are promising, the heterogeneity within the literature is such that many underpowered studies contribute rather little to the outcome, as evident by our inclusion / exclusion analysis. Moreover, we see a need for consensus on clinical protocols and inclusion of much larger clinical samples. Furthermore, we conclude that future research should entail advanced TMS procedures with multiple brain region stimulation (sequential or concurrent), and address issues of TMS maintenance and improved coil engineering for targeting deeper structures.


Site-Specific Ubiquitination of Tau Amyloids Promoted by the E3 Ligase CHIP.
Post-translational modifications of Tau are emerging as key players in determining the onset and progression of different tauopathies such as Alzheimer's disease, and are recognized to mediate the structural diversity of the disease-specific Tau amyloids. Here we show that the E3 ligase CHIP catalyzes the site-specific ubiquitination of Tau filaments both in vitro and in cellular models, proving that also Tau amyloid aggregates are direct substrate of PTMs. Transmission electron microscopy and mass spectrometry analysis on ubiquitin-modified Tau amyloids revealed that the conformation of the filaments restricts CHIP-mediated ubiquitination to specific positions of the repeat domain, while only minor alterations in the structure of the fibril core were inferred using seeding experiments in vitro and in a cell-based tauopathy model. Overexpression of CHIP significantly increased the ubiquitination of exogenous PHF, proving that the ligase can interact and modify Tau aggregates also in a complex cellular environment.


Pathologic detection of occult metastases in regional lymph nodes in patients with head and neck cancer.
Squamous carcinomas of the head and neck region are exceedingly common problems in the routine practice of head and neck tumour surgery. Well-defined treatment protocols have evolved to manage patients afflicted with such tumours. This article explores the role of the hospital pathologist in the detection of occult metastases. The conventional approach to evaluation of cervical nodes from a neck dissection is reviewed, and then the potential utility of more recently developed diagnostic approaches (such as immunohistochemistry and polymerase chain reaction) is explored.


[Routes of salmonellosis spread beyond the confines of a swine-breeding farm complex].
Salmonella contamination of swine and morbidity rates among the workers of swine-breeding complexes and the members of their families, as well as among the population inhabiting the zone of possible influence rendered by such complexes on the environment, have been studied as exemplified by 4 complexes for large-scale swine breeding, differing in their technology of swine raising and fattening, their systems of the purification and utilization of manure-containing sewage. Besides, the influence of the raw meat (pork) and meat products, contaminated with salmonellae, sold in town, on salmonellosis morbidity among the urban population has been analyzed. The study has revealed that salmonellae are spread from swine-breeding complexes with the fluid and solid fractions of manure-containing sewage, as well as with the animals supplied to the meat-packing plant; the contamination of the workers of swine-breeding complexes with salmonellae becomes possible due to the low culture of the production and to the breach of sanitary and epidemic-control regulations and the contamination of the population occurs through meat and meat products.


"You've Gotta Be That Tough Crust Exterior Man": Depression and Suicide in Rural-Based Men.
Suicide rates in Canada are highest among rural men. Drawing on photovoice interviews with 13 women and two men living in a small rural Canadian town who lost a man to suicide, we inductively derived three themes to describe how contextual factors influence rural men's experiences of depression and responses to suicidal thoughts: (a) hiding depression and its cause, (b) manly self-medicating, and (c) mobilizing prevention. Further discussed is how gender relations and ideals of masculinity within rural milieu can inhibit men's acknowledgment of and help seeking for mental illness issues. Participants strongly endorsed a multifaceted approach to the destabilization of dominant ideals of masculinity that likely contribute to depression and suicide in rural men.


Longitudinal Changes in Victimized Youth's Social Anxiety and Solitary Behavior.
This investigation's aims were to assess normative trends in social anxiety and preference for solitude by gender from early childhood to late adolescence and examine the associations among the timing and duration of peer victimization and patterns of continuity or change in social anxiety and preference for solitude across this age period. A sample of 383 children (193 girls) was followed from kindergarten (Mage = 5.50) through grade 12 (Mage = 17.89), and measures of peer victimization, social anxiety, and preference for solitude were repeatedly administered across this epoch. Five victimization trajectory subtypes emerged, capturing individual differences in victimization frequency and continuity (i.e., high-chronic, moderate-emerging, early victims, low victims, and non-victims). Results supported the conclusion that chronic victimization, a key stressor in children's peer environments, plays a different role in the development of social anxiety and preference for solitude. Whereas chronic victimization was associated with the maintenance of social anxiety, it accompanied gains in preference for solitude. The findings provide a more complete account of the overall prevalence, stability, and developmental course of victimized youths' social anxiety and preference for solitude than has been reported to date.


Identification and characterization of putative stem cells in the adult pig ovary.
Recently, the concept of 'neo-oogenesis' has received increasing attention, since it was shown that adult mammals have a renewable source of eggs. The purpose of this study was to elucidate the origin of these eggs and to confirm whether neo-oogenesis continues throughout life in the ovaries of the adult mammal. Adult female pigs were utilized to isolate, identify and characterize, including their proliferation and differentiation capabilities, putative stem cells (PSCs) from the ovary. PSCs were found to comprise a heterogeneous population based on c-kit expression and cell size, and also express stem and germ cell markers. Analysis of PSC molecular progression during establishment showed that these cells undergo cytoplasmic-to-nuclear translocation of Oct4 in a manner reminiscent of gonadal primordial germ cells (PGCs). Hence, cells with the characteristics of early PGCs are present or are generated in the adult pig ovary. Furthermore, the in vitro establishment of porcine PSCs required the presence of ovarian cell-derived extracellular regulatory factors, which are also likely to direct stem cell niche interactions in vivo. In conclusion, the present work supports a crucial role for c-kit and kit ligand/stem cell factor in stimulating the growth, proliferation and nuclear reprogramming of porcine PSCs, and further suggests that porcine PSCs might be the culture equivalent of early PGCs.


GammaPlan-Leksell Gamma Knife radiosurgery treatment planning verification method.
This work provides a method for an independent check of Gamma Knife GammaPlan radiosurgery calculations, named the spherical approximation method or SAM. Based on skull dimension measurements, the treated volume of the head is modeled as a sphere of radius R. With this approximation, an analytical solution for fast ray tracing of the path length, for each of the 201 beamlets, of the Gamma Knife helmet collimator was possible. The dose rate at the focus of a single shot is the sum of the contributions of all active beamlets adjusted for both the collimator factor and attenuation. For an arbitrary point, the dose rate is derived at the beamlet level from the focus values adjusted for the new path length attenuation and the appropriate collimators' off-axis profiles. The sum over all beamlets' contributions gives the dose rate at that particular point. At the single shot level, SAM independent check results agree with the GammaPlan for patient calculations to better than +/-6% and, as expected, in spherical phantoms the agreements improve to better than +/-1.0%. For an arbitrary point, multi-shot procedure, the agreement is better than +/-3% and +/-1.5, respectively.


Can water-based EEG caps record robust movement-related cortical potentials (MRCPs) for single and multiple joint movements?
Movement-related cortical potentials (MRCPs) have been used extensively in the literature to develop rehabilitation interventions for people with neurological conditions. In this pilot study, we recorded and extracted MRCPs using a water-based cap to determine whether water-based caps are effective. Five participants took part in the study, where their EEG was recorded during single-joint (dorsiflexion) and multiple-joint (sit-to-stand) lower limb movements. We were able to see clear MRCPs for both movement types with an average peak negativity (PN) latency of +22ms for dorsiflexion and +218ms for sit-to-stand. Similarly, the PN amplitude of -14.89μV was recorded for dorsiflexion and -43.54μV for sit-to-stand. These values were comparable to the values reported in studies using gel-based caps. Based on these results, water-based caps can be an effective way to produce robust MRCPs, which can have many advantages over gel-based caps.Clinical Relevance- The study provides clinicians with a more viable method of collecting EEGs and extracting MRCPs, thus allowing them to design more robust interventions for people with neurological disorders.


Diabetes mellitus in Egypt: glycaemic control and microvascular and neuropathic complications.
We performed a cross-sectional, population-based survey of persons 20 years of age and older living in Cairo and surrounding rural villages. The purpose was to describe glycaemic control and the prevalence of microvascular and neuropathic complications among Egyptians with diagnosed diabetes, previously undiagnosed diabetes, impaired glucose tolerance, and normal glucose tolerance. A total of 6052 households were surveyed. The response rate was 76% for the household survey and 72% for the medical examination. Among people with previously diagnosed diabetes, mean haemoglobin A1c, was 9.0%. Forty-two per cent had retinopathy, 21% albuminuria, and 22% neuropathy. Legal blindness was prevalent (5%) but clinical nephropathy (7%) and foot ulcers (1%) were uncommon in persons with diagnosed diabetes. Among people with diagnosed diabetes, microvascular and neuropathic complications were associated with hyperglycaemia. Retinopathy was also associated with duration of diabetes; albuminuria with hypertension and hypercholesterolaemia; and neuropathy with age, female sex, and hypercholesterolaemia. Albuminuria was as common in people with previously undiagnosed diabetes (22%) as those with diagnosed disease (21%). Mean haemoglobin A1c was lower (7.8%) and retinopathy (16%) and neuropathy (14%) were less prevalent in people with previously undiagnosed disease. Ocular conditions, blindness, and neuropathy were prevalent in the non-diabetic population. The microvascular and neuropathic complications of diabetes are a major clinical and public health problem in Egypt.


