Interventions for supporting pregnant women's decision-making about mode of birth after a caesarean.
Pregnant women who have previously had a caesarean birth and who have no contraindication for vaginal birth after caesarean (VBAC) may need to decide whether to choose between a repeat caesarean birth or to commence labour with the intention of achieving a VBAC. Women need information about their options and interventions designed to support decision-making may be helpful. Decision support interventions can be implemented independently, or shared with health professionals during clinical encounters or used in mediated social encounters with others, such as telephone decision coaching services. Decision support interventions can include decision aids, one-on-one counselling, group information or support sessions and decision protocols or algorithms. This review considers any decision support intervention for pregnant women making birth choices after a previous caesarean birth. To examine the effectiveness of interventions to support decision-making about vaginal birth after a caesarean birth.Secondary objectives are to identify issues related to the acceptability of any interventions to parents and the feasibility of their implementation. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 June 2013), Current Controlled Trials (22 July 2013), the WHO International Clinical Trials Registry Platform Search Portal (ICTRP) (22 July 2013) and reference lists of retrieved articles. We also conducted citation searches of included studies to identify possible concurrent qualitative studies. All published, unpublished, and ongoing randomised controlled trials (RCTs) and quasi-randomised trials with reported data of any intervention designed to support pregnant women who have previously had a caesarean birth make decisions about their options for birth. Studies using a cluster-randomised design were eligible for inclusion but none were identified. Studies using a cross-over design were not eligible for inclusion. Studies published in abstract form only would have been eligible for inclusion if data were able to be extracted. Two review authors independently applied the selection criteria and carried out data extraction and quality assessment of studies. Data were checked for accuracy. We contacted authors of included trials for additional information. All included interventions were classified as independent, shared or mediated decision supports. Consensus was obtained for classifications. Verification of the final list of included studies was undertaken by three review authors. Three randomised controlled trials involving 2270 women from high-income countries were eligible for inclusion in the review. Outcomes were reported for 1280 infants in one study. The interventions assessed in the trials were designed to be used either independently by women or mediated through the involvement of independent support. No studies looked at shared decision supports, that is, interventions designed to facilitate shared decision-making with health professionals during clinical encounters.We found no difference in planned mode of birth: VBAC (risk ratio (RR) 1.03, 95% confidence interval (CI) 0.97 to 1.10; I² = 0%) or caesarean birth (RR 0.96, 95% CI 0.84 to 1.10; I² = 0%). The proportion of women unsure about preference did not change (RR 0.87, 95% CI 0.62 to 1.20; I² = 0%).There was no difference in adverse outcomes reported between intervention and control groups (one trial, 1275 women/1280 babies): permanent (RR 0.66, 95% CI 0.32 to 1.36); severe (RR 1.02, 95% CI 0.77 to 1.36); unclear (0.66, 95% CI 0.27, 1.61). Overall, 64.8% of those indicating preference for VBAC achieved it, while 97.1% of those planning caesarean birth achieved this mode of birth. We found no difference in the proportion of women achieving congruence between preferred and actual mode of birth (RR 1.02, 95% CI 0.96 to 1.07) (three trials, 1921 women).More women had caesarean births (57.3%), including 535 women where it was unplanned (42.6% all caesarean deliveries and 24.4% all births). We found no difference in actual mode of birth between groups, (average RR 0.97, 95% CI 0.89 to 1.06) (three trials, 2190 women).Decisional conflict about preferred mode of birth was lower (less uncertainty) for women with decisional support (standardised mean difference (SMD) -0.25, 95% CI -0.47 to -0.02; two trials, 787 women; I² = 48%). There was also a significant increase in knowledge among women with decision support compared with those in the control group (SMD 0.74, 95% CI 0.46 to 1.03; two trials, 787 women; I² = 65%). However, there was considerable heterogeneity between the two studies contributing to this outcome ( I² = 65%) and attrition was greater than 15 per cent and the evidence for this outcome is considered to be moderate quality only. There was no difference in satisfaction between women with decision support and those without it (SMD 0.06, 95% CI -0.09 to 0.20; two trials, 797 women; I² = 0%). No study assessed decisional regret or whether women's information needs were met.Qualitative data gathered in interviews with women and health professionals provided information about acceptability of the decision support and its feasibility of implementation. While women liked the decision support there was concern among health professionals about their impact on their time and workload. Evidence is limited to independent and mediated decision supports. Research is needed on shared decision support interventions for women considering mode of birth in a pregnancy after a caesarean birth to use with their care providers.


Fine-needle aspiration cytology in the management of gynecologic oncology patients.
Fine-needle aspiration cytology has received little attention by physicians involved in the care of gynecologic oncology patients. Concerns over diagnostic accuracy and complications such as rupture of cystic ovarian tumors with resultant tumor dissemination have limited the technique's utilization. Recent studies have shown the method to have a diagnostic accuracy (percent of neoplasms correctly categorized as benign or malignant) of approximately 95% for ovarian tumors [2-8]. The method is generally free of major complication when patients are properly selected, but severe pelvic infections have followed transvaginal or transrectal puncture of cystic ovarian neoplasms, resulting in a complication rate of about 1.6% [28]. Presently, FNA of ovarian tumors has a role in the workup of cystic lesions in young women where epithelial malignancies are unlikely and preservation of ovarian function is highly desirable. In peri- or postmenopausal women with adnexal masses, operative intervention is appropriate in most cases. Sevin and colleagues defined four clinical situations where FNA is useful [16]. These are 1) workup of primary neoplasms, 2) biopsy of superficial masses in patients with known prior disease, 3) follow-up of irradiated patients, and 4) follow-up of patients undergoing chemotherapy. From the available data, FNA has an accuracy of approximately 90% [10,18] and a low complication rate. The technique is an excellent method for the detection of recurrent or metastatic disease in patients being followed for gynecologic malignancies. When FNA is used for the investigation of newly discovered adnexal masses, patient selection is critical. FNA is helpful in carefully selected young women with cystic ovarian masses. However, its utility is limited in peri- or postmenopausal women with solid and solid-cystic adnexal masses, because these should be investigated by operative intervention.


Characterization of a catalase-deficient strain of Neisseria gonorrhoeae: evidence for the significance of catalase in the biology of N. gonorrhoeae.
We obtained a catalase-deficient (Kat-) strain of Neisseria gonorrhoeae isolated from a patient who had been unsuccessfully treated with penicillin. Quantitative enzyme assays and electrophoresis of cell extracts on native polyacrylamide gels subsequently stained for catalase and peroxidase activities failed to detect both enzymes. The strain exhibited no growth anomalies or unusual requirements when grown under ordinary laboratory conditions. However, the Kat- strain proved extremely sensitive to exogenous hydrogen peroxide, and analysis of the bacterial DNA after such exposure showed extensive single-strand breakage in both chromosomal and plasmid DNAs. Partial characterization of the gonococcal catalase from a Kat+ laboratory strain revealed that the enzyme had the physical and chemical properties of both catalase and peroxidase.


Does methadone maintenance treatment based on the new national guidelines work in a primary care setting?
General practitioners (GPs) are being encouraged to treat more drug users but there are few studies to demonstrate the effectiveness of primary care treatment. To determine whether patients retained on methadone maintenance treatment for one year in a modern British primary care setting, with prescribing protocols based on the new national guidelines, can achieve similar harm reduction outcomes to those demonstrated in other settings, using objective outcome measures where available. Longitudinal cohort study. The Primary Care Clinic for Drug Dependence, Sheffield. The intervention consisted of a methadone maintenance treatment provided by GPs with prescribing protocols based on the 1999 national guidelines. The first 96 eligible consenting patients entering treatment were recruited; 65 completed the study. Outcome measures were current drug use, HIV risk-taking behaviour, social functioning, criminal activity, and mental and physical health, supplemented by urinalysis and criminal record data. Frequency of heroin use was reduced from a mean of 3.02 episodes per day (standard deviation [SD] = 1.73) to a mean of 0.22 episodes per day (SD = 0.54), (chi 2 = 79.48, degrees of freedom [df] = 2, P < 0.001), confirmed by urinalysis. Mean numbers of convictions and cautions were reduced by 62% (z = 3.378, P < 0.001) for all crime. HIV risk-taking behaviour, social functioning, and physical and psychological wellbeing all showed significant improvements. Patients retained on methadone maintenance treatment for one year in a primary care setting can achieve improvements on a range of harm reduction outcomes similar to those shown by studies in other, often more highly structured programmes.


A human perspective on body donation: A case study from a psychosocial perspective.
Using a case study of how a son consented to his mother becoming a body donor, the factors that may have contributed to that decision are outlined. Social and psychological considerations about body donation in general are presented. These are followed by suggestions for organisational improvements for healthcare facilities and medical schools, including ease of access to accurate information for both medical professionals and members of the public. Finally, it is recommended that medical school staff dealing with potential donors and their families should be trained to communicate empathically and with compassion.


Structural, functional, and idiotypic characteristics of a phosphorylcholine-binding IgA myeloma protein of C57BL/ka allotype.
An IgA phosphorylcholine (PC)-binding myeloma protein with IgCH allotypic determinants different from those of BALB/c mice is characterized. The myeloma, CBPC 2, was induced in the CB-20 strain of mice which is congenic to BALB/c but differs from it by carrying the A15 allotypic determinant of C57BL/ka mice. Sequence analysis of the CBPC 2 light chain through the first hypervariable region, as well as isoelectric point analysis, show that this chain is indistinguishable from that of T15, a PC-binding myeloma protein of BALB/c origin. The heavy chains of CBPC 2 and T15 differ by only two amino acids (positions 14 and 16) through the first hypervariable region. As measured by inhibition of precipitation, both CBPC 2 and T15 have the same specificity for PC, glycerophosphorylcholine, acetylcholine, and choline. In addition, CBPC 2 possesses the binding site-associated idiotypic determinant which is present on T15. However, like normal or induced C57BL/6 anti-PC antibody, it does not possess the nonbinding site idiotypic determinant.


