Balancing expectations amidst limitations: the dynamics of food decision-making in rural Kerala.
Food decision-making is a complex process and varies according to the setting, based on cultural and contextual factors. The study aimed to understand the process of food decision-making in households in rural Kerala, India, to inform the design of a dietary behaviour change intervention. Three focus group discussions (FGDs) and 17 individual interviews were conducted from September 2010 to January 2011 among 13 men and 40 women, between 23 and 75 years of age. An interview guide facilitated the process to understand: 1) food choices and decision-making in households, with particular reference to access; and 2) beliefs about foods, particularly fruits, vegetables, salt, sugar and oil. The interviews and FGDs were transcribed verbatim and analysed using qualitative content analysis. The analysis revealed one main theme: 'Balancing expectations amidst limitations' with two sub-themes: 'Counting and meeting the costs'; and 'Finding the balance'. Food decisions were made at the household level, with money, time and effort costs weighed against the benefits, estimated in terms of household needs, satisfaction and expectations. The most crucial decisional point was affordability in terms of money costs, followed by food preferences of husband and children. Health and the risk of acquiring chronic diseases was not a major consideration in the decision-making process. Foods perceived as essential for children were purchased irrespective of cost, reportedly owing to the influence of food advertisements. The role of the woman as the homemaker has gendered implications, as the women disproportionately bore the burden of balancing the needs and expectations of all the household members within the available means. The food decision-making process occurred at household level, and within the household, by the preferences of spouse and children, and cost considerations. The socio-economic status of households was identified as limiting their ability to manoeuvre this fine balance. The study has important policy implications in terms of the need to raise public awareness of the strong link between diet and chronic non-communicable diseases.


Flowerlike vanadium sesquioxide: solvothermal preparation and electrochemical properties.
A novel 3D hierarchical flowerlike vanadium sesquioxide (V(2)O(3)) nano/microarchitecture consisting of numerous nanoflakes is prepared via a solvothermal approach followed by an appropriate heating treatment. The as-obtained nanostructured V(2)O(3) flower is characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), Brunauer-Emmett-Teller (BET) analysis, and transmission electron microscopy (TEM) (or/and high-resolution TEM, HRTEM), and it is found that the V(2)O(3) flower is constructed by single-crystalline nanoflakes. Furthermore, it is demonstrated that the surface of the flowerlike V(2)O(3) material is composed of nanostructured pores, which derive from the adsorption/desorption of nitrogen, and that the pore-size distribution depends on the unique three-dimensional interconnection between nanoflakes and on their intrinsic properties. The electrochemical behavior of the V(2)O(3) flower for lithium-ion insertion/extraction in non-aqueous solution as well as the faradaic capacitance for pesudocapacitors in a neutral aqueous solution are also investigated. A reversible discharge capacity as high as 325 mA h g(-1) is obtained at a current density of 0.02 A g(-1) from a LiClO(4)/EC:DEC electrolyte solution (i.e. LiClO(4) in ethyl carbonate and diethyl carbonate). When used as the cathode material of pesudocapacitors in Li(2)SO(4), the flowerlike oxide displayed a very high initial capacitance of 218 F g(-1) at a current density of 0.05 A g(-1). We believe that the good performance of the flowerlike V(2)O(3) electrode is most probably due to its unique 3D hierarchical nano/microarchitecture, which shows that the electrochemical properties of a cathodic material do not only depend on the oxidation state of that material but also-to a large extent-on its crystalline structure and morphology. The aforementioned properties suggest that the present V(2)O(3) flower materials may have a great potential to be employed as electrode materials in rechargeable lithium batteries and pesudocapacitors.


Plasmonic holographic imaging with V-shaped nanoantenna array.
In this article, a novel method of holographic imaging with Au nanoantenna array is presented. In order to obtain the plasmonic holographic plate for a preset letter "NANO", the phase distribution of the hologram is firstly generated by the weighted Gerchberg-Saxton (GSW) algorithm, and then 16 kinds of V-shaped nanoantennas with different geometric parameters are designed to evenly cover the phase shift of 0 to 2π by finite-difference time-domain (FDTD) method. Through orienting these nanoantennas according to the phase distribution of the hologram, the plasmonic array hologram is obtained. Very good imaging quality is observed with our nanoantenna array hologram plate. This method can be used for holographic imaging of arbitrary shape, and may find potential applications in holographic memory, printing and holographic display.


[Clinical significance of assessment of the metabolism of connective-tissue biopolymers in patients with type 1 diabetes mellitus and with diabetic nephropathy].
The purpose of the case study was to define a degree of destructive changes in the connective tissue at different stages of diabetic nephropathy (DN) progression. One hundred and twenty eight DN patients with type 1 diabetes mellitus, disease duration-5 to 20 years (classification according C. Mogensen, 1983) were examined. Special biochemical tools were used to evaluate the connective-tissue condition. The parameters of metabolism of the connective-tissue biopolymers were investigated in blood, urea and saliva, i.e. general and sulphated glucosamine glycine (GAG), sialic acid (SA) and oxyproline fractions. The results showed an increasing value of total and sulphated GAG and SA with a worsening DN severity, which is indicative of a destruction degree of glycoprotein-complexes in the microvascular basal membranes. A high level of bound oxyproline fractions denotes the fibril-genesis processes, which start to activate yet at the preclinical DN stage. The changes detected previously in the parameters of metabolism of the connective-tissue biopolymers, as observed in DN patients, ensure a timely choice of a therapy and a proper monitoring of its efficiency.


Calcaneal insufficiency fractures following total knee arthroplasty: Classification and clinical findings.
Calcaneal insufficiency fracture (IF) following total knee arthroplasty (TKA) is a rare disorder. This study aimed to examine the prevalence and clinical findings of calcaneal IF following TKA. We retrospectively reviewed 3,585 consecutive patients undergoing primary TKA between 2012 and 2017 in four hospitals. Calcaneal IF following TKA was diagnosed by plain radiography or magnetic resonance imaging. First, we investigated the prevalence and clinical findings of calcaneal IF following TKA. Second, we classified calcaneal IF into three types based on its location: type 1, fracture by traction force around the Achilles tendon insertion; type 2, compression fracture around the posterior subtalar joint; and type 3, fracture by ground reaction force at the bottom of the calcaneus. Finally, we compared the clinical findings between calcaneal IF with and without TKA. Calcaneal IF following TKA was seen in 17 (0.5%) of the 3,585 patients undergoing primary TKA. All patients were female, with a mean age of 76.5 ± 5.9 years, relatively high body mass index (BMI), and osteoporosis. All fractures achieved bone union with conservative treatment. Type 1 fractures were the most common. Calcaneal IFs following TKA were significantly shorter in height and the patients had higher BMI than those without TKA. The locations of calcaneal IF following TKA varied, while only type 1 calcaneal IFs were seen in cases without TKA. However, there were no significant differences with regard to the bone union period or malunion between the two groups. Calcaneal IF should be suspected in patients presenting with ipsilateral foot pain following TKA, particularly in female patients with a relatively high BMI and osteoporosis. Calcaneal IF can be classified into three types based on the fracture location. These variations in calcaneal IF may be due to differences in conditions and changes in mechanical loading of the lower extremity and bone quality following TKA.


Study protocol for a comparative effectiveness trial of two models of perinatal integrated psychosocial assessment: the PIPA project.
Studies examining psychosocial and depression assessment programs in maternity settings have not adequately considered the context in which psychosocial assessment occurs or how broader components of integrated care, including clinician decision-making aids, may optimise program delivery and its cost-effectiveness. There is also limited evidence relating to the diagnostic accuracy of symptom-based screening measures used in this context. The Perinatal Integrated Psychosocial Assessment (PIPA) Project was developed to address these knowledge gaps. The primary aims of the PIPA Project are to examine the clinical- and cost-effectiveness of two alternative models of integrated psychosocial care during pregnancy: 'care as usual' (the SAFE START model) and an alternative model (the PIPA model). The acceptability and perceived benefit of each model of care from the perspective of both pregnant women and their healthcare providers will also be assessed. Our secondary aim is to examine the psychometric properties of a number of symptom-based screening tools for depression and anxiety when used in pregnancy. This is a comparative-effectiveness study comparing 'care as usual' to an alternative model sequentially over two 12-month periods. Data will be collected from women at Time 1 (initial antenatal psychosocial assessment), Time 2 (2-weeks after Time 1) and from clinicians at Time 3 for each condition. Primary aims will be evaluated using a between-groups design, and the secondary aim using a within group design. The PIPA Project will provide evidence relating to the clinical- and cost- effectiveness of psychosocial assessment integrated with electronic clinician decision making prompts, and referral options that are tailored to the woman's psychosocial risk, in the maternity care setting. It will also address research recommendations from the Australian (2011) and NICE (2015) Clinical Practice Guidelines. ACTRN12617000932369.


The effects of smoking and zinc on the oxidative reactions of human neutrophils.
Human neutrophils in whole blood and after isolation were examined for their capacity to produce superoxide anions when stimulated by zymosan. The isolation procedure caused neutrophils to lose some of this capacity. The neutrophils of smokers produced less particle-stimulated superoxide than those of non-smokers when the whole blood method was used but not when using isolated cells. Zinc inhibited this aspect of the respiratory burst of isolated neutrophils but enhanced it when the whole blood method was used. We emphasize the importance of methodology when interpreting results.


What comes first? How selective attentional processes regulate the activation of a motor routine in a manual search task.
An intriguing error has been observed in toddlers presented with a 3-location search task involving invisible displacements of an object, namely, the C-not-B task. In 3 experiments, the authors investigated the dynamics of the attentional focus process that is suspected to be involved in this task. In Experiment 1, 2.5-year-old children were tested on a new adaptation of the C-not-B task in which the opening of the experimenter's hand between cloths provided visual information about the correct localization of the toy. Children still emitted a strong response bias toward the last hiding place. In Experiment 2, 2.5-year-old children were tested on a new version of the task that was designed to investigate the role of the central location in the task. This 2nd experiment demonstrated that changing the hand's movement from A to C to B did not enable children to succeed in the task. In Experiment 3, 2.5-year-old children were tested in a situation that is analogous to the C-not-B with open hands task except for the fact that the experimenter dropped the toy under the 1st cloth in the path. Toddlers succeeded when the toy was hidden at Location A but not when it was hidden at Location B. Data indicate that attentional focus on the experimenter's hand motion is contingent on whether that stimulus is critical to performing the task. We argue that these findings provide a potential mechanism through which motor routines can be regulated in accordance with strategic intentions.