The effect of incidental hypothermia on elderly surgical patients.
Elderly surgical patients are especially susceptible to incidental hypothermia. Thermoregulatory mechanisms and cardiopulmonary systems are limited in recovery potential. To prevent postoperative shock secondary to decreased cardiac output an hypoxia, temperature should be carefully monitored with vital signs during and after surgery.


Maternal HCV infection is associated with intrauterine fetal growth disturbance: A meta-analysis of observational studies.
Since the evidence regarding the association between maternal hepatitis C virus (HCV) infection and impaired intrauterine fetal growth had not been conclusive, the aim of the present study was to evaluate the risk of maternal HCV infection in association with intrauterine fetal growth restriction (IUGR) and/or low birth weight infants (LBW). We performed an extensive literature search of PubMed, MEDLINE, and EMBASE through December 1, 2015. The odds ratios (ORs) of HCV infection and IUGR/LBW were calculated and reported with 95% confidence intervals (95% CIs). Statistical analysis was performed using RevMen 5.3 and Stata 10.0. Seven studies involving 4,185,414 participants and 5094 HCV infection cases were included. Significant associations between HCV infection and IUGR (OR = 1.53, 95% CI: 1.40-1.68, fixed effect model) as well as LBW were observed (OR = 1.97, 95% CI: 1.43-2.71, random effect model). The results still indicated consistencies after adjusting for multiple risk factors which could affect fetal growth, including maternal age, parity, maternal smoking, alcohol abuse, drugs abuse, coinfected with HBV/HIV and preeclampsia. Our findings suggested that maternal HCV infection was significantly associated with an increased risk of impaired intrauterine fetal growth. In clinical practice, a closer monitoring of intrauterine fetal growth by a series of ultrasound might be necessary for HCV-infected pregnant population.


A Feasibility Study of IMRT of Lung Cancer Using Gafchromic EBT3 Film.
Intensity modulated radiation therapy (IMRT) is an advanced method for delivery of three dimensional therapies, which provides optimal dose distribution with giving multiple nonuniform fluency to the patient. The complex dose distribution of IMRT should be checked to ensure that the accurate dose is delivered. Today, film dosimetry is a powerful tool for radiotherapy treatment Quality Assurance (QA) and a good method to verify dose distribution in phantoms. This study aimed to evaluate the accuracy of IMRT treatment planning system, Prowess Panther® software, with Gafchromic EBT3 films in a inhomogeneity phantom. The IMRT plan was generated by Prowess Panther® treatment planning system (TPS) version 5.2 on a inhomogeneity phantom, then it was irradiated by ONCOR linear accelerator (Linac) with 6 (MV) photon beam energy. The Gafchromic EBT3 film located between the phantom has measured the dose distribution. To compare between TPS calculated doses and film measured doses, Gamma criteria 3%/3 mm, 4%/4 mm, 5%/5 mm, 6%/6 mm and 7%/7 mm Dose Difference (DD) and Distance to Agreement (DTA), respectively were used. Gammas passing rates for PTV are obtained 67.5% for 3%/3mm, 78.8% for 4%/4mm, 86.3% for 5%/5mm, 91.2% for 6%/6mm and 94.3% for 7%/7mm and for organs at risk is 72.4% for 3%/3mm, 82.8% for 4%/4mm, 89.8% for 5%/5mm, 93.3% for 6%/6mm and 95.4% for 7%/7mm (respectively DD/DTA). By increasing the range of criteria the capability increased. The results show that the use of EBT3 film in a inhomogeneity phantoms allows us to evaluate the dose differences between the EBT3 measured dose distribution and TPS calculated dose distribution .Hence, a result Prowess Panther® TPS can be used for IMRT technique treatment.


Long-term neuroprotective effect of postischemic hypothermia in a neonatal rat model of severe hypoxic ischemic encephalopathy: a comparative study on the duration and depth of hypothermia.
It is not known whether deeper or longer hypothermia (HT) can achieve better neuroprotection against hypoxic ischemic encephalopathy (HIE) in neonates. To compare the neuroprotective effects of different durations and temperatures of postischemic HT in neonatal rats with severe HIE, 7-d-old rats were subjected to the Rice-Vannucci model for 150 min hypoxia. Only the rats with identified brain lesions in diffusion-weighted MRI were assigned to normothermia (NT, 36° C/48 h) or four HT (HT-30° C/48 h; HT-30° C/24 h; HT-33° C/48 h; and HT-33° C/24 h) groups. H-magnetic resonance spectroscopy (H-MRS) and T2-weighted MRI were obtained serially, and functional studies were performed. HT groups showed significantly greater residual hemispheric volume and better rotarod and cylinder tests than did the NT group at 5 wk postischemia. HT groups also showed lower lactate-plus-lipid level in H-MRS than did the NT group at 7 d postischemia. All of these outcome variables, however, did not differ among the 4 HT subgroups, despite a trend toward greater residual brain volume in the 48-h HT versus 24-h HT subgroups. In conclusion, neither reducing the target temperature from 33 to 30° C nor prolonging the duration from 24 to 48 h produced further improvements in neurologic outcomes in neonatal rat with HIE.


Four principles that lead to greater productivity.
A healthcare organization's productivity review should cut across department lines, similar to the way a patient moves through a hospital. A periodic system-wide analysis includes defining activities performed, determining the mix of skills involved, identifying duplicated efforts, and analyzing why and how certain activities are triggered. To help ensure success, productivity should be treated as a management philosophy and as part of strategic planning.


N-acetylglutamate and N-acetylaspartate in soybeans (Glycine max L.), maize (Zea mays L.), [corrected] and other foodstuffs.
N-Acetylglutamate (NAG) and N-acetylaspartate (NAA) are amino acid derivatives with reported activities in a number of biological processes. However, there is no published information on the presence of either substance in foodstuffs. We developed a method for extracting and quantifying NAG and NAA from soybean seeds and maize grain using ultra performance liquid chromatography-electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS). The lower limit of quantification for both NAG and NAA was 1 ng/mL. The method was then utilized to quantify NAG and NAA in other foodstuffs (fruits, vegetables, meats, grains, milk, coffee, tea, cocoa, and others). Both NAG and NAA were present in all of the materials analyzed. The highest concentration of NAG was found in cocoa powder. The highest concentration of NAA was found in roasted coffee beans. Both NAG and NAA were found at quantifiable concentrations in all foods tested indicating that these two acetylated amino acids are common components of the human diet.


Microfluidic PicoArray synthesis of oligodeoxynucleotides and simultaneous assembling of multiple DNA sequences.
Large DNA constructs of arbitrary sequences can currently be assembled with relative ease by joining short synthetic oligodeoxynucleotides (oligonucleotides). The ability to mass produce these synthetic genes readily will have a significant impact on research in biology and medicine. Presently, high-throughput gene synthesis is unlikely, due to the limits of oligonucleotide synthesis. We describe a microfluidic PicoArray method for the simultaneous synthesis and purification of oligonucleotides that are designed for multiplex gene synthesis. Given the demand for highly pure oligonucleotides in gene synthesis processes, we used a model to improve key reaction steps in DNA synthesis. The oligonucleotides obtained were successfully used in ligation under thermal cycling conditions to generate DNA constructs of several hundreds of base pairs. Protein expression using the gene thus synthesized was demonstrated. We used a DNA assembly strategy, i.e. ligation followed by fusion PCR, and achieved effective assembling of up to 10 kb DNA constructs. These results illustrate the potential of microfluidics-based ultra-fast oligonucleotide parallel synthesis as an enabling tool for modern synthetic biology applications, such as the construction of genome-scale molecular clones and cell-free large scale protein expression.


Can obtaining informed consent alter self-reported drinking behaviour? A methodological experiment.
Informed consent is the foundation of the ethical conduct of health research. Obtaining informed consent may unwittingly interfere with the data collected in research studies, particularly if they concern sensitive behaviours that participants are requested to report on. To address gaps in evidence on such research participation effects, we conducted a methodological experiment evaluating the impact of the informed consent procedure on participants' reporting behaviour, specifically on their self-report of drinking behaviour as measured by Alcohol Use Disorder Identification Test (AUDIT). A two arm double blinded randomised controlled trial was used. University students present in London student unions at the time of recruitment were contacted in two phases (an initial run-in phase followed by the main phase). Those providing positive responses to verbal questions: 1) "are you a student?"; 2) "do you drink alcohol?"; 3) "would you like to take part in a brief health survey, which will take around 5 minutes?" were recruited. Participants received one of the two envelopes by chance, with the sequence generated by an online random sequence generator. One contained the participant information sheet, informed consent form and the AUDIT questionnaire (the intervention group), while the other contained only the AUDIT questionnaire (the comparator group). The primary outcome was the mean AUDIT score, which ranges from 0 to 40. The secondary outcome was the proportion of participants in each group scoring 8 or more on the AUDIT, the threshold score for hazardous and harmful drinking warranting intervention. A total of 380 participants were successfully recruited, resulting in 190 participants in each group, of which 378 were included in the final analysis. There is no evidence of any statistically significant difference between groups in the primary outcome. A statistically significant difference in the secondary outcome was found in the run-in phase only, and not in the main phase, or overall. Moreover, between-group outcome differences between the two phases suggest an important influence of setting on reporting behaviour. There is no strong evidence that completion of informed consent itself alters self-reporting behaviour with regards to alcohol, though the effect of settings needs to be further studied.


