Work-related fatigue: the specific case of highly educated women in the Netherlands.
This study aims to establish the prevalence of high work-related fatigue (need for recovery, NFR) among employees and to explain group differences categorized by gender, age, and education. The study particularly aims to clarify prevalence and explanatory factors in highly educated women. In 2005 and 2006, large representative samples of 80,000 Dutch employees (net response rate 33.0%; N = 47,263) received the Netherlands working conditions survey questionnaire. First, we calculated the prevalence of high NFR for men and women with different age and education levels. The average prevalence of high NFR was 28.8% and was highest among highly educated women (35.2%) in particular those aged 50-64 years (40.3%). Second, logistic regression analyses were used to compare subgroups' NFR in relation to situational factors, working conditions, and health. Three comparisons were made: (1) highly educated women versus men; (2) highly educated versus lower educated women and; (3) older highly educated versus younger highly educated women. The situational, working conditions and health factors in our model did not explain the gender differences among highly educated employees (OR = 1.37; CI = 1.3-1.5, adjusted for all factors OR = 1.32; CI = 1.2-1.5). Despite that lower autonomy and workplace violence explained highly educated women's NFR, working fewer hours counterbalanced this. Time pressure in work largely explained the differences in NFR among women at different education levels (crude OR 1.44; CI = 1.4-1.5, adjusted OR 1.14; CI = 1.0-1.3). In the age comparison, lower health ratings, more adverse working conditions, and working as a teacher explained older highly educated women's high prevalence of high NFR (crude OR 1.32; CI = 1.2-1.5, adjusted OR 0.94; CI = 0.8-1.2). NFR has high prevalence in highly educated women (35.2%) in particular those aged 50-64 years (40.3%). Our model did not explain gender differences in NFR, because working fewer hours counterbalanced the effects of lower autonomy and external workplace violence. Our model, in particular time pressure, largely explained differences in NFR between women at different education levels. Age differences in the prevalence of high NFR among highly educated women's were fully explained by our model. Main factors were lower health ratings, adverse working conditions, and working as a teacher.


Charlson co-morbidity index as a predictor of outcome after surgery for renal cell carcinoma with renal vein, vena cava or right atrium extension.
Surgery is the most effective treatment for renal cell carcinoma with tumor thrombus but predictors of outcome and patient survival are variable. Co-morbidity may affect therapeutic decision making and survival, although to our knowledge this factor has not been studied in patients with tumor thrombus. We analyzed the Charlson co-morbidity index as a predictor of outcome after surgery. From 1970 to 1998, 303 patients underwent surgical resection. The Charlson index, surgical era, completeness of resection, patient age, sex, tumor level, TNM stage, grade and perinephric fat invasion were studied retrospectively as univariate and multivariate predictors of outcome. The level of tumor thrombus was 0 (renal vein only) in 127 patients, and I to IV in 66, 58, 36 and 16, respectively. At 5 years overall, cause specific and metastasis-free survival were 32%, 42% and 41%, while at 10 years they were 21%, 32% and 30%, respectively. For the whole cohort significant multivariate predictors of cause specific survival were metastasis (p = 0.0001), grade (p = 0.0001), perinephric fat involvement (p = 0.02) and tumor levels 0 versus I to IV (p = 0.048). The Charlson index did not predict outcome (univariate model p = 0.65). Characteristics of the primary tumor remained the most important predictors of cause specific survival in this cohort. The Charlson index did not predict cause specific survival in this cohort of surgically treated patients. Prospective assessment of co-morbidity in patients treated with surgery versus conservative therapy is warranted.


Linkage disequilibrium and persistence of phase in Holstein-Friesian, Jersey and Angus cattle.
When a genetic marker and a quantitative trait locus (QTL) are in linkage disequilibrium (LD) in one population, they may not be in LD in another population or their LD phase may be reversed. The objectives of this study were to compare the extent of LD and the persistence of LD phase across multiple cattle populations. LD measures r and r(2) were calculated for syntenic marker pairs using genomewide single-nucleotide polymorphisms (SNP) that were genotyped in Dutch and Australian Holstein-Friesian (HF) bulls, Australian Angus cattle, and New Zealand Friesian and Jersey cows. Average r(2) was approximately 0.35, 0.25, 0.22, 0.14, and 0.06 at marker distances 10, 20, 40, 100, and 1000 kb, respectively, which indicates that genomic selection within cattle breeds with r(2) >or= 0.20 between adjacent markers would require approximately 50,000 SNPs. The correlation of r values between populations for the same marker pairs was close to 1 for pairs of very close markers (<10 kb) and decreased with increasing marker distance and the extent of divergence between the populations. To find markers that are in LD with QTL across diverged breeds, such as HF, Jersey, and Angus, would require approximately 300,000 markers.


Immunohistochemical characterization of teratomatous and fetal neuroendocrine pancreas.
Six extragonadal teratomas that contained pancreatic tissue were retrieved from archival material at the University of Minnesota Hospital, Minneapolis. The neuroendocrine cells were studied immunohistochemically for insulin, glucagon, somatostatin, pancreatic polypeptide, vasoactive intestinal polypeptide, gastrin, chromogranin, and synaptophysin. Pancreatic tissue from autopsies of 10 stillbirths (20 to 40 weeks' gestational age) was evaluated similarly. The features of the teratomatous pancreatic tissue were compared with those of the fetal pancreata and with data from previous studies of normal pancreatic development and adult pancreata. The pancreatic tissue in all six teratomas contained abundant mature islets that contained beta, alpha, delta, and pancreatic polypeptide cells; however, they also showed widespread nesidioblastosis with the same cell types, resembling third-trimester fetal and neonatal pancreata. Increased proportions of alpha and delta cells were observed in three and five cases (relative to those of adult tissue), respectively, providing further evidence of immaturity. Two cases showed a lack of alpha cells. None of the teratomas contained pancreatic cells that were positive for vasoactive intestinal polypeptide or gastrin. Mechanisms that regulate neuroendocrine cell differentiation in the normal pancreas also seem to operate in the teratomatous pancreas; they may eventuate in features similar to those of the late fetal and neonatal pancreas. Abnormal differentiation in teratomas may result in deficient hormone production.


Women's perspective of maternity care in Cambodia.
Consideration of the needs of pregnant women and their ability and willingness to attend maternal services and pay for them is central to the provision of accessible and acceptable maternal care. Women's satisfaction with maternal services is poorly understood in many developing countries, including Cambodia in South East Asia. The objective of this study was to investigate women's perceptions and experiences of private and public skilled birth attendants, including midwives, during childbirth in Cambodia. A qualitative design using a naturalistic inquiry approach was undertaken to seek sensitive personal issue. Thirty individual in-depth interviews were conducted with women who had recently given birth at private and public health facilities in one province in Cambodia. Data were analysed using a thematic approach. Women's choice of health facility was influenced by their perceptions of safety and staff attitudes. Reported barriers to the effective utilisation of public maternity services were costs associated with the birth, staff attitudes and a lack of supportive care during labour and in the postpartum period. Although private health care is more expensive than public health care, some women reported a preference for private birth attendants as they perceived them to provide safer and more supportive care in labour. Women expect, but do not always receive humane, professional, supportive and respectful treatment from public skilled birth attendants. While the removal of unexpected costs and geographical barriers are important to increasing public maternity care and service utilisation, improvements in maternity services should focus on addressing provider attitudes and enhancing communication skills during labour, birth and the immediate postpartum period.


GCNet: Graph Completion Network for Incomplete Multimodal Learning in Conversation.
Conversations have become a critical data format on social media platforms. Understanding conversation from emotion, content and other aspects also attracts increasing attention from researchers due to its widespread application in human-computer interaction. In real-world environments, we often encounter the problem of incomplete modalities, which has become a core issue of conversation understanding. To address this problem, researchers propose various methods. However, existing approaches are mainly designed for individual utterances rather than conversational data, which cannot fully exploit temporal and speaker information in conversations. To this end, we propose a novel framework for incomplete multimodal learning in conversations, called "Graph Complete Network (GCNet)," filling the gap of existing works. Our GCNet contains two well-designed graph neural network-based modules, "Speaker GNN" and "Temporal GNN," to capture temporal and speaker dependencies. To make full use of complete and incomplete data, we jointly optimize classification and reconstruction tasks in an end-to-end manner. To verify the effectiveness of our method, we conduct experiments on three benchmark conversational datasets. Experimental results demonstrate that our GCNet is superior to existing state-of-the-art approaches in incomplete multimodal learning.


Form-specific visual priming in the left and right hemispheres.
Word fragment completion performance was examined for items that were presented in the same or different letter case at study and test. During the study phase words and nonwords were presented at central fixation, then during the test phase a divided visual field technique was used in which word fragments were presented briefly to the right hemisphere (left visual field) or the left hemisphere (right visual field). Previous research using the word stem completion task indicated that only the right hemisphere was sensitive to case changes in words from study to test. In contrast, the current results indicate that in the fragment completion task the priming effects for the test items presented to either hemisphere were greater when the fragments were in the same compared to different letter case at study and test. These results indicate that both hemispheres are capable of supporting form-specific visual implicit memory.


Shaping markets to benefit global health - A 15-year history and lessons learned from the pentavalent vaccine market.
Market shaping for health products used in lower-income countries strives to benefit public health. As a funder of vaccines, Gavi, The Vaccine Alliance (Gavi) has goals for its market shaping efforts, achieved through a strategy developed and implemented by the Gavi Secretariat, UNICEF, the World Health Organization (WHO) and the Bill & Melinda Gates Foundation (BMGF). A case-study of Gavi's fifteen-year engagement with a vaccine against diphtheria, tetanus, pertussis, hepatitis B and haemophilus influenzae type b (pentavalent) provides evidence of the benefits and potential risks of trying to influence markets. During 2001-18, Gavi disbursed US$3.5 billion to support use of 50 million pentavalent doses annually before 2005, increasing to ∼300 million doses annually by 2016. During this time, eight manufacturers invested in vaccine development and manufacturing and the first two manufacturers have subsequently ceased production. Following its strategy, Gavi implemented coordinated market interventions including technical assistance to manufacturers, improving market information transparency, risk-sharing agreements and innovative procurement aiming to stimulate and capitalize on a competitive market. In 2018 supply allows ∼80 million children per year to be immunised, a sixteen-fold increase from 2005, with vaccine-related costs per child for donors and countries of one-quarter the 2005 level. Lessons learned include the importance of frameworks and strategies; the need to adjust interventions with changing conditions; the important role of manufacturers; and the potentially powerful effects of interconnected markets. This case study is limited by its focus on a single health product in a specific market, however the lessons can inform other market shaping efforts when taken in context. While countries and children have improved vaccine access, risks of financial sustainability and continued manufacturer investment in Gavi vaccine markets are being monitored. Gavi should continue implementing a market shaping strategy, adjust with market conditions and expect and measure unintended consequences.