Nucleotide selection by the Y-family DNA polymerase Dpo4 involves template translocation and misalignment.
Y-family DNA polymerases play a crucial role in translesion DNA synthesis. Here, we have characterized the binding kinetics and conformational dynamics of the Y-family polymerase Sulfolobus solfataricus P2 DNA polymerase IV (Dpo4) using single-molecule fluorescence. We find that in the absence of dNTPs, the binary complex shuttles between two different conformations within ∼1 s. These data are consistent with prior crystal structures in which the nucleotide binding site is either occupied by the terminal base pair (preinsertion conformation) or empty following Dpo4 translocation by 1 base pair (insertion conformation). Most interestingly, on dNTP binding, only the insertion conformation is observed and the correct dNTP stabilizes this complex compared with the binary complex, whereas incorrect dNTPs destabilize it. However, if the n+1 template base is complementary to the incoming dNTP, a structure consistent with a misaligned template conformation is observed, in which the template base at the n position loops out. This structure provides evidence for a Dpo4 mutagenesis pathway involving a transient misalignment mechanism.


Integrating body movement into attractiveness research.
People judge attractiveness and make trait inferences from the physical appearance of others, and research reveals high agreement among observers making such judgments. Evolutionary psychologists have argued that interest in physical appearance and beauty reflects adaptations that motivate the search for desirable qualities in a potential partner. Although men more than women value the physical appearance of a partner, appearance universally affects social perception in both sexes. Most studies of attractiveness perceptions have focused on third party assessments of static representations of the face and body. Corroborating evidence suggests that body movement, such as dance, also conveys information about mate quality. Here we review evidence that dynamic cues (e.g., gait, dance) also influence perceptions of mate quality, including personality traits, strength, and overall attractiveness. We recommend that attractiveness research considers the informational value of body movement in addition to static cues, to present an integrated perspective on human social perception.


Metabolic organization and effects of feeding on enzyme activities of the dogfish shark (Squalus acanthias) rectal gland.
In order to investigate the metabolic poise of the elasmobranch rectal gland, we conducted two lines of experimentation. First, we examined the effects of feeding on plasma metabolites and enzyme activities from several metabolic pathways in several tissues of the dogfish shark, Squalus acanthias, after starvation and at 6, 20, 30 and 48 h post-feeding. We found a rapid and sustained ten-fold decrease in plasma beta-hydroxybutyrate at 6 h and beyond compared with starved dogfish, suggesting an upregulation in the use of this substrate, a decrease in production, or both. Plasma acetoacetate levels remain unchanged, whereas there was a slight and transient decrease in plasma glucose levels at 6 h. Several enzymes showed a large increase in activity post-feeding, including beta-hydroxybutyrate dehydrogenase in rectal gland and liver, and in rectal gland, isocitrate dehydrogenase, citrate synthase, lactate dehydrogenase, aspartate amino transferase, alanine amino transferase, glutamine synthetase and Na(+)/K(+) ATPase. Also notable in these enzyme measurements was the overall high level of activity in the rectal gland in general. For example, activity of the Krebs' TCA cycle enzyme citrate synthase (over 30 U g(-1)) was similar to activities in muscle from other species of highly active fish. Surprisingly, lactate dehydrogenase activity in the gland was also high (over 150 U g(-1)), suggesting either an ability to produce lactate anaerobically or use lactate as an aerobic fuel. Given these interesting observations, in the second aspect of the study we examined the ability of several metabolic substrates (alone and in combination) to support chloride secretion by the rectal gland. Among the substrates tested at physiological concentrations (glucose, beta-hydroxybutyrate, lactate, alanine, acetoacetate, and glutamate), only glucose could consistently maintain a viable preparation. Whereas beta-hydroxybutyrate could enhance gland activity when presented in combination with glucose, surprisingly it could not sustain chloride secretion when used as a lone substrate. Our results are discussed in the context of the in vivo role of the gland and mechanisms of possible upregulation of enzyme activities.


Robotic total thyroidectomy with modified radical neck dissection via unilateral retroauricular approach.
Traditionally, total thyroidectomy was performed through an open transcervical incision; in cases where there was evident nodal metastasis, the conventional surgical approach was to extend the incision into a large single transverse incision to complete the required neck dissection. However, recent innovation in the surgical technique of thyroidectomy has offered the opportunity to reduce the patient's burden from these prominent surgical scars in the neck. Minimally invasive surgical techniques have been developed and applied by many institutions worldwide, and more recently, various techniques of remote access surgery have been suggested and actively applied.1-6 Since the advent of robotic surgical systems, some have adopted the concept of remote access surgery into developing various robotic thyroidectomy techniques. The more former and widely acknowledged robotic thyroidectomy technique uses a transaxillary (TA) approach, which has been developed by Chung et al. in Korea.7,8 This particular technique has some limitations in the sense that accessing the lymph nodes of the central compartment is troublesome. Terris et al. realized some shortcomings of robotic TA thyroidectomy, especially in their patients in the United States, and developed and reported the feasibility of robotic facelift thyroidectomy.9-13 In cases of thyroid carcinomas with lateral neck node metastases, most abandoned the concept of minimally invasive or remote access surgery and safely adopted conventional open surgical methods to remove the tumor burden. However, Chung et al. have attempted to perform concomitant modified radical neck dissection (MRND) after robotic thyroidectomy through the same TA port.14 This type of robot-assisted neck dissection (RAND) had some inherent limitations, due to fact that lymph nodes of the upper neck were difficult to remove. Over the past few years, we have developed a RAND via modified facelift (MFL) or retroauricular (RA) approach and reported the feasibility and safety of this technique.15, 16 Since then, we have actively applied such RAND techniques in various head and neck cancers. In our country, almost all cases of robotic total thyroidectomy utilize the TA approach. According to the reports made by Terris et al., robotic facelift thyroidectomy technique has been solely applied for ipsilateral hemithyroidectomy. For total thyroidectomy, Terris et al. performed the robotic surgery with bilateral RA incisions. Here, we intend to introduce our novel surgical method after successfully attempting simultaneous robotic total thyroidectomy and RAND via a single RA approach without an axillary incision. To our knowledge, this is the first to report in the medical literature. We present four cases of our surgical experience since the beginning of 2013. All patients received robotic total thyroidectomy with MRND via single RA port without axillary incision after approval from the institutional review board at Severance Hospital, Yonsei University College of Medicine. The inclusion criteria for this operation were as follows: (1) patients with malignant carcinomas of the thyroid gland with evident cervical lymph node metastasis on preoperative imaging studies which are indicated for surgery; (2) patients with no previous history of treatment for thyroid carcinoma. The exclusion criteria were as follows: (1) patients with recurred thyroid tumors; (2) patients with thyroid carcinomas that showed gross invasion to local structures or extensive extrathyroidal capsular spread; (3) patients with clinically evident neck nodal metastasis with extracapsular spread; (4) patients with past history of neck surgery of any kind. In order to assess the extent of disease, neck ultrasonography with fine needle aspiration, neck CT or MRI and PET-CT were performed as preoperative evaluation. All patients were given full information of the possible treatment options for their thyroid cancer comprising of open transcervical approach and robotic surgery via RA approach, including the advantages and disadvantages of each treatment choice and provided written, informed consents before the surgery. General clinical information of the patients is outlined in Table 1. The skin incision for the operation was designed just like the approach for robotic facelift thyroidectomy by Terris et al. and RAND, which has been first reported by our institution.11 (,) 16 The operation was performed by the following sequence. Initially, the skin-subplatysmal flap was elevated after making the skin incision to create sufficient working space. During this process, the elevated skin flap was retracted and maintained by retractors held by the assistant. After application of the self-retaining retractor (Sangdosa Inc., Seoul), neck dissection of the upper neck levels was performed under gross vision. Next, RAND through the RA incision was conducted followed by ipsilateral thyroidectomy with central compartment neck dissection (CCND) via the same approach. Finally, contralateral thyroidectomy with CCND was performed via the single RA port. During these steps, the operator is aided by the bedside assistant with long-suction tips to manipulate and direct the dissected specimen to maintain optimal surgical view or to suck out the fume created by the thermocoagulation from the Harmonic shears. The da Vinci robotic surgical system (Intuitive Surgical, Sunnyvale, CA) was introduced via the RA port with a facedown 30° dual-channel endoscopic arm placed in the center, and two instrument arms equipped at either side with 5-mm Maryland forceps and Harmonic curved shears. During the step of robotic contralateral thyroidectomy, a ProGrasp forceps was utilized at times, instead of 5-mm Maryland forceps. The rest of the surgery was completed with the robotic system (see Video for demonstration of operation for patient 2). Table 1 Clinical characteristics of the patients Patient Sex/age (yr) BMI Side(a) Approach Pathology(b) Tumor size(c) (cm) CCND(d) MRND(d) Drain removal day Drainage amount (ml) Hospital stay (days) 1 F/38 23.8 L RA PC 0.7 2/5 8/23 8 788 11 2 F/18 18.3 L RA PC 0.8 2/8 7/35 6 398 9 3 F/44 23.1 L RA PC 0.9 5/12 5/27 6 607 9 4 F/26 32.9 L RA PC 1.4 3/14 9/48 7 476 15 BMI body mass index, RA retroauricular approach, PC papillary carcinoma, CCND central compartment neck dissection, MRND modified radical neck dissection (a)Side refers to the site of main lesion (b)Pathology refers to the primary tumor within the thyroid gland (c)Tumor size refers to the diameter of the largest tumor in the thyroid gland (d)For each type of lymph node dissection, the number of positive nodes/total number of retrieved nodes is stated For all of the patients, robotic total thyroidectomy with MRND (levels II, III, IV, V) via unilateral RA approach was successfully completed without any significant intraoperative complications or conversion to open or other approach methods. The total operation time was defined as the time from initial skin incision to removal of the final specimen, which was an average 306.1 ± 11.1 min (Table 2). This included the time for skin flap elevation and neck dissection under gross vision (87 ± 2.8 min), setting up the robotic system for RAND (6.8 ± 2.4 min), console time using the robotic system for RAND (59.3 ± 2.2 min), flap elevation for thyroidectomy (11.3 ± 2.5 min), robotic arms docking for ipsilateral thyroidectomy (6.3 ± 2.5 min), console time for ipsilateral thyroidectomy (61.3 ± 2.1 min), robotic arms docking for contralateral thyroidectomy (6.3 ± 2.5 min), and console time for contralateral thyroidectomy (61.8 ± 2.1 min). The working space created from RA incision was sufficient, and manipulations of the robotic instruments through this approach were technically feasible and safe without any mutual collisions throughout the entire operation. It also allowed for an excellent magnified surgical view enabling visualization of important local anatomical structures. There was no postoperative vocal cord palsy due to recurrent laryngeal nerve injury. However, two patients developed transient hypoparathyroidism, which resolved in the end without the need for calcium or vitamin D supplementation after certain period of medical management (Table 3). Also, there was no incidence of postoperative hemorrhage or hematoma formation, although a single patient developed a postoperative seroma on postoperative day 9, which was managed conservatively without the need for further surgical intervention. On average, the wound catheter was removed 6.8 ± 1 days after surgery and the patient was discharged from the hospital at an average 11 ± 2.8 days from admission (Table 1). Final surgical pathology confirmed the diagnosis of papillary carcinoma for every patient. The total number of cervical nodes retrieved from CCND and MRND was 9.8 ± 4 and 33.1 ± 11 respectively, and the number of positive metastatic nodes was 3 ± 1.4 and 7.3 ± 1.7 respectively (Table 1). In three patients (patients 2, 3, and 4), the presence of one parathyroid gland was each verified in the pathology specimen. All four patients have received high-dose (150 mCi) radioiodine ablation (RAI) therapy after the operation and are being followed up (average 11.3 months, range 9-13 months) on a regular basis with no evidence of recurrence (post-RAI, most recent, nonsuppressed thyroglobulin range 0.1-0.4 ng/ml, antithyroglobulin antibody range 13.7-147.5 IU/ml). (ABSTRACT TRUNCATED)