Clinical and neuroimaging correlates in a pilot randomized trial of aerobic exercise for major depression.
Aerobic exercise (AE) combined with pharmacotherapy is known to reduce depressive symptoms; however, studies have not focused on long-term AE for volumetric changes of brain regions (amygdala, thalamus, and nucleus accumbens [NAcc]) linked to the control of affective responses and hopelessness in individuals with major depression (MD). In addition, AE with motor complexity (AEMC) would be more effective than AE in causing brain plasticity. We compared the effects of 24 weeks of AE and AEMC combined with pharmacotherapy on clinical and volumetric outcomes in individuals with MD. Forty medicated individuals with MD were randomly assigned to nonexercising control (C), AE, and AEMC groups. The training groups exercised for 60 min, twice a week for 24 weeks. Clinical and volumetric outcomes were assessed before and after the 24 weeks. Effect size (ES) and confidence interval (CI) were calculated for within-group and between-groups changes. AE and AEMC reduced hopelessness (ES = -0.73 and ES = -0.62, respectively) and increased affective responses (ES = 1.24 and ES = 1.56, respectively). Only AE increased amygdala (ES = 0.27 left and ES = 0.34 right), thalamus (ES = 0.33 left and ES = 0.26 right) and left NAcc (ES = 0.54) volumes. AE was more effective than the C group in reducing hopelessness and causing brain plasticity. The changes in the right amygdala volume showed a strong trend in explaining 72 % of the changes in affective responses following AE (p = 0.06). Lack of posttraining follow-up and small sample size. These preliminary data indicate that AE combined with pharmacotherapy can cause clinical improvement and brain plasticity in individuals with MD.


FasL gene knock-down therapy enhances the antiglioma immune response.
Malignant glioma is a lethal form of brain cancer that is very difficult to treat. The aggressive behavior of these neoplasms and their limited responsiveness to therapy has been attributed in part to the ability of these tumors to evade the immune system. Gliomas, like many other solid tumors, express components of numerous immune escape mechanisms, including immunosuppressive proteins such as TGF-beta, IL-10, and FasL. Here, we show that FasL expression can support the growth of experimental intracranial glioma. We show that FasL is readily detected in human glioblastoma multiforme clinical specimens. FasL was found to be expressed by three well-characterized rat glioma cell lines (9L, F98, and C6) and glioma cell-derived FasL mediated the death of phytohemagglutinin-stimulated Jurkat T-lymphocytes when cocultured with glioma cells in vitro. We asked if inhibiting 9L-derived FasL altered the growth of experimental glioma. FasL expression knockdown using shRNA reduced the growth of subcutaneous and intracranial 9L gliomas by approximately 50% in immune competent Fisher 344 rats. In contrast, FasL expression knockdown had no affect on the growth of intracranial 9L glioma in T-cell deficient athymic rats. Intracranial tumors derived from FasL knockdown 9L glioma cells contained up to 3-fold more tumor infiltrating T-cells than tumors derived from control 9L cells. These results demonstrate that down-regulating FasL expression and/or function in glial malignancies can enhance T-cell tumor infiltration and inhibit tumor growth. The findings suggest that targeting endogenous FasL in glial malignancies could enhance the efficacy of emerging immune-based treatment strategies.


Haemodynamic effects of hyperbaric hyperoxia in healthy volunteers: an echocardiographic and Doppler study.
In the present study, we observed the haemodynamic changes, using echocardiography and Doppler, in ten healthy volunteers during 6 h of compression in a hyperbaric chamber with a protocol designed to reproduce the conditions as near as possible to a real dive. Ambient pressure varied from 1.6 to 3 atm (1 atm=101.325 kPa) and partial pressure of inspired O2 from 1.2 to 2.8 atm. Subjects performed periods of exercise with breathing through a closed-circuit self-contained underwater breathing apparatus (SCUBA). Subjects did not eat or drink during the study. Examinations were performed after 15 min and 5 h. After 15 min, stroke volume (SV), left atrial (LA) diameter and left ventricular (LV) end-diastolic diameter (LVEDD) decreased. Heart rate (HR) and cardiac output (CO) did not vary, but indices of the LV systolic performance decreased by 10% and the LV meridional wall stress increased by 17%. After 5 h, although weight decreased, the serum protein concentration increased. Compared with values obtained after 15 min, SV and CO decreased, but LV systolic performance, LA diameter, LVEDD and LV meridional wall stress remained unchanged. Compared with the reference values obtained at sea level, total arterial compliance decreased, HR remained unchanged and CO decreased. In conclusion, hyperbaric hyperoxia results in significant haemodynamic changes. Initially, hyperoxia and the SCUBA system are responsible for reducing LV preload, increasing LV afterload and decreasing LV systolic performance, although CO did not change. Prolonged exposure resulted in a further decrease in LV preload, because of dehydration, and in a further increase in LV afterload, due to systemic vasoconstriction, with the consequence of decreasing CO.


Are recommended daily allowances for vitamin C adequate?
The Recommended Dietary Allowance of vitamin C (ascorbic acid) for adults has now been set at 45 mg day(-1) by the U.S. Food and Nutrition Board. This intake suffices to prevent scurvy in most people. It is, however, much less than the optimum intake, the intake that leads to the best of health. A larger intake decreases the incidence and severity of the common cold and other diseases. Ascorbic acid has antiviral and antibacterial activity and is required for phagocytic activity of leukocytes. Several arguments indicate that for different human beings the optimum intake lies between 250 mg day(-1) and a much higher value, 5000 mg day(-1) or more. It is proposed that the present Recommended Dietary Allowance of 45 mg day(-1) of vitamin C for adults be renamed the Minimum Dietary Allowance, defined as the amount needed to prevent scurvy, and that, after consideration of the evidence about intake and the best of health, there be formulated another category of values, the Recommended Daily Intake, with the suggested range of 250 mg day(-1) to 4000 mg day(-1) of ascorbic acid for an adult.


Gestational Trophoblastic Neoplasia Treatment at the Butaro Cancer Center of Excellence in Rwanda.
Gestational trophoblastic neoplasia (GTN) is a highly treatable disease, most often affecting young women of childbearing age. This study reviewed patients managed for GTN at the Butaro Cancer Center of Excellence (BCCOE) in Rwanda to determine initial program outcomes. A retrospective medical record review was performed for 35 patients with GTN assessed or treated between May 1, 2012, and November 30, 2014. Stage, risk score, and low or high GTN risk category were based on International Federation of Gynecology and Obstetrics staging and the WHO scoring system and determined by beta human chorionic gonadotropin level, chest x-ray, and ultrasound per protocol guidelines for resource-limited settings. Pathology reports and computed tomography scans were assessed when possible. Treatment was based on a predetermined protocol stratified by risk status. Of the 35 patients (mean age, 32 years), 26 (74%) had high-risk and nine (26%) had low-risk disease. Nineteen patients (54%) had undergone dilation and curettage and 11 (31%) had undergone hysterectomy before evaluation at BCCOE. Pathology reports were available in 48% of the molar pregnancy surgical cases. Systemic chemotherapy was initiated in 30 of the initial 35 patients: 13 (43%) received single-agent oral methotrexate, 15 (50%) received EMACO (etoposide, methotrexate, dactinomycin, cyclophosphamide, and vincristine), and two (7%) received alternate regimens. Of the 13 patients initiating methotrexate, three had their treatment intensified to EMACO. Four patients experienced treatment delays because of medication stockouts. At a median follow-up of 7.8 months, the survival probability for low-risk patients was 1.00; for high-risk patients, it was 0.63. This experience demonstrates the feasibility of GTN treatment in rural, resource-limited settings. GTN is a curable disease and can be treated following the BCCOE model of cancer care.


The association between premature plantarflexor muscle activity, muscle strength, and equinus gait in patients with various pathologies.
This study provides an overview on the association between premature plantarflexor muscle activity (PPF), muscle strength, and equinus gait in patients with various pathologies. The purpose was to evaluate whether muscular weakness and biomechanical alterations are aetiological factors for PPF during walking, independent of the underlying pathology. In a retrospective design, 716 patients from our clinical database with 46 different pathologies (orthopaedic and neurologic) were evaluated. Gait analysis data of the patients included kinematics, kinetics, electromyographic activity (EMG) data, and manual muscle strength testing. All patients were clustered three times. First, patients were grouped according to their primary pathology. Second, all patients were again clustered, this time according to their impaired joints. Third, groups of patients with normal EMG or PPF, and equinus or normal foot contact were formed to evaluate the association between PPF and equinus gait. The patient groups derived by the first two cluster methods were further subdivided into patients with normal or reduced muscle strength. Additionally, the phi correlation coefficient was calculated between PPF and equinus gait. Independent of the clustering, PPF was present in all patient groups. Weak patients revealed PPF more frequently. The correlations of PPF and equinus gait were lower than expected, due to patients with normal EMG during loading response and equinus. These patients, however, showed higher gastrocnemius activity prior to foot strike together with lower peak tibialis anterior muscle activity in loading response. Patients with PPF and a normal foot contact possibly apply the plantarflexion-knee extension couple during loading response. While increased gastrocnemius activity around foot strike seems essential for equinus gait, premature gastrocnemius activity does not necessarily produce an equinus gait. We conclude that premature gastrocnemius activity is strongly associated with muscle weakness. It helps to control the knee joint under load independent from the underlying disease, and it is therefore a secondary deviation. If treated as primary target, caution should be exercised.