Helix straightening as an activation mechanism in the gelsolin superfamily of actin regulatory proteins.
Villin and gelsolin consist of six homologous domains of the gelsolin/cofilin fold (V1-V6 and G1-G6, respectively). Villin differs from gelsolin in possessing at its C terminus an unrelated seventh domain, the villin headpiece. Here, we present the crystal structure of villin domain V6 in an environment in which intact villin would be inactive, in the absence of bound Ca(2+) or phosphorylation. The structure of V6 more closely resembles that of the activated form of G6, which contains one bound Ca(2+), rather than that of the calcium ion-free form of G6 within intact inactive gelsolin. Strikingly apparent is that the long helix in V6 is straight, as found in the activated form of G6, as opposed to the kinked version in inactive gelsolin. Molecular dynamics calculations suggest that the preferable conformation for this helix in the isolated G6 domain is also straight in the absence of Ca(2+) and other gelsolin domains. However, the G6 helix bends in intact calcium ion-free gelsolin to allow interaction with G2 and G4. We suggest that a similar situation exists in villin. Within the intact protein, a bent V6 helix, when triggered by Ca(2+), straightens and helps push apart adjacent domains to expose actin-binding sites within the protein. The sixth domain in this superfamily of proteins serves as a keystone that locks together a compact ensemble of domains in an inactive state. Perturbing the keystone initiates reorganization of the structure to reveal previously buried actin-binding sites.


Uridylylation of the P(II) protein in the photosynthetic bacterium Rhodospirillum rubrum.
The regulatory protein P(II) has been studied in great detail in enteric bacteria; however, its function in photosynthetic bacteria has not been clearly established. As a number of these bacteria have been shown to regulate nitrogenase activity by a metabolic control system, it is of special interest to establish the role of P(II) in these diazotrophs. In this study, we show that P(II) in Rhodospirillum rubrum is modified in response to the N status in the cell and that addition of ammonium or glutamine leads to demodification. We also provide evidence that P(II) is uridylylated. In addition, we show that not only these compounds but also NAD+ promotes demodification of P(II), which is of particular interest as this pyridine nucleotide has been shown to act as a switch-off effector of nitrogenase. Demodification of P(II) by ammonium or NAD+ did not occur in cultures treated with an inhibitor of glutamine synthetase (methionine sulfoximine), whereas treatment with the glutamate synthase inhibitor 6-diazo-5-oxo-norleucine led to total demodification of P(II) without any other addition. The results indicate that P(II) probably is not directly involved in darkness switch-off of nitrogenase but that a role in ammonium switch-off cannot be excluded.


Exercise testing and indirect assessment of myocardial oxygen consumption in evaluation of angina pectoris.
Exercise testing is an important means of evaluating the patient with angina pectoris, providing objective data not available from conventional clinical assessment. In utilizing exercise to determine functional impairment in angina, it is essential to distinguish between external stress, or the load on the skeletal muscles, and internal or cardiac stress. Evaluation of external exercise capacity alone is limited as a measure of cardiac peformance since the relationship between external function and cardiac performance is not necessarily direct. A readily applicable approach to determination of cardiac capacity in angina is afforded by indirect assessment of myocardial oxygen consumption (MVO2). This is achieved through derived indexes utilizing heart rate and blood pressure, two major determinants of MVO2, in the form of the product of heart rate and systolic blood pressure. Although this approach does not encompass all the major determinants of MVO2, changes in the heart rate-blood pressure product bear a close correlation to alterations in directly measured MVO2. Within limits and employed with caution, indirect assessment of MVO2 is useful in elucidating mechanisms of action of extracardiac and intrinsic myocardial factors in the provocation and therapy of angina pectoris.


[Primary optic nerve meningioma].
Pathognomonic for primary optic nerve meningioma (intraorbital, intracanalicular or intracranial) is the diagnostic triad of progressive deterioration of vision (often over a period of years), primary optic atrophy and optociliary shunts ( Hoyt -Spencer sign) in a patient (frequently women) over 20 years of age. Above all at the beginning, the suspected diagnosis is retrobulbar neuritis. The correct diagnosis is made by computer tomography (enhancement with contrast, coronal sections). The author discusses whether surgical treatment ( orbitotomy or craniotomy) is to be preferred to conservative radiation therapy.


Live holding of red king crab (Paralithodes camtschaticus) and snow crab (Chionoecetes opilio) - Effect on microbial growth in processed leg meat during refrigerated storage.
The red king crab (RKC, Paralithodes camtschaticus) and snow crab (SC, Chionoecetes opilio) are valuable decapods that can undergo live holding (LH) in onshore facilities before either live export or processing into two cooked-frozen sections (i.e., clusters). This study investigated the effect of the LH time (up to two months without feeding) and temperature (5│10 °C for RKC; 1│5 °C for SC) on the total viable psychrotrophic count (TVCP) and Pseudomonas spp. in the leg meat of cooked RKC and SC. The effect of freezing after cooking was also evaluated. The counts were determined during storage at 4 °C after cooking on the clusters undergoing either immediate refrigeration (IR) or 24-month frozen storage before refrigeration (FBR). In the RKC cooked leg meat, the LH temperature significantly affected the TVCP, with LH at 10 °C leading to higher counts, while the Pseudomonas spp. levels were mainly influenced by the freezing, with lower levels in FBR samples compared to their IR counterparts. In the SC cooked leg meat, the LH conditions did not significantly affect the counts, which were instead significantly lowered by the freezing. From an industrial and commercial standpoint, it can be concluded that LH of RKC at high temperature (10 °C) led to a shorter microbial shelf-life of cooked RKC clusters, with the clusters undergoing FBR showing longer microbial shelf-life than their IR counterparts. By contrast, with the mild cooking regime applied, the LH time and temperature of SC had a lower influence on the microbial shelf-life of cooked SC clusters than that given by the choice of the storage type (IR or FBR) after cooking.


Experimental infection of pregnant gilts with Leptospira interrogans serovar mozdok.
Three pregnant gilts were experimentally infected with leptospires of the serovar mozdok, isolated from an aborted pig fetus from a Portuguese pig farm with abortion problems. All the gilts aborted dead or dying piglets on days 105 or 106 of pregnancy. Serovar mozdok was isolated from 12 of the 22 piglets in the three litters. Histological examination of the livers and kidneys of the gilts at the end of the experiment revealed evidence of disease, and leptospires were isolated from their kidneys. Their serological responses up to 42 days after inoculation were monitored by means of a microscopic agglutination test, using 21 antigens from 18 serogroups. Cross reactions to heterologous antigens belonging to the Grippotyphosa, Australis, Icterohaemorrhagiae and Cynopteri groups were observed in all of them.


Standard and long-acting depot neuroleptics in chronic schizophrenics: an 18-month open multicentric study.
The overall objective of this 18-month open study was to compare standard neuroleptics and long-acting depot neuroleptics following the current psychiatric practice in order to determine the best therapy. Thirty French psychiatrists from 15 different wards participated in this experiment. One hundred eighty-one chronic schizophrenic patients were randomly assigned to receive one of the following three treatments: standard neuroleptics, pipotiazine palmitate, or fluphenazine decanoate. Criteria used for evaluation were an overall clinical evaluation by a psychiatrist, a Brief Psychiatric Rating Scale, and a Nurse's Observation Scale for Inpatient Evaluation. No significant difference (P greater than .05) was observed between the three groups in drug effectiveness or tolerance.


Computerized health maintenance tracking systems: a clinician's guide to necessary and optional features. A report from the American Cancer Society Advisory Group on Preventive Health Care Reminder Systems.
To promote preventive health care by primary care physicians and the development of computerized health maintenance tracking systems, the American Cancer Society sponsored an expert advisory group to define necessary and desirable, but optional features of computer-based health maintenance tracking software for use in primary care practice. Systematic literature review and structured consensus development were followed by independent expert critique. Necessary input features include a comprehensive, practice-specific health maintenance protocol, multiple entry codes to indicate the current status of each procedure, and a mechanism for patient-specific exclusion or alteration of procedure frequency. Necessary features of the information management system include a linkage to a demographic data system, optional tracking of all or selected patients, identification of each patient's primary provider, and the ability to provide either a paper or electronic interface for the provider. Necessary outputs include provider reminders, patient reminders sent regularly regardless of visit status, and summary reports of provider and patient compliance. Although the ideal computer-based health maintenance tracking system is still evolving, knowledge of these necessary and optional features can aid clinicians interested in buying or developing a system for their own practice.


Exaggerated blood pressure response to static exercise in hindlimb ischemia-reperfusion.
Peripheral artery disease (PAD) reduces the blood flow supply in the affected limbs as one of the significant cardiovascular concerns. Revascularization surgery in the femoral artery plays a central role in treating PAD. Exercise is also a rehabilitation strategy suggested for PAD patients to improve vascular functions. However, the effects of limb ischemia-reperfusion (IR), one of the most predominant complications in revascularization surgery, on exercise-induced arterial blood pressure (BP) response are poorly understood. In the present study, we determined 1) the blood flow status in the hindlimb muscles of rats (plantar muscle, red and white portions of gastrocnemius) with different time points of the hindlimb IR; and 2) the BP response to static muscle contraction in rats at different time points after the blood flow reperfusion procedure. Results of this study indicated that, compared with the Sham group, the blood flow in the hindlimb muscles evaluated by Evans blue concentration was significantly reduced at 6 h of femoral artery occlusion (FAO 6 h) (vs. sham control, p < 0.05). The decreased blood flow was gradually recovered after the blood flow reperfusion for 18 (IR 18 h), 66 (IR 66 h), and 114 (IR 114 h) hours (p < 0.05 vs. FAO 6 h for all IR groups). The response of mean arterial pressure was 20 ± 4 mmHg in Sham rats (n = 7); 32 ± 10 mmHg in IR 18 h rats (n = 10); 27 ± 7 mmHg in IR 66 h rats (n = 13); 26 ± 4 mmHg in IR 114 h rats (n = 9) (p < 0.05 vs. Sham for all groups). No significant difference was observed in the peak-developed tension during muscle contraction among all the groups (p > 0.05). In conclusion, static exercise-induced BP response is exaggerated following IR. Whereas the BP response is not statistically significant but tends to decrease with a prolonged IR time, the exaggerated BP response remains through time points from post-IR 18 h-114 h.