Allogeneic hematopoietic cell transplantation in patients with myelodysplastic syndromes.
Despite new developments in innovative and potentially targeted drugs like hypomethylating agents (HMA), allogeneic hematopoietic stem cell transplantation (HCT) is still the only potentially curative treatment option for patients with myelodysplastic syndromes (MDS). Improvements in donor selection and supportive care, as well as the introduction of reduced-intensity conditioning, have improved the feasibility of this approach by reducing early mortality. As a result, the number of allogeneic HCTs performed in MDS patients mainly above the age of 60 years has significantly increased over the last decade. However, the main drawbacks of this procedure, including graft-versus-host disease (GVHD) and hematologic relapse, remain a challenge in daily patient care. Thus, optimization of the pretransplant remission status and post-transplant outcome, eg, by new GVHD prophylaxis regimens or pharmacological maintenance or pre-emptive therapy of minimal residual disease to prevent relapse, is an important goal of current clinical research. There is an urgent need for prospective randomized trials to identify the subgroup of MDS patients who could achieve a better long-term disease control by allogeneic HCT compared to treatment with current standards of care, including HMA.


Inference of hyperedges and overlapping communities in hypergraphs.
Hypergraphs, encoding structured interactions among any number of system units, have recently proven a successful tool to describe many real-world biological and social networks. Here we propose a framework based on statistical inference to characterize the structural organization of hypergraphs. The method allows to infer missing hyperedges of any size in a principled way, and to jointly detect overlapping communities in presence of higher-order interactions. Furthermore, our model has an efficient numerical implementation, and it runs faster than dyadic algorithms on pairwise records projected from higher-order data. We apply our method to a variety of real-world systems, showing strong performance in hyperedge prediction tasks, detecting communities well aligned with the information carried by interactions, and robustness against addition of noisy hyperedges. Our approach illustrates the fundamental advantages of a hypergraph probabilistic model when modeling relational systems with higher-order interactions.


Self-trapping and flipping of double-charged vortices in optically induced photonic lattices.
We report what is believed to be the first observation of self-trapping and charge-flipping of double-charged optical vortices in two-dimensional photonic lattices. Both on- and off-site excitations lead to the formation of rotating quasi-vortex solitons, reversing the topological charges and the direction of rotation through a quadrupole-like transition state. Experimental results are corroborated with numerical simulations.


Rapid Modulation of PSMA Expression by Androgen Deprivation: Serial 68Ga-PSMA-11 PET in Men with Hormone-Sensitive and Castrate-Resistant Prostate Cancer Commencing Androgen Blockade.
Prostate-specific membrane antigen (PSMA) may be targeted for both diagnostic and therapeutic purposes in the management of prostate cancer (PCa). In preclinical models, androgen blockade (AB) increases expression of PSMA in both hormone-sensitive and castrate-resistant xenotypes. The aim of this study was to evaluate the effect of AB treatment on 68Ga-PSMA-11 PET imaging in hormone-naive (luteinizing hormone-releasing hormone [LHRH] ± bicalutamide) and in castrate-resistant men (enzalutamide or abiraterone) with metastatic PCa. Methods: Serial 68Ga-PSMA-11 PET was prospectively performed at baseline and on days 9, 18, and 28 in 8 men with measurable metastatic hormone-sensitive PCa commencing LHRH ± bicalutamide (cohort 1) and 7 men with castrate-resistant PCa commencing either enzalutamide or abiraterone (cohort 2). Gleason score, age, time since diagnosis, and prior treatments were documented. Testosterone and prostate-specific antigen (PSA) were measured at baseline and all imaging time points. PET/CT was quantitatively analyzed for SUVmax, SUVmean, and total tumor volume. Results: In cohort 1, a median 30% (interquartile range [IQR], 5-61) reduction in SUVmax was recorded by day 9 after AB. A reduction from baseline SUVmax occurred in 86.5% (6/7) men by day 9 (P < 0.04), with an associated PSA response in 100% men (P < 0.03). Total tumor volume reduced in all men by 74.5% (IQR, 27-97) (P < 0.02). After day 9, PSMA response heterogeneity was noted, with persistently high or increasing SUVmax in 37.5% (3/8) and marked reduction in 62.5% (5/8). In cohort 2, a median 45% (IQR, 12.7-66) increase in intensity of PSMA SUV was recorded by day 9 after AB. All men demonstrated an increase in SUVmax and SUVmean on PSMA PET compared with baseline (P < 0.04). This increase at day 9 plateaued by day 28. PSA responses were more delayed in cohort 2 (-15% [IQR, 70-138]), with 2 of 7 men demonstrating PSA progression. Conclusion: There is rapid dichotomous response on 68Ga-PSMA PET imaging to AB-dependent on the presence of a hormone-sensitive or castrate-resistant PCa phenotype. This has important implications for interpretation of PSMA PET, and in the timing and sequencing of PSMA-targeted therapy.


Targeting of a conditionally replicative adenovirus agent to human squamous cell carcinomas of the head and neck.
Conventional cancer treatments are not adequate for the majority of most patients stricken with squamous cell carcinomas of the head and neck (SCCHN). Conditionally replicating adenoviruses (CRAds) represent a promising new modality for treating of neoplastic diseases, including SCCHN. Specifically, CRAd agents infect tumor cells and selectively replicate within them, thus causing their death while sparing surrounding normal cells in the host. Oncolysis results from the replicative life cycle of the virus, which lyses infected tumor cells and releases viral progeny for propagation of infection and resultant lysis of neighboring cancer cells, sparing normal host cells. However, to date there have been two main limitations to successful clinical application of these CRAd agents: poor infectivity and poor tumor specificity. Here we report the construction of a CRAd agent, CRAd-CXCR4.F5/3, in which the adenovirus E1 gene is driven by a tumor-specific CXCR4 promoter, and the viral infectivity is enhanced by a fiber modification, F5/3, containing an Ad3 knob chimeric fiber protein. As expected, this agent improved both of the viral infectivity and tumor specificity as evaluated in established SCCHN tumor cell lines and in primary tumor tissues from multiple patients. As an added benefit, the activity of the CXCR4 promoter was low in human liver as described previously. Based on these data, the CRAd-CXCR4.F5/3 is a promising novel CRAd agent for SCCHN targeting with low host toxicity.


Association between short leukocyte telomere length, endotoxemia, and severe periodontitis in people with diabetes: a cross-sectional survey.
OBJECTIVE Shortened leukocyte telomere length (LTL) and diagnosis of periodontitis are associated with an increased risk of complications and mortality in diabetes. This study investigated the association between LTL, endotoxemia, and severity of periodontitis in a large cohort of people with diabetes. RESEARCH DESIGN AND METHODS Six hundred thirty individuals (371 with type 2 and 259 with type 1 diabetes) were recruited from the University College Hospital in London, U.K. During a baseline visit, blood was collected for standard biochemical tests and DNA extraction, while a dental examination was performed to determine diagnosis and extent of periodontitis. LTL was measured by real-time PCR, and endotoxemia was assessed by the limulus amoebocyte lysate method. RESULTS Two hundred fifty-five individuals were diagnosed with gingivitis, 327 with periodontitis (114 with moderate and 213 with severe disease), and 48 with edentulous. Diagnosis of periodontitis was associated with shorter LTL (P = 0.04). A negative association between LTL and endotoxemia was found in the severe periodontitis and type 2 diabetes groups (P = 0.01 for both). Shorter LTL was associated with increased extent of periodontitis (P = 0.01) and increased insulin resistance (homeostatic model assessment). Multiple adjustments for biochemical, anthropometric, and medication-use variables did not affect the results. CONCLUSIONS LTL is associated with endotoxemia and diagnosis of periodontitis in people with diabetes. LTL shortening might represent a novel biological pathway accounting for previous epidemiological data that documented higher prevalence of diabetes and its complications in people with periodontitis and vice versa.


Occurrence of antimicrobial resistance in fish-pathogenic and environmental bacteria associated with four danish rainbow trout farms.
Surveillance of bacterial susceptibility to five antimicrobial agents was performed during a 1-year period in and around four freshwater fish farms situated along a stream in western Denmark. Besides assessing the levels of antibiotic resistance among the culturable fraction of microorganisms in fish, water, and sediment samples, two major fish pathogens (88 Flavobacterium psychrophilum isolates and 134 Yersinia ruckeri isolates) and 313 motile Aeromonas isolates, representing a group of ubiquitous aquatic bacteria, were isolated from the same samples. MICs were obtained applying a standardized agar dilution method. A markedly decreased susceptibility of F. psychrophilum isolates to most antimicrobial agents presently available for use in Danish aquaculture was detected, while the collected Y. ruckeri isolates remained largely sensitive to all therapeutic substances. Comparing the inlet and outlet samples, the increase of the antibiotic-resistant proportions observed among the culturable microflora was more pronounced and statistically significant among the motile aeromonads. High levels of individual and multiple antimicrobial resistances were demonstrated within the collected flavobacteria and aeromonads, thus indicating a substantial impact of fish farming on several groups of bacteria associated with aquacultural environments.