Persistent Theiler's murine encephalomyelitis virus infection in mice depends on plaque size.
Theiler's murine encephalomyelitis virus (TMEV) is an enteric pathogen of mice which causes acute and chronic neurological disorders in the natural host. When brain-derived stocks of TMEV isolates are adapted to cell culture they predominantly form either large or small plaques. In this study the type of central nervous system (CNS) infection (acute versus chronic) and the associated disease occurring in mice inoculated intracerebrally with large and small plaque strains of TMEV was investigated. Large and small plaque strains of TMEV were found to vary in virulence, type of neurological disease produced and ability to establish persistent CNS infection in mice. Two large plaque strains, GDVII and FA viruses, were highly virulent, produced acute encephalitis, but were cleared from the nervous systems of surviving animals. Therefore, it appears that these large plaque variants do not cause persistent CNS infection in mice. In contrast, five small plaque strains, DA, WW, TO4, Yale and BeAn8386 viruses, were relatively avirulent, usually produced no illness during the first month after inoculation, but readily established persistent CNS infection in mice. Persistently infected mice later developed demyelinating disease. Having identified strains of TMEV that differ regarding their ability to persist, we now hope to be able to exploit this difference in elucidating the basic mechanism(s) of TMEV persistence.


Evaluation of unilateral cleft lip and palate treatment: long term results.
Fifty-seven consecutive complete unilateral cleft lip and palate patients were followed longitudinally from birth to 21 years of age. All patients were operated with the same primary surgical procedures. Reevaluation at age 21 with respect to speech, dental condition, need for secondary surgery, and skeletal and soft tissue facial growth was completed. Speech results indicated that 13 patients (23 percent) had required a pharyngeal flap, and that at age 21 only one patient still had unacceptable speech. The majority of patients had slight speech disturbances related to articulation and voice quality. Fifty-one patients had acceptable occlusion following orthodontic treatment, twenty-two patients (39 percent) without need for prosthodontic treatment of the cleft area. Secondary surgery for correction of nasal deformities was required for fifty-two patients. Growth analysis demonstrated deficiency in growth; however, normal and acceptable profiles were obtained in 50/57 of the patients.


Lisuride infusion pump: a device for the treatment of motor fluctuations in Parkinson's disease.
Intravenous levodopa or lisuride infusions can successfully reduce daily motor fluctuations in Parkinson's disease, which indicates adequate striatal dopaminergic mechanisms even in severe cases. In 3 patients who received continuous subcutaneous administration of lisuride, by means of a portable mini-infusion pump, in addition to oral levodopa plus decarboxylase inhibitor, mobility improved considerably and "off" periods were reduced or abolished. This response was maintained for 4 to 7 months without toxic side-effects, but increased dyskinetic movements were observed. All 3 patients were discharged and have been able to live independently during the months on treatment. These results suggest that continuous dopaminergic stimulation with the use of a portable delivery system can be a practical therapeutic tool in parkinsonian patients with complicated motor fluctuations.


Red cell alloimmunization in sickle-cell anaemia patients.
This study in King Fahd Hospital of the University, Saudi Arabia, assessed the frequency of alloimmunization to red cell antigens in sickle-cell anaemia patients over 1996-2004 in order to evaluate the risk of alloimmunization and identify the most common alloantibodies. A retrospective analysis of the transfusion history and medical records of 350 patients aged 2 to 75 years who had received at least 1 transfusion found that 48 patients had developed alloantibodies (13.7%). The most common alloantibodies detected were: anti-E alone (18.8%), nonspecific (12.5%), inconclusive (12.5%), anti-K (10.4%) and anti-c 3 (6.3%). Some patients had 1 alloantibody, while others more than 1 and even multiple antibodies. Nine patients had a persistent positive direct antiglobulin test.


On the Aggregation and Nucleation Mechanism of the Monoclonal Antibody Anti-CD20 Near Liquid-Liquid Phase Separation (LLPS).
The crystallization of Anti-CD20, a full-length monoclonal antibody, has been studied in the PEG400/Na2SO4/Water system near Liquid-Liquid Phase Separation (LLPS) conditions by both sitting-drop vapour diffusion and batch methods. In order to understand the Anti-CD20 crystallization propensity in the solvent system of different compositions, we investigated some measurable parameters, normally used to assess protein conformational and colloidal stability in solution, with the aim to understand the aggregation mechanism of this complex biomacromolecule. We propose that under crystallization conditions a minor population of specifically aggregated protein molecules are present. While this minor species hardly contributes to the measured average solution behaviour, it induces and promotes crystal formation. The existence of this minor species is the result of the LLPS occurring concomitantly under crystallization conditions.


T cell depletion in untreated adult coeliac disease.
The proportional and absolute numbers of circulating thymus dependent lymphocytes (T cells) were reduced in untreated patients with coeliac disease but were normal after treatment with a gluten free diet. There was an inverse correlation between circulating T cell numbers and jejunal intraepithelial lymphocytes. This evidence suggests a possible role for T cells in the pathogenesis of coeliac disease and is a further example of disturbed cell mediated immunity in this condition.


Immunological effects of anti-coagulant unfractionated heparin in pregnant Chinese women with cryptic recurrent miscarriages.
Anti-coagulant unfractionated heparin of low molecular weight (ACUHlmw) therapy is popularly practised in the therapy of recurrent miscarriages (RMC) due to its anti-coagulant properties. However, several in vitro investigations have hypothesized about the possible immunological effects of ACUHlmw. We examined pregnant women with cryptic RMC (cRMC) to determine whether ACUHlmw could regulate the immune reaction in vivo during their pregnancy. In this study, a total of 51 women were subjected to tinzaparin and 48 patients were considered as control women on the basis of an open single-centre randomized controlled trial. During different fertilization weeks (FW) 7, 19, 29, and 35 plasma samples were acquired for eleven chemokine and cytokine levels and then investigated by multiplex bead technology and selected to portray T-helper subset-related immunity. We did not find any difference in chemokine C-C motif ligand-2, -17, -22, chemokine C-X-C motif ligand-1, -8, -12, -13 or cytokine interleukin-6 when a mixed linear model test was carried out on ACUHlmw in both the study and control women. However, differences were observed in the mixed linear model test on ACUHlmw in both the study and control women during pregnancy of the Th1/Th17 related chemokine C-X-C motif ligand-10 (p = 0.01), -11 (p < 0.001) and chemokine C-C motif ligand-20 (p = 0.04) respectively. A positive outcome of ACUHlmw therapy in vivo was observed, thus establishing its potential proinflammatory effect. During 2nd and 3rd trimesters, the observed harmonious enlargement in Th1/Th17 related chemokine and cytokine levels does not recommend a fruitful immunological impact of ACUHlmw therapy in vivo.


Motor conduction velocity in the human spinal cord: slowed conduction in multiple sclerosis and radiation myelopathy.
Transcutaneous electrical stimulation of the central nervous system was used to measure motor conduction velocity in the human spinal cord in 21 subjects aged 22 to 75 years (mean 55 years), none of whom had neurological disease. The motor conduction velocity between the sixth cervical (C6) and first lumbar (L1) vertebral levels was 67.4 +/- 9.1 m/s. This probably represents conduction velocity in the corticospinal tracts. In these subjects the motor conduction velocity in the cauda equina, between the first lumbar (L1) and fourth lumbar (L4) vertebral levels, was 57.9 +/- 10.3 m/s. In four of five patients with multiple sclerosis, all with corticospinal signs in the legs, motor conduction velocity between C6 and L1 was slowed (41.8 +/- 16.8 m/s), but cauda equina conduction was normal (55.8 +/- 7.8 m/s). Similar slowing of spinal cord motor conduction was found in a patient with radiation myelopathy. This method should provide a relevant, simple clinical test in patients with spinal cord disease.


Comparative imaging technologies in the cardiac catheterization laboratory.
Evaluation of digital technology in the cardiac cath lab has introduced a desire to extend these technologies into electronic storage capability. Cine film is the current standard for image archiving because it meets the most important requirements of superior resolution, long-term stability, universal viewing and single-patient unit record capabilities. The major limitations of film include serial viewing (versus random access) and its incompatibility with computer techniques, such as quantitative angiography. Manufacturers and vendors have introduced several archiving alternatives that address the limitations of film. These options currently require trade offs and/or compromises in image quality, longevity, cost and numerous other requirements. Investments in alternatives should be made after comprehensive review of the expected productivity gains, anticipated media, equipment and supporting service cost improvements and prospective technological enhancements. This article has introduced a number of the issues that should be considered in comparing archiving media. As technology evolves and standards are developed, this task will become easier. In the meantime, no system to date has been able to achieve the existing advantages of film while overcoming its limitations.


Thrombin regulation of endothelin-1 gene in isolated human pulmonary endothelial cells.
Endothelin (ET)-1 is a potent vasoconstrictor elicited from endothelial cells in response to a variety of stimuli and an important mediator for a variety of vascular diseases including pulmonary hypertension. In this paper, we describe the molecular regulation of the ET-1 gene in response to a vasoactive mediator, thrombin, in human pulmonary endothelial cells. Thrombin induces preproET-1 mRNA through a transcriptionally dependent mechanism, with a peak induction after 1 h of exposure. Analysis of chromatin structure identified several DNase I-hypersensitive regions under both basal and thrombin-stimulated conditions that reside in the 5'-promoter region, indicating that the ET-1 promoter is a constitutive promoter. Deletion analysis was employed as a functional assay to identify regions of the ET-1 promoter that are important in transcriptional regulation. We found that sites between -141 and -378 bp are essential for basal activity and that those between -378 and -484 bp are essential for thrombin-stimulated activity. However, full expression under both conditions required an element(s) within -952 bp.


Genetic variability maintained in a finite population under mutation and autocorrelated random fluctuation of selection intensity.
By using the diffusion equation method, the level of genetic variability maintained under mutation pressure in a finite population is investigated, assuming autocorrelated random fluctuation of selection intensity. An appropriate mathematical model was formulated to treat the change of gene frequencies, incorporating mutation pressure and fluctuating selection. Extensive Monte Carlo simulation experiments were also performed to supplement the theoretical treatments. Excellent agreement between the two results suggests the validity of the present diffusion model for the autocorrelated selection. One of the most important findings from the simulation studies is that mutations and random sampling drift largely determine the level of genetic variability, and that the presence of autocorrelated selection can significantly lower genetic variability only when its strength, as measured by the cumulative variance of selection intensity, is larger than about 10(3) times the mutation rate. It is pointed out that the effects of both mutations and random sampling drift have to be incorporated in order to assess the role of various factors for the maintenance of genetic variability in natural populations.