Idiopathic Parkinson's disease: epidemiology, diagnosis and management.
Since the introduction of levodopa therapy for idiopathic Parkinson's disease over 20 years ago, there has been an awakening of research interest in this chronic neuro-degenerative disorder. This paper describes current understanding of the role of genetic and environmental factors in the aetiology of idiopathic Parkinson's disease and problems associated with both diagnosis and management. It briefly outlines both pharmacological and non-pharmacological options for treatment. Despite an increasing armoury of available treatments, the optimum management for this condition remains controversial.


A novel versatile concept of cardioplegia delivery in cardiac surgery: The ReverseTWO cardioplegia circuit system.
Nowadays, the necessity of having a cardioplegia circuit capable of being adapted in order to administer different types of cardioplegia is strategically fundamental, both for the perfusionist and for the cardiac surgeon. This allows to avoid cutting tubes, guarantees sterility and, most of all, limits the number of cardioplegia circuits for the different strategies of cardiac arrest. The novel "ReverseTWO cardioplegia circuit system" is the development of the precedent "Reverse system" where mainly the 4:1 and crystalloid cardioplegia were used, It has the advantage of allowing immediate change of cardioplegia set-up versus four types of cardioplegia technique, when the strategy is unexpectedly changed before the beginning of cardiopulmonary bypass (CPB), is safe and enables the perfusionist to use one single custom pack of cardioplegia. Two pediatric roller pumps are usually used in our centre for cardioplegia administration; they have a standardized calibration (the leading with ¼ inch and the follower with 1/8 inch) and the circuit consequently has two different tube diameters for the two different pumps. The presence in the circuit of two different shunts coupled with two different coloured clamps allows the immediate set-up for different cardioplegia administration techniques utilizing a colour-coding mechanism The aim of this manuscript is to present the new ReverseTWO Circuit. This novel system allows to administer four different cardioplegic solutions (4:1, 1:4, crystalloid, ematic) based on multiple tubes, which can be selectively clamped, identified through a color-coding method. The specificity of this circuit is the great versatility, which leads to numerous advantages, such as reduced risk of perfusion accident and reduced costs related not only to the purchase of different cardioplegia kits but also to the storage. https://youtu.be/ovJBE4ok2Ds.


Professional's Information Link (PiL): a web-based asynchronous consultation service.
Despite the massive growth of on-line information resources, many clinicians still prefer to obtain information from other clinicians, particularly those to whom they refer patients. Based on this notion and an information needs assessment, we developed the Professional's Information Link (PiL), a Web-based asynchronous consultation service to facilitate question answering between rural clinicians and an academic medical center. The system aims to provide answers to questions within two working days. It also includes patient handouts and continuing medical education resources. Our preliminary evaluation demonstrates modest but enthusiastic use of the system.


Evaluation of the internal and external biofidelity of current rear impact ATDs to response targets developed from moderate-speed rear impacts of PMHS.
The goal of this study is to evaluate both the internal and external biofidelity of existing rear impact anthropomorphic test devices (BioRID II, RID3D, Hybrid III 50th) in two moderate-speed rear impact sled test conditions (8.5g, 17 km/h; 10.5g, 24 km/h) by quantitatively comparing the ATD responses to biomechanical response targets developed from PMHS testing in a corresponding study. The ATDs and PMHS were tested in an experimental seat system that is capable of simulating the dynamic seat back rotation response of production seats. The experimental seat contains a total of fourteen load cells installed such that external loads from the ATDs and PMHS can be measured to evaluate external biofidelity. The PMHS were instrumented to correspond to the instrumentation contained in the ATDs so that direct comparison between ATDs and PMHS could be made to evaluate internal biofidelity. The NHTSA Biofidelity Ranking system was used to quantitatively evaluate the biofidelity of the ATDs and an additional tool was introduced and utilized which allows for the biofidelity score to be partitioned into components of amplitude, phase, and shape. For internal biofidelity, the BioRID II and RID3D were more biofidelic than the Hybrid III in the 17 km/h test, and the BioRID II was most biofidelic in the 24 km/h test. For external biofidelity, the BioRID II was most biofidelic in the 17 km/h test, while both the BioRID II and the RID3D were more biofidelic than the Hybrid III in the 24 km/h test. Overall, the BioRID II demonstrated the best biofidelity in both the 17 km/h and 24 km/h tests.


Renal neuraminidase. Characterization in normal rat kidney and measurement in experimentally induced nephrotic syndrome.
Several lines of evidence suggest that increased neuraminidase activity may be responsible for the loss of glomerular N-acetylneuraminic acid (AcNeu) observed in various glomerular diseases. However, virtually no information is available on the activity of neuraminidase in glomeruli or the potential role of this enzyme in glomerular pathophysiology. Utilizing 2'-(4-methylumbelliferyl)-alpha-D-N-acetylneuraminic acid (4MU-AcNeu) as substrate, we defined optimal assay conditions and characterized neuraminidase activity in glomeruli and, for comparison, in other renal fractions and liver. Neuraminidase activity in glomeruli, cortex and tubules was maximal at pH 4.4. The Km for 4MU-AcNeu was estimated to be 195 microM for glomeruli and 226 microM for cortex. Glomerular neuraminidase was inhibited by AcNeu (90% at 25 mM) and high concentrations of Triton X-100 (26% at 0.5%), but unaffected by CaCl2, EDTA or N-ethylmaleimide (each 1 mM). Neuraminidase activity (nmol/h per mg of protein; mean +/- S.E.M.) in normal rat kidney was: cortex, 14.47 +/- 0.76; medulla, 7.85 +/- 0.64; papilla, 2.64 +/- 0.11; tubules, 13.79 +/- 0.70; glomeruli, 5.57 +/- 0.28. In comparison, neuraminidase activity in rat liver was 2.58 +/- 0.14. Puromycin aminonucleoside (PAN)-induced nephrotic syndrome is a model of glomerular disease in which the loss of glomerular AcNeu is well documented. In two separate studies, we observed no change in the specific activity of neuraminidase in either glomeruli or cortex isolated from rats treated with PAN (15 mg/100 g, intraperitoneally) and killed at either the onset or the peak of proteinuria. Results were similar whether neuraminidase activity was expressed per mg of protein or per microgram of DNA.


Safety and efficacy of 2% chlorhexidine gluconate aqueous versus 2% chlorhexidine gluconate in 70% isopropyl alcohol for skin disinfection prior to percutaneous central venous catheter insertion in preterm neonates: the ARCTIC randomised-controlled feasibility trial protocol.
Catheter-related sepsis is one of the most dangerous complications of neonatal intensive care and is associated with significant morbidity and mortality. Use of catheter-care 'bundles' has reduced the incidence of catheter-related sepsis, although individual components have not been well studied. Better evidence is needed to guide selection of the most appropriate antiseptic solution for skin disinfection in preterm neonates. This study will inform the feasibility and design of the first randomised controlled trial to examine the safety and efficacy of alcohol-based versus aqueous-based chlorhexidine antiseptic formulations for skin disinfection prior to percutaneous central venous catheterisation in preterm neonates. The antiseptics to be compared are 2% chlorhexidine gluconate (CHG) aqueous and 2% CHG in 70% isopropyl alcohol. The Antiseptic Randomised Controlled Trial for Insertion of Catheters (ARCTIC) is a two-centre randomised-controlled feasibility trial. At least 100 preterm infants born at <34 weeks' gestation and due to undergo percutaneous insertion of a central venous catheter will be randomly allocated to receive prior skin disinfection with one of the two antiseptic solutions. Outcomes include: i) recruitment and retention rates; ii) completeness of data collection; iii) numbers of enrolled infants meeting case definitions for definite catheter-related sepsis, catheter-associated sepsis and catheter colonisation and iv) safety outcomes of skin morbidity scores recorded daily from catheter insertion until 48 hours post removal. The key feasibility metrics will be reported as proportions with 95% CIs. Estimated prevalence of catheter colonisation will allow calculation of sample size for the large-scale trial. The data will inform whether it will be feasible to progress to a large-scale trial. ARCTIC has been approved by the National Health Service Health Research Authority National Research Ethics Service Committee East of England (Cambridge South) (IRAS ID 163868), was adopted onto the National Institute of Health Research Clinical Research Network portfolio (CPMS ID 19899) and is registered with an International Standard Randomised Control Trials Number (ISRCTN: 82571474; Pre-results) and European Clinical Trials Database number 2015-000874-36. Dissemination plans include presentations at scientific conferences, scientific publications and sharing of the findings with parents via the support of Bliss baby charity. ISRCTN82571474; Pre-results.


Safety of interferon beta treatment for chronic HCV hepatitis.
Hepatitis C is a major cause of liver-related morbidity and mortality worldwide. In fact, chronic hepatitis C is considered as one of the primary causes of chronic liver disease, cirrhosis and hepatocellular carcinoma, and is the most common reason for liver transplantation. The primary objectives for the treatment of HCV-related chronic hepatitis is to eradicate infection and prevent progression of the disease. The treatment has evolved from the use of alpha-interferon (IFNalpha) alone to the combination of IFNalpha plus ribavirin, with a significant improvement in the overall efficacy, and to the newer PEG-IFNs which have further increased the virological response, used either alone or in combination with ribavirin. Despite these positive results, in terms of efficacy, concerns are related to the safety and adverse events. Many patients must reduce the dose of PEG-IFN or ribavirin, others must stop the treatment and a variable percentage of subjects are not suitable owing to intolerance toward drugs. IFNbeta represents a potential therapeutic alternative for the treatment of chronic viral hepatitis and in some countries it plays an important role in therapeutic protocols. Aim of the present paper was to review available data on the safety of IFNbeta treatment in HCV-related chronic hepatitis. The rates of treatment discontinuation and/or dose modification due to the appearance of severe side effects during IFNbeta are generally low and in several clinical studies no requirements for treatment discontinuation and/or dose modifications have been reported. The most frequent side effects experienced during IFNbeta treatment are flu-like syndromes, fever, fatigue and injection-site reactions. No differences in terms of side-effect frequency and severity between responders and non-responders have been reported. A more recent study, performed to compare IFNbeta alone or in combination with ribavirin, confirmed the good safety profile of both treatments. Similar trends of adverse event frequency have been observed in subpopulations such as patients with genotype-1b HCV hepatitis unresponsive to IFNalpha treatment or with HCV-related cirrhosis and patients with acute viral hepatitis. If further studies will confirm the efficacy of combined IFNbeta and ribavirin treatment, this regimen could represent a safe and alternative therapeutic option in selected patients.