Broadly directed SARS-CoV-2-specific CD4+ T cell response includes frequently detected peptide specificities within the membrane and nucleoprotein in patients with acute and resolved COVID-19.
The aim of this study was to define the breadth and specificity of dominant SARS-CoV-2-specific T cell epitopes using a comprehensive set of 135 overlapping 15-mer peptides covering the SARS-CoV-2 envelope (E), membrane (M) and nucleoprotein (N) in a cohort of 34 individuals with acute (n = 10) and resolved (n = 24) COVID-19. Following short-term virus-specific in vitro cultivation, the single peptide-specific CD4+ T cell response of each patient was screened using enzyme linked immuno spot assay (ELISpot) and confirmed by single-peptide intracellular cytokine staining (ICS) for interferon-γ (IFN-γ) production. 97% (n = 33) of patients elicited one or more N, M or E-specific CD4+ T cell responses and each patient targeted on average 21.7 (range 0-79) peptide specificities. Overall, we identified 10 N, M or E-specific peptides that showed a response frequency of more than 36% and five of them showed high binding affinity to multiple HLA class II binders in subsequent in vitro HLA binding assays. Three peptides elicited CD4+ T cell responses in more than 55% of all patients, namely Mem_P30 (aa146-160), Mem_P36 (aa176-190), both located within the M protein, and Ncl_P18 (aa86-100) located within the N protein. These peptides were further defined in terms of length and HLA restriction. Based on this epitope and restriction data we developed a novel DRB*11 tetramer (Mem_aa145-164) and examined the ex vivo phenotype of SARS-CoV-2-specific CD4+ T cells in one patient. This detailed characterization of single T cell peptide responses demonstrates that SARS-CoV-2 infection universally primes a broad T cell response directed against multiple specificities located within the N, M and E structural protein.


Telomere lengths, pulmonary fibrosis and telomerase (TERT) mutations.
Telomerase is an enzyme that catalyzes the addition of nucleotides on the ends of chromosomes. Rare loss of function mutations in the gene that encodes the protein component of telomerase (TERT) have been described in patients with idiopathic pulmonary fibrosis (IPF). Here we examine the telomere lengths and pulmonary fibrosis phenotype seen in multiple kindreds with heterozygous TERT mutations. We have identified 134 individuals with heterozygous TERT mutations from 21 unrelated families. Available medical records, surgical lung biopsies and radiographs were evaluated retrospectively. Genomic DNA isolated from circulating leukocytes has been used to measure telomere lengths with a quantitative PCR assay. We find that telomere lengths of TERT mutation carriers decrease in an age-dependent manner and show progressive shortening with successive generations of mutation inheritance. Family members without TERT mutations have a shorter mean telomere length than normal, demonstrating epigenetic inheritance of shortened telomere lengths in the absence of an inherited TERT mutation. Pulmonary fibrosis is an age-dependent phenotype not seen in mutation carriers less than 40 years of age but found in 60% of men 60 years or older; its development is associated with environmental exposures including cigarette smoking. A radiographic CT pattern of usual interstitial pneumonia (UIP), which is consistent with a diagnosis of IPF, is seen in 74% of cases and a pathologic pattern of UIP is seen in 86% of surgical lung biopsies. Pulmonary fibrosis associated with TERT mutations is progressive and lethal with a mean survival of 3 years after diagnosis. Overall, TERT mutation carriers demonstrate reduced life expectancy, with a mean age of death of 58 and 67 years for males and females, respectively. A subset of pulmonary fibrosis, like dyskeratosis congenita, bone marrow failure, and liver disease, represents a "telomeropathy" caused by germline mutations in telomerase and characterized by short telomere lengths. Family members within kindreds who do not inherit the TERT mutation have shorter telomere lengths than controls, demonstrating epigenetic inheritance of a shortened parental telomere length set-point.


Helminth component community of the loggerhead sea turtle, Caretta caretta, from Madeira Archipelago, Portugal.
The helminth fauna of pelagic-stage loggerhead sea turtles, Caretta caretta, is still poorly known. Here, we describe the helminth-component community of healthy, free-ranging juvenile loggerhead sea turtles captured in the waters around Madeira Island, Portugal. Fifty-seven were used in this study. The esophagus, stomach, intestine, liver, gallbladder, spleen, kidneys, trachea, bronchi, urinary bladder, heart, left and right aortas, and coelomic cavity were macroscopically inspected; organs and tissues were removed and washed through a sieve. A search for parasites was made using a stereoscopic microscope; recovered parasites were fixed and stored in 70% alcohol until staining and identification. Prevalence, mean intensity, and mean abundance values were recorded. In total, 156 parasite specimens belonging to 9 species were found: nematodes included Anisakis simplex s.l. (larvae) and an unidentified species; digenetic trematodes present were Enodiotrema megachondrus, Rhytidodes gelatinosus, Pyelosomum renicapite, and Calycodes anthos; acanthocephalans included Bolbosoma vasculosum and Rhadinorhynchus pristis; a single cestode, Nybelinia sp., was present. Parasite infections were found to have both low prevalences and intensities. Possible reasons for this include the oligotrophic conditions of the pelagic habitat around Madeira; a 'dilution effect' because of the vastness of the area; and the small size, and thus ingestion rate, of the turtles. Results are discussed in terms of the various turtle populations that may use the waters surrounding Madeira. This work provides valuable information on the parasite fauna of a poorly known stage in the life of loggerhead sea turtles, thereby filling a fundamental gap with regard to features of the parasite fauna in this species.


Regulation of low temperature stress in plants by microRNAs.
Low temperature is one of the most common environmental stresses that seriously affect the growth and development of plants. However, plants have the plasticity in their defence mechanisms enabling them to tolerate and, sometimes, even survive adverse environmental conditions. MicroRNAs (miRNAs) are small non-coding RNAs, approximately 18-24 nucleotides in length, and are being increasingly recognized as regulators of gene expression at the post-transcriptional level and have the ability to influence a broad range of biological processes. There is growing evidence in the literature that reprogramming of gene expression mediated through miRNAs is a major defence mechanism in plants enabling them to respond to stresses. To date, numerous studies have established the importance of miRNA-based regulation of gene expression under low temperature stress. Individual miRNAs can modulate the expression of multiple mRNA targets, and, therefore, the manipulation of a single miRNA has the potential to affect multiple biological processes. Numerous functional studies have attempted to identify the miRNA-target interactions and have elaborated the role of several miRNAs in cold-stress regulation. This review summarizes the current understanding of miRNA-mediated modulation of the expression of key genes as well as genetic and regulatory pathways, involved in low temperature stress responses in plants.


A polarization-modulation method for the near-field mapping of laterally grown InGaN samples.
Epitaxial Laterally overgrown (ELOG) InGaN materials are investigated using a polarization modulated scanning near-field optical microscope. The authors found that luminescence has spatial inhomogeneities and it is partially polarized. Near-field photoluminescence shows polarization phase fluctuation up to 45 degrees over adjacent domains. These results point toward the existence of asymmetries in carrier confinement due to structural anisotropic strain within the framework of the ELOG structure.


Electrolytic lesions within central complex neuropils of the cockroach brain affect negotiation of barriers.
Animals must negotiate obstacles in their path in order to successfully function within natural environments. These actions require transitions from walking to other behaviors, many of which are more involved than simple reflexes. For these behaviors to be successful, insects must evaluate objects in their path and then use that information to change posture or re-direct leg movements. Some of this control may occur within a region of the brain known as the central complex (CC). We used discrete electrolytic lesions to examine the role of certain sub-regions of the CC in various obstacle negotiation behaviors. We found that cockroaches with lesions to the protocerebral bridge (PB) and ellipsoid body (EB) exhibit abnormalities in turning and dealing with shelf-like objects; whereas, individuals with lesions to the fan-shaped body (FB) and lateral accessory lobe (LAL), exhibit abnormalities of those behaviors as well as climbing over blocks and up walls to a horizontal plane. Abnormalities in block climbing include decreased success rate, changes in climbing strategy, and delayed response to the block. Increases in these abnormal behaviors were significant in individuals with lesions to the FB and LAL. Although turning abnormalities are present in individuals with lesions to the LAL, EB and the lateral region of the FB, there are some differences in how these deficits present. For instance, the turning deficits seen in individuals with lateral FB lesions only occurred when turning in the direction opposite to the side of the brain on which the lesion occurred. By contrast, individuals with lesions to the EB and LAL exhibited turning abnormalities in both directions. Lesions in the medial region of the FB did not result in directional turning deficits, but in abnormalities in block climbing.