Statins and pancreatitis: a systematic review of observational studies and spontaneous case reports.
Many anecdotal reports have suggested that therapy with HMG-CoA reductase inhibitors ('statins') can cause acute pancreatitis. We aimed to quantify the association between statins and pancreatitis and to classify the adverse effect under the dose, time, susceptibility (DoTS) system. We searched for controlled observational studies that assessed the risk of pancreatitis in patients receiving statins. In order to identify case reports of statin-induced pancreatitis, we looked for reports published in scientific journals and manually reviewed reports within the Canadian Adverse Drug Event Monitoring System (CADRMP) database. Two observational studies were identified and the data pooled together in a meta-analysis. This yielded an odds ratio of 1.41 (95% CI 1.15, 1.74) for the risk of acute pancreatitis in patients with a past history of exposure to statins. We also identified 20 published case reports and 33 spontaneous reports from the CADRMP database. These data showed that pancreatitis can occur at both high and low doses, with 12 cases developing pancreatitis at less than the dose equivalent of simvastatin 20 mg daily. Statin-induced pancreatitis can occur at any time but seems to be very uncommon early on and more likely to occur after many months of therapy. There does not appear to be a cumulative dose effect and increasing age does not appear to be a major susceptibility factor. These finding should help clinicians to better manage and diagnose patients who are at risk of statin-induced pancreatitis.


Mirtazapine versus fluoxetine in the treatment of panic disorder.
Mirtazapine is an antidepressant whose side effect profile differs from that of first-line agents (selective serotonin reuptake inhibitors) used in the treatment of panic disorder. The present study compared the effect of mirtazapine and fluoxetine in the treatment of panic disorder in a double-blind, randomized, flexible-dose trial conducted with outpatients. After a 1-week single-blind placebo run-in, 27 patients entered an 8-week double-blind phase in which they were randomly assigned to treatment with either mirtazapine or fluoxetine. Both groups improved significantly in all but one efficacy measure (P < or = 0.01). ANOVA showed no significant differences between the two treatment groups in number of panic attacks, Hamilton Anxiety Scale or Sheehan Phobic Scale, whereas measures of patient global evaluation of phobic anxiety were significantly different between groups (F1,20 = 6.91, P = 0.016) favoring mirtazapine. For the 22 patients who completed the study, the mean daily dose of mirtazapine was 18.3 +/- 1.3 vs 14.0 +/- 1.0 mg for fluoxetine at the endpoint. Weight gain occurred more frequently in the mirtazapine group (50 vs 7.7%, P = 0.04) and nausea and paresthesia occurred more often in the fluoxetine group (P = 0.01). Results suggest that mirtazapine has properties that make it attractive for the treatment of panic disorder.


The HIV epidemic among older men who have sex with men.
The authors present HIV prevalence and risk behavior data for urban men who have sex with men (MSM) aged 50 years or older. Data are based on a probability sample of MSM conducted in 1997 (n = 2881 total; 507 older MSM) in New York, Los Angeles, Chicago, and San Francisco. The authors determined HIV status through self-report and biologic measures. Risk behavior was assessed through self-report. The authors found that HIV prevalence was 19% (95% CI: 14, 25) for men in their 50s and 3% (95% CI: 1, 10) for men in their 60s. No men in their 70s were HIV-positive. Prevalence was at high levels for older blacks (30%), MSM who are injection drug users (21%), moderately heavy drug users (35%), and less closeted men (21%). High-risk sex between serodiscordant partners was relatively constant (4%-5%) across age groups older than 30 years of age and decreased among MSM in their 70s. Current levels of HIV among older urban MSM in the United States are very high, particularly among those in their 50s. High mortality rates among MSM with AIDS up to 1996 (before highly active antiretroviral therapy [HAART]) would account for the lower levels among men in their 60s and 70s. Because of HAART, we would expect HIV levels to increase in these age groups. Given high levels of risk behavior among MSM through the sixth decade of life, the authors would expect an older MSM epidemic of substantially larger proportion than that observed in the 1980s and 1990s.


The physiological stimulus for the BarA sensor kinase.
The two-component signal transduction system (TCS) BarA/UvrY activates transcription of CsrB and CsrC noncoding RNAs, which act by sequestering the RNA-binding global regulatory protein CsrA. Here, we show that the metabolic end products formate and acetate provide a physiological stimulus for this TCS and thus link posttranscriptional regulation by the Csr system to the metabolic state of the cell.


The impact of acupuncture and craniosacral therapy interventions on clinical outcomes in adults with asthma.
Synergy has been proposed between modalities operating at different levels of action. Acupuncture and craniosacral therapy are two very different modalities for which synergy has been proposed. This study sought to test for such synergy and to determine if complementary therapies would improve pulmonary function and quality of life for people suffering from asthma, as well as reducing anxiety, depression, and medication usage. Subjects were randomly assignment to one of five groups: acupuncture, craniosacral therapy, acupuncture and craniosacral, attention control, and waiting list control. Subjects received 12 sessions of equal length with pretreatment and posttreatment assessment of pulmonary function, asthma quality of life, depression, and anxiety. Medication use was also assessed. Synergy was not demonstrated. When treatment was compared with the control group, statistically treatment was significantly better than the control group in improving asthma quality of life, whereas reducing medication use with pulmonary function test results remained the same. However, the combination of acupuncture and craniosacral treatment was not superior to each therapy alone. In fact, although all active patients received 12 treatment sessions, those who received all treatments from one practitioner had statistically significant reductions in anxiety when compared with those receiving the same number of treatments from multiple practitioners. No effects on depression were found. Acupuncture and/or craniosacral therapy are potentially useful adjuncts to the conventional care of adults with asthma, but the combination of the two does not provide additional benefit over each therapy alone.


Communicative signals support abstract rule learning by 7-month-old infants.
The mechanisms underlying the discovery of abstract rules like those found in natural language may be evolutionarily tuned to speech, according to previous research. When infants hear speech sounds, they can learn rules that govern their combination, but when they hear non-speech sounds such as sine-wave tones, they fail to do so. Here we show that infants' rule learning is not tied to speech per se, but is instead enhanced more broadly by communicative signals. In two experiments, infants succeeded in learning and generalizing rules from tones that were introduced as if they could be used to communicate. In two control experiments, infants failed to learn the very same rules when familiarized to tones outside of a communicative exchange. These results reveal that infants' attention to social agents and communication catalyzes a fundamental achievement of human learning.


Changes among male and female visitors to practitioners of complementary and alternative medicine in a large adult Norwegian population from 1997 to 2008 (The HUNT studies).
The aim was to investigate changes in the prevalence and characteristics of male and female visitors to practitioners of complementary and alternative medicine (CAM) in a large adult population from 1997 to 2008. Two cross sectional adult total population health surveys from Central Norwegian (the Nord-Trøndelag Health Studies (HUNT)). In 1997 42,277 and in 2008 50,713 respondents were included. Variables included demographics (age, education, working status), lifestyle (daily smoker, did hard physical activities), health status (self-rated health status, recent complaints, chronic complaints, psychiatric complaints, a range of diseases) and health care use (visit general practitioner, chiropractor). A test of difference between the results of multivariable logistic regression models for each year, including all variables, was used to analyse changes from 1997 to 2008. In 1997 9.4% (95%CI 9.1-9.6) of the population had visited a CAM practitioner in the last 12 months and this increased to 12.6% (12.3-12.9) in 2008 (p < 0.001 for difference). Prevalence of CAM use in females was almost twice as high as that in males both years. For males, the significant changes from 1997 to 2008 (p < 0.05) were an increase in odds of visiting for those under 50 years, who had a recent complaint, were widower or did hard physical activities. There was a decrease for males who had a university degree, psychiatric complaint or hay fever. For females there was an increase in the odds for those under 50 years, who had a recent complaint or chronic complaint. It was a decrease for females with reported fair global health, psychiatric complaint, hay fever or if they had visited a chiropractor. The increase in visits was mainly among younger people of both genders with more limited complaints. A larger proportion of the more healthy part of the population is increasing their visits to CAM practitioners.


When randomisation is not good enough: Matching groups in intervention studies.
Randomised assignment of individuals to treatment and controls groups is often considered the gold standard to draw valid conclusions about the efficacy of an intervention. In practice, randomisation can lead to accidental differences due to chance. Researchers have offered alternatives to reduce such differences, but these methods are not used frequently due to the requirement of advanced statistical methods. Here, we recommend a simple assignment procedure based on variance minimisation (VM), which assigns incoming participants automatically to the condition that minimises differences between groups in relevant measures. As an example of its application in the research context, we simulated an intervention study whereby a researcher used the VM procedure on a covariate to assign participants to a control and intervention group rather than controlling for the covariate at the analysis stage. Among other features of the simulated study, such as effect size and sample size, we manipulated the correlation between the matching covariate and the outcome variable and the presence of imbalance between groups in the covariate. Our results highlighted the advantages of VM over prevalent random assignment procedure in terms of reducing the Type I error rate and providing accurate estimates of the effect of the group on the outcome variable. The VM procedure is valuable in situations whereby the intervention to an individual begins before the recruitment of the entire sample size is completed. We provide an Excel spreadsheet, as well as scripts in R, MATLAB, and Python to ease and foster the implementation of the VM procedure.