Prevalence of BK polyomavirus infection and association with renal dysfunction in pediatric heart transplant recipients.
BK polyomavirus (BKV) infection and nephropathy complicate renal allografts; however, their effect in the native kidneys of pediatric heart transplant (HTx) recipients is unknown. We assessed the prevalence of BKV infection and its association with kidney dysfunction in survivors of pediatric HTx. A single-center retrospective study compared pediatric (aged <18 years ) HTx recipients, with and without BKV (controls), who received an allograft from May 1989 to July 2013. Screening of urine for BKV was performed in patients with chronic kidney disease (CKD) stage ≥2 since 2006, and since April 2012 in all HTx recipients at least at an annual evaluation. Serum for BKV DNA was assayed if BK viruria was present. Data collected included recipient and donor demographics, the immunosuppressive regimen, and history of Epstein-Bar virus (EBV) and cytomegalovirus infection. Statistics included Fisher's exact test, chi-square test, Student's t-test, and multivariate logistic regression. Of 98 eligible recipients, 83 (85%) were screened: 28 (34%) had BK viruria, and 7 had BK viremia. One viremic patient had biopsy-proven BKV nephropathy that progressed to end-stage renal disease. Risk factors for BK viruria were (1) longer duration since HTx (6.02 vs 2.95 years; p = 0.01), (2) worsening estimated glomerular filtration rate (71.3 vs 86.3 ml/min/1.73 m(2), p = 0.03), (3) history of EBV infection (p = 0.0002), and (4) use of sirolimus (p = 0.0003). After multivariate logistic-regression, only history of EBV infection remained associated with BKV infection (p = 0.015). BKV may lead to BK viremia and BK nephropathy in pediatric HTx patients. Routine screening for BK viruria should be considered.


Seasonal H3N2 and 2009 Pandemic H1N1 Influenza A Viruses Reassort Efficiently but Produce Attenuated Progeny.
Reassortment of gene segments between coinfecting influenza A viruses (IAVs) facilitates viral diversification and has a significant epidemiological impact on seasonal and pandemic influenza. Since 1977, human IAVs of H1N1 and H3N2 subtypes have cocirculated with relatively few documented cases of reassortment. We evaluated the potential for viruses of the 2009 pandemic H1N1 (pH1N1) and seasonal H3N2 lineages to reassort under experimental conditions. Results of heterologous coinfections with pH1N1 and H3N2 viruses were compared to those obtained following coinfection with homologous, genetically tagged, pH1N1 viruses as a control. High genotype diversity was observed among progeny of both coinfections; however, diversity was more limited following heterologous coinfection. Pairwise analysis of genotype patterns revealed that homologous reassortment was random while heterologous reassortment was characterized by specific biases. pH1N1/H3N2 reassortant genotypes produced under single-cycle coinfection conditions showed a strong preference for homologous PB2-PA combinations and general preferences for the H3N2 NA, pH1N1 M, and H3N2 PB2 except when paired with the pH1N1 PA or NP. Multicycle coinfection results corroborated these findings and revealed an additional preference for the H3N2 HA. Segment compatibility was further investigated by measuring chimeric polymerase activity and growth of selected reassortants in human tracheobronchial epithelial cells. In guinea pigs inoculated with a mixture of viruses, parental H3N2 viruses dominated but reassortants also infected and transmitted to cage mates. Taken together, our results indicate that strong intrinsic barriers to reassortment between seasonal H3N2 and pH1N1 viruses are few but that the reassortants formed are attenuated relative to parental strains.IMPORTANCE The genome of IAV is relatively simple, comprising eight RNA segments, each of which typically encodes one or two proteins. Each viral protein carries out multiple functions in coordination with other viral components and the machinery of the cell. When two IAVs coinfect a cell, they can exchange genes through reassortment. The resultant progeny viruses often suffer fitness defects due to suboptimal interactions among divergent viral components. The genetic diversity generated through reassortment can facilitate the emergence of novel outbreak strains. Thus, it is important to understand the efficiency of reassortment and the factors that limit its potential. The research described here offers new tools for studying reassortment between two strains of interest and applies those tools to viruses of the 2009 pandemic H1N1 and seasonal H3N2 lineages, which currently cocirculate in humans and therefore have the potential to give rise to novel epidemic strains.


Mid-term outcomes of the Absorb BVS versus second-generation DES: A systematic review and meta-analysis.
Bioresorbable Vascular Scaffolds (BVS) were introduced to overcome some of the limitations of drug-eluting stent (DES) for PCI. Data regarding the clinical outcomes of the BVS versus DES beyond 2 years are emerging. To study mid-term outcomes. We searched online databases (PubMed/Medline, Embase, CENTRAL), several websites, meeting presentations and scientific session abstracts until August 8th, 2017 for studies comparing Absorb BVS with second-generation DES. The primary outcome was target lesion failure (TLF). Secondary outcomes were all-cause mortality, myocardial infarction, target lesion revascularization (TLR) and definite/probable device thrombosis. Odds ratios (ORs) with 95% confidence intervals (CIs) were derived using a random effects model. Ten studies, seven randomized controlled trials and three propensity-matched observational studies, with a total of 7320 patients (BVS n = 4007; DES n = 3313) and a median follow-up duration of 30.5 months, were included. Risk of TLF was increased for BVS-treated patients (OR 1.34 [95% CI: 1.12-1.60], p = 0.001, I2 = 0%). This was also the case for all myocardial infarction (1.58 [95% CI: 1.27-1.96], p<0.001, I2 = 0%), TLR (1.48 [95% CI: 1.19-1.85], p<0.001, I2 = 0%) and definite/probable device thrombosis (of 2.82 (95% CI: 1.86-3.89], p<0.001 and I2 = 40.3%). This did not result in a difference in all-cause mortality (0.78 [95% CI: 0.58-1.04], p = 0.09, I2 = 0%). OR for very late (>1 year) device thrombosis was 6.10 [95% CI: 1.40-26.65], p = 0.02). At mid-term follow-up, BVS was associated with an increased risk of TLF, MI, TLR and definite/probable device thrombosis, but this did not result in an increased risk of all-cause mortality.


Importance of maintained atrio-ventricular synchrony in patients with pacemakers.
The effect of atrial contraction on cardiac function is reviewed in patients with dual chamber and rate-responsive ventricular pacemakers. The question posed was is there any haemodynamic, clinical or prognostic advantage of AV synchrony in dual chamber pacemakers in comparison to rate-responsive ventricular pacemakers? Optimal AV delay in dual chamber pacing favours cardiac performance at rest, while during exercise the increase in heart rate rather than AV synchrony influences cardiac performance and working capacity. However, there is little information on the benefit of maintained AV synchrony in patients' daily activities. Patients with pacemakers which maintain AV synchrony seem to have less morbidity and mortality than patients with ventricular stimulation alone, and there are comparable rates of complication in carriers of single and dual chamber pacemakers, the former showing problems with the pacemaker syndrome and the latter with atrial sensing and pacemaker-induced tachycardias. The disadvantage of dual chamber pacemakers are higher costs and time-consuming controls.


Does penis size influence condom slippage and breakage?
This study examined the effect of penis dimensions on the probability of complete condom slippage and condom breakage in actual use. Men were recruited through advertising, used the condoms supplied and completed a diary sheet for each condom used. A total of 3658 condoms were used by 184 men of which 1.34% broke and 2.05% slipped off. No significant effect was demonstrated for penile dimensions on the probability of complete condom slippage. However, condom breakage was strongly associated with penile circumference. These findings suggest that condom manufacturers may need to increase the range of condom sizes available, or some aspects of their performance, in order to ensure that condoms meet the needs of all men without unduly exposing them to risk.


BST2/Tetherin Overexpression Modulates Morbillivirus Glycoprotein Production to Inhibit Cell-Cell Fusion.
The measles virus (MeV), a member of the genus Morbillivirus, is an established pathogen of humans. A key feature of morbilliviruses is their ability to spread by virus-cell and cell-cell fusion. The latter process, which leads to syncytia formation in vitro and in vivo, is driven by the viral fusion (F) and haemagglutinin (H) glycoproteins. In this study, we demonstrate that MeV glycoproteins are sensitive to inhibition by bone marrow stromal antigen 2 (BST2/Tetherin/CD317) proteins. BST2 overexpression causes a large reduction in MeV syncytia expansion. Using quantitative cell-cell fusion assays, immunolabeling, and biochemistry we further demonstrate that ectopically expressed BST2 directly inhibits MeV cell-cell fusion. This restriction is mediated by the targeting of the MeV H glycoprotein, but not other MeV proteins. Using truncation mutants, we further establish that the C-terminal glycosyl-phosphatidylinositol (GPI) anchor of BST2 is required for the restriction of MeV replication in vitro and cell-cell fusion. By extending our study to the ruminant morbillivirus peste des petits ruminants virus (PPRV) and its natural host, sheep, we also confirm this is a broad and cross-species specific phenotype.