Lower impact forces but greater burden for the musculoskeletal system in running shoes with greater cushioning stiffness.
In a recent randomised trial investigating running shoe cushioning, injury risk was greater in recreational runners who trained in the shoe version with greater cushioning stiffness (Stiff) compared to those using the Soft version. However, vertical impact peak force (VIPF) was lower in the Stiff version. To investigate further the mechanisms involved in the protective effect of greater cushioning, the present study used an intra-subject design and analysed the differences in running kinematics and kinetics between the Stiff and Soft shoe versions on a subsample of 41 runners from the previous trial. Data were recorded in the two shoe conditions using an instrumented treadmill at 10 km.h-1. VIPF was confirmed to be lower in the Stiff version compared to the Soft version (1.39 ± 0.25 vs. 1.50 ± 0.25 BW, respectively; p = 0.009, d = 0.42), but not difference was observed in vertical loading rate (p = 0.255 and 0.897 for vertical average and instantaneous loading rate, respectively). Ankle eversion maximal velocity was not different (p = 0.099), but the Stiff version induced greater ankle negative work (-0.55 ± 0.09 vs. -0.52 ± 0.10 J.kg-1; p = 0.009, d = 0.32), maximal ankle negative power (-7.21 ± 1.90 vs. -6.96 ± 1.92 W.kg-1; p = 0.037, d = 0.13) and maximal hip extension moment (1.25 ± 0.32 vs.1.18 ± 0.30 N.m.kg-1; p = 0.009, d = 0.22). Our results suggest that the Stiff shoe version is related to increased mechanical burden for the musculoskeletal system, especially around the ankle joint.Trial registration: ClinicalTrials.gov identifier: NCT03115437.


On the formulation of the image reconstruction problem in magnetic particle imaging.
In magnetic particle imaging (MPI), the spatial distribution of magnetic nanoparticles is determined by applying various static and dynamic magnetic fields. Due to the complex physical behavior of the nanoparticles, it is challenging to determine the MPI system matrix in practice. Since the first publication on MPI in 2005, different methods that rely on measurements or simulations for the determination of the MPI system matrix have been proposed. Some methods restrict the simulation to an idealized model to speed up data reconstruction by exploiting the structure of an idealized MPI system matrix. Recently, a method that processes the measurement data in x-space rather than frequency space has been proposed. In this work, we compare the different approaches for image reconstruction in MPI and show that the x-space and the frequency space reconstruction techniques are equivalent.


Reaction coupling through interdomain contacts in imidazole glycerol phosphate synthase.
Imidazole glycerol phosphate (IGP) synthase, a triad glutamine amidotransferase, catalyzes the fifth step in the histidine biosynthetic pathway, where ammonia from glutamine is incorporated into N1-[(5'-phosphoribulosyl)-formimino]-5-aminoimidazole-4-carboxamide ribonucleotide (PRFAR) to yield IGP and 5'-(5-aminoimidazole-4-carboxamide) ribonucleotide (AICAR). The triad family of glutamine amidotransferases is formed by the coupling of two disparate subdomains, an acceptor domain and a glutamine hydrolysis domain. Each of the enzymes in this family share a common glutaminase domain for which the glutaminase activity is tightly regulated by an acceptor substrate domain. In IGP synthase the glutaminase and PRFAR binding sites are separated by 30 A. Using kinetic analyses of site-specific mutants and molecular dynamic simulations, we have determined that an interdomain salt bridge in IGP synthase between D359 and K196 (approximately 16 A from the PRFAR binding site) plays a key role in mediating communication between the two active sites. This interdomain contact modulates the glutaminase loop containing the histidine and glutamic acid of the catalytic triad to control glutamine hydrolysis. We propose this to be a general principle of catalytic coupling that may be applied to the entire triad glutamine amidotransferase family.


M inverted V glansplasty: an update on technique and outcomes 30 years later.
Distal hypospadias is a common congenital urology anomaly for which numerous corrective procedures have been described. Over the last 40 years, the gold-standard operative technique for distal hypospadias has switched from the meatal advancement and glanuloplasty (MAGPI) procedure to the tubularized incised plate (TIP) urethroplasty. A modification to the MAGPI procedure, first described 30 years ago, is the M inverted V (MIV) glansplasty, which improved upon the MAGPI procedure to reduce instances of meatal retraction. The MIV glansplasty is unique compared to many commonly used procedures as it does not require a formal urethroplasty or incorporation of a dartos flap, and it does not always necessitate as extensive mobilization of the glans wings. We describe our updated technique and outcomes of the MIV glansplasty and delineate situations where the MIV is best employed.


A support vector machine formulation to PCA analysis and its kernel version.
In this paper, we present a simple and straightforward primal-dual support vector machine formulation to the problem of principal component analysis (PCA) in dual variables. By considering a mapping to a high-dimensional feature space and application of the kernel trick (Mercer theorem), kernel PCA is obtained as introduced by Scholkopf et al. (2002). While least squares support vector machine classifiers have a natural link with the kernel Fisher discriminant analysis (minimizing the within class scatter around targets +1 and -1), for PCA analysis one can take the interpretation of a one-class modeling problem with zero target value around which one maximizes the variance. The score variables are interpreted as error variables within the problem formulation. In this way primal-dual constrained optimization problem interpretations to the linear and kernel PCA analysis are obtained in a similar style as for least square-support vector machine classifiers.


Patient-clinician communication about end-of-life care for Dutch and US patients with COPD.
Improving patient-clinician communication about end-of-life care is important in order to enhance quality of care for patients with chronic obstructive pulmonary disease (COPD). Our objective was to compare quality of patient-clinician communication about end-of-life care, and endorsement of barriers and facilitators to this communication in the Netherlands and the USA. The present study was an analysis of survey data from 122 Dutch and 391 US outpatients with COPD. We compared quality of patient-clinician communication about end-of-life care (Quality of Communication questionnaire) and barriers and facilitators to communication about end-of-life care (Barriers and Facilitators Questionnaire) between the Netherlands and the USA, controlling for patients' demographic and illness characteristics. Although Dutch patients in this study had worse lung function and disease-specific health status than US patients, Dutch patients reported lower quality of communication about end-of-life care (median score 0.0 (interquartile range 0.0-2.0) versus 1.4 (0.0-3.6); adjusted p<0.005). Clinicians in both countries rarely discussed life-sustaining treatment preferences, prognoses, dying processes or spiritual issues. Quality of communication about end-of-life care needs to improve in the Netherlands and the USA. Future studies to improve this communication should be designed to take into account international differences and patient-specific barriers and facilitators to communication about end-of-life care.


[Subtypes of schizophrenics patients with attempted suicide].
During the last decades, numerous research works have tried to determine what risk factors are associated with the schizophrenic patient's suicidal behavior but they have yielded contradictory results. Thus we hypothesized that these results' variability could be due, among other reasons, to the heterogeneity of suicidal schizophrenic population. Thirty-two Schizophrenics patients who had made Attempted suicide were studied. They were assessed through a battery of Clinical scales for negative, positive, hopelessness, insight and depressive symptoms. Two suicidal subtypes were identified according to the reasons that patients stated for attempting suicide. These two subtypes showed significant differences in two of the analyzed variables, namely hopelessness and PANSS positive subscale. Clinical implications coming from these results are discussed in the present paper.


FOXP3+ Tregs require WASP to restrain Th2-mediated food allergy.
In addition to the infectious consequences of immunodeficiency, patients with Wiskott-Aldrich syndrome (WAS) often suffer from poorly understood exaggerated immune responses that result in autoimmunity and elevated levels of serum IgE. Here, we have shown that WAS patients and mice deficient in WAS protein (WASP) frequently develop IgE-mediated reactions to common food allergens. WASP-deficient animals displayed an adjuvant-free IgE-sensitization to chow antigens that was most pronounced for wheat and soy and occurred under specific pathogen-free as well as germ-free housing conditions. Conditional deletion of Was in FOXP3+ Tregs resulted in more severe Th2-type intestinal inflammation than that observed in mice with global WASP deficiency, indicating that allergic responses to food allergens are dependent upon loss of WASP expression in this immune compartment. While WASP-deficient Tregs efficiently contained Th1- and Th17-type effector differentiation in vivo, they failed to restrain Th2 effector responses that drive allergic intestinal inflammation. Loss of WASP was phenotypically associated with increased GATA3 expression in effector memory FOXP3+ Tregs, but not in naive-like FOXP3+ Tregs, an effect that occurred independently of increased IL-4 signaling. Our results reveal a Treg-specific role for WASP that is required for prevention of Th2 effector cell differentiation and allergic sensitization to dietary antigens.


Thyroid evaluation in patients with primary hyperparathyroidism.
We evaluated the efficacy of preoperative high-resolution ultrasonography (US) for diagnosing possible concomitant thyroid disease which affects the surgical management in patients with primary hyperparathyroidism (pHPT). One hundred and nine patients with sporadic pHPT underwent US with or without ultrasound-guided fine-needle aspiration biopsy (US-FNAB). Diagnosis of concomitant thyroid nodules by US and US-FNAB were compared with the histopathological findings. Of the 109 patients, 19 (17.4%) had malignant thyroid nodules, 26 (23.9%) had benign thyroid nodules alone, and 12 (11.0%) had diffuse goiter. The sensitivity, specificity, and accuracy of diagnosing 72 thyroid nodules were 91.3%, 91.8%, and 91.7% for US, 57.9%, 94.3%, and 81.5% for US-FNAB, and 95.7%, 91.8%, and 93.1% for combined US and US-FNAB, respectively. True positive/false negative ratio of US-FNAB diagnosis was significantly lower in nodules of 5-9 mm than nodules of 10 mm or more. Four unexpected thyroid cancers existed at a different site in 3 of the 39 patients with palpable thyroid disease. Five thyroid cancers were histopathologically confirmed in 5 (7.1%) of 70 patients without palpable thyroid disease. Eight (88.9%) of the 9 non-palpable thyroid cancers were accurately diagnosed by combined US and US-FNAB. Preoperative US is useful for evaluation of possible concomitant thyroid disease, especially for prediction of malignancy.