USF inhibits cell proliferation through delay in G2/M phase in FRTL-5 cells.
Upstream stimulatory factor (USF) has a negative effect on the cell proliferation in some cell types. However, its effect on thyrocytes is not clear. Therefore, we investigated the effects of USF on the proliferation and function of thyroid follicular cells. Complementary DNAs of the USF-1 and USF-2 were synthesized using RT-PCR from FRTL-5 cells, and each was transfected to FRTL-5 cells and papillary thyroid carcinoma cell lines. Cyclic AMP (cAMP) production and [methyl-3H] thymidine uptake after thyroid stimulating hormone (TSH) treatment were measured in FRTL-5 cells. In the carcinoma cell lines, 5-bromo-2'-deoxyuridine (BrdU) uptake was assayed to evaluate cell proliferation. Apoptosis was tested by Hoechst staining and cell cycle analysis was done using a fluorescence activated cell sorting. Expression of cell cycle regulating genes was evaluated by Northern and Western blotting. Overexpression of USF-1 and USF-2 significantly suppressed TSH-stimulated [methyl-3H] thymidine uptake (p<0.05), while it maintained TSH-stimulated cAMP production in FRTL-5 cells. Overexpression of USF significantly suppressed BrdU uptake in each carcinoma cell line, NPA and TPC-1 cells (p<0.05). It induced delay of cell cycle at the G2/M phase, but did not increase apoptosis in FRTL-5 cells. It was accompanied by a decrease of cyclin B1 and cyclin-dependent kinase (CDK)-1, and an increase of p27 expression. USF-1 and USF-2 suppressed cell proliferation of normal thyrocytes and thyroid carcinoma cells. However, they retained the ability to produce cAMP after TSH stimulation. Their inhibitory effect on cell proliferation might be caused partly by the delay in G2/M phase.


A functional characterisation of a wide range of cover crop species: growth and nitrogen acquisition rates, leaf traits and ecological strategies.
Cover crops can produce ecosystem services during the fallow period, as reducing nitrate leaching and producing green manure. Crop growth rate (CGR) and crop nitrogen acquisition rate (CNR) can be used as two indicators of the ability of cover crops to produce these services in agrosystems. We used leaf functional traits to characterise the growth strategies of 36 cover crops as an approach to assess their ability to grow and acquire N rapidly. We measured specific leaf area (SLA), leaf dry matter content (LDMC), leaf nitrogen content (LNC) and leaf area (LA) and we evaluated their relevance to characterise CGR and CNR. Cover crop species were positioned along the Leaf Economics Spectrum (LES), the SLA-LDMC plane, and the CSR triangle of plant strategies. LA was positively correlated with CGR and CNR, while LDMC was negatively correlated with CNR. All cover crops could be classified as resource-acquisitive species from their relative position on the LES and the SLA-LDMC plane. Most cover crops were located along the Competition/Ruderality axis in the CSR triangle. In particular, Brassicaceae species were classified as very competitive, which was consistent with their high CGR and CNR. Leaf functional traits, especially LA and LDMC, allowed to differentiate some cover crops strategies related to their ability to grow and acquire N. LDMC was lower and LNC was higher in cover crop than in wild species, pointing to an efficient acquisitive syndrome in the former, corresponding to the high resource availability found in agrosystems. Combining several leaf traits explained approximately half of the CGR and CNR variances, which might be considered insufficient to precisely characterise and rank cover crop species for agronomic purposes. We hypothesised that may be the consequence of domestication process, which has reduced the range of plant strategies and modified the leaf trait syndrome in cultivated species.


Granulomatous amebic encephalitis caused by Acanthamoeba in an immuncompetent child.
Sütçü M, Aktürk H, Gülümser-Şişko S, Acar M, Erol OB, Somer A, Bilgiç B, Salman N. Granulomatous amebic encephalitis caused by Acanthamoeba in an immuncompetent child. Turk J Pediatr 2018; 60: 340-343. Acanthamoeba may lead to granulomatous amebic encephalitis (GAE) with high mortality rates generally in patients with immunosupression and/or chronic disease. Here, we present a rare GAE case, who was a previously healthy child. A Georgian 9 year old boy presented with focal seizure on his left arm and confusion. Since computed tomography (CT) demonstrated hypodense lesion on right occipital lobe, brain biopsy was performed. Histopathological examination of the biopsy material revealed Acanthamoeba cysts and trophozoites together with granulomatous inflammation. The patient, who had no clinical and laboratory findings consistent with immunedeficiency, was diagnosed as GAE. He was treated with a combination drug therapy. Even if it is very rare, amebic meningoencephalitis may also be seen in immunocompetent children, as in our case. Definitive diagnosis is made by microbiological and histopathological examination of brain biopsy material.


Validation of a perfusion registry: methodological approach and initial findings.
Although regional and national registries exist to measure and report performance of cardiac surgical programs, few registries exist dedicated to the practice of cardiopulmonary bypass (CPB). We developed and implemented a cardiovascular perfusion registry (Perfusion Measures and outcomes [PERForm] Registry) within the structure of the Michigan Society of Thoracic and Cardiovascular Surgeons (MSTCVS) to improve our understanding of the practice of CPB. The PERForm Registry comprises data elements describing the practice of CPB. Fourteen medical centers within MSTCVS have voluntarily reported these data on procedures in which CPB is used. We validated the case count among procedures performed between January 1, 2011 to December 31, 2011, and validated the values among 20 fields at three medical centers. We queried database managers at all 14 medical centers to identify the infrastructure that contributed to best overall data collection performance. We found that 98% of all records submitted to the PERForm and 95% of those submitted to the Society of Thoracic Surgeons (STS) matched. We found quite favorable agreement in our audit of select fields (95.8%). Those centers with the most favorable performance in this validation study were more likely to use electronic data capture, have a perfusionist as the STS database manager, and have involvement of the STS database manager in the PERForm or STS databases. We successfully and accurately collected data concerning cardiovascular perfusion among 14 institutions in conjunction with the MSTCVS. Future efforts will focus on expanding data collection to all MSTCVS participating institutions as well as more broadly outside of Michigan.


Rheumatoid arthritis patients' perceptions of mutuality in conversations with spouses/partners and their links with psychological and physical health.
Mutuality, measured as subjects' perceptions of responsiveness in conversations with their spouse/partners, is linked with women's psychological health. Our objectives were to examine physical and psychological health outcomes of married/partnered patients with rheumatoid arthritis (RA) in relation to their perceptions of their own responsiveness (self-mutuality), their partner's responsiveness (partner-mutuality), and combined responsiveness (overall mutuality), and to examine potential sex differences in the links between mutuality and depressive symptoms. Symptoms of depression and anxiety, physical disability, and arthritis impact reported by RA patients were examined in correlation matrices with their perceptions of overall mutuality, partner-mutuality, and self-mutuality in conversations with spouses/partners in the whole sample (n = 148) and separately for men (n = 34) and women (n = 114). Sex moderation of the links between mutuality and depression was tested in hierarchical regressions. In the whole sample and among women, all mutuality measures had significant inverse correlations with all health outcomes. In men, physical disability was unrelated to mutuality measures, but otherwise correlations approximated those in the whole sample and for women. Sex (being female) interacted with self-mutuality, but not overall or partner-mutuality, in predicting fewer depressive symptoms. RA patients' perceptions of mutuality in conversations with spouses/partners predicted better health across a spectrum of outcomes. Overall mutuality and partner-mutuality predicted fewer depressive symptoms for both men and women, but self-mutuality appeared more important for women than for men. The clinical relevance of findings and their implications for behavioral interventions with RA patients are discussed.


Evolution of protein bound Maillard reaction end-products and free Amadori compounds in low lactose milk in presence of fructosamine oxidase I.
Thermal treatments and storage influence milk quality, particularly in low lactose milk as the higher concentration of reducing sugars can lead to the increased formation of the Maillard reaction products (MRPs). The control of the Amadori products (APs) formation is the key step to mitigate the Maillard reaction (MR) in milk. The use of fructosamine oxidases, (Faox) provided promising results. In this paper, the effects of Faox I were evaluated by monitoring the concentration of free and bound MRPs in low lactose milk during shelf life. Results showed that the enzyme reduced the formation of protein-bound MRPs down to 79% after six days at 37°C. Faox I lowered the glycation of almost all the free amino acids resulting effective on basic and polar amino acids. Data here reported corroborate previous findings on the potentiality of Faox enzymes in controlling the early stage of the MR in foods.


Automated ribotyping using different enzymes to improve discrimination of Listeria monocytogenes isolates, with a particular focus on serotype 4b strains.
To develop improved automated subtyping approaches for Listeria monocytogenes, we characterized the discriminatory power of different restriction enzymes for ribotyping. When 15 different restriction enzymes were used for automated ribotyping of 16 selected L. monocytogenes isolates, the restriction enzymes EcoRI, PvuII, and XhoI showed high discriminatory ability (Simpson's index of discrimination > 0.900) and produced complete and reproducible restriction cut patterns. These three enzymes were thus evaluated for their ability to differentiate among isolates representing the two major serotype 4b epidemic clones, those having ribotype reference pattern DUP-1038 (51 isolates) and those having pattern DUP-1042 (20 isolates). Among these isolates, PvuII provided the highest discrimination for a single enzyme (nine different subtypes; index of discrimination = 0.518). A combination of PvuII and XhoI showed the highest discriminatory ability (index of discrimination = 0.590) for these isolates. A group of 44 DUP-1038 isolates and a group of 12 DUP-1042 isolates were identical to each other even when the combined data for all three enzymes were used. We conclude that automated ribotyping using different enzymes allows improved discrimination of L. monocytogenes isolates, including epidemic serotype 4b strains. We furthermore confirm that most of the isolates representing the genotypes linked to the two major epidemic L. monocytogenes clonal groups form two genetically homogeneous groups.


Reinfusion of mediastinal blood in CABG patients: impact on homologous transfusions and rate of re-exploration.
Reinfusion of mediastinal shed blood after cardiac surgery has been used in some centers to reduce exposure to homologous blood transfusions. The method has not been widely applied mostly because some studies have failed to demonstrate a significant benefit. A group of 675 consecutive patients undergoing first-time, isolated coronary artery bypass surgery (CABG) was studied. Prospective data was collected on the first 375 patients receiving autotransfusion (ATS) of mediastinal shed blood. The charts of 338 patients immediately preceding the institution of the ATS program at our institution (NO ATS group) were retrospectively reviewed. Transfusion of homologous blood products and rate of re-exploration for bleeding were closely monitored. The two groups were identical. The net blood loss was significantly less in the ATS group than in the NO ATS group (1013 +/- 431 cc vs 1371 +/- 631 cc, p < 0.0001). Rate of exploration for postoperative bleeding was 1.5% in the ATS group and 5.0% in the NO ATS group (p < 0.01). In the ATS group, 51.9% of patients were not exposed to any homologous blood product (vs 17.8% in the NO ATS group, p < 0.0001). The ATS patients received on the average 2.9 +/- 7.2 units of blood products versus 6.4 +/- 9.7 units in the NO ATS group (p < 0.0001). Reinfusion of mediastinal shed blood significantly reduces exposure to homologous blood transfusions and rate of reexploration. The ATS system reduces the number of re-explorations for coagulopathy-related postoperative hemorrhage.