Italian Recommendations for Placental Transfusion Strategies.
At delivery, if the cord is not clamped, blood continues to pass from the placenta to the newborn during the first minutes of life, allowing the transfer of 25-35 ml/kg of placental blood to the newborn, depending on gestational age, the timing of cord clamping, the position of the infant at birth, the onset of respiration, and administration of uterotonics to the mother. However, deriving benefits from delayed cord clamping (DCC) are not merely related to placental-to-fetal blood transfusion; establishing spontaneous ventilation before cutting the cord improves venous return to the right heart and pulmonary blood flow, protecting the newborn from the transient low cardiac output, and systemic arterial pressure fluctuations. Recent meta-analyses showed that delayed cord clamping reduces mortality and red blood cell transfusions in preterm newborns and increases iron stores in term newborns. Various authors suggested umbilical cord milking (UCM) as a safe alternative when delayed cord clamping is not feasible. Many scientific societies recommend waiting 30-60 s before clamping the cord for both term and preterm newborns not requiring resuscitation. To improve the uptake of placental transfusion strategies, in 2016 an Italian Task Force for the Management of Umbilical Cord Clamping drafted national recommendations for the management of cord clamping in term and preterm deliveries. The task force performed a detailed review of the literature using the GRADE methodological approach. The document analyzed all clinical scenarios that operators could deal with in the delivery room, including cord blood gas analysis during delayed cord clamping and time to cord clamping in the case of umbilical cord blood banking. The panel intended to promote a more physiological and individualized approach to cord clamping, specifically for the most preterm newborn. A feasible option to implement delayed cord clamping in very preterm deliveries is to move the neonatologist to the mother's bedside to assess the newborn's clinical condition at birth. This option could safely guarantee the first steps of stabilization before clamping the cord and allow DCC in the first 30 s of life, without delaying resuscitation. Contra-indications to placental transfusion strategies are clinical situations that may endanger mother 's health and those that may delay immediate newborn's resuscitation when required.


[Impact of health care reform on human resources and employment management].
According to those in charge of health sector reform, human resources are the key component of health sector reform processes and offer health services their greatest competitive advantage. With the help of the Observatory for Human Resources within Health Sector Reform promoted by the Pan American Health Organization and other groups, countries of the Region of the Americas have now begun to gather, in a methodical fashion, tangible evidence of the decisive importance of human resources within health sector reform initiatives and particularly of the impact of these initiatives on health personnel. This mutual influence is the main theme of this article, which explores the most disturbing aspects of health sector reform from a human resources perspective, including job instability and conflicting interests of employers and employees.


Vascular Changes of the Choroid and Their Correlations With Visual Acuity in Pathological Myopia.
Photoreceptor loss plays a role in visual impairment in pathological myopia. As the nutrition and oxygen demands of photoreceptors are mainly supported by the choroidal vessels, we aimed to investigate changes in the choroidal vasculature and their correlations with visual acuity in pathological myopia. The cohort was composed of 136 eyes from 80 participants, including 42 eyes from 21 participants with emmetropia/low myopia, 48 eyes from 26 participants with simple high myopia, and 46 eyes from 33 participants with pathological myopia. Swept-source optical coherence tomography (OCT) was used to image the eyes with a 12-mm radial line scan protocol. The parameters for 6-mm diameters of macula area centered on the fovea were analyzed. A custom deep learning algorithm based on a modified residual U-Net architecture was used to segment the choroidal boundaries. Then, the distance between the two boundaries was determined and choroidal thickness (CT), luminal area (LA), and stromal area (SA) were demarcated based on Niblack's auto-local threshold algorithm after binarization of the OCT images. Finally, the ratio of LA and total choroidal area was defined as the choroidal vascularity index (CVI). The choroidal parameters in three groups were compared, and correlations of the choroidal parameters with age, gender, axial length, and best-corrected visual acuity (BCVA) were analyzed. The CVI, CT, LA, and SA values were lower in pathological myopia than in emmetropia/low myopia and simple high myopia (P < 0.05). The CT, LA, and SA values were lower in simple high myopia than in emmetropia/low myopia (P < 0.05), whereas there was no difference between the CVIs in the emmetropia/low myopia and high myopia groups (P > 0.05). The CVI was nonlinear with increases in axial length (AL), and there was a critical AL flexion point, approximately 27.26 mm; however, the CT, LA, and SA were negatively correlated with AL. Further analysis showed that only younger subjects (40 years old or less) showed significant AL flexion points. Simple and multiple regression models showed that the CVI was correlated with BCVA (P < 0.05). Choroidal vascular alterations, especially decreased CVI, occurred in patients with pathological myopia. The CVI decreased with axial elongation beyond the flexion point and was correlated with visual impairment, indicating that the CVI might be a reliable imaging biomarker to monitor the progression of pathological myopia.


Pathogenicity of GB virus C on virus hepatitis and hemodialysis patients.
To determine the pathogenicity of GB virus C (GBV-C) on liver and the effects of its co-infection on the clinical features and prognosis of patients with hepatitis B and C. Cross-sectional study was carried out in 413 patients with acute, chronic hepatitis B or liver cirrhosis, and in 67 hemodialysis patients. A 20-month prospective cohort study was carried out in 95 hepatitis B and 80 hepatitis C patients. A reverse transcriptase nested polymerase chain reaction (RT-nPCR) of the 5'-noncoding region was used to detect circulating GBV-C RNA. Liver function was determined by an automated analyzer for all patients. The prevalence of GBV-C in the high-risk populations with the virus transmitted via blood was high, ranging from 16.2 to 28.8 %. Co-infection with GBV-C in hepatitis B patients did not affect the clinical features of the disease or liver function. The dialysis patients infected with GBV-C alone did not develop functional changes to the liver. Prospective cohort study showed that GBV-C co-infection did not affect the clinical features, prognosis or negative serum conversion rate of chronic hepatitis B and C. The results suggest that GBV-C has no marked pathogenicity on liver, so it may not be a hepatitis virus.


Landau theory for smectic-A-hexatic-B coexistence in smectic films.
We explain theoretical peculiarities of the smectic-A-hexatic-B equilibrium phase coexistence in a finite-temperature range recently observed experimentally in free-standing smectic films [I. A. Zaluzhnyy et al., Phys. Rev. E 98, 052703 (2018)2470-004510.1103/PhysRevE.98.052703]. We quantitatively describe this unexpected phenomenon within Landau phase transitions theory assuming that the film state is close to a tricritical point. We found that the surface hexatic order diminishes the phase coexistence range as the film thickness decreases, shrinking it to zero at some minimal film thickness L_{c}, of the order of a few hexatic correlation length. We established universal laws for the temperature width of the phase coexistence range in terms of the reduced variables. Our theory is in agreement with the existing experimental data.


Photophysics of alloxazines on cellulose.
We report the UV-Vis absorption, fluorescence and transient absorption spectra of selected methylalloxazines adsorbed on cellulose from a polar solvent. The ground-state properties of these probe molecules in the cellulose matrix are similar to those in polar protic solvents. Fluorescence decay data allowed identification of three emitting species for every molecule studied, excluding 1-methyllumichrome which lacks the capacity to rearrange into an isoalloxazinic form. The short-lived emission component was attributed to the neutral form of the molecule, and the two longer-lived components were assigned to the two distinct deprotonated monoanionic forms resulting from dissociation at the respective N(3) and N(1) nitrogen atoms. The two monoanions coexist due to their very similar pKa, values. Transient absorption experiments detected two species created by the laser pulse in these systems. The short-lived species was identified as the triplet excited state, and the long-lived species as the semireduced radical, formed by hydrogen atom or proton transfer from the glycosidic unit to the alloxazine carbonyl group.


The Spatial Morphology of Intraluminal Thrombus Influences Type II Endoleak after Endovascular Repair of Abdominal Aortic Aneurysms.
Type 2 endoleaks (T2Es) after endovascular repair (EVAR) of abdominal aortic aneurysm (AAA) can lead to sac expansion or failure of sac regression, and often present as a management dilemma. The intraluminal thrombus (ILT) may influence the likelihood of endoleaks after EVAR and can be characterized using routine preoperative imaging. We examined the relationship between preoperative spatial morphology of ILT and the incidence of postoperative T2E. All patients who underwent EVAR at the John Radcliffe Hospital (Oxford, UK) were prospectively entered in a clinical database. Computed tomography angiograms (CTAs) were performed as part of routine clinical care. The ILT morphology of each patient was determined using the preoperative CTA. Arterial phase cross-sectional images of the AAA were analyzed according to the presence and morphology of the thrombus in each quadrant. The overall ILT morphology was defined by measurements obtained over a 4-cm segment of the AAA. The diagnosis of T2Es during EVAR surveillance was confirmed by CTAs. The relation between the ILT morphology and T2E was assessed using logistic regression. Between September 2009 and July 2016, 271 patients underwent EVAR for infrarenal AAAs (male: 241, age = 79 ± 7). The ILT was present in 265 (98%) of AAAs. Mean follow-up was 1.9 ± 1.6 years. The T2E was observed in 77 cases. Sixty-one percent of T2Es were observed within the first week after surgery. The T2E was observed in 50% (3/6) of cases without the ILT (no-ILT). Compared with no-ILT, the presence of circumferential or posterolateral ILTs was protective from T2Es (odds ratio = 0.33 and 0.37; P = 0.002 and P = 0.047, respectively). The spatial ILT morphology on routine preoperative CTA imaging can be a biomarker for post-EVAR T2Es. ILTs that cover the posterolateral aspects of the lumen, or circumferential ILTs, are protective of T2Es. This information can be useful in the preoperative planning of EVARs.