Effects of Bacillus subtilis PB6 supplementation on production, metabolism, inflammatory biomarkers, and gastrointestinal tract permeability in transition dairy cows.
Objectives were to evaluate the effects of Bacillus subtilis PB6 (BSP) on gastrointestinal tract permeability, metabolism, inflammation, and production parameters in periparturient Holstein cows. Multiparous cows (n = 48) were stratified by previous 305 mature equivalent milk yield and parity and assigned to 1 of 2 top-dressed dietary treatments 21 d before expected calving through 63 DIM: 1) CON (13 g/d calcium carbonate; n = 24) or 2) BSP (13 g/d BSP; CLOSTAT; Kemin Industries, Des Moines, IA; n = 24). Gastrointestinal tract permeability was evaluated in vivo using the oral paracellular marker chromium (Cr)-EDTA. Effects of treatment, time, and treatment × time were assessed using PROC MIXED of SAS. Prepartum dry matter intake (DMI) was unaffected by treatment; however, BSP supplementation decreased postpartum DMI relative to CON (0.7 kg). Milk yield, energy corrected milk (ECM), fat corrected milk (FCM), and solids corrected milk (SCM) increased in BSP cows compared with CON (1.6, 1.8, 1.6, and 1.5 kg, respectively). Decreased DMI and increased production collectively improved feed efficiency of milk yield, ECM, FCM, and SCM for BSP cows (6, 5, 5, and 5%, respectively). No treatment differences were observed for concentrations of milk fat, protein, total solids, somatic cell count, somatic cell score, body weight, or body condition score. Milk urea nitrogen concentrations decreased (5%), whereas milk protein and lactose yield increased (5 and 2%, respectively) with BSP supplementation. Prepartum fecal pH did not differ among treatments; conversely, postpartum fecal pH was increased with BSP supplementation (0.09 pH units). Prepartum fecal dry matter percentage, starch, acetic acid, propionic acid, butyric acid, and ethanol did not differ among treatments. Postpartum concentrations of the aforementioned fecal parameters were also unaffected by treatment, but fecal propionic acid concentration was decreased (24%) in BSP cows relative to CON. Circulating glucose, nonesterified fatty acids, L-lactate, and insulin were similar between treatments both pre and postpartum. Prepartum BHB did not differ between treatments, but postpartum BSP supplementation decreased (21%) circulating BHB relative to CON. Regardless of treatment, inflammatory markers (serum amyloid A and haptoglobin) peaked immediately following parturition and progressively decreased with time, but this pattern was not influenced by treatment. Postpartum lipopolysaccharide binding protein tended to be decreased on d 3 in BSP relative to CON cows (19%). Neither treatment nor time affected Cr-EDTA area under the curve. In summary, supplementing BSP had no detectable effects prepartum, but increased key postpartum production parameters. Bacillus subtilis PB6 consistently increased postpartum fecal pH and decreased fecal propionate concentrations but did not appear to have an effect of gastrointestinal tract permeability.


[The effect of captopril on lipid peroxidation in patients with myocardial infarct complicated by acute left ventricular failure].
Overall fifty-five patients with myocardial infarction were examined. Activation of free radical oxidation of lipids and decrease in activity of enzymes of the antioxidant defence were especially pronounced in those patients with myocardial infarction presenting with acute left ventricular failure. Captopril administered by 6.25 mg daily increasing the dose to 37.5 mg a day over 2-3 days improves parameters characterizing central and cardiohemodynamics and has a beneficial effect on lipid peroxidation. Antioxidant effect of captopril is believed to be due to increase in enzymes of bodily antioxidant defense, such as glutathioneperoxidaze, glutathionereductaze, and elevation in blood levels of vitamin E and reduced glutathione.


Learning styles of medical students - implications in education.
The term "learning style" refers to the fact that each person has a different way of accumulating knowledge. While some prefer listening to learn better, others need to write or they only need to read the text or see a picture to later remember. According to Fleming and Mills the learning styles can be classified in Visual, Auditory and Kinesthetic. There is no evidence that teaching according to the learning style can help a person, yet this cannot be ignored. In this study, a number of 230 medical students were questioned in order to determine their learning style. We determined that 73% of the students prefer one learning style, 22% prefer to learn using equally two learning style, while the rest prefer three learning styles. According to this study the distribution of the learning styles is as following: 33% visual, 26% auditory, 14% kinesthetic, 12% visual and auditory styles equally, 6% visual and kinesthetic, 4% auditory and kinesthetic and 5% all three styles. 32 % of the students that participated at this study are from UMF Craiova, 32% from UMF Carol Davila, 11% University of Medicine T Popa, Iasi, 9% UMF Cluj Iulius Hatieganu. The way medical students learn is different from the general population. This is why it is important when teaching to considerate how the students learn in order to facilitate the learning.


Verbal bias in recognition of facial emotions in children with Asperger syndrome.
Thirteen children and adolescents with diagnoses of Asperger syndrome (AS) were matched with 13 nonautistic control children on chronological age and verbal IQ. They were tested on their ability to recognize simple facial emotions, as well as facial emotions paired with matching, mismatching, or irrelevant verbal labels. There were no differences between the groups at recognizing simple emotions but the Asperger group performed significantly worse than the control group at recognizing emotions when faces were paired with mismatching words (but not with matching or irrelevant words). The results suggest that there are qualitative differences from nonclinical populations in how children with AS process facial expressions. When presented with a more demanding affective processing task, individuals with AS showed a bias towards visual-verbal over visual-affective information (i.e., words over faces). Thus, children with AS may be utilizing compensatory strategies, such as verbal mediation, to process facial expressions of emotion.


Usefulness of mean platelet volume as a biomarker for long-term clinical outcomes after percutaneous coronary intervention in Korean cohort: a comparable and additive predictive value to high-sensitivity cardiac troponin T and N-terminal pro-B type natriuretic peptide.
The aim of this study was to determine the associations of the mean platelet volume (MPV) high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-B type natriuretic peptide (NT-proBNP) with the development of adverse outcomes after percutaneous coronary intervention (PCI). MPV hs-cTnT and NT-proBNP were analyzed in 372 patients who underwent PCI. The primary endpoint was cardiac death. The secondary endpoint analyzed was cardiovascular events (CVE): the composite of cardiac death, myocardial infarction (MI), target vessel revascularization (TVR), ischemic stroke and stent thrombosis (ST). The median MPV hs-cTnT and NT-proBNP levels were 8.20 (IQR 7.70-8.70) fL, 0.291 (IQR 0.015-3.785) ng/mL, and 105.25 (IQR 50.84-1128.5) pg/mL, respectively. There were 21 events of cardiac death, 10 MI (including 4 events of ST), 7 ischemic strokes and 29 TVR during a mean of 25.8 months of follow-up. The Kaplan-Meier analysis revealed that the higher MPV group (>8.20 fL, median) had a significantly higher cardiac death rate than the lower MPV group (≤8.20 fL; 9.4% vs. 2.1%, log-rank: p = 0.0026). When the MPV cut-off level was set to 8.20 fL using the receiver operating characteristic curve, the sensitivity was 81% and the specificity was 53.3% for differentiating between the group with cardiac death and the group without cardiac death. This value was more useful in patients with myocardial injury (hs-cTnT ≥ 0.1 ng/mL) or heart failure (NT-proBNP ≥ 450 pg/mL). The results of this study show that MPV is a predictive marker for cardiac death after PCI; its predictive power for cardiac death is more useful in patients with myocardial injury or heart failure.


Transitioning from electrodialysis to reverse electrodialysis stack design for energy generation from high concentration salinity gradients.
In this study, stack design for high concentration gradient reverse electrodialysis operating in recycle is addressed. High concentration gradients introduce complex transport phenomena, which are exacerbated when recycling feeds; a strategy employed to improve system level energy efficiency. This unique challenge indicates that membrane properties and spacer thickness requirements may differ considerably from reverse electrodialysis for lower concentration gradients (e.g. seawater/river water), drawing closer parallels to electrodialysis stack design. Consequently, commercially available electrodialysis and reverse electrodialysis stack design was first compared for power generation from high concentration gradients. Higher gross power densities were identified for the reverse electrodialysis stack, due to the use of thinner membranes characterised by a higher permselectivity, which improved current. However, energy efficiency of the electrodialysis stack was twice that recorded for the reverse electrodialysis stack at low current densities, which was attributed to: (i) an increased residence time provided by the larger intermembrane distance, and (ii) reduced exergy losses of the electrodialysis membranes, which provided comparatively lower water permeance. Further in-depth investigation into membrane properties and spacer thickness identified that membranes characterised by an intermediate water permeability and ohmic resistance provided the highest power density and energy efficiency (Neosepta ACS/CMS), while wider intermembrane distances up to 0.3 mm improved energy efficiency. This study confirms that reverse electrodialysis stacks for high concentration gradients in recycle therefore demand design more comparable to electrodialysis stacks to drive energy efficiency, but when selecting membrane properties, the trade-off with permselectivity must also be considered to ensure economic viability.


Molecular epidemiology of a hepatitis C virus epidemic in a haemodialysis unit: outbreak investigation and infection outcome.
HCV is a leading cause of liver chronic diseases all over the world. In developed countries the highest prevalence of infection is reported among intravenous drug users and haemodialysis (HD) patients. The present report is to identify the pathway of HCV transmission during an outbreak of HCV infection in a privately run haemodialysis (HD) unit in Italy in 2005. Dynamics of the outbreak and infection clinical outcomes were defined through an ambi-directional cohort study. Molecular epidemiology techniques were used to define the relationships between the viral variants infecting the patients and confirm the outbreak. Risk analysis and auditing procedures were carried out to define the transmission pathway(s). Of the 50 patients treated in the HD unit 5 were already anti-HCV positive and 13 became positive during the study period (AR = 28.9%). Phylogenic analysis identified that, all the molecularly characterized incident cases (10 out of 13), were infected with the same viral variant of one of the prevalent cases. The multivariate analysis and the auditing procedure disclosed a single event of multi-dose vials heparin contamination as the cause of transmission of the infection in 11 out of the 13 incident cases; 2 additional incident cases occurred possibly as a result of inappropriate risk management. More than 30% of all HCV infections in developed countries results from poor application of standard precautions during percutaneous procedures. Comprehensive strategy which included: educational programmes, periodical auditing on standard precaution, use of single-dose vials whenever possible, prospective surveillance for blood-borne infections (including a system of prompt notification) and risk assessment/management dedicated staff are the cornerstone to contain and prevent outbreaks in HD CONCLUSIONS: The outbreak described should serve as a reminder to HD providers that patients undergoing dialysis are at risk for HCV infection and that HCV may be easily transmitted whenever standard precautions are not strictly applied.