Return of motor function after segmental nerve loss in a rat model: comparison of autogenous nerve graft, collagen conduit, and processed allograft (AxoGen).
An effective alternative to nerve autograft is needed to minimize morbidity and solve limited-availability issues. We hypothesized that the use of processed allografts and collagen conduits would allow recovery of motor function that is equivalent to that seen after the use of autografts. Sixty-five Lewis rats were divided into three experimental groups. In each group, a unilateral 10-mm sciatic nerve defect was repaired with nerve autograft, allograft treated by AxoGen Laboratories, or a 2.0-mm-inner-diameter collagen conduit. The animals were studied at twelve and sixteen weeks postoperatively. Evaluation included bilateral measurement of the tibialis anterior muscle force and muscle weight, electrophysiology, assessment of ankle contracture, and peroneal nerve histomorphometry. Muscle force was measured with use of our previously described and validated method. Results were expressed as a percentage of the values on the contralateral side. Two-way analysis of variance (ANOVA) corrected by the Ryan-Einot-Gabriel-Welsch multiple range test was used for statistical investigation (α = 0.05). At twelve weeks, the mean muscle force (and standard deviation), as compared with that on the contralateral (control) side, was 45.2% ± 15.0% in the autograft group, 43.4% ± 18.0% in the allograft group, and 7.0% ± 9.2% in the collagen group. After sixteen weeks, the recovered muscle force was 65.5% ± 14.1% in the autograft group, 36.3% ± 15.7% in the allograft group, and 12.1% ± 16.0% in the collagen group. Autograft was statistically superior to allograft and the collagen conduit at sixteen weeks with regard to all parameters except histomorphometric characteristics (p < 0.05). The collagen-group results were inferior. All autograft-group outcomes improved from twelve to sixteen weeks, with the increase in muscle force being significant. The use of autograft resulted in better motor recovery than did the use of allograft or a collagen conduit for a short nerve gap in rats. A longer evaluation time of sixteen weeks after segmental nerve injuries in rats would be beneficial as more substantial muscle recovery was seen at that time.


High school science fair: Ethnicity trends in student participation and experience.
In this paper, we report ethnicity trends in student participation and experience in high school science and engineering fair (SEFs). SEF participation showed significant ethnic diversity. For survey students, the approximate distribution was Asian-32%; Black-11%; Hispanic-20%; White-33%; Other-3%. Comparing the SEF level at which students competed from school to district to region to state levels, we observed that black students made up only 4.5% of the students who participated in SEF beyond the school level, whereas students from other ethnic groups were more equally represented at all levels. The lower percentage of Black students resulted from a combination of lower overall participation in SEF and lower percentage of those students who did participate to advance to SEFs beyond the school level. Students who advanced to SEFs beyond the school level frequently received help from scientists, coaching for the interview, and were not required to participate in SEF. Black students received the least help from scientists, were least likely to receive coaching for the interview, and were most likely to be required to participate in SEF. They also were most likely to receive no help from parents, teachers, or scientists. Asian and Hispanic students (63.8% and 56.8%) indicated a greater interest in careers in science and engineering (S&E) compared to Black and White students (43.7% & 50.7%). In addition to career interest, the most important experiences that correlated with students who indicated that SEF increased their interests in S&E were getting help from the internet, books and magazines; getting help fine tuning the report; and overcoming obstacles by doing more background research, making a timeline, and perseverance. Black students did not report a positive effect of any of these strategies but experienced time pressure as more of an obstacle than did other students. Our findings identify a wide range of student experiences associated with positive SEF outcomes that could be enhanced for all students but especially Black students. More involvement of scientists in helping students who participate in SEFs would be particularly valuable.


Transient neonatal myasthenia gravis revealing a myasthenia gravis and a systemic lupus erythematosus in the mother: case report and review of the literature.
Transient neonatal myasthenia gravis (TNMG) and neonatal lupus are rare conditions due to the transplacental passage of antibodies. We describe a unique case of TNMG, revealing a myasthenia gravis (MG) associated with systemic lupus erythematosus (SLE) in the mother. J. M., 8 days of age, was admitted for jaundice. Examination revealed poor sucking, facial weakness, and hypotonicity. TNMG was confirmed with a high level of antiacetylcholine receptor antibodies in the infant and his mother. No sign of neonatal lupus was observed. Clinical recovery was obtained. The elder brother had autism. In case of previous maternal MG, a low percentage of infants develop TNMG (10 to 20%), but monitoring is required at birth. Improvement is usually obtained within 3 weeks. No correlation has been found between maternal symptoms, antibodies titer, and signs of TNMG. Most cases of neonatal lupus are associated with positive anti-SSA/SSB antibodies in the mother. Both conditions, MG and SLE, are reported, but pregnancies are very few. Autism in the brother focuses on its relationship with immune diseases.


Salivary gland pathologies: evolution in classification and association with unique genetic alterations.
The correct classification of salivary gland pathologies is crucial for choosing a treatment method and determining the prognosis. Better outcomes are now achievable thanks to the introduction of new therapy approaches, such as targeted therapies for malignant salivary gland tumors. To apply these in clinical routine, a clear classification of the lesions is required. The following review examines all changes from the first World Health Organization (WHO) Classification of salivary gland pathologies from 1972 to fifth edition from 2022. Possible developments in the diagnosis and classification of salivary gland pathology are also presented. The current WHO classification is the fifth edition. With the development of new diagnostic methods, based on genetic alterations, it provides insight into the molecular basis of lesions. This has resulted in the evolution of classification, introduction of new entities and reclassification of existing ones. Genetic alterations will become increasingly more significant in the identification of salivary gland pathologies in the future. These alterations will be helpful as prognostic and predictive biomarkers, and may also serve as targets for anti-cancer therapies.


The pentose moiety of adenosine and inosine is an important energy source for the fermented-meat starter culture Lactobacillus sakei CTC 494.
The genome sequence of Lactobacillus sakei 23K has revealed that the species L. sakei harbors several genes involved in the catabolism of energy sources other than glucose in meat, such as glycerol, arginine, and nucleosides. In this study, a screening of 15 L. sakei strains revealed that arginine, inosine, and adenosine could be used as energy sources by all strains. However, no glycerol catabolism occurred in any of the L. sakei strains tested. A detailed kinetic analysis of inosine and adenosine catabolism in the presence of arginine by L. sakei CTC 494, a fermented-meat starter culture, was performed. It showed that nucleoside catabolism occurred as a mixed-acid fermentation in a pH range (pH 5.0 to 6.5) relevant for sausage fermentation. This resulted in the production of a mixture of acetic acid, formic acid, and ethanol from ribose, while the nucleobase (hypoxanthine and adenine in the case of fermentations with inosine and adenosine, respectively) was excreted into the medium stoichiometrically. This indicates that adenosine deaminase activity did not take place. The ratios of the different fermentation end products did not vary with environmental pH, except for the fermentation with inosine at pH 5.0, where lactic acid was produced too. In all cases, no other carbon-containing metabolites were found; carbon dioxide was derived only from arginine catabolism. Arginine was cometabolized in all cases and resulted in the production of both citrulline and ornithine. Based on these results, a pathway for inosine and adenosine catabolism in L. sakei CTC 494 was presented, whereby both nucleosides are directly converted into their nucleobase and ribose, the latter entering the heterolactate pathway. The present study revealed that the pentose moiety (ribose) of the nucleosides inosine and adenosine is an effective fermentable substrate for L. sakei. Thus, the ability to use these energy sources offers a competitive advantage for this species in a meat environment.


Distinct effects in primary macrophages and lymphocytes of the human immunodeficiency virus type 1 accessory genes vpr, vpu, and nef: mutational analysis of a primary HIV-1 isolate.
Macrophages and lymphocytes are the two main targets for productive HIV-1 infection in vivo. To compare the effects of the "nonessential" HIV-1 accessory genes vpr, vpu, and nef on viral replication in these primary cell types, we generated a panel of mutant viruses derived from a molecularly cloned macrophage-tropic HIV-1 primary isolate. Mutant viruses had markedly different patterns of replication in macrophages, in contrast to lymphocytes in which differences were modest. Loss of vpr or vpu reduced viral antigen production in macrophages by up to 1000-fold, while replication in lymphocytes was only marginally affected. Loss of nef did not affect lymphocyte infection, but decreased replication in macrophages to a small extent. Mutation of multiple accessory genes restricted replication in both cell types, but to a much greater extent in macrophages, and frequently resulted in nonproductive infection. The degree to which replication depended on intact accessory genes varied in macrophages from different donors. The essential functions of these accessory genes in HIV-1 infection may be related to their combined effects in facilitating productive infection of macrophages.


Marker optimization for facial motion acquisition and deformation.
A long-standing problem in marker-based facial motion capture is what are the optimal facial mocap marker layouts. Despite its wide range of potential applications, this problem has not yet been systematically explored to date. This paper describes an approach to compute optimized marker layouts for facial motion acquisition as optimization of characteristic control points from a set of high-resolution, ground-truth facial mesh sequences. Specifically, the thin-shell linear deformation model is imposed onto the example pose reconstruction process via optional hard constraints such as symmetry and multiresolution constraints. Through our experiments and comparisons, we validate the effectiveness, robustness, and accuracy of our approach. Besides guiding minimal yet effective placement of facial mocap markers, we also describe and demonstrate its two selected applications: marker-based facial mesh skinning and multiresolution facial performance capture.


Optimization of extraction of genomic DNA from archived dried blood spot (DBS): potential application in epidemiological research & bio banking.
Background: Limited infrastructure is available to collect, store and transport venous blood in field epidemiological studies. Dried blood spot (DBS) is a robust potential alternative sample source for epidemiological studies & bio banking. A stable source of genomic DNA (gDNA) is required for long term storage in bio bank for its downstream applications. Our objective is to optimize the methods of gDNA extraction from stored DBS and with the aim of revealing its utility in large scale epidemiological studies. Methods: The purpose of this study was to extract the maximum amount of gDNA from DBS on Whatman 903 protein saver card. gDNA was extracted through column (Qiagen) & magnetic bead based (Invitrogen) methods. Quantification of extracted gDNA was performed with a spectrophotometer, fluorometer, and integrity analyzed by agarose gel electrophoresis. Result: Large variation was observed in quantity & purity (260/280 ratio, 1.8-2.9) of the extracted gDNA. The intact gDNA bands on the electrophoresis gel reflect the robustness of DBS for gDNA even after prolonged storage time. The extracted gDNA amount 2.16 - 24 ng/µl is sufficient for its PCR based downstream application, but unfortunately it can't be used for whole genome sequencing or genotyping from extracted gDNA. Sequencing or genotyping can be achieved by after increasing template copy number through whole genome amplification of extracted gDNA. The obtained results create a base for future research to develop high-throughput research and extraction methods from blood samples. Conclusion: The above results reveal, DBS can be utilized as a potential and robust sample source for bio banking in field epidemiological studies.