L-cysteine reversibly inhibits glucose-induced biphasic insulin secretion and ATP production by inactivating PKM2.
Increase in the concentration of plasma L-cysteine is closely associated with defective insulin secretion from pancreatic β-cells, which results in type 2 diabetes (T2D). In this study, we investigated the effects of prolonged L-cysteine treatment on glucose-stimulated insulin secretion (GSIS) from mouse insulinoma 6 (MIN6) cells and from mouse pancreatic islets, and found that the treatment reversibly inhibited glucose-induced ATP production and resulting GSIS without affecting proinsulin and insulin synthesis. Comprehensive metabolic analyses using capillary electrophoresis time-of-flight mass spectrometry showed that prolonged L-cysteine treatment decreased the levels of pyruvate and its downstream metabolites. In addition, methyl pyruvate, a membrane-permeable form of pyruvate, rescued L-cysteine-induced inhibition of GSIS. Based on these results, we found that both in vitro and in MIN6 cells, L-cysteine specifically inhibited the activity of pyruvate kinase muscle isoform 2 (PKM2), an isoform of pyruvate kinases that catalyze the conversion of phosphoenolpyruvate to pyruvate. L-cysteine also induced PKM2 subunit dissociation (tetramers to dimers/monomers) in cells, which resulted in impaired glucose-induced ATP production for GSIS. DASA-10 (NCGC00181061, a substituted N,N'-diarylsulfonamide), a specific activator for PKM2, restored the tetramer formation and the activity of PKM2, glucose-induced ATP production, and biphasic insulin secretion in L-cysteine-treated cells. Collectively, our results demonstrate that impaired insulin secretion due to exposure to L-cysteine resulted from its direct binding and inactivation of PKM2 and suggest that PKM2 is a potential therapeutic target for T2D.


Association of infectious mononucleosis with multiple sclerosis. A population-based study.
Genetic and environmental factors have important roles in multiple sclerosis (MS) susceptibility. Several studies have attempted to correlate exposure to viral illness with the subsequent development of MS. Here in a population-based Canadian cohort, we investigate the relationship between prior clinical infection or vaccination and the risk of MS. Using the longitudinal Canadian database, 14,362 MS index cases and 7,671 spouse controls were asked about history of measles, mumps, rubella, varicella and infectious mononucleosis as well as details about vaccination with measles, mumps, rubella, hepatitis B and influenza vaccines. Comparisons were made between cases and spouse controls. Spouse controls and stratification by sex appear to correct for ascertainment bias because with a single exception we found no significant differences between cases and controls for all viral exposures and vaccinations. However, 699 cases and 165 controls reported a history of infectious mononucleosis (p < 0.001, corrected odds ratio 2.06, 95% confidence interval 1.71-2.48). Females were more aware of disease history than males (p < 0.001). The data further confirms a reporting distortion between males and females. Historically reported measles, mumps, rubella, varicella and vaccination for hepatitis B, influenza, measles, mumps and rubella are not associated with increased risk of MS later in life. A clinical history of infectious mononucleosis is conspicuously associated with increased MS susceptibility. These findings support studies implicating Epstein-Barr virus in MS disease susceptibility, but a co-association between MS susceptibility and clinically apparent infectious mononucleosis cannot be excluded.


Neck support pillows: a comparative study.
Special neck support pillows claiming to improve rest and reduce neck pain are currently being advertised. To test whether neck pillows have any positive effect on neck pain and quality of sleep compared with usual pillows and, if so, to find the optimal characteristics of such a pillow. Thirty-seven hospital employees and 18 neck patients were asked to test six neck pillows with different shapes and consistency randomly over the course of 3 wk, to grade them according to comfort and to describe the characteristics of an ideal pillow. Thirty-six of 55 persons found the pillows positively affected sleep and 27 of 42 found that they positively affected neck pain. The ideal pillow should be soft and not too high, should provide neck support and should be allergy-tested and washable. The pillow that included two firmer supporting cores for neck lordosis received the best rating. A neck pillow with good shape and consistency and with firm support for cervical lordosis can be recommended as a part of treatment for neck pain.


Towards a barnacle tree of life: integrating diverse phylogenetic efforts into a comprehensive hypothesis of thecostracan evolution.
Barnacles and their allies (Thecostraca) are a biologically diverse, monophyletic crustacean group, which includes both intensely studied taxa, such as the acorn and stalked barnacles, as well as cryptic taxa, for example, Facetotecta. Recent efforts have clarified phylogenetic relationships in many different parts of the barnacle tree, but the outcomes of these phylogenetic studies have not yet been combined into a single hypothesis for all barnacles. In the present study, we applied a new "synthesis" tree approach to estimate the first working Barnacle Tree of Life. Using this approach, we integrated phylogenetic hypotheses from 27 studies, which did not necessarily include the same taxa or used the same characters, with hierarchical taxonomic information for all recognized species. This first synthesis tree contains 2,070 barnacle species and subspecies, including 239 barnacle species with phylogenetic information and 198 undescribed or unidentified species. The tree had 442 bifurcating nodes, indicating that 79.3% of all nodes are still unresolved. We found that the acorn and stalked barnacles, the Thoracica, and the parasitic Rhizocephala have the largest amount of published phylogenetic information. About half of the thecostracan families for which phylogenetic information was available were polyphyletic. We queried publicly available geographic occurrence databases for the group, gaining a sense of geographic gaps and hotspots in our phylogenetic knowledge. Phylogenetic information is especially lacking for deep sea and Arctic taxa, but even coastal species are not fully incorporated into phylogenetic studies.


Genetics, Insurance and Professional Practice: Survey of the Australasian Clinical Genetics Workforce.
In Australia and New Zealand, by contrast with much of the developed world, insurance companies can use genetic test results to refuse cover or increase premiums for mutually-rated insurance products, including life, income protection and disability insurance. Genetics professionals regularly discuss insurance implications with clients and report the issue as a clinical challenge, yet no studies have examined clinical practices or opinions. This study surveyed genetic counsellors and clinical geneticists from Australia and New Zealand to (i) investigate variability in professional practice across the Australasian clinical genetic workforce relating to the insurance implications of genetic testing, and (ii) ascertain views regarding current regulation of the issue. There was considerable variability in training and clinical policies, especially around the communication of insurance implications. Almost half of participants reported receiving no training on the insurance implications of genetic testing, and almost 40% were unsure whether they could adequately advise clients. A number of deficits in professional knowledge and understanding of the issue were identified. Widespread concerns regarding regulation of this area were reported, with < 10% of Australian participants considering current Australian regulations as adequate to protect clients from genetic discrimination. The findings from this study highlight scope for greater education, consistency and professional training on the issue of genetics and insurance in Australasia, and strong agreement about the need for regulatory reform.


Comment on "Plant species richness and ecosystem multifunctionality in global drylands".
Maestre et al. (Reports, 13 January 2012, p. 214) reported a general, but weak, positive relationship between plant diversity and ecosystem multifunctionality in global drylands. We show that the strength of this relationship changes consistently along multiple environmental gradients, becoming strongly positive in stressed habitats. This suggests that biodiversity loss may have especially strong consequences in harsh environments.


Lack of efficacy of L-759274, a novel neurokinin 1 (substance P) receptor antagonist, for the treatment of generalized anxiety disorder.
Preclinical studies suggest that substance P acting at neurokinin 1 (NK1) receptors may be involved in stress responses and NK1 receptor antagonists show activity in tests of anxiety. These data raise the possibility that NK1 receptor antagonists could be potential anxiolytic treatments in humans. We evaluated this hypothesis clinically using the NK1 antagonist L-759274. This is a randomized, double-blind, placebo- and active-controlled, multicentre, proof-of-concept trial. Patients with generalized anxiety disorder were randomized 1:1:1 to 6 wk of treatment with 40 mg L-759274 (n = 73), 1-6 mg lorazepam (n = 69) or placebo (n = 71). Efficacy was assessed using the Hamilton Anxiety Scale (HAMA). A positron emission tomography (PET) study was also performed in 16 healthy subjects to determine the relationship between NK1 receptor occupancy and plasma levels of L-759274 to verify adequate target engagement by the doses tested during the clinical trial. No statistically significant difference in mean change from baseline HAMA score at 6 wk was seen for L-759274 vs. placebo [difference = 1.0 (95% confidence intervals (CI) -1.2 to 3.2), p = 0.359] whereas the lorazepam group did show a significant improvement vs. placebo (difference = -2.7, 95% CI -5.0 to -0.4, p = 0.020) and L-759274 (difference = 3.7, 95% CI 1.5-6.0, p = 0.001]. Results from the PET study indicated that the L-759274 dosing regimen used in the clinical trial likely provided high levels of NK1 receptor occupancy (>90%), supporting the view that it was an adequate proof-of-concept trial. The NK1 receptor antagonist L-759274 does not appear to be efficacious for the treatment of generalized anxiety disorder.