A consensus sequence polymer inhibits in vivo expression of heat shock genes.
Promoter function for hsp70 gene expression in Drosophila melanogaster was studied with an in vivo competition assay. A polymer of 40 tandem copies of the pair of regulatory elements of the hsp70 gene was constructed and cloned into a plasmid vector. Various marked genes were cotransfected with the polymer plasmid into Schneider line 2 cells, and their expression was determined by enzyme activity measurements. The polymer dramatically inhibited expression of cotransfected hsp70, hsp26, and hsp83 genes, but not cotransfected copia and histone genes. Our results indicate that in vivo, a trans-acting, positive regulatory factor, which can be titrated by heat shock consensus sequences, is required for activation of heat shock genes and is specific for these genes; the coordinate induction of different heat shock genes appears to be mediated by similar, but not identical, interactions of the trans-acting induction factor and the cis-acting heat shock consensus sequences; and the uninduced or basal level expression of the transfected hsp70 gene is also due to interaction of the consensus sequence with a positively acting factor.


Atypical conduction aphasia. A disconnection syndrome.
Conduction aphasia was originally proposed to result from separation of the posterior language comprehension area and the anterior motor speech area of the left hemisphere. The arcuate fasciculus has been the most frequently suggested site of such a disconnection, but the syndrome has been reported in cases in which the abnormality involved the dominant Wernicke's area. This challenges the arcuate fasciculus theory, and it has been suggested that a cortical lesion, not a disconnection, is the crucial factor. Three new cases in which the lesion does not lie in the arcuate fasciculus are reported, two in left-handed patients with left temporoparietal lesions and one in a right-handed patient with a right temporoparietal infarct, a "crossed" aphasia. While atypical, these cases offer evidence that disconnection of the circuit linking language comprehension to motor speech output, not damage to a specific cortical region, underlies the syndrome of conduction aphasia.


Serum Magnesium Levels in Preterm Infants Are Higher Than Adult Levels: A Systematic Literature Review and Meta-Analysis.
Magnesium (Mg) is an essential mineral in the body, impacting the synthesis of biomacromolecules, bone matrix development, energy production, as well as heart, nerve, and muscle function. Although the importance of Mg is evident, reference values for serum Mg (sMg) in pediatric patients (more specifically, in neonates) are not well established. This systematic literature review and meta-analysis (using 47 eligible studies) aims to quantify normal and tolerable ranges of sMg concentrations during the neonatal period and to highlight the factors influencing Mg levels and the importance of regulating sMg levels during pregnancy and birth. In newborns without Mg supplementation during pregnancy, magnesium levels at birth (0.76 (95% CI: 0.52, 0.99) mmol/L) were similar to that of mothers during pregnancy (0.74 (95% CI: 0.43, 1.04) mmol/L), but increased during the first week of life (0.91 (95% CI: 0.55, 1.26) mmol/L) before returning to adult levels. This pattern was also seen in newborns with Mg supplementation during pregnancy, where the average was 1.29 (95% CI: 0.50, 2.08) mmol/L at birth and 1.44 (95% CI: 0.61, 2.27) mmol/L during the first week of life. Factors influencing these levels include prenatal Mg supplementation, gestational age, birth weight, renal maturity/function, and postnatal Mg intake. Elevated Mg levels (>2.5 mmol/L) have been associated with an increased risk of mortality, admission into intensive care, hypotonia, hypotension, and respiratory depression but sMg concentrations up to 2.0 mmol/L appear to be well tolerated in neonates, requiring adequate survey and minimal intervention.


Changes in antipsychotic drug prescribing by general practitioners in the United Kingdom from 1991 to 2000: a population-based observational study.
To estimate changes in the frequency of use of various antipsychotic drugs in the UK from 1991 to 2000 and to relate these changes to patients' characteristics. We conducted a population-based observational study using data from general practices that contribute information to the General Practice Research Database (GPRD). The study population comprised men and women 10-99 years old. We estimated annual use, first-time use, duration of use and, in a sample of 200 patients, indications for use of various antipsychotic drugs, and we observed how these measures had changed over the past decade. The annual use of antipsychotic drugs increased from 10.5 per thousand in 1991 to 12.2 per thousand in 2000, an overall increase of 16%. The increase was greater in men (25.2%) than women (2.7%). At the same time, the rate of new use of antipsychotic drugs was stable in men and decreased by 21% in women. The difference between patterns of annual use and rates of new use is attributable to the increasing average annual duration of treatment in both men and women during the past decade. Thioridazine, which the UK Committee on the Safety of Medicines (CSM) recently recommended should be used only for second-line treatment of schizophrenia in adults, was the most commonly prescribed antipsychotic throughout the study period. Its use increased as a proportion of all antipsychotic drug use from 1991 to 2000 in men and women aged 10-69 years, but decreased in older users. More than half of all first-time use of antipsychotic drugs in the sample of patients we evaluated was for treatment of depression, anxiety states, and panic disorders, while less than 10% was for treatment of schizophrenia and other psychoses. The use of antipsychotic drugs has increased in the UK during the past decade, primarily due to increased average annual duration of use rather than higher rates of new use. Most antipsychotic drug use appears to have been prescribed to treat nonpsychotic disorders. It will be of interest to see whether the use of thioridazine, which was the most widely prescribed antipsychotic during 1991-2000, decreases during the next decade in response to the recent CSM recommendation.


Empirical and hermeneutic approaches to phenomenological research in psychology: a comparison.
Empirical phenomenology and hermeneutic phenomenology, the 2 most common approaches to phenomenological research in psychology, are described, and their similarities and differences examined. A specific method associated with each form of phenomenological inquiry was used to analyze an interview transcript of a woman's experience of work-family role conflict. A considerable degree of similarity was found in the resulting descriptions. It is argued that such convergence in analyses is due to the human capacities of reflection and intuition and the presence of intersubjective meanings. The similarity in the analyses is also encouraging about researchers' ability to reveal meaning despite the use of different methods and the difficulties associated with interpreting meaning.


[Evaluation of 100 attempted percutaneous coronary angioplasties in the treatment of coronary insufficiency].
Between November 1983 and June 1985, 100 coronary angioplasties were performed in the department of cardiology of the Pitié-Salpêtrière hospital, in 96 patients and 101 vessels. 71 attempts were successful (70%). There were no deaths. 8 bypass grafts were performed because of a symptomatic occlusive dissection in 3 cases, arterial trauma proximal to the stenosis in 2 cases and coronary artery thrombosis following a failed attempt at dilatation in 3 cases. There were 3 infarcts. The success rate improved from 56 per cent in the first 25 patients to 77 per cent in the last 25 patients. The success rate was maximal in patients with stenosis of the IVA, where it was as high as 90 per cent in the last 50 patients. In this last series, the success rate was identical in cases of stable and unstable angina. The rate of re-stenosis was low: 12 per cent in patients with a follow-up of at least 6 months.


Alternative binding modes of an inhibitor to two different kinases.
Protein kinases are targets for therapeutic agents designed to intervene in signaling processes in the diseased state. Most kinase inhibitors are directed towards the conserved ATP binding site. Because the essential features of this site are conserved in all eukaryotic protein kinases, it is generally assumed that the same compound will bind in a similar manner to different protein kinases. The inhibitor 4,5,6,7-tetrabromobenzotriazole (TBB) is a selective inhibitor for the protein kinase CK2 (IC50 1.6 micro m) (Sarno et al. (2001) FEBS Letts.496, 44-48). Three other kinases [cyclin-dependent protein kinase 2 (CDK2), phosphorylase kinase and glycogen synthase kinase 3beta] exhibit approximately 10-fold weaker affinity for TBB than CK2. We report the crystal structure of TBB in complex with phospho-CDK2-cyclin A at 2.2 A resolution and compare the interactions with those observed for TBB bound to CK2. TBB binds at the ATP binding site of both kinases. In CDK2, each of the four bromine atoms makes polar contacts either to main chain oxygens in the hinge region of the kinase or to water molecules, in addition to several van der Waals contacts. The mode of binding of TBB to CDK2 is different from that to CK2. TBB in CDK2 is displaced more towards the hinge region between the N- and C-terminal lobes and rotated relative to TBB in CK2. The ATP binding pocket is wider in CDK2 than in CK2 resulting in fewer van der Waals contacts but TBB in CK2 does not contact the hinge. The structures show that, despite the conservation of the ATP binding pocket, the inhibitor is able to exploit different recognition features so that the same compound can bind in different ways to the two different kinases.


Occurrence and distribution of the entomopathogenic nematodes Steinernema spp. and Heterorhabditis indica in Indonesia.
Soil samples from 79 sites on five islands of Indonesia were baited with insects for the recovery of entomopathogenic nematodes. Heterorhabditis and Steinernema were equally prevalent, and were recovered from 11.7% of samples representing 20.3% of sites sampled. Both genera were recovered from coastal sites only. Entomopathogenic nematodes were more prevalent on the Moluccan islands of Ambon and Seram than on Java or Bali. They were not detected on Sulawesi, where non-coastal sites only were sampled. RFLP analysis was used in the identification of nematode isolates. Heterorhabditis indica was the only heterorhabditid identified. Two RFLP types of Steinernema were identified.


Oral anticoagulant therapy and bleeding events with vitamin K antagonists in patients with atrial fibrillation in a Hungarian county hospital.
Vitamin K antagonists, despite their tight therapeutic spectrum and the fear of bleeding complications, were long the most important drugs used in anticoagulant therapy. The aim of this study was to evaluate the quality of anticoagulant therapy and its relation with bleedings in everyday clinical practice. We analyzed the data of 272 patients with non-valvular atrial fibrillation treated in our county hospital using retrospective data collection of the last 1008±384 days. The INR (International Normalized Ratio) values and the time in therapeutic range (TTR) were analyzed. We asked patients about bleeding complications and searched the medical records. The TTR proved to be 64% and there was no statistically significant difference between that of 252 (92.7%) patients taking acenocoumarol and 20 (7.3%) on warfarin. Analyzing various factors leading to TTR under 70%, we found that none of them have a significant impact. Significantly more bleeding events occurred in the first 3 months after the initiation of anticoagulant therapy and in patients with TTR under 70%, but the latter was not significant after adjustment for factors influencing bleeding (OR 1.607, CI 0.571-4.522, p=0.392). Although the present study's TTR values were similar to those found in the warfarin branch of various large-scale international trials and in real-life settings, further improvement of vitamin K antagonist therapy are necessary. As the possibilities for this are limited, we believe that the new type anticoagulant agents have a place in everyday clinical practice.