Considering the test performance for three class data using linear discriminant analysis: a case study.
The results of a European Centre for the Validation of Alternative Methods validation study on the embryonic stem (ES) cell test were used as an example for the test performance for "three-class" data using linear discriminant analysis (LDA). Applying LDA, a biostatistical prediction model was developed to assign test chemicals to three classes of embryotoxicity. Three endpoint values were identified to classify the embryotoxic potential of chemicals: a) the inhibition of differentiation of ES cells into cardiomyocytes (ID50), b) the decrease of viability of adult 3T3 cells (IC503T3), and c) the decrease of viability of ES cells (IC50D3) in an MTT cytotoxicity test. It could be demonstrated that an objective statistical method was required in order to minimise the probability of misclassification. The management team of the validation study defined performance criteria, taking into consideration the hit rate for three classes obtained just by chance. An additional purpose of the study reported here was to calculate a hypothetical prevalence and evaluate its influence on the classification results.


A Behavior Genetic Analysis of Pleasant Events, Depressive Symptoms, and Their Covariation.
Although pleasant events figure prominently in behavioral models of depression, little is known regarding characteristics that may predispose people to engage in pleasant events and derive pleasure from these events. The present study was conducted to evaluate genetic and environmental influences on the experience of pleasant events, depressive symptoms, and their covariation in a sample of 148 twin pairs. A multivariate twin modeling approach was used to examine the genetic and environmental covariance of pleasant events and depressive symptoms. Results indicated that the experience of pleasant events was moderately heritable and that the same genetic factors influence both the experience of pleasant events and depressive symptoms. These findings suggest that genetic factors may give rise to dispositional tendencies to experience both pleasant events and depression.


Activation of protein kinase C-zeta and phosphatidylinositol 3'-kinase and promotion of macrophage differentiation by insulin-like growth factor-I.
Phosphoinositides that are phosphorylated at the D3 position have been reported to activate an atypical, Ca2-independent protein kinase C (PKC) isoform designated PKC-zeta, and overexpression of this enzyme leads to monocytic differentiation. In this study, we cultured human HL-60 promyeloid cells with vitamin D3 and insulin-like growth factor-I (IGF-I), a 70-amino-acid peptide that activates phosphatidylinositol 3'-kinase (PI 3-kinase) in murine promyeloid cells. Two days later, the proportion of cells differentiating into macrophages in serum-free medium, as assessed by expression of the alpha-subunit of the beta2 integrin CD11b, increased from 5 +/- 1% to 25 +/- 3%. Addition of IGF-I increased the proportion of cells differentiating into CD11b-positive macrophages to 78 +/- 5%. In the absence of vitamin D3, IGF-I did not induce expression of CD11b (6 +/- 1%). The IGF-I-promoted macrophage differentiation was blocked specifically by preincubation of HL-60 cells with a mAb (alphaIR3) directed against the IGF type I receptor. Similarly, pretreatment of cells with either alphaIR3 or an IGF-binding protein, IGFBP-3, led to a 75% inhibition of CD11b expression when cells were cultured with vitamin D3 in serum-containing medium. IGF-I, but not vitamin D3, caused a sevenfold increase in the enzymatic activity of both PI 3-kinase and atypical PKC-zeta. Inhibition of IGF-I-inducible PI 3-kinase with either wortmannin or LY294002 abrogated the IGF-I-induced activation of PKC-zeta and totally blocked the enhancement in macrophage differentiation caused by IGF-I. These data establish that PKC-zeta is a putative downstream target of PI 3-kinase that is activated during IGF-I-promoted macrophage differentiation.


Operationally defined apoplastic and symplastic aluminum fractions in root tips of aluminum-intoxicated wheat.
Knowledge of the mechanistic basis of differential aluminum (Al) tolerance depends, in part, on an improved ability to quantify Al located in the apoplastic and symplastic compartments of the root apex. Using root tips excised from seedlings of an Al-tolerant wheat cultivar (Triticum aestivum L. cv Yecora Rojo) grown in Al solutions for 2 d, we established an operationally defined apoplastic Al fraction determined with six sequential 30-min washes using 5 mm CaCl(2) (pH 4.3). Soluble symplastic Al was eluted by freezing root tips to rupture cell membranes and performing four additional 30-min CaCl(2) washes, and a residual fraction was determined via digestion of root tips with HNO(3). The three fractions were then determined in Yecora Rojo and a sensitive wheat cultivar (Tyler) grown at 18, 55, or 140 mum total solution Al (Al(T)). When grown at equal Al(T), Tyler contained more Al than Yecora Rojo in all fractions, but both total Al and fractional distribution were similar in the two cultivars grown at Al(T) levels effecting a 50% reduction in root growth. Residual Al was consistently 50 to 70% of the total, and its location was elucidated by staining root tips with the fluorophore morin and examining them using fluorescence and confocal laser scanning microscopy. Wall-associated Al was only observed in tips prior to any washing, and the residual fraction was manifested as distinct staining of the cytoplasm and nucleus but not of the apoplastic space. Accordingly, the residual fraction was allocated to the symplastic compartment for both cultivars, and recalculated apoplastic Al was consistently approximately 30 to 40% of the total. Distributions of Al in the two cultivars did not support a symplastic detoxification hypothesis, but the role of cytoplasmic exclusion remains unsettled.


Characterization of Blood Immune Cells in Patients With Decompensated Cirrhosis Including ACLF.
Patients with cirrhosis and acute-on-chronic liver failure (ACLF) have immunosuppression, indicated by an increase in circulating immune-deficient monocytes. The aim of this study was to investigate simultaneously the major blood-immune cell subsets in these patients. Blood taken from 67 patients with decompensated cirrhosis (including 35 critically ill with ACLF in the intensive care unit), and 12 healthy subjects, was assigned to either measurements of clinical blood counts and microarray (genomewide) analysis of RNA expression in whole-blood; microarray (genomewide) analysis of RNA expression in blood neutrophils; or assessment of neutrophil antimicrobial functions. Several features were found in patients with ACLF and not in those without ACLF. Indeed, clinical blood count measurements showed that patients with ACLF were characterized by leukocytosis, neutrophilia, and lymphopenia. Using the CIBERSORT method to deconvolute the whole-blood RNA-expression data, revealed that the hallmark of ACLF was the association of neutrophilia with increased proportions of macrophages M0-like monocytes and decreased proportions of memory lymphocytes (of B-cell, CD4 T-cell lineages), CD8 T cells and natural killer cells. Microarray analysis of neutrophil RNA expression revealed that neutrophils from patients with ACLF had a unique phenotype including induction of glycolysis and granule genes, and downregulation of cell-migration and cell-cycle genes. Moreover, neutrophils from these patients had defective production of the antimicrobial superoxide anion. Genomic analysis revealed that, among patients with decompensated cirrhosis, those with ACLF were characterized by dysregulation of blood immune cells, including increases in neutrophils (that had a unique phenotype) and macrophages M0-like monocytes, and depletion of several lymphocyte subsets (including memory lymphocytes). All these lymphocyte alterations, along with defective neutrophil superoxide anion production, may contribute to immunosuppression in ACLF, suggesting targets for future therapies.


Supine Pharyngeal Width Is Associated With Complete Concentric Palatal Collapse During Drug-Induced Sleep Endoscopy and Hypoglossal Nerve Stimulator Outcomes.
Hypoglossal nerve stimulation (HNS) implantation in the US requires preoperative drug-induced sleep endoscopy (DISE) screening for complete concentric palatal collapse (CCC) to establish treatment candidacy. We hypothesized that supine pharyngeal width (SPW) in awake patients is associated with CCC and HNS therapy outcomes. Adults with moderate to severe obstructive sleep apnea underwent awake measurement of SPW followed by DISE screening for CCC. Eligible patients electing for HNS implantation underwent postoperative polysomnography per standard of care. SPW was measured in 73 patients. For SPW >20 mm, the positive likelihood ratio for absence of CCC was 6.67 with pre- and post-test odds of 6.3 and 42.0, respectively. Postoperative PSG data were available from 31 of 44 (70.5%) patients subsequently implanted with HNS. Patients with SPW >20 mm had a greater rate of HNS response than those with SPW ≤20 (62 vs 30%; P < .05). Only SPW and BMI were significantly associated with CCC and HNS response in regression models. In a retrospective cohort study, SPW was significantly associated with CCC and postoperative apnea-hypopnea index following HNS implantation. SPW may be a viable screening tool for HNS candidacy.


P2RX7 Enhances Tumor Control by CD8+ T Cells in Adoptive Cell Therapy.
Expression of the purinergic receptor P2RX7 by CD8+ T cells promotes the generation of memory populations following acute infections. However, data suggest that P2RX7 may limit the efficacy of antitumor responses. Herein, we show that P2RX7 is beneficial for optimal melanoma control in a mouse CD8+ T-cell adoptive transfer model. Tumor-specific P2rx7-/- CD8+ T cells exhibited impaired mitochondrial maintenance and function but did not display signs of overt exhaustion early in the antitumor response. However, as the tumor burden increased, the relative frequency of P2RX7-deficient CD8+ T cells declined within the tumor; this correlated with reduced proliferation, increased apoptosis, and mitochondrial dysfunction. Extending these studies, we found that the transient in vitro stimulation of P2RX7 using the ATP analogue BzATP led to enhanced B16 melanoma control by CD8+ T cells. These findings are in keeping with the concept that extracellular ATP (eATP) sensing by P2RX7 on CD8+ T cells is required for their ability to efficiently eliminate tumors by promoting mitochondrial fitness and underscore the potential for P2RX7 stimulation as a novel therapeutic treatment to enhance tumor immunotherapy.


Determination of vortioxetine and its degradation product in bulk and tablets, by LC-DAD and MS/MS methods.
Vortioxetine hydrobromide (VOR), is a novel antidepressant used for the treatment of major depressive disorder. It has a chemical structure susceptible to degradation, therefore it is important to have suitable analytical methods to determine VOR in presence of its main degradation products (DP), because if the compound degrades, this could result in diminution of the therapeutic activity and safety. A simple HPLC method with photodiode array detection was developed and validated for determination of VOR in bulk and tablets, in the presence of its major DP. The drug was subjected to oxidative, hydrolytic, and photolytic stress conditions, showing significant degradation under oxidation with the formation of one DP, which was identified by ESI-MS/MS. A C18 column was used, with mobile phase consisting of acetonitrile and water with acetic acid and triethylamine in isocratic elution mode, with detection at 228 nm and 1.0 mL/min flow rate. The assay was linear in the 25-125 μg/mL concentration range. For precision, the RSD was <1.8%, the recovery was 100.0-101.6%, and the method demonstrated adequate selectivity. The method was successfully applied to quantify VOR in tablets. The results showed that the method is useful for routine analysis and for quality control purposes.