Radiative Rotational Lifetimes and State-Resolved Relative Detachment Cross Sections from Photodetachment Thermometry of Molecular Anions in a Cryogenic Storage Ring.
Photodetachment thermometry on a beam of OH^{-} in a cryogenic storage ring cooled to below 10 K is carried out using two-dimensional frequency- and time-dependent photodetachment spectroscopy over 20 min of ion storage. In equilibrium with the low-level blackbody field, we find an effective radiative temperature near 15 K with about 90% of all ions in the rotational ground state. We measure the J=1 natural lifetime (about 193 s) and determine the OH^{-} rotational transition dipole moment with 1.5% uncertainty. We also measure rotationally dependent relative near-threshold photodetachment cross sections for photodetachment thermometry.


Facial anatomy.
Dermatologic problems of the face affect both function and aesthetics, which are based on complex anatomical features. Treating dermatologic problems while preserving the aesthetics and functions of the face requires knowledge of normal anatomy. When performing successfully invasive procedures of the face, it is essential to understand its underlying topographic anatomy. This chapter presents the anatomy of the facial musculature and neurovascular structures in a systematic way with some clinically important aspects. We describe the attachments of the mimetic and masticatory muscles and emphasize their functions and nerve supply. We highlight clinically relevant facial topographic anatomy by explaining the course and location of the sensory and motor nerves of the face and facial vasculature with their relations. Additionally, this chapter reviews the recent nomenclature of the branching pattern of the facial artery.


[Inhibiting and facilitating influences from the caudate nucleus on alimentary conditioned reflexes].
Alimentary conditioned reflexes were studied in dogs during electrical stimulation of different zones of the caudate nucleus head with a 80 to 100 microampere current, of 5 c/s frequency and 0.5 msec pulse duration. The inhibitory influences came from the ventrolateral, and the activating ones, from the dorsal and central zones of the caudate nucleus head. Changes of conditioned reflexes resulting from its stimulation depended on the strength of the conditioned signals: the conditioned reflex to a weak stimulus (light) was more readily subject to changes as compared with the one to a strong signal (a metronome). The magnitude of unconditioned reflexes did not change in these experiments.


3D human foreskin model for testing topical formulations of sildenafil citrate.
Sildenafil citrate is an approved drug used for the treatment of erectile dysfunction and premature ejaculation. Despite a widespread application, sildenafil citrate shows numerous adverse cardiovascular effects in high-risk patients. Local transdermal drug delivery of this drug is therefore being explored as an interesting and noninvasive alternative administration method that avoids adverse effects arised from peak plasma drug concentrations. Although human and animal skin represents the most reliable models to perform penetration studies, they involve a series of ethical issues and restrictions. For these reasons new in vitro approaches based on artificially reconstructed human skin or "human skin equivalents" are being developed as possible alternatives for transdermal testing. There is little information, however, on the efficiency of such new in vitro methods on cutaneous penetration of active ingredients. The objective of the current study was to investigate the sildenafil citrate loaded in three commercial transdermal vehicles using 3D full-thickness skin equivalent and compare the results with the permeability experiments using porcine skin. Our results demonstrated that, while the formulation plays an imperative role in an appropriate dermal uptake of sildenafil citrate, the D coefficient results obtained by using the 3D skin equivalent are comparable to those obtained by using the porcine skin when a simple drug suspension is applied (1.17 × 10-10 ± 0.92 × 10-10 cm2/s vs 3.5 × 102 ± 3.3 × 102 cm2/s), suggesting that in such case, this 3D skin model can be a valid alternative for ex-vivo skin absorption experiments.


Facile synthesis of 1,2-aminoalcohols via α-C-H aminoalkylation of alcohols by photoinduced hydrogen-atom transfer catalysis.
1,2-Aminoalcohols are common motifs found in a wide range of natural products and pharmaceutical compounds. Here we report a photocatalytic method for the direct conversion of readily available aliphatic alcohols into synthetically valuable 1,2-aminoalcohols. A dual catalytic system consisting of an acridinium photoredox catalyst and a cationic hydrogen-atom transfer (HAT) catalyst based on 1,4-diazabicyclo[2.2.2]octane (DABCO) enables an efficient and site-selective HAT from the α-C-H bonds of unprotected primary and secondary alcohols. The subsequent radical addition to a newly designed chiral N-sulfinyl α-iminoester afforded various 1,2-aminoalcohols, including enantiomerically enriched ones, under mild photochemical conditions with high atom and step economy.


Analysis of cardiac mitochondrial Na+-Ca2+ exchanger kinetics with a biophysical model of mitochondrial Ca2+ handling suggests a 3:1 stoichiometry.
Calcium is a key ion and is known to mediate signalling pathways between cytosol and mitochondria and modulate mitochondrial energy metabolism. To gain a quantitative, biophysical understanding of mitochondrial Ca(2+) regulation, we developed a thermodynamically balanced model of mitochondrial Ca(2+) handling and bioenergetics by integrating kinetic models of mitochondrial Ca(2+) uniporter (CU), Na(+)-Ca(2+) exchanger (NCE), and Na(+)-H(+) exchanger (NHE) into an existing computational model of mitochondrial oxidative phosphorylation. Kinetic flux expressions for the CU, NCE and NHE were developed and individually parameterized based on independent data sets on flux rates measured in purified mitochondria. While available data support a wide range of possible values for the overall activity of the CU in cardiac and liver mitochondria, even at the highest estimated values, the Ca(2+) current through the CU does not have a significant effect on mitochondrial membrane potential. This integrated model was then used to analyse additional data on the dynamics and steady-states of mitochondrial Ca(2+) governed by mitochondrial CU and NCE. Our analysis of the data on the time course of matrix free [Ca(2+)] in respiring mitochondria purified from rabbit heart with addition of different levels of Na(+) to the external buffer medium (with the CU blocked) with two separate models--one with a 2:1 stoichiometry and the other with a 3:1 stoichiometry for the NCE--supports the hypothesis that the NCE is electrogenic with a stoichiometry of 3:1. This hypothesis was further tested by simulating an additional independent data set on the steady-state variations of matrix free [Ca(2+)] with respect to the variations in external free [Ca(2+)] in purified respiring mitochondria from rat heart to show that only the 3:1 stoichiometry model predictions are consistent with the data. Based on these analyses, it is concluded that the mitochondrial NCE is electrogenic with a stoichiometry of 3:1.


Phase I/II study of bortezomib plus docetaxel in patients with advanced androgen-independent prostate cancer.
To determine the dose-limiting toxicities and maximum tolerated dose, and evaluate the antitumor activity of bortezomib/docetaxel combination therapy in androgen-independent prostate cancer. Two bortezomib doses (1.3 and 1.6 mg/m(2)/dose) in combination with four docetaxel doses (25-40 mg/m(2)/dose) were evaluated. Both drugs were administered weekly for 2 out of 3 weeks. Antitumor activity was evaluated using prostate-specific antigen (PSA) levels and Response Evaluation Criteria in Solid Tumors guidelines. Eighty-three patients received at least one dose of study drug. No dose-limiting toxicities were observed despite escalation to the highest dose level. PSA response (>or=50% decline in PSA levels from the baseline) occurred in 19 (28%) of 67 evaluable patients and was maintained for >or=4 weeks in 14 patients (21%). According to Response Evaluation Criteria in Solid Tumors guidelines, 11% achieved a partial response, and an additional 67% had stable disease. The degree of proteasome inhibition was similar to that reported with single-agent bortezomib. Treatment was well tolerated; fatigue was the most common drug-related adverse event, whereas diarrhea was the most common drug-related grade 3/4 adverse event. No clinically significant febrile neutropenia or neuropathy occurred. The maximum tolerated dose of this 21-day regimen has not been reached. The highest dose level (1.6 mg/m(2) bortezomib plus 40 mg/m(2) docetaxel) was feasible and tolerable; bortezomib plus docetaxel showed antitumor activity. Activity and tolerability results were consistent with previous studies of bortezomib alone or in combination with docetaxel. Further investigations are warranted to determine activity and optimize bortezomib/docetaxel therapy in androgen-independent prostate cancers.


[Adverse effects of antipsychotics and quality of life].
New antipsychotics are associated with fewer adverse effects than classical ones. However, an increase in the patient's quality of life is not clear, given the complex relationship between quality of life and schizophrenia. To show there are no real differences in adverse effects and quality of life of schizophrenic patients treated with atypical and typical neuroleptics. Transversal study. The sample (78 male and female patients between 18 and 80 years old) was divided into three treatment groups: atypical, typical and both kinds of neuroleptics. Measurement instruments used were Udvalg Für Kliniske Undersogesler (UKU) for adverse effects and Quality of Life Scale (QLS) for quality of life. Treatment with atypical antipsychotic is significantly associated with fewer extrapyramidal adverse effects but not with a better quality of life in the scales applied. Probably quality of life does not only depend on treatment. It may also be affected by other several factors such as negative symptomatology and a long-term evolution of schizophrenia, which are not included in the quality of life scales used. However, this is a pilot study, in which we have used only a quality of life scale and a small sample chosen without previous sample calculus. Taking this into account, general conclusions on efficacy and global acceptance of antipsychotics cannot be deduced.