Sigma Factor-Mediated Tuning of Bacterial Cell-Free Synthetic Genetic Oscillators.
Cell-free transcription-translation provides a simplified prototyping environment to rapidly design and study synthetic networks. Despite the presence of a well characterized toolbox of genetic elements, examples of genetic networks that exhibit complex temporal behavior are scarce. Here, we present a genetic oscillator implemented in an E. coli-based cell-free system under steady-state conditions using microfluidic flow reactors. The oscillator has an activator-repressor motif that utilizes the native transcriptional machinery of E. coli: the RNAP and its associated sigma factors. We optimized a kinetic model with experimental data using an evolutionary algorithm to quantify the key regulatory model parameters. The functional modulation of the RNAP was investigated by coupling two oscillators driven by competing sigma factors, allowing the modification of network properties by means of passive transcriptional regulation.


Predictors of treatment initiation with tumor necrosis factor-α inhibitors in patients with rheumatoid arthritis.
Introduction of biologic disease-modifying antirheumatic drugs (DMARDs) has revolutionized treatment in patients with rheumatoid arthritis (RA). However, due to substantially higher costs of biologics compared with nonbiologics, patients with less insurance generosity may have difficulty affording these agents, which may lead to potential access disparities. To identify factors affecting treatment initiation with tumor necrosis factor (TNF)-α inhibitor biologics in patients with RA. Health insurance claims data derived from Truven's MarketScan Commercial Claims and Encounters and Medicare Supplemental and Coordination of Benefits (2007-2010) were used to conduct a retrospective cohort study. Two separate cohorts of RA patients were identified: (1) monotherapy nonbiologic DMARD users and (2) combination therapy nonbiologic DMARD users. The primary outcome was TNF-α inhibitor initiation 12 months following an index inpatient or outpatient RA visit during 2008-2009. Predictors were measured 12 months pre-index and grouped into predisposing, enabling, or need factors based on Andersen's Behavior Model. Predisposing variables included age, sex, and geographic location; enabling variables included insurance-related factors such as capitation, payer type, and insurance generosity, which was defined using cost-sharing information from prescriptions filled by the patients in the previous year; and need variables included disease-related factors such as severity of RA, use of pain control medications, and presence of other comorbidities. Hierarchical logistic regression models were used to derive estimates of the impact of individual predictors. Initiation of TNF-α inhibitors was observed in 10.31% of the monotherapy nonbiologic DMARD users (1,922 of 18,641) and 13.09% of combination nonbiologic DMARD users (983 of 7,508). Among monotherapy nonbiologic DMARD users, initiation with TNF-α inhibitors was associated with the predisposing factors of age (OR = 0.98, 95% CI = 0.97-0.98 for each year increase) and geographic region (Midwest vs. South OR = 0.83, 95% CI = 0.73-0.93; Northeast vs. South OR = 0.77, 95% CI = 0.64-0.92; and West vs. South OR = 0.86, 95% CI = 0.74-0.99); enabling factors of visit to rheumatologists (1 visit vs. no visit OR = 1.22, 95% CI = 1.01-1.46), health insurance type (commercial vs. Medicare supplemental OR = 0.79, 95% CI = 0.66-0.95), and drug benefit generosity (above average vs. poor OR = 1.16, 95% CI = 1.01-1.34 and most generous vs. poor OR = 1.21, 95% CI = 1.05-1.40); and need factors of RA severity (OR = 1.19, 95% CI = 1.14-1.23 for each unit increase in a claims-based RA severity index [CIRAS]), pre-index pain reliever use (steroids OR = 1.81, 95% CI = 1.62-2.02; nonselective nonsteroidal anti-inflammatory drugs [NSAID] OR = 1.17, 95% CI = 1.05-1.31; COX-2 inhibitors OR = 1.22, 95% CI = 1.05-1.41), and comorbidities (OR = 0.94, 95% CI = 0.90-0.99 for each unit increase in a comorbidity index). Treatment initiation with TNF-α inhibitors among patients with combination therapy nonbiologic DMARDs use at baseline was associated with age (OR = 0.98, 95% CI = 0.97-0.99 for each year increase) and region (Midwest vs. South OR = 0.81, 95% CI = 0.68-0.96). Stronger associations with some of the need factors were observed (CIRAS OR = 1.28, 95% CI = 1.21-1.35 for each unit increase, steroids use OR = 2.05, 95% CI = 1.73-2.42, and nonselective NSAID use OR = 1.36, 95% CI = 1.17-1.58) in these patients compared with the monotherapy nonbiologic DMARD users. However, unlike the monotherapy DMARD user group, the enabling factors of health insurance type and drug benefit generosity were not found to be associated with TNF-α inhibitor initiation among nonbiologic DMARD combination therapy users. Potential disparities in the initiation of TNF-α inhibitors among RA patients on monotherapy DMARDs at baseline were noted among older patients, patients in certain geographic region of the United States, and patients with less generous prescription drug benefits. Although future research should examine the impact of these disparities on health outcomes, payers should be aware of the potential for undertreatment among these groups of RA patients when making formulary decisions.


Molecular epidemiology for vector research on leishmaniasis.
Leishmaniasis is a protozoan disease caused by the genus Leishmania transmitted by female phlebotomine sand flies. Surveillance of the prevalence of Leishmania and responsive vector species in endemic and surrounding areas is important for predicting the risk and expansion of the disease. Molecular biological methods are now widely applied to epidemiological studies of infectious diseases including leishmaniasis. These techniques are used to detect natural infections of sand fly vectors with Leishmania protozoa and are becoming powerful tools due to their sensitivity and specificity. Recently, genetic analyses have been performed on sand fly species and genotyping using PCR-RFLP has been applied to the sand fly taxonomy. In addition, a molecular mass screening method has been established that enables both sand fly species and natural leishmanial infections to be identified simultaneously in hundreds of sand flies with limited effort. This paper reviews recent advances in the study of sand flies, vectors of leishmaniasis, using molecular biological approaches.


HIV Sexual Risk Behavior and Health Insurance Coverage in Men Who Have Sex with Men.
Research on the association between health insurance coverage and sexual risk behavior among men who have sex with men (MSM) is sparse. We hypothesized that MSM with health insurance would be less likely to engage in risky sexual behavior based on previous research showing that insured persons increase contact with providers which can improve health knowledge, decrease tendency to engage in unhealthy behaviors, and raise awareness about health risks. As part of a study testing an online HIV prevention intervention, we collected information on health insurance and sexual behavior from MSM (n=650). Overall, men with health insurance had a 28% reduced prevalence of unprotected anal intercourse male partners (UAIMP) in the 90 days prior to the survey. Potential explanations include access to healthcare providers and awareness of sexual health. Additional research is needed to identify the mechanism through which health insurance is protective.


Contribution of hypoxia to Alzheimer's disease: is HIF-1alpha a mediator of neurodegeneration?
The mammalian brain is extremely sensitive to alterations in cellular homeostasis as a result of environmental or physiological insults. In particular, hypoxic/ischemic challenges (i.e. reduced oxygen and/or glucose delivery) cause severe and detrimental alterations in brain function and can trigger neuronal cell death within minutes. Unfortunately, as we age, oxygen delivery to cells and tissues is impaired, thereby increasing the susceptibility of neurons to damage. Thus, hypoxic (neuronal) adaptation is significantly compromised during aging. Many neurological diseases, such as stroke, Alzheimer's disease (AD), Parkinson's disease and diabetes, are characterized by hypoxia, a state that is believed to only exacerbate disease progression. However, the contribution of hypoxia and hypoxia-mediated pathways to neurodegeneration remains unclear. This review discusses current evidence on the contribution of oxygen deprivation to AD, with an emphasis on hypoxia inducible transcription factor-1 (HIF-1)-mediated pathways and the association of AD with the cytoskeleton regulator cyclin-dependent kinase 5.


Percutaneous arthrodesis of sacro-iliac joint: a pilot study.
Between 15-30% of patients presenting with low back pain have some SI joint involvement. The diagnosis of SI joint involvement in low back pain is quite difficult and depends on a detailed combination of clinical manoeuvres and injection tests. In 5% of patients with SI joint pain, the joint is physically unstable (termed disruption) resulting in ineffective medical and conservative therapeutic options. In this study we present the results of the first 12 cases of SI joint disruption treated using a minimally invasive SI joint arthrodesis system in order to evaluate the safety and the efficacy of this system. Medical charts at a single center were reviewed for demographics, perioperative metrics, patient reported outcomes for pain, function and quality of life (NRS, ODI and RDQ respectively), as well as satisfaction with surgery (yes/no) and results of postoperative CT scan. Mean age was 53 years (range 36-71) and all patients were female. Patient reported outcomes at follow up (range 8-18 months) improved clinically as well as statistically as evidenced by a mean improvement in pain on NRS of 4 points, back related function on ODI by 19.4 points, and in quality of life measured using RDQ of 13.6 points (all P=0.01). Local hematoma requiring drainage was apparent in 2 patients. Patient satisfaction was 100%. All 3 month CT scans showed initial fusion. The results of this study confirm that MIS SI joint fusion using the iFuse Implant System is safe and effective method of treating patients with SI joint disruption.