Indigenous dadih lactic acid bacteria: cell-surface properties and interactions with pathogens.
Cell surface properties of dadih lactic acid bacteria strains were studied for adhesion to hydrocarbons (BATH) and aggregation abilities. Autoaggregation correlates with adhesion, which is a prerequisite for colonization and infection of the gastrointestinal tract by many pathogens, whereas coaggregation has been related to the ability to interact closely with pathogens. The results demonstrated significant differences in cell surface properties among the tested natural lactic acid bacteria food strains. Hydrophobicity increased when the cells were heat inactivated. All strains showed aggregation abilities with the pathogen strains tested, but the coaggregation properties were strain-specific. Our results indicate that the ability to autoaggregate, together with cell surface hydrophobicity and coaggregation abilities with pathogen strains, can be used for preliminary screening in order to identify potentially probiotic bacteria suitable for human or animal use. This study suggest the importance to identify and characterize bacterial cell-wall properties to understand their role in adhesion to hydrocarbons, autoaggregation and relation to coaggregation mechanisms, and also the relevance to future probiotic food development from natural strains.


Targeted Delivery of MicroRNA125a-5p by Engineered Lipid Nanoparticles for the Treatment of HER2 Positive Metastatic Breast Cancer.
MicroRNAs (miRNAs) are endogenous regulators of gene expression that play a pivotal role in biological processes spanning from global homeostasis to disease onset and progression. The ability to manipulate and induce cellular reequilibrium of deregulated miRNA expression profiles by inhibition of oncogenic miRNA or overexpression of tumor suppressor miRNA is a promising cancer strategy, but is currently hindered in application by the lack of nonviral delivery systems. Here we present a lipid nanoparticle (LNP) platform surface coated with Hyaluronic Acid (HA) for the delivery of mature tumor suppressor MicroRNA125a-5p to treat HER2 positive metastatic breast cancer. The delivery platform actively targets patient-derived metastatic breast cancer cells (21MT-1) isolated from the metastatic pleural effusion over normal breast tissue via an intrinsic HA-CD44 mediated endocytosis event, and has the ability to escape from the intracellular endolysosomal pathway for potent gene silencing. Knockdown of the HER2 proto-oncogene at the level of transcription and translation was achieved following HA-LNP mediated transfection with MicroRNA125a-5p. In addition, the PI3K/AKT and MAPK hyperactivated signaling pathways, cellular proliferation, and migration potential were also potently suppressed. Furthermore, the therapeutic efficacy of MicroRNA125a-5p by the HA-LNP platform was demonstrated to be significantly improved as compared to a commercial transfection reagent. This study highlights the therapeutic potential of MicroRNA125a-5p as a standalone treatment of HER2+ metastatic breast cancer via a translational nonviral delivery platform. These findings have major implications on future gene therapy regimens for breast cancer.


The benefit of minocycline on negative symptoms in early-phase psychosis in addition to standard care - extent and mechanism (BeneMin): study protocol for a randomised controlled trial.
Negative symptoms of psychosis do not respond to the traditional therapy with first- or second-generation antipsychotics and are among main causes of a decrease in quality of life observed in individuals suffering from the disorder. Minocycline, a broad-spectrum tetracyclic antibiotic displaying neuroprotective properties has been suggested as a new potential therapy for negative symptoms. In the two previous clinical trials comparing minocycline and placebo, both added to the standard care, patients receiving minocycline showed increased reduction in negative symptoms. Three routes to neuroprotection by minocycline have been identified: neuroprotection against grey matter loss, anti-inflammatory action and stabilisation of glutamate receptors. However, it is not yet certain what the extent of the benefit of minocycline in psychosis is and what its mechanism is. We present a protocol for a multi-centre double-blind randomised placebo-controlled clinical trial entitled The Benefit of Minocycline on Negative Symptoms of Psychosis: Extent and Mechanism (BeneMin). After providing informed consent, 226 participants in the early phase of psychosis will be randomised to receive either 100 mg modified-release capsules of minocycline or similar capsules with placebo for 12 months in addition to standard care. The participants will be tested for outcome variables before and after the intervention period. The extent of benefit will be tested via clinical outcome measures, namely the Positive and Negative Syndrome Scale score, social and cognitive functioning scores, antipsychotic medication dose equivalent and level of weight gain. The mechanism of action of minocycline will be tested via blood screening for circulating cytokines and magnetic resonance imaging with three-dimensional T1-weighted rapid gradient-echo, proton density T2-weighted dual echo and T2*-weighted gradient echo planar imaging with N-back task and resting state. Eight research centres in UK and 15 National Health Service Trusts and Health Boards will be involved in recruiting participants, performing the study and analysing the data. The BeneMin trial can inform as to whether in minocycline we have found a new and effective therapy against negative symptoms of psychosis. The European Union Clinical Trial Register: EudraCT 2010-022463-35 with the registration finalised in July 2011. The recruitment in the trial started in January 2013 with the first patient recruited in March 2013.


Myocardial infarction in women.
Cardiovascular disease is the leading cause of mortality in the United States regardless of gender. Women infrequently present with myocardial infarction as the initial presentation of coronary heart disease and have unrecognized infarctions more frequently than men. Myocardial infarction in women has a similar clinical presentation as in men, with the exception of an increased incidence of non-Q wave myocardial infarctions. Complications of acute infarction in women are probably similar although the majority of data has been drawn from studies involving predominantly men. Women do however experience more strokes and have less postinfarction pericarditis than their male counterparts. Left ventricular function remains the key prognostic determinant in both sexes. Recurrent infarction is increased in women with resultant elevated mortality rates. However, complex ventricular ectopy following myocardial infarction is not predictive of cardiovascular mortality in women. Early and late survival is decreased in women, an effect probably related to the increase in mean age of women as compared with men. Overall, gender distinctions are not usually made in the majority of studies involving myocardial infarction. As epidemiologic, pathophysiologic and clinical factors may be different regarding heart disease in women, further research in this important area is warranted.


CD301b+ Macrophages Are Essential for Effective Skin Wound Healing.
Regeneration of skin's barrier function after injury requires temporally coordinated cellular interactions between multiple cell types. Macrophages are essential inflammatory cells in skin wound regeneration. These cells switch their phenotype from inflammatory in the early regenerative stages to anti-inflammatory in the midstages of healing to coordinate skin repair. However, little is known about how different subsets of anti-inflammatory macrophages contribute to skin wound healing. Here, we characterize midstage macrophages (CD45(+)/CD11b(+)/F4-80(+)) and identify two major populations: CD206(+)/CD301b(+) and CD206(+)/CD301b(-). The numbers of CD206(+)/CD301b(+) macrophages increased concomitantly with repair, when the anti-inflammatory phenotype switch occurs in midstage healing. Using diphtheria toxin-mediated depletion models in mice, we show that selective depletion of midstage CD301b-expressing macrophages phenocopied wound healing defects observed in mice where multiple myeloid lineages are depleted. Additionally, when FACS-isolated subpopulations of myeloid cells were transplanted into 3-day wounds of syngeneic mice, only CD206(+)/CD301b(+) macrophages significantly increased proliferation and fibroblast repopulation. These data show that the CD301b-expressing subpopulation of macrophages is critical for activation of reparative processes during the midstage of cutaneous repair.


Finnish dentists as tobacco counselors.
The first nationwide survey of Finnish dentists' use of tobacco, their inquiring about and advising patients on tobacco use, and their attitudes toward anti-tobacco health education (ATHE) was carried out at the end of 1987. A questionnaire mailed to 540 dentists produced 435 answers (81%). One fourth of the male dentists and 6% of the female dentists currently were smokers, and 11% of men and 2% of women smoked daily. Information on smoking practices of patients was obtained always by 8%, often by 18%, and occasionally by 62% of the dentists. Four percent of the dentists advised always and 15% often their patients about smoking, and 62% did so occasionally. The majority of the dentists agreed that dentists should take part in ATHE and that dentists can encourage patients to stop using tobacco. The respondents supporting the involvement of dentists in ATHE reported having an active role in tobacco counseling (TC) significantly more frequently than those not sharing the idea of involvement. It was concluded that Finnish dentists could be a valuable resource in TC because of their positive attitudes.


Opportunities for better value wound care: a multiservice, cross-sectional survey of complex wounds and their care in a UK community population.
Complex wounds impose a substantial health economic burden worldwide. As wound care is managed across multiple settings by a range of healthcare professionals with varying levels of expertise, the actual care delivered can vary considerably and result in the underuse of evidence-based interventions, the overuse of interventions supported by limited evidence and low value healthcare. To quantify the number, type and management of complex wounds being treated over a two-week period and to explore variations in care by comparing current practices in wound assessment, prevention and treatment. A multiservice cross-sectional survey. This survey spanned eight community services within five Northern England NHS Trusts. The point prevalence of complex wounds in this community-based population was 16.4 per 10 000 (95% CI 15.9 to 17.0). Based on data from 3179 patients, antimicrobial dressings were being used as the primary dressing for 36% of patients with complex wounds. Forty per cent of people with leg ulcers either had not received the recommended Doppler-aided Ankle Brachial Pressure Index assessment or it was unclear whether a recording had been taken. Thirty-one per cent of patients whose most severe wound was a venous leg ulcer were not receiving compression therapy, and there was limited use of two-layer compression hosiery. Of patients with a pressure ulcer, 39% were not using a pressure-relieving cushion or mattress. Marked variations were found in care, underuse of evidence-based practices and overuse of practices that are not supported by robust research evidence. Significant opportunities for delivering better value wound care therefore exist. Efforts should now focus on developing strategies to identify, assess and disinvest from products and practices supported by little or no evidence and enhance the uptake of those that are.