A Prospective Comparison of Standard and Modified Acute Malnutrition Treatment Protocols during COVID-19 in South Sudan.
A non-randomized prospective cohort study was conducted in 2022 to compare recovery rate and length of stay (LoS) for acutely malnourished children treated under South Sudan's standard Community Management of Acute Malnutrition (CMAM) protocol and a COVID-modified protocol. Children aged 6-59 months received acute malnutrition (AM) treatment under the standard or modified protocol (mid-upper-arm circumference-only entry/exit criteria and simplified dosing). Primary (recovery rate and LoS) were compared for outpatient therapeutic (OTP) and therapeutic supplementary feeding programs (TSFP) using descriptive statistics and mixed-effects models. Children admitted to OTP under both protocols were similar in age and sex; children admitted to TSFP were significantly older under the modified protocol than the standard protocol. Shorter LoS and higher recovery rates were observed under the modified protocol for both OTP (recovery: 93.3% vs. 87.2%; LoS: 38.3 vs. 42.8 days) and TSFP (recovery: 79.8% vs. 72.7%; LoS: 54.0 vs. 61.9 days). After adjusting for site and child characteristics, neither differences in adjusted odds of recovery [OTP: 2.63; TSFP 1.80] nor LoS [OTP -10.0; TSFP -7.8] remained significant. Modified protocols for AM performed well. Adjusted models indicate similar treatment outcomes to the standard protocol. Adopting simplified protocols could be beneficial post-pandemic; however, recovery and relapse will need to be monitored.


Fatal primary amoebic meningoencephalitis in a Norwegian tourist returning from Thailand.
Primary amoebic meningoencephalitis (PAM) is a rare disease caused by the free-living amoeba Naegleria fowleri. Infection occurs by insufflation of water containing amoebae into the nasal cavity, and is usually associated with bathing in freshwater. Nasal irrigation is a more rarely reported route of infection. A fatal case of PAM in a previously healthy Norwegian woman, acquired during a holiday trip to Thailand, is described. Clinical findings were consistent with rapidly progressing meningoencephalitis. The cause of infection was discovered by chance, owing to the unexpected detection of N. fowleri DNA by a PCR assay targeting fungi. A conclusive diagnosis was established based on sequencing of N. fowleri DNA from brain biopsies, supported by histopathological findings. Nasal irrigation using contaminated tap water is suspected as the source of infection. The clinical presentation of PAM is very similar to severe bacterial meningitis. This case is a reminder that when standard investigations fail to identify a cause of infection in severe meningoencephalitis, it is of crucial importance to continue a broad search for a conclusive diagnosis. PAM should be considered as a diagnosis in patients with symptoms of severe meningoencephalitis returning from endemic areas.


Clinical and immunological analysis of 23 adult patients with common variable immunodeficiency.
Common variable immunodeficiency (CVID) is characterized by hypogammaglobulinemia, defective antibody production, and recurrent upper and lower airway tract infections. To reveal the clinical heterogeneity of this condition, analyze the high frequency of respiratory and gastrointestinal complications despite satisfactory trough immunoglobulin (Ig) G levels, and determine the main difficulties in management and treatment. We performed a retrospective analysis of 23 patients (13 male and 10 female) diagnosed with CVID between 2001 and 2008. The median diagnostic delay for females and males was 15 years (range, 1-32 years) and 8 years (range, 1-31 years), respectively. Restrictive, obstructive, and combined pulmonary function defects were determined in 23%, 27%, and 14% of patients, respectively. The most frequent findings on the thoracic computed tomography scan were bronchiectasis, mediastinal lymphadenopathy, fibrosis, ground-glass patterns, mosaic oligemia, peribronchial cuffing, and parenchymal nodules. Giardiasis and duodenal lymphoid hyperplasia were detected in 52% and 42% of the patients, respectively, and Helicobacter pylori in 42%. Vitamin A levels were normal, although beta-carotene and/or vitamin E levels were decreased in patients presenting malabsorption-related symptoms. Malignancy was documented in 3 patients and decreased bone mineral density in 9 patients (3 had osteoporosis and 3 had osteomalacia). CVID is a multisystemic disease that should be managed by a multidisciplinary team. Intravenous immunoglobulin therapy and antibiotics do not seem to have a suppressive effect on granulomatous or inflammatory manifestations. More comprehensive studies based not only on peripheral blood but also on immunohistological analysis are necessary to shed light on the pathogenesis of these life-threatening complications.


Follow-up care of the spinal cord injury patient.
Follow-up care of the spinal cord injury patient is often inadequate after discharge from the rehabilitation center. The family physician must pay particular attention to the genitourinary and respiratory systems; autonomic dysfunction, including temperature variation; skin care; contractures and spasticity; the prevention of thromboembolic disease, and nutritional intake. continuing psychosocial support is mandatory, as well as conservative management of pain. The prognosis for a full, rewarding life is becoming a reality.


The relationship between peripheral levels of leukocytes and neutrophils and periodontal disease status in a patient with congenital neutropenia.
Congenital neutropenia is characterized by an almost total absence of neutrophils and increased susceptibility to infection. Oral manifestations include ulcerations of mucous membranes, acute gingival inflammation with focal necrosis, and rapid loss of attachment. Treatment with recombinant human granulocyte colony-stimulating factor (rhG-CSF) increases neutrophil numbers and ameliorates the periodontal status. We report the treatment of a 22-year-old male with congenital neutropenia (Kostman syndrome), referred to us due to periodontal disease, and the effect of treatment on peripheral neutropenia. Diagnosis of neutropenia was made at year 1; at age 15, the patient started to receive injections of rhG-CSF, reducing the occurrence of infection and improving neutrophil count, although levels remained below normal. The patient underwent extraction of a molar at age 8; scaling, root planing, and modified Widman flaps at age 9; and oral hygiene maintenance every 2 to 3 months from age 18 to 21. At age 23, he initiated treatment at our periodontal clinic. The patient's gingiva was severely inflamed, and the dentition was covered with plaque and calculus. Attachment loss was advanced, all teeth were mobile, and bone loss was approximately 75% in most sites. Neutrophil counts were below normal, but other hematologic parameters were normal. Scaling and root planing were performed and the patient received antibiotics and chlorhexidine rinses twice each day for 2 weeks. Extracoronal splinting was performed, fluoride varnish was used to desensitize cervical areas, and tooth FDI #46 was restored. Root planing and deplaquing were repeated, and the patient received subgingival chlorhexidine irrigation 13 times over one year. Assessments were made on presentation, after the initial treatment, and at 1 and 2 years post-treatment. Mean probing depth was reduced posttreatment with a further reduction during the maintenance period. This was correlated with an increase in attachment levels. Total white blood cells increased, due in part to an increase in neutrophils, reaching normal levels. This report demonstrates for the first time that periodontal therapy, resulting in decreased bacterial load, may result in restoration of normal levels of circulating neutrophils in individuals with congenital neutropenia under treatment with rhG-CSF. The results also suggest that periodontal pathogens may be associated with depressed neutrophil levels, even when patients receive treatment for neutropenia.


Quantitative assessment of the complex dynamics of G1, S, and G2-M checkpoint activities.
Although studies of cell cycle perturbation and growth inhibition are common practice, they are unable to properly measure the activity of cell cycle checkpoints and frequently convey misinterpretation or incomplete pictures of the response to anticancer treatment. A measure of the strength of the treatment response of all checkpoints, with their time and dose dependence, provides a new way to evaluate the antiproliferative activity of the drugs, fully accounting for variation of the cell fates within a cancer cell line. This is achieved with an interdisciplinary approach, joining information from independent experimental platforms and interpreting all data univocally with a simple mathematical model of cell cycle proliferation. The model connects the dynamics of checkpoint activities at the molecular level with population-based flow cytometric and growth inhibition time course measures. With this method, the response to five drugs, characterized by different molecular mechanisms of action, was studied in a synoptic way, producing a publicly available database of time course measures with different techniques in a range of drug concentrations, from sublethal to frankly cytotoxic. Using the computer simulation program, we were able to closely reproduce all the measures in the experimental database by building for each drug a scenario of the time and dose dependence of G(1), S, and G(2)-M checkpoint activities. We showed that the response to each drug could be described as a combination of a few types of activities, each with its own strength and concentration threshold. The results gained from this method provide a means for exploring new concepts regarding the drug-cell cycle interaction.