Venus: halide cloud condensation and volatile element inventories.
Several recently suggested Venus cloud condensates, including aluminum chloride and halides, oxides, and sulfides of arsenic and antimony, are assessed for their thermodynamic and geochemical plausibility. Aluminum chloride can confidently be ruled out, and condensation of arsenic sulfides on the surface will cause arsenic compounds to be too rare to produce the observed clouds. Antimony may be sufficiently volatile, but the expected molecular form is gaseous antimony sulfide, not the chloride. Arsenic and antimony compounds in the atmosphere will be regulated at very low levels by sulfide precipitation, irrespective of the planetary inventory of arsenic and antimony. Thus arguments for a volatile-deficient origin for Venus based on depletion of water and mercury (relative to the earth) cannot be tested by a search for atmospheric arsenic or antimony.


Deep Neck Infection: A Review of 130 Cases in Southern China.
The study aims to present our experience of the clinical course and management of deep neck infection and try to determine if the characteristics of this kind of infection were similar between the children and adults in southern China.Patients diagnosed with deep neck infection in the Division of Otolaryngology in the First Affiliated Hospital of Sun Yat-sen University between January 2002 and December 2011 were screened retrospectively for demographic characteristics, presenting symptoms, antibiotic therapy before admission, the history of antibiotics abuse, leucocyte count, etiology, bacteriology, disease comorbidity, imaging, treatment, complications, and outcomes.One hundred thirty patients were included and 44 (33.8%) were younger than 18 years old (the children group), 86 patients (66.2%) were older than 18 years old (the adults group). Fever, trismus, neck pain, and odynophagia were the most common symptoms in both groups. Forty children (90.9%) and 49 adults (57.0%) had been treated with broad-spectrum antibiotic therapy before admission. Thirty one children (70.5%) and 24 adults (27.9%) had a history of antibiotics abuse. In children group, the site most commonly involved was the parapharyngeal space (18 patients, 40.9%). In adults group, the site most commonly involved was multispace (30 patients, 34.9%). In children group, the most common cause was branchial cleft cyst (5 patients, 11.4%) and the cause remained unknown in 31 patients (70.5%). In adults group, the most common cause was pharyngeal infection (19 patients, 22.2%). All of the 27 patients with associated disease comorbidity were adults and 17 were diabetes mellitus (DM). Streptococcus viridans was the most common pathogen in both children and adults groups. Eighty six (66.2%) underwent surgical drainage and complications were found in 31 patients (4 children, 27 adults).Deep neck infection in adults is easier to have multispace involvement and lead to complications and appears to be more serious than that in children. Understanding the different characteristics between the children and adults with deep neck infection may be helpful in accurate evaluation and proper management.


The influence of selected polymers on the surface tension of solutions developed for the preparation of eye drops.
Many substances are used to increase the viscosity of eye drops and reduce their surface tension. Their function is to prolong the persistence of the product on the surface of the eyeball and to increase the bioavailability of the pharmacologically active ingredient. To investigate the surface tension of substances added to the eye drops, with the main aim of modulating properties of the preparation. Five substances contained in solutions proposed for the development of eye drops were studied: sodium hyaluronate macromolecular (H-Na W), sodium hyaluronate ultramolecular (H-Na UM), hyaluronic acid 4% (K-H), methylcellulose (MC), and polyacrylic acid (PA). The main method was to study the surface tension using the du Noüy ring tensiometer. The research presented in this paper shows the various effects of different eye drop ingredients on the surface tension of the solutions. The surface tension values of PA solutions are in the range of 48.89-56.03 mN/m, of MC in the range of 68.94-89.32 mN/m, of K-H 54.54-65.66 mN/m, of H-Na UM 67.18-70.97 mN/m, and of H-Na W 67.09-71.73 mN/m. The use of different polymers affects the surface tension of model solutions proposed for use in ophthalmic preparations. Compounds containing carboxyl groups and anionic polymers have a similar effect on reducing the surface tension of the solution as classical surfactant compounds.


Clinical Value of lncRNA MEG3 in High-Grade Serous Ovarian Cancer.
Long non-coding RNAs (lncRNAs) are emerging as regulators in cancer development and progression, and aberrant lncRNA profiles have been reported in several cancers. Here, we evaluated the potential of using the maternally expressed gene 3 (MEG3) tissue level as a prognostic marker in high-grade serous ovarian cancer (HGSOC), the most common and deadliest gynecologic malignancy. To the aim of the study, we measured MEG3 transcript levels in 90 pre-treatment peritoneal biopsies. We also investigated MEG3 function in ovarian cancer biology. We found that high MEG3 expression was independently associated with better progression-free (p = 0.002) and overall survival (p = 0.01). In vitro and in vivo preclinical studies supported a role for MEG3 as a tumor suppressor in HGSOC, possibly through modulation of the phosphatase and tensin homologue (PTEN) network. Overall, results from this study demonstrated that decreased MEG3 is a hallmark for malignancy and tumor progression in HGSOC.


Pb/InAs nanowire josephson junction with high critical current and magnetic flux focusing.
We have studied mesoscopic Josephson junctions formed by highly n-doped InAs nanowires and superconducting Ti/Pb source and drain leads. The current-voltage properties of the system are investigated by varying temperature and external out-of-plane magnetic field. Superconductivity in the Pb electrodes persists up to ∼7 K and with magnetic field values up to 0.4 T. Josephson coupling at zero backgate voltage is observed up to 4.5 K and the critical current is measured to be as high as 615 nA. The supercurrent suppression as a function of the magnetic field reveals a diffraction pattern that is explained by a strong magnetic flux focusing provided by the superconducting electrodes forming the junction.


WAVOS: a MATLAB toolkit for wavelet analysis and visualization of oscillatory systems.
Wavelets have proven to be a powerful technique for the analysis of periodic data, such as those that arise in the analysis of circadian oscillators. While many implementations of both continuous and discrete wavelet transforms are available, we are aware of no software that has been designed with the nontechnical end-user in mind. By developing a toolkit that makes these analyses accessible to end users without significant programming experience, we hope to promote the more widespread use of wavelet analysis. We have developed the WAVOS toolkit for wavelet analysis and visualization of oscillatory systems. WAVOS features both the continuous (Morlet) and discrete (Daubechies) wavelet transforms, with a simple, user-friendly graphical user interface within MATLAB. The interface allows for data to be imported from a number of standard file formats, visualized, processed and analyzed, and exported without use of the command line. Our work has been motivated by the challenges of circadian data, thus default settings appropriate to the analysis of such data have been pre-selected in order to minimize the need for fine-tuning. The toolkit is flexible enough to deal with a wide range of oscillatory signals, however, and may be used in more general contexts. We have presented WAVOS: a comprehensive wavelet-based MATLAB toolkit that allows for easy visualization, exploration, and analysis of oscillatory data. WAVOS includes both the Morlet continuous wavelet transform and the Daubechies discrete wavelet transform. We have illustrated the use of WAVOS, and demonstrated its utility for the analysis of circadian data on both bioluminesence and wheel-running data. WAVOS is freely available at http://sourceforge.net/projects/wavos/files/


Comparison of suprofen and ibuprofen in the treatment of pain secondary to osteoarthritis.
43 patients with osteoarthritis of the knee and/or hip(s) were treated with suprofen 800 mg/day or ibuprofen 1,600 mg/day for 14 days. Both drugs produced an improvement in subjective symptoms by day 7, although the most rapid analgesic effect was obtained with suprofen. Patients receiving suprofen experienced a significantly greater improvement in pain on motion at day 7 than did patients taking ibuprofen. Patients and investigators evaluated both drugs as having good to very good efficacy in the great majority (over 75%) of cases. Both drugs were well tolerated, with only a single drug withdrawal in the ibuprofen group.


Mutagenesis of a specificity-determining residue in tyrosine hydroxylase establishes that the enzyme is a robust phenylalanine hydroxylase but a fragile tyrosine hydroxylase.
The aromatic amino acid hydroxylases tyrosine hydroxylase (TyrH) and phenylalanine hydroxylase (PheH) have essentially identical active sites; however, PheH is nearly incapable of hydroxylating tyrosine, while TyrH can readily hydroxylate both tyrosine and phenylalanine. Previous studies have indicated that Asp425 of TyrH is important in determining the substrate specificity of that enzyme [Daubner, S. C., Melendez, J., and Fitzpatrick, P. F. (2000) Biochemistry 39, 9652-9661]. Alanine-scanning mutagenesis of amino acids 423-427, a mobile loop containing Asp425, shows that only mutagenesis of Asp425 alters the activity of the enzyme significantly. Saturation mutagenesis of Asp425 results in large (up to 10(4)) decreases in the V(max) and V(max)/K(tyr) values for tyrosine hydroxylation, but only small decreases or even increases in the V(max) and V(max)/K(phe) values for phenylalanine hydroxylation. The decrease in the tyrosine hydroxylation activity of the mutant proteins is due to an uncoupling of tetrahydropterin oxidation from amino acid hydroxylation with tyrosine as the amino acid substrate. In contrast, with the exception of the D425W mutant, the extent of coupling of tetrahydropterin oxidation and amino acid hydroxylation is unaffected or increases with phenylalanine as the amino acid substrate. The decrease in the V(max) value with tyrosine as the substrate shows a negative correlation with the hydrophobicity of the amino acid residue at position 425. The results are consistent with a critical role of Asp425 being to prevent a hydrophobic interaction that results in a restricted active site in which hydroxylation of tyrosine does not occur.