Mild Copper-Catalyzed, l-Proline-Promoted Cross-Coupling of Methyl 3-Amino-1-benzothiophene-2-carboxylate.
Cu-catalyzed N-arylation is a useful tool for the chemical modification of aromatic heterocycles. Herein, an efficient carbon-nitrogen cross-coupling of methyl 3-amino-1-benzothiophene-2-carboxylate with a range of (hetero)aryl iodides using CuI, l-proline and Cs2CO3 in dioxane at moderate temperature is described. The procedure is an extremely general, relatively cheap, and experimentally simple way to afford the N-substituted products in moderate to high yields. The structures of the new heterocyclic compounds were confirmed by NMR spectroscopy and HRMS investigation.


A Straw Can Break a Neural Network's Back and Lead to Seizures-But Only When Delivered at the Right Time.
Loss of Neuronal Network Resilience Precedes Seizures and Determines the Ictogenic Nature of Interictal Synaptic Perturbations Chang WC, Kudlacek J, Hlinka J, et al. Nat Neurosci. 2018; 21(12):1742-1752. doi:10.1038/s41593-018-0278-y. PMID: 30482946. The mechanism of seizure emergence and the role of brief interictal epileptiform discharges (IEDs) in seizure generation are 2 of the most important unresolved issues in modern epilepsy research. We found that the transition to seizure is not a sudden phenomenon, but is instead a slow process that is characterized by the progressive loss of neuronal network resilience. From a dynamical perspective, the slow transition is governed by the principles of critical slowing, a robust natural phenomenon that is observable in systems characterized by transitions between dynamical regimes. In epilepsy, this process is modulated by synchronous synaptic input from IEDs. The IEDs are external perturbations that produce phasic changes in the slow transition process and exert opposing effects on the dynamics of a seizure-generating network, causing either antiseizure or proseizure effects. We found that the multifaceted nature of IEDs is defined by the dynamical state of the network at the moment of the discharge occurrence.


The status of telomerase enzyme activity in benign and malignant gynaecologic pathologies.
Telomeres are essential for the function and stability of eukaryotic chromosomes. Telomerase consists of three subunits: human telomerase reverse transcriptase (hTERT), human telomerase RNA (hTR), and telomerase protein 1 (TP1). The hTERT subunit determines the activity of telomerase as an enzyme and is detected in most human tumors and regenerative cells. Telomerase activity is a useful cancer-cell detecting marker in some types of cancers. The aim of this study was to assess of telomerase hTERT mRNA in gynaecological tumors for diagnosis of malignancy. Cross-sectional study. A total of 55 gynaecologic tumor samples (35 ovarian, 13 endometrial, 6 cervical and 1 placental site trophoblastic tumor tissue) were obtained at the time of surgery. Quantification of hTERT mRNA was performed in a real-time reverse transcriptase polymerase chain reaction (RT-PCR) using the LightCycler TeloTAGGG hTERT Quantification Kit. It was histopathologically detected that 18 of the tissue samples were malignant and 37 of the samples were benign. 16 of the malignant tissue samples (88.9%) and 3 (8.1%) (endometrial tissue in proliferative phase, mucinous cyst adenoma and endometriosis) of the benign tissue samples were found to be hTERT positive. With the presence of these data, sensitivity and specificity of hTERT for the diagnosis of malignancy were calculated to be 88.9% and 91.9%, respectively. It was suggested that the measurement of telomerase activity in gynaecologic tumors, except for endometrial tissue in the reproductive phase, is a valuable method for pathological investigation.


Understanding herders' stocking rate decisions in response to policy initiatives.
Overgrazing is widely accepted to be the main driver of grassland degradation. However, policies designed to reduce overgrazing are poorly understood in terms of their political acceptability and their effectiveness in improving the sustainability of grassland management. This study was conducted to explore herders' preferences across a range of policies aimed at reducing stocking rates and how those policies impact on their stocking rate decisions. Choice Modelling and Contingent Behavior methods were used in a survey distributed to a sample of Inner Mongolian herders. It was found that while increasing the extent of loan payments and subsidies were popular amongst the herder respondents; these policy options are predicted to have no significant effect on stocking rates. In contrast, less preferred policies such as increasing the probability of being caught exceeding stocking rate limits and increasing the financial penalties associated with such breaches would be effective in reducing grazing pressure. Only the policy of increasing pension payments was shown to be both popular amongst respondents and effective in reducing stocking rates. The results from this research provide useful information to policy makers in their consideration of new policy initiatives.


Crystal structure and a giant magnetoresistance effect in the new Zintl compound Eu3Ga2P4.
Single-crystalline samples of a new Zintl compound, Eu(3)Ga(2)P(4), have been synthesized by a Ga-flux method. Eu(3)Ga(2)P(4) is found to crystallize in a monoclinic unit cell, space group C2/c, isostructural to Ca(3)Al(2)As(4). The structure is composed of a pair of edge-shared GaP(4) tetrahedra, which link by corner-sharing to form Ga(2)P(4) two-dimensional layers, separated by Eu(2+) ions. Magnetic susceptibility showed a Curie-Weiss behavior with an effective magnetic moment consistent with the value for Eu(2+) magnetic ions. Below 15 K, ferromagnetic ordering was observed and the saturation magnetic moment was 6.6 μ(B). Electrical resistivity measurements on a single crystal showed semiconducting behavior. Resistivity in the temperature range between 280 and 300 K was fit by an activation model with an energy gap of 0.552(2) eV. The temperature dependence of the resistivity is better described by the variable-range-hopping model for a three-dimensional conductivity, suggesting that Eu-P bonds are involved in the conductivity. A large magnetoresistance, up to -30%, is observed with a magnetic field H = 2 T at T = 100 K, suggesting strong coupling of carriers with the Eu(2+) magnetic moment.


Assessment of cellular and serum proteome from tongue squamous cell carcinoma patient lacking addictive proclivities for tobacco, betel nut, and alcohol: Case study.
The intriguing molecular pathways involved in oral carcinogenesis are still ambiguous. The oral squamous cell carcinoma (OSCC) ranks as the most common type constituting more than 90% of the globally diagnosed oral cancers cases. The elevation in the OSCC incidence rate during past 10 years has an alarming impression on human healthcare. The major challenges associated with OSCC include delayed diagnosis, high metastatic rates, and low 5-year survival rates. The present work foundations on reverse genetic strategy and involves the identification of genes showing expressional variability in an OSCC case lacking addictive proclivities for tobacco, betel nut, and/or alcohol, major etiologies. The expression modulations in the identified genes were analyzed in 16 patients comprising oral pre-cancer and cancer histo-pathologies. The genes SCCA1 and KRT1 were found to down regulate while DNAJC13, GIPC2, MRPL17, IG-Vreg, SSFA2, and UPF0415 upregulated in the oral pre-cancer and cancer pathologies, implicating the genes as crucial players in oral carcinogenesis.


The concept of mental disorder. On the boundary between biological facts and social values.
Although the concept of mental disorder is fundamental to theory and practice in the mental health field, no agreed on and adequate analysis of this concept currently exists. I argue that a disorder is a harmful dysfunction, wherein harmful is a value term based on social norms, and dysfunction is a scientific term referring to the failure of a mental mechanism to perform a natural function for which it was designed by evolution. Thus, the concept of disorder combines value and scientific components. Six other accounts of disorder are evaluated, including the skeptical antipsychiatric view, the value approach, disorder as whatever professionals treat, two scientific approaches (statistical deviance and biological disadvantage), and the operational definition of disorder as "unexpectable distress or disability" in the revised third edition of the Diagnostic and Statistical Manual of Mental Disorders (American Psychiatric Association, 1987). The harmful dysfunction analysis is shown to avoid the problems while preserving the insights of these other approaches.


Energizing porters by proton-motive force.
It is generally accepted that the chemistry of water was the most crucial determinant in shaping life on earth. Among the more important chemical features of water is its dissociation into protons and hydroxyl ions. The presence of relatively high proton concentrations in the ambient solution resulted in the evolution of proton pumps during the dawn of life on earth. These proton pumps maintained neutral pH inside the cells and generated electrochemical gradients of protons (proton-motive force) across their membranes. The existence of proton-motive force enabled the evolution of porters driven by it that are most probably among the more primitive porters in the world. The directionality of the substrate transport by the porters could be to both sides of the membranes because they can serve as proton symporters or antiporters. One of the most important subjects of this meeting is the mechanism by which proton-motive and other ion-motive forces drive the transport processes through porters. Is there a common mechanism of action for all proton-driven porters? Is there some common partial reaction by which we can identify the way that porters are energized by proton-motive force? Is there a common coupling between proton movement and uptake or secretion of certain molecules? Even a partial answer to one of these questions would advance our knowledge... or confusion. As my mentor Efraim Racker used to say: 'If you are not totally confused you do not understand the issue'.


Characterization of Volatile Profiles of Six Popular Edible Mushrooms Using Headspace-Solid-Phase Microextraction Coupled with Gas Chromatography Combined with Chemometric Analysis.
The classification of six mushroom species (white beech, brown beech, button, oyster, king oyster, and enoki mushrooms) was successfully achieved using canonical discriminant analysis (CDA) on volatile metabolite data sets obtained by headspace-solid-phase microextraction gas chromatography (HS-SPME-GC). Twenty-seven major volatile compounds in six edible mushrooms were positively identified by HS-SPME-GC mass spectroscopy. The total volatile content was highest in brown beech mushroom (P < 0.05). Significant difference in volatile profile was observed between brown beach and white beech mushrooms. Button mushroom contained significantly higher contents of benzaldehyde and benzyl alcohol than the other mushrooms (P < 0.05). Oyster mushroom contained 1-octen-3-ol as the most prevalent volatile, representing 67% out of total volatiles. Hexanal (35.0%) and 1-octen-3-ol (22.5%) were the most abundant volatiles found in king oyster. Hexanal (29.1%) was the most prevalent volatile in enoki mushroom only. Several volatile pairs with very high positive correlation in their levels were identified, representing the highest correlation coefficient (r = 0.970) for the pair of t-2-octenal and 2,4-octandienal. CDA was much more efficient than principal component analysis for the differentiation of mushroom species. PRACTICAL APPLICATION: The present study provided the important information on the volatile metabolite profiles of popular six commercial mushroom species. The present data will be useful for the quality control of mushrooms cultivated in farms and mushroom products processed in food industry. The strategy of canonical discriminant analysis in combination with HS-SPME-GC could be expanded for the determining the authentication of mushroom species.