Temperature-dependent structural changes of Parkinson's alpha-synuclein reveal the role of pre-existing oligomers in alpha-synuclein fibrillization.
Amyloid fibrils of α-synuclein are the main constituent of Lewy bodies deposited in substantial nigra of Parkinson's disease brains. α-Synuclein is an intrinsically disordered protein lacking compact secondary and tertiary structures. To enhance the understanding of its structure and function relationship, we utilized temperature treatment to study α-synuclein conformational changes and the subsequent effects. We found that after 1 hr of high temperature pretreatment, >80°C, α-synuclein fibrillization was significantly inhibited. However, the temperature melting coupled with circular dichroism spectra showed that α-synuclein was fully reversible and the NMR studies showed no observable structural changes of α-synuclein after 95°C treatment. By using cross-linking and analytical ultracentrifugation, rare amount of pre-existing α-synuclein oligomers were found to decrease after the high temperature treatment. In addition, a small portion of C-terminal truncation of α-synuclein also occurred. The reduction of pre-existing oligomers of α-synuclein may contribute to less seeding effect that retards the kinetics of amyloid fibrillization. Overall, our results showed that the pre-existing oligomeric species is a key factor contributing to α-synuclein fibrillization. Our results facilitate the understanding of α-synuclein fibrillization.


[Pneumococcus pathogenicity factors and their protective properties].
Owing to rapid development of molecular-biological and genetic methods of research in infectology as well as use of adequate models (tissue colonization of human respiratory epithelium, mice models of colonization, sepsis and meningitis), a significant progress in the field of pneumococcus pathogenicity factors has been made in the last decades. Aside from the well-known pathogenicity factor--capsule polysaccharide, to date several dozens of surface proteins providing adhesion, colonization and invasion have been detected in pneumococcus. Pneumolysin is a toxic factor and at the same time brain invasion factor. Many of the known pathogenicity factors play a role in formation of biofilm that facilitates prolonged colonization of nasopharynx. Protective activity has been proved for some of the surface proteins and pneumolysin that forms the base for development of novel rational pneumococcal vaccines as an alternative to polysaccharide.


Genome-based Salmonella serotyping as the new gold standard.
Salmonella enterica is the second most reported bacterial cause of food-borne infections in Europe. Therefore molecular surveillance activities based on pathogen subtyping are an important measure of controlling Salmonellosis by public health agencies. In Germany, at the federal level, this work is carried out by the National Reference Center for Salmonella and other Bacterial Enteric Pathogens (NRC). With rise of next generation sequencing techniques, the NRC has introduced whole-genome-based typing methods for S. enterica in 2016. In this study we report on the feasibility of genome-based in silico serotyping in the German setting using raw sequence reads. We found that SeqSero and seven gene MLST showed 98% and 95% concordance, respectively, with classical serotyping for the here evaluated serotypes, including the most common German serotypes S. Enteritidis and S. Typhimurium as well as less frequently found serotypes. The level of concordance increased to >99% when the results of both in silico methods were combined. However, both tools exhibited misidentification of monophasic variants, in particular monophasic S. Typhimurium and therefore need to be fine-tuned for reliable detection of this epidemiologically important variant. We conclude that with adjustments Salmonella genome-based serotyping might become the new gold standard.


circPVT1 Facilitates Invasion and Metastasis by Regulating miR-205-5p/c-FLIP Axis in Osteosarcoma.
As a key subtype of non-coding RNAs, circular RNA (circRNA) has been well documented to play a key role in the tumorigenesis of osteosarcoma (OS). circPVT1 was revealed to participate in the progression of multiple human tumors; however, the roles of circPVT1 in OS invasion and metastasis and its potential mechanisms remain elusive. RNA expression in OS tissues and cells was examined by qRT-PCR, protein expression was measured by Western blot. circPVT1 knockdown in vitro was achieved by transfecting OS cells with specific siRNAs. OS cell proliferation was assessed via CCK-8 and colony formation assays. OS cell migration and invasion were evaluated by transwell assay. Interaction between miR-205-5p and circPVT1 or c-FLIP was validated through dual-luciferase reporter assay. Rescue experiments were performed to explore the regulatory net among circPVT1, miR-205-5p and c-FLIP in OS progression in vitro. circPVT1 and c-FLIP were highly expressed, while miR-205-5p was lowly expressed in OS tissues and cell lines. Knockdown of circPVT1 repressed cell proliferation, migration and invasion via inhibiting epithelial-mesenchymal transition (EMT) in OS. circPVT1 functioned as a sponge of miR-205-5p, and c-FLIP was targeted by miR-205-5p in OS cells. Furthermore, circPVT1 indirectly regulated c-FLIP expression through competitively binding to miR-205-5p. Inhibition of miR-205-5p or overexpression of c-FLIP abolished the effects of si-circPVT1 on cell proliferation, migration and invasion. Our study demonstrated circPVT1 functions as a sponge for miR-205-5p to promote c-FLIP expression, thereby enhancing EMT and inducing OS invasion and metastasis in vitro, implying that circPVT1 might be a potential therapeutic target for further clinical therapy of OS.


Toxoplasma gondii: inconsistent dissemination patterns following oral infection in mice.
Since Toxoplasma gondii is transmitted in the wild through the ingestion of infective cysts, oral infection is a preferred model for studying the natural mode of parasite dissemination and pathogenesis. Using luciferase-expressing strains of T. gondii and in vivo imaging, we observed different patterns of disease progression in mice depending of the method of oral infection. Oral gavage of infective cysts (e.g., bradyzoites) resulted in an inconsistent pattern of parasite dissemination; in the majority (20/29) of infected mice, luciferase-derived signal (indicating high numbers of Toxoplasma tachyzoites) was first observed in the right chest area. At later time points this signal spread to other parts of the mouse, including the abdominal area. In the remaining mice (9/29), parasites were first observed replicating in the abdominal area, as might be expected. In contrast, when mice were infected naturally (either via ingestion of whole brains from previously infected mice or brain cyst homogenate-soaked bread), parasites were first observed replicating in the abdominal area in all mice examined (10/10). Based on the inconsistency of infections initiated with oral gavage, it is recommended that natural feeding be used to infect mice when a consistent oral infection is desired.


Death beliefs, superstitious beliefs and health anxiety.
The present study explored the association between beliefs about death, superstitious beliefs, and health anxiety. It was hypothesized that negative beliefs about death and superstitious beliefs would be positively correlated with health anxiety. Conversely, positive beliefs about death were hypothesized to be negatively correlated with health anxiety. A cross-sectional, correlational and multiple regression design was adopted. A sample of 106 Roman Catholics and 197 Atheists completed a questionnaire measuring aspects of health anxiety, spiritual beliefs, and control variables consisting of demographics. Negative beliefs about death and superstitious beliefs were related to health anxiety within both the Roman Catholic and Atheist samples. The expected negative relationship between positive beliefs about death and health anxiety was not supported in either sample. Multiple regression analyses indicated that death beliefs and superstitious beliefs, in combination with background variables, significantly predicted health anxiety in the Roman Catholic sample. For Atheists, although death and superstitious beliefs were identified as significant predictors, when considered with other variables, the additional variance accounted for was not significant. Negative beliefs about death and superstitious beliefs appear to be positively associated with health anxiety. These types of beliefs may have the potential to offer a useful addition to cognitive-behavioural models of health anxiety.


Discovery of Novel Herpes Simplexviruses in Wild Gorillas, Bonobos, and Chimpanzees Supports Zoonotic Origin of HSV-2.
Viruses closely related to human pathogens can reveal the origins of human infectious diseases. Human herpes simplexvirus type 1 (HSV-1) and type 2 (HSV-2) are hypothesized to have arisen via host-virus codivergence and cross-species transmission. We report the discovery of novel herpes simplexviruses during a large-scale screening of fecal samples from wild gorillas, bonobos, and chimpanzees. Phylogenetic analysis indicates that, contrary to expectation, simplexviruses from these African apes are all more closely related to HSV-2 than to HSV-1. Molecular clock-based hypothesis testing suggests the divergence between HSV-1 and the African great ape simplexviruses likely represents a codivergence event between humans and gorillas. The simplexviruses infecting African great apes subsequently experienced multiple cross-species transmission events over the past 3 My, the most recent of which occurred between humans and bonobos around 1 Ma. These findings revise our understanding of the origins of human herpes simplexviruses and suggest that HSV-2 is one of the earliest zoonotic pathogens.


Influence of Varying Training Set Composition and Size on Support Vector Machine-Based Prediction of Active Compounds.
Support vector machine (SVM) modeling is one of the most popular machine learning approaches in chemoinformatics and drug design. The influence of training set composition and size on predictions currently is an underinvestigated issue in SVM modeling. In this study, we have derived SVM classification and ranking models for a variety of compound activity classes under systematic variation of the number of positive and negative training examples. With increasing numbers of negative training compounds, SVM classification calculations became increasingly accurate and stable. However, this was only the case if a required threshold of positive training examples was also reached. In addition, consideration of class weights and optimization of cost factors substantially aided in balancing the calculations for increasing numbers of negative training examples. Taken together, the results of our analysis have practical implications for SVM learning and the prediction of active compounds. For all compound classes under study, top recall performance and independence of compound recall of training set composition was achieved when 250-500 active and 500-1000 randomly selected inactive training instances were used. However, as long as ∼50 known active compounds were available for training, increasing numbers of 500-1000 randomly selected negative training examples significantly improved model performance and gave very similar results for different training sets.