[The evaluation of hospital management of sanitary waste in the principality of Asturias].
With the object of evaluating the management of sanitary waste of 12 publicly funded Asturian hospitals, a visit was paid to the hospital services, particularly significant as regards the generation of waste (a total of 91 services). The evaluated hospitals represent 75.10% of the total hospital beds in the Principality. Interviews with personnel from 91 different services were undertaken, always by the same interviewer, and according to the rules of the Joint Commission of Health Care Organizations. The information obtained was afterwards verified by the interviewer by means of direct observation. Amongst the most relevant results, the absence of adequate containers for "clinical" waste in 28.5% of the services visited, stands out. Into the bargain, 82.4% of the services classify this type of waste incorrectly. The percentage of incorrect classification is 1.1% for "special" waste. In large hospitals (with over 300 beds), 60% of the services have information on the handling of waste, but only 40% of these hospitals have adequate supervision over the management of waste by the Service of Preventive Medicine or another equivalent service. The level of incorrect classification of sanitary waste which has been discovered suggests that, in order to improve the intra-hospital management of waste, it is necessary to increase the amount of information, modify certain attitudes of the hospital staff and reinforce the level of supervision executed by the Services of Preventive Medicine.


Mapping cannabis potency in medical and recreational programs in the United States.
Cannabis related online searches are associated with positive attitudes toward medical cannabis, particularly when information is obtained from dispensaries. Since pain is the main reason for medicinal cannabis use, information from dispensary websites has the potential to shape the attitude of pain patients towards cannabis. This is relevant because cannabis has demonstrated efficacy in neuropathic pain with low tetrahydrocannabinol (THC) concentrations (< 5-10%), in contrast to potent cannabis (>15% THC), which is highly rewarded in the recreational realm. The role of CBD in pain is not clear, however it has gained popularity. Thus, we hypothesize that the potency of medical cannabis that is advertised online is similar to the cannabis advertised for recreational purposes, which would potentially create a misconception towards medical cannabis. The current lack of knowledge surrounding advertised potencies in the legal cannabis market limits the ability to generate clear policies regarding online advertising to protect patients that are willing to use cannabis for their condition. Thus, we evaluated the advertised THC and CBD content of cannabis products offered online in dispensaries in the United States to determine products' suitability to medicinal use and compare the strength of products offered in legal medical and recreational programs. We recorded THC and CBD concentrations for all herb cannabis products provided by dispensary websites and compared them between or within states. Four Western states (CA, CO, NM, WA) and five Northeastern states (ME, MA, NH, RI, VT) were included. A total of 8,505 cannabis products across 653 dispensaries were sampled. Despite the clear differences between medicinal and recreational uses of cannabis, the average THC concentration advertised online in medicinal programs was similar (19.2% ±6.2) to recreational programs (21.5% ±6.0) when compared between states with different programs, or between medicinal and recreational programs within the same states (CO or WA). Lower CBD concentrations accompanied higher THC products. The majority of products, regardless of medicinal or recreational programs, were advertised to have >15% THC (70.3% - 91.4% of products). These stated concentrations seem unsuitable for medicinal purposes, particularly for patients with chronic neuropathic pain. Therefore, this information could induce the misconception that high potency cannabis is safe to treat pain. This data is consistent with reports in which THC and CBD in products from legal dispensaries or in nationwide products from the illegal market were actually measured, which indicates that patients consuming these products may be at risk of acute intoxication or long-term side effects. Our study offers grounds to develop policies that help prevent misconceptions toward cannabis and reduce risks in pain patients.


Early postoperative MRI in detecting hematoma and dural compression after lumbar spinal decompression: prospective study of asymptomatic patients in comparison to patients requiring surgical revision.
Early postoperative MRI after spinal surgery is difficult to interpret because of confounding postoperative mass effects and frequent occurrence of epidural hematomas. Purpose of this prospective study is to evaluate prevalence, extent and significance of hematoma in the first postoperative week in asymptomatic patients after decompression for lumbar stenosis and to determine the degree of clinically significant dura compression by comparing with the patients with postoperative symptoms. MRI was performed in 30 asymptomatic patients (47 levels) in the first week after lumbar spine decompression for degenerative stenosis. Eleven patients requiring surgical revision (16 levels) for symptomatic early postoperative hematoma were used for comparison. In both groups the cross-sectional area of the maximum dural compression (bony stenosis and dural sac expansion) was measured preoperatively and postoperatively by an experienced radiologist. Epidural hematoma was seen in 42.5% in asymptomatic patients (20/47 levels). The median area of postoperative hematoma at the operated level was 176 mm(2) in asymptomatic patients and 365 mm(2) in symptomatic patients. The median cross-sectional area of the dural sac at the operated level was 128.5 and 0 mm(2) in asymptomatic and symptomatic patients, respectively, at the site of maximal compression. In the symptomatic group 75% of the patients had a maximal postoperative dural sac area of 58.5 mm(2) or less, whereas in the asymptomatic group 75% of patients with epidural hematoma had an area of 75 mm(2) or more. The size of hematoma and the degree of dural sac compression were significantly larger in patients with symptoms needing surgical revision. Dural sac area of less than 75 mm(2) in early postoperative MRI was found to be the threshold for clinical significance.


An In vitro Study to Assess the Effectiveness of the Shear Bond Strength of Mineral Trioxide Aggregate with Different Adhesive Systems.
Mineral trioxide aggregate (MTA) is a biocompatible material and has excellent sealing ability. It is proved and claimed that it provides double seal due to its physical sealing ability as well as ability to induce cementogenesis that provides biological seal. The aim of the study was to assess the shear bond strength of MTA with three different types of adhesive systems: (1) self-adhering flowable composite, (2) etch and rinse (ER) adhesive system, and (3) self-etch (SE) adhesive system. Ninety MTA specimens were prepared using cylindrical acrylic blocks, having a central cavity with 2 mm depth and 4 mm diameter. MTA was mixed and placed in the prepared cavity and was covered with moist cotton pellet and temporary filling material (Cavit). They were further divided into three groups which were further divided into two subgroups. After the bonding agents was applied, the composite resin was placed over the MTA surface. The specimens were then tested for shear bond strength; statically analysis was done. After 24 h, the mean value of ER group was found to be significantly higher than SE and the self-adhering composite groups. Among the 45 min groups, there was no significant difference observed. In single visit, after 45 min, self-adhering flowable can be used successfully as a final restorative material in place of conventional flowable composite without using any alternative adhesive system over MTA.


Notch and NOXA-related pathways in melanoma cells.
Notch receptor-mediated intracellular events represent an ancient cell signaling system, and alterations in Notch expression are associated with various malignancies in which Notch may function as an oncogene or less commonly as a tumor suppressor. Notch signaling regulates cell fate decisions in the epidermis, including influencing stem cell dynamics and growth/differentiation control of cells in skin. Because of increasing evidence that the Notch signaling network is deregulated in human malignancies, Notch receptors have become attractive targets for selective killing of malignant cells. Compared with proliferating normal human melanocytes, melanoma cell lines are characterized by markedly enhanced levels of activated Notch-1 receptor. By using a small molecule gamma-secretase inhibitor (GSI) consisting of a tripeptide aldehyde, N-benzyloxycarbonyl-Leu-Leu-Nle-CHO, which can block processing and activation of all four different Notch receptors, we identified a specific apoptotic vulnerability in melanoma cells. GSI triggers apoptosis in melanoma cells, but only G2/M growth arrest in melanocytes without subsequent cell death. Moreover, GSI treatment induced a pro-apoptotic BH3-only protein, NOXA, in melanoma cells but not in normal melanocytes. The use of GSI to induce NOXA induction overcomes the apoptotic resistance of melanoma cells, which commonly express numerous cell survival proteins such as Mcl-1, Bcl-2, and survivin. Taken together, these results highlight the concept of synthetic lethality in which exposure to GSI, in combination with melanoma cells overexpressing activated Notch receptors, has lethal consequences, producing selective killing of melanoma cells, while sparing normal melanocytes. By identifying signaling pathways that contribute to the transformation of melanoma cells (e.g. Notch signaling), and anti-cancer agents that achieve tumor selectivity (e.g., GSI-induced NOXA), this experimental approach provides a useful framework for future therapeutic strategies in cutaneous oncology.


Clustered Core- and Pan-Genome Content on Rhodobacteraceae Chromosomes.
In Bacteria, chromosome replication starts at a single origin of replication and proceeds on both replichores. Due to its asymmetric nature, replication influences chromosome structure and gene organization, mutation rate, and expression. To date, little is known about the distribution of highly conserved genes over the bacterial chromosome. Here, we used a set of 101 fully sequenced Rhodobacteraceae representatives to analyze the relationship between conservation of genes within this family and their distance from the origin of replication. Twenty-two of the analyzed species had core genes clustered significantly closer to the origin of replication with representatives of the genus Celeribacter being the most apparent example. Interestingly, there were also eight species with the opposite organization. In particular, Rhodobaca barguzinensis and Loktanella vestfoldensis showed a significant increase of core genes with distance from the origin of replication. The uneven distribution of low-conserved regions is in particular pronounced for genomes in which the halves of one replichore differ in their conserved gene content. Phage integration and horizontal gene transfer partially explain the scattered nature of Rhodobacteraceae genomes. Our findings lay the foundation for a better understanding of bacterial genome evolution and the role of replication therein.


A population health approach in education to support children's early development: A Critical Interpretive Synthesis.
The primary objective of this review is to investigate what is currently known about early childhood education planning, population health models and their relation to children's development. A systematic review using the Critical Interpretive Synthesis method was undertaken, guided by a preliminary research question, "How can a population heath approach be applied to educational planning to support children's early development?" which acted as a compass and guide throughout the process. The initial search yielded 20,122 results, of which 42 were included in the review. Four synthetic constructs emerged (1) Elements of population health models exist within communities and can help improve outcomes for more children, (2) Inter-disciplinary collaboration and partnerships possess unique opportunities to influence children's development, (3) Children's development can be influenced at a variety of levels, and (4) System change requires a range of drivers and supports. Within education, there are several models which are used to improve outcomes for children and families. Although a population health approach to planning does not explicitly exist, the results from this review indicate that it would indeed be plausible to adapt the population health approach to sites and schools, and that doing so would be advantageous for children's development. However, implementing such an approach requires more than desire for change and demands system changes and supports. A protocol for the review was published on the International Prospective Register of Systematic Reviews (PROSPERO), registration number CRD42018098835 on 31st July 2018.