A new definition of wrist sprain necessary after findings in a prospective MRI study.
Wrist injuries with negative X-rays are diagnosed as acute wrist sprains. The prognosis is usually good, but some patients suffer from long-lasting pain and reduced wrist function, probably due to missed diagnosis followed by inappropriate treatment. The aim of this study was to investigate acute wrist sprains with MRI to detect the pathoanatomy of the injury. This prospective magnetic resonance imaging (MRI) study included patients between 18 and 49 years, who attended the Accident and Emergency Department (A&E) Bergen, Norway, after sustaining an acute wrist trauma within the previous week. Initial X-rays of the wrist were normal. MRI was done within a median of 1 day (range 0-31 days) after the trauma, 80% within 4 days. The study period lasted from 5 November 2009 to 4 November 2010. A total of 155 acute MRIs were done, out of which 30 were completely normal. Patients with positive MRI had a median of two (range 0-8) pathological findings. We found 54 fractures and 56 bone bruises, mostly located to the radius followed by the scaphoid, the triquetrum, the capitate and the lunate. There were 73 soft-tissue injuries, which included 15 injuries to the triangular fibrocartilage complex (TFCC) and five scapho-lunate (SL) ligament lesions. Wrist sprain is an inaccurate diagnosis. In four out of five patients with normal X-rays, MRI identified pathological findings and a large variety of injuries in different structures. We suggest that wrist sprain should be defined as "occult partial or complete soft tissue (ligament, tendon, muscle) or bony injury in relation to a trauma with negative X-ray". The MRI findings led to a more differentiated treatment in more than a third of the patients. We recommend that MRI should be considered as a part of an early investigation, especially when the wrist pain does not settle within the first couple of weeks.


Tryptase-positive mast cells correlate with angiogenesis in early breast cancer patients.
Literature data indicate that mast cells (MCs) are involved in tumor angiogenesis due to the release of several pro-angiogenetic factors among which tryptase, a serine protease stored in MCs granules, is one of the most active. However, no data are available concerning the role of MCs in angiogenesis in primary human breast cancer. In this study, we have evaluated the correlations between the number of MCs positive to tryptase (MCDPT), the area occupied by MCs positive to tryptase (MCAPT) and microvascular density (MVD) and endothelial area (EA) in a series of 88 primary T1-3, N0-2 M0 female breast cancer, by means of immunohistochemistry and image analysis methods. Data demonstrated a significant (r = from 0.78 to 0.89; p-value from 0.001 to 0.002 by Pearson's analysis respectively) correlation between MCDPT, MCAPT, MVD, EA to each other. No correlation concerning MCDPT, MCAPT, MVD, EA and the main clinicopathological features was found. Our results suggest that tryptase-positive MCs play a role in breast cancer angiogenesis. In this context several tryptase inhibitors such as gabexate mesilate and nafamostat mesilate might be evaluated in clinical trials as a new anti-angiogenetic approach.


PARP-1 activity in normal and cancerous human endometrium and its relationship with quantity of abasic sites (AP).
Poly (ADP-ribose) polymerase (PARP-1) is involved in the processes of DNA repair contributing to the maintenance of genomic stability. Recent data suggest that polymerase is involved in the development of endometrial adenocarcinomas and more advanced tumors displaying lowest enzyme protein expression. Data on PARP-1 activity regarding carcinogenesis in human endometrium are scarce. That was the reason why the authors of the present work wished to investigate the enzyme activity in human uterine hormone-dependent cancer and to compare the results with those obtained for normal endometrial tissue. The next aim was to check whether enzyme activity in normal and cancerous endometrium depends on the number of AP sites, which are widely known as oxidative stress DNA damage markers and PARP-1 activity stimulators. Universal Colorimetric PARP Assay Kit was used to estimate the enzyme activity in units/ mg protein. Apurinic sites/105 base pairs (bp) were measured by Oxidative DNA Damage Kit Quantitative. Results were calculated for 47 endometrial samples and 15 uterine adenocarcinomas specimens. Finally the PARP-1 activity was analyzed for histological and some clinical features of neoplasms. 1. no differences in PARP-1 activity were found in non-cancerous types of human endometrium; 2. mean enzyme activity was lower in sporadic endometrial cancers than in noncancerous endometrial specimens (2.89 +/- 0.55 vs 6.39 +/- 0.06; p < 0.005); 3. mean PARP-1 activity in lower grade neoplasms was higher than in G3 tumors and was lower in adenocarcinomas displaying deep uterine wall infiltration; 4. there was no relationship between PARP-1 activity and AP level.


Recommendations on health-related quality of life research to support labeling and promotional claims in the United States.
Health-related quality of life (HRQL) outcomes evaluation is becoming an important component of clinical trials of new pharmaceuticals and medical devices. HRQL research provides patients, providers, and decision makers with important information on the impact of disease and treatment on physical, psychological, and social functioning and well-being. These outcomes are also useful to the pharmaceutical and device industries as they attempt to understand and communicate product value to physicians, patients, health insurers and others. HRQL labeling and promotional claims in the US are likely to increase over the next few years. The evidentiary requirements to make such a claim should be based on accepted scientific standards of HRQL evaluation and consistent with the regulatory requirements for clinical efficacy. This report outlines the scientific practices that should be considered in the evaluation of evidence for an HRQL claim, including the selection of appropriate domains, evidence to support the reliability and validity of HRQL measurement, considerations in research design and statistical analyses, and the issue of clinical significance. Representatives from the pharmaceutical and device industries, regulatory agencies, and the HRQL scientific community should work together to make certain the use of HRQL in labeling and promotion are based on sound scientific evidence, and that these messages are clearly and accurately reported to the consumers.


Human anthrax as a re-emerging disease.
Anthrax is primarily a disease of herbivores and the etiological agent is B. anthracis which is a gram-positive, aerobic, spore-forming, and rod shaped bacterium. Bacillus anthracis spores are highly resistant to heat, pressure, ultraviolet and ionizing radiation, chemical agents and disinfectants. For these reasons, B. anthracis spores are an attractive choice as biological agents for the use of bioweapon and/or bioterrorism. Soil is the main reservoir for the infectious agent. The disease most commonly affects wild and domestic mammals. Human are secondarily infected by contact with infected animals and contaminated animal products or directly expose to B. anthracis spores. Anthrax occurs worldwide. This infection is still endemic or hyperendemic in both animals and humans in some part of areas of the world; particularly in Middle East, West Africa, Central Asia, some part of India, South America. However, some countries are claiming free of anthrax, and anthrax has become a re-emerging disease in western countries with the intentional outbreak. Currently, anthrax is classified according to its setting as (1) naturally occurring anthrax, (2) bioterrorism-related anthrax. Vast majority of human anthrax are occurring as naturally occurring anthrax in the world. It is also a threaten disease for western countries. The aim of this paper is to review the relevant patents, short historical perspective, microbiological and epidemiological features, clinical presentations and treatment.


Analyzing asymmetric effects of cryptocurrency demand on environmental sustainability.
When bitcoin (BTC), the first pioneering cryptocurrency was released in 2009, it was considered an apolitical currency. Besides, the possible effect of BTC and other cryptocurrencies on either financial markets or transactions has been widely discussed. However, the environmental effects of cryptocurrency demand have been ignored. Here, this study examines the nexus between cryptocurrencies and environmental degradation by employing standard and asymmetric causality methods. The Toda-Yamamoto and bootstrap-augmented Toda-Yamamoto test results reveal Bitcoin and Ethereum (ETH) excluding Ripple (XRP) have causal effects on environmental degradation. The Fourier-augmented Toda-Yamamoto test results show causal effects running from Bitcoin and Ripple to environmental degradation, whereas no causal effect runs from Ethereum to environmental degradation. The asymmetric causality shows causal effects from the positive shock of Bitcoin demand, negative shocks of Ripple and Ethereum demands to positive shocks of environmental degradation. Further discussions and policy implications are provided in the relevant sections of this study.


Silkworm pathogenic bacteria infection model for identification of novel virulence genes.
Silkworms are killed by injection of pathogenic bacteria, such as Staphylococcus aureus and Streptococcus pyogenes, into the haemolymph. Gene disruption mutants of S. aureus whose open reading frames were previously uncharacterized and that are conserved among bacteria were examined for their virulence in silkworms. Of these 100 genes, three genes named cvfA, cvfB, and cvfC were required for full virulence of S. aureus in silkworms. Haemolysin production was decreased in these mutants. The cvfA and cvfC mutants also had attenuated virulence in mice. S. pyogenes cvfA-disrupted mutants produced less exotoxin and had attenuated virulence in both silkworms and mice. These results indicate that the silkworm-infection model is useful for identifying bacterial virulence genes.


Long-term health-related and economic consequences of short-term outcomes in evaluation of perinatal interventions.
Many perinatal interventions are performed to improve long-term neonatal outcome. To evaluate the long-term effect of a perinatal intervention follow-up of the child after discharge from the hospital is necessary because serious sequelae from perinatal complications frequently manifest themselves only after several years. However, long-term follow-up is time-consuming, is not in the awareness of obstetricians, is expensive and falls outside the funding-period of most obstetric studies. Consequently, short-term outcomes are often reported instead of the primary long-term end-point. With this project, we will assess the current state of affairs concerning follow-up after obstetric RCTs and we will develop multivariable prediction models for different long-term health outcomes. Furthermore, we would like to encourage other researchers participating in follow-up studies after large obstetric trials (> 350 women) to inform us about their studies so that we can include their follow-up study in our systematic review. We would invite these researchers also to join our effort and to collaborate with us on the external validation of our prediction models. A systematic review of neonatal follow-up after obstetric studies will be performed. All reviews of the Cochrane Pregnancy and Childbirth group will be assessed for reviews on interventions that aimed to improve neonatal outcome. Reviews on interventions primary looking at other aspects than neonatal outcome such as labour progress will also be included when these interventions can change the outcome of the neonate on the short or long-term. Our review will be limited to RCTs with more than 350 women. Information that will be extracted from these RCTs will address whether, how and for how long follow-up has been performed. However, in many cases long-term follow-up of the infants will not be feasible. An alternative solution to limited follow-up could be to develop prediction models to estimate long-term health outcomes of the newborn based on specific perinatal outcomes and other covariates. For the development of multivariable prediction models for several health outcomes, we will use data available from a Dutch cohort study of preterm (< 32 weeks) and/or small for gestational age infants (< 1500 g). These infants were born in The Netherlands in 1983 and followed until they reached the age of 19. The systematic review will provide insight in the extent and methods used for follow-up assessments after obstetric RCTs in the past. The prediction models can be used by future studies to extrapolate short-term outcomes to a long-term horizon or to indicate for which neonates long-term follow-up is required, as their outcomes (either absence or presence of sequelae) cannot be adequately predicted from short-term outcomes and clinical background characteristics.