Heat shock protein 90 inhibition depletes TrkA levels and signaling in human acute leukemia cells.
Nerve growth factor (NGF) induces autophosphorylation and downstream progrowth and prosurvival signaling from the receptor tyrosine kinase TrkA. Overexpression or activating mutation of TrkA has been described in human acute myeloid leukemia cells. In the present study, we show the chaperone association of TrkA with heat shock protein 90 (hsp90) and the inhibitory effect of the hsp90 inhibitor, 17-DMAG, on TrkA levels and signaling in cultured and primary myeloid leukemia cells. Treatment with 17-DMAG disrupted the binding of TrkA with hsp90 and the cochaperone cdc37, resulting in polyubiquitylation, proteasomal degradation, and depletion of TrkA. Exposure to 17-DMAG inhibited NGF-induced p-TrkA, p-AKT, and p-ERK1/2 levels, as well as induced apoptosis of K562, 32D cells with ectopic expression of wild-type TrkA or the constitutively active mutant Delta TrkA, and of primary myeloid leukemia cells. Additionally, 17-DMAG treatment inhibited NGF-induced neurite formation in the rat pheochromocytoma PC-12 cells. Cotreatment with 17-DMAG and K-252a, an inhibitor of TrkA-mediated signaling, induced synergistic loss of viability of cultured and primary myeloid leukemia cells. These findings show that TrkA is an hsp90 client protein, and inhibition of hsp90 depletes TrkA and its progrowth and prosurvival signaling in myeloid leukemia cells. These findings also support further evaluation of the combined activity of an hsp90 inhibitor and TrkA antagonist against myeloid leukemia cells.


Construction a magneto carbon paste electrode using synthesized molecularly imprinted magnetic nanospheres for selective and sensitive determination of mefenamic acid in some real samples.
A novel magneto multiwalled carbon nanotube/carbon paste electrode (MMW/CPE) for the determination of mefenamic acid (MFA) was introduced. Magnetic molecularly imprinted polymer nanoparticles (MMIPNPs) were synthesized and then added to the solution of MFA. After stirring for 20 min, the MMW/CPE was immersed in the solution of MFA (contain MMIPNPs) and the MMIPNPs were captured by it. Then oxidation of MFA was analyzed by differential pulse voltammetry (DPV). Electrochemical impedance spectroscopy, cyclic voltammetry, and DPV were employed to characterize the MMW/CPE. The MMIPNPs exhibited a high selectivity and sensitivity toward MFA. The effect of various experimental parameters including pH, MMIPNPs dosage, stirring time, accumulation potential and time on the voltammetric response of MFA were investigated. Under the optimal conditions, selective detection of MFA in a linear concentration range of 2.0-1000.0 nmol L(-1) was performed with the detection limit of 1.2 nmol L(-1) (3S/N). To further study the practical applicability of this method, it was applied to the analysis of some real samples and the obtained results were satisfactory.


Neural correlates of state- and strength-based perception.
Perceptual judgments can be based on two kinds of information: state-based perception of specific, detailed visual information, or strength-based perception of global or relational information. State-based perception is discrete in the sense that it either occurs or fails, whereas strength-based perception is continuously graded from weak to strong. The functional characteristics of these types of perception have been examined in some detail, but whether state- and strength-based perception are supported by different brain regions has been largely unexplored. A consideration of empirical work and recent theoretical proposals suggests that parietal and occipito-temporal regions may be differentially associated with state- and strength-based signals, respectively. We tested this parietal/occipito-temporal state/strength hypothesis using fMRI and a visual perception task that allows separation of state- and strength-based perception. Participants made same/different judgments on pairs of faces and scenes using a 6-point confidence scale where "6" responses indicated a state of perceiving specific details that had changed, and "1" to "5" responses indicated judgments based on varying strength of relational match/mismatch. Regions in the lateral and medial posterior parietal cortex (supramarginal gyrus, posterior cingulate cortex, and precuneus) were sensitive to state-based perception and were not modulated by varying levels of strength-based perception. In contrast, bilateral fusiform gyrus activation was increased for strength-based "different" responses compared with misses and did not show state-based effects. Finally, the lateral occipital complex showed increased activation for state-based responses and additionally showed graded activation across levels of strength-based perception. These results offer support for a state/strength distinction between parietal and temporal regions, with the lateral occipital complex at the intersection of state- and strength-based processing.


Does the Revised Child Anxiety and Depression Scale (RCADS) measure anxiety symptoms consistently across adolescence? The TRAILS study.
We assessed if the Revised Child Anxiety and Depression Scale (RCADS) measures anxiety symptoms similarly across age groups within adolescence. This is crucial for valid comparison of anxiety levels between different age groups. Anxiety symptoms were assessed biennially in a representative population sample (n = 2226) at three time points (age range 10-17 years) using the RCADS anxiety subscales (generalized anxiety disorder [GAD], obsessive-compulsive disorder [OCD], panic disorder [PD], separation anxiety [SA], social phobia [SP]). We examined longitudinal measurement invariance of the RCADS, using longitudinal confirmatory factor analysis, by examining the factor structure (configural invariance), factor loadings (metric invariance) and thresholds (strong invariance). We found that all anxiety subtypes were configural invariant. Metric invariance held for items on the GAD, OCD, PD and SA subscales; yet, for the SP subscale three items showed modest longitudinal variation at age 10-12. Model fit decreased modestly when enforcing additional constraints across time; however, model fit for these models was still adequate to excellent. We conclude that the RCADS measures anxiety symptoms similarly across time in a general population sample of adolescents; hence, measured changes in anxiety symptoms very likely reflect true changes in anxiety levels. We consider the instrument suitable to assess anxiety levels across adolescence.


N-acetylglucosamine kinase, HXK1 is involved in morphogenetic transition and metabolic gene expression in Candida albicans.
Candida albicans, a common fungal pathogen which diverged from the baker's yeast Saccharomyces cerevisiae has the unique ability to utilise N-acetylglucosamine, an amino sugar and exhibits phenotypic differences. It has acquired intricate regulatory mechanisms at different levels in accordance with its life style. N-acetylglucosamine kinase, a component of the N-acetylglucosamine catabolic cascade is an understudied gene since Saccharomyces cerevisiae lacks it. We report HXK1 to act as both positive and negative regulator of transcription of genes involved in maintaining cellular homeostasis. It is involved in repression of hyphal specific genes in addition to metabolic genes. Its regulation of filamentation and GlcNAc metabolism is independent of the known classical regulators like EFG1, CPH1, RAS1, TPK2 or TUP1. Moreover, Hxk1-GFP is localised to cytoplasm, nucleus and mitochondria in a condition specific manner. By employing two-step affinity purification, we report the interaction of HXK1 with SIR2 under filamentation inducing conditions. Our work highlights a novel regulatory mechanism involved in filamentation repression and attempts to decipher the GlcNAc catabolic regulatory cascade in eukaryotes.


Effects of Caffeine Ingestion on Physical Performance in Elite Women Handball Players: A Randomized, Controlled Study.
To investigate the effects of acute caffeine (CAFF) intake on physical performance in elite women handball players. A total of 15 elite women handball players participated in a randomized, double-blind study. In 2 different trials, participants ingested either a placebo (cellulose) or 3 mg of CAFF per kilogram of body mass (mg/kg bm) before undergoing a battery of neuromuscular tests consisting of handball throws, an isometric handgrip strength test, a countermovement jump, a 30-m sprint test (SV) and a modified version of the agility T test. Then, participants performed a simulated handball game (2 × 20 min), and movement patterns were recorded with a local positioning system. Compared with the placebo, CAFF increased ball velocity in all ball throws (P = .021-.044; effect size [ES] = 0.39-0.49), strength in isometric handgrip strength test (350.8 [41.2] vs 361.6 [46.1] N, P = .034; ES = 0.35), and countermovement-jump height (28.5 [5.5] vs 29.8 [5.5] cm; P = .006; ES = 0.22). In addition, CAFF decreased running time in the SV (4.9 [0.2] vs 4.8 [0.3] s; P = .042; ES = -0.34). In the simulated game, CAFF increased the frequency of accelerations (18.1 [1.2] vs 18.8 [1.0] number/min; P = .044; ES = 0.54), decelerations (18.0 [1.2] vs 18.7 [1.0] number/min; P = .032; ES = 0.56), and body impacts (20 [8] vs 22 [10] impacts/min; P = .032; ES = 0.30). However, postexercise surveys about self-reported feelings of performance indicate that players did not feel increased performance with CAFF. Preexercise ingestion of 3 mg/kg bm of CAFF improved ball-throwing velocity, jump, and sprint performance and the frequency of in-game accelerations and decelerations in elite women handball players.


Lymphocytotoxic antibodies in family members of patients with systemic lupus erythematosus.
57% of sera from 124 relatives of 28 patients with systemic lupus erythematosus (SLE) were found to have antibody directed against lymphocytes. The incidence in 60 members of 16 control families was 3%. Both consanguineous and nonconsanguineous relatives had the antibody in their sera. 68% of close household contacts of the SLE patients showed lymphocytotoxic antibody whereas only 23% of consanguineous relatives who had no household contact with the probands had this antibody. These data suggest that environmental factors may be important in the pathogenesis of SLE.


Fat mass- and obesity-associated genotype, dietary intakes and anthropometric measures in European adults: the Food4Me study.
The interplay between the fat mass- and obesity-associated (FTO) gene variants and diet has been implicated in the development of obesity. The aim of the present analysis was to investigate associations between FTO genotype, dietary intakes and anthropometrics among European adults. Participants in the Food4Me randomised controlled trial were genotyped for FTO genotype (rs9939609) and their dietary intakes, and diet quality scores (Healthy Eating Index and PREDIMED-based Mediterranean diet score) were estimated from FFQ. Relationships between FTO genotype, diet and anthropometrics (weight, waist circumference (WC) and BMI) were evaluated at baseline. European adults with the FTO risk genotype had greater WC (AA v. TT: +1·4 cm; P=0·003) and BMI (+0·9 kg/m2; P=0·001) than individuals with no risk alleles. Subjects with the lowest fried food consumption and two copies of the FTO risk variant had on average 1·4 kg/m2 greater BMI (Ptrend=0·028) and 3·1 cm greater WC (Ptrend=0·045) compared with individuals with no copies of the risk allele and with the lowest fried food consumption. However, there was no evidence of interactions between FTO genotype and dietary intakes on BMI and WC, and thus further research is required to confirm or refute these findings.