Behçet disease with vascular involvement: effects of different therapeutic regimens on the incidence of new relapses.
Vascular involvement is one of the major causes of mortality and morbidity in Behçet disease (BD). There are no controlled studies for the management of vascular BD (VBD), and according to the EULAR recommendations, only immunosuppressive (IS) agents are recommended. In this study, we aimed to investigate the therapeutic approaches chosen by Turkish physicians during the initial event and relapses of VBD and the association of different treatment options with the relapses retrospectively.Patients with BD (n = 936, female/male: 347/589, mean age: 37.6 ± 10.8) classified according to ISG criteria from 15 rheumatology centers in Turkey were included. The demographic data, clinical characteristics of the first vascular event and relapses, treatment protocols, and data about complications were acquired.VBD was observed in 27.7% (n = 260) of the patients during follow-up. In 57.3% of the VBD patients, vascular involvement was the presenting sign of the disease. After the first vascular event, ISs were given to 88.8% and AC treatment to 59.8% of the patients. Median duration of AC treatment was 13 months (1-204) and ISs, 22 months (1-204). Minor hemorrhage related to AC treatment was observed in 7 (4.7%) patients. A second vascular event developed in 32.9% (n = 86) of the patients. The vascular relapse rate was similar between patients taking only ISs and AC plus IS treatments after the first vascular event (29.1% vs 22.4%, P = 0.28) and was significantly higher in group taking only ACs than taking only ISs (91.6% vs 29.1%, P < 0.001). During follow-up, a third vascular event developed in 17 (n = 6.5%) patients. The relapse rate was also similar between the patients taking only ISs and AC plus IS treatments after second vascular event (25.3% vs 20.8%, P = 0.93). When multivariate analysis was performed, development of vascular relapse negatively correlated with only IS treatments.We did not find any additional positive effect of AC treatment used in combination with ISs in the course of vascular involvement in patients with BD. Severe complications related to AC treatment were also not detected. Our results suggest that short duration of IS treatments and compliance issues of treatment are the major problems in VBD associated with vascular relapses during follow-up.


Evaluation of board certification in nutrition support pharmacy.
Credentialing of healthcare professionals is a topic that has received increasing attention. The Board of Pharmaceutical Specialties (BPS) has recognized nutrition support pharmacy as a specialty for more than 10 years. There has recently been concern about the decline in the number of pharmacists seeking board certification or recertification as specialists in nutrition support and changes in the job responsibilities of nutrition support pharmacists. These factors have resulted in a need to evaluate the current system of certification of nutrition support pharmacists. A national survey was developed and sent to pharmacist members of the American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) and members of the Home Care Section of the American Society of Health-System Pharmacists (ASHP). The objectives of this study were to describe the activities of nutrition support pharmacists, determine the benefits and barriers to board certification, and assess the current system of certification. Two hundred and fifty-eight of 486 surveys were returned for an overall response rate of 53%. There has been a decrease in the amount of professional time devoted to nutrition support activities. The most highly ranked benefit to certification was peer recognition. The most highly ranked barrier to certification was the examination cost. There is satisfaction with the current system; however, alternative methods were supported if the current method cannot sustain itself There is a need to evaluate the cost of the examination and increase marketing efforts to candidates for whom the examination is intended.


Comparative evaluation of different rat models with co-existing diabetes-mellitus and hypertension.
We have evaluated the suitability of different rat models for the study of effects of antihypertensives on cardiovascular and metabolic complications of diabetes mellitus and hypertension. IDDM was induced in Wistar and spontaneously hypertensive (SH) rats by single tail vein injection of STZ (45 mg/kg, i.v.). Neonatal STZ-diabetes (nSTZ) was induced by administering STZ, 70 mg/kg (i.p.) to 5 day old Wistar rat pups. DOCA-hypertension was induced in Wistar and STZ-diabetic rats using deoxycorticosterone acetate (DOCA, 5 mg/kg, s.c.) and NaCl (2%) in drinking water. Intravenous injection of STZ produced cardinal signs of diabetes mellitus including hyperglycemia, loss of body weight, polyphagia and polydipsia. STZ-diabetic rats also showed hyperlipidemia and hypoinsulinemia. STZ-treated rats developed hypertension and bradycardia. nSTZ rats were found to have mild hyperglycemia and were hypertensive and hyperinsulinemic. The OGTT and ITT revealed that nSTZ rats are insulin resistant. SH rats were also found to be hyperinsulinemic and hypertensive. Although, these rats were found to be insulin resistant, they did not demonstrate hyperglycemia. DOCA-treated STZ-diabetic rats were found to have milder hyperglycemia when compared to STZ-diabetic rats not treated with DOCA. Although, DOCA treatment was not found to alter serum levels of glucose and insulin, results of OGTT revealed enhanced glucose disposal in DOCA-treated Wistar rats, suggesting that DOCA probably produces some effect on glucose homeostasis in rats. The present data also suggest that STZ-diabetic rat may be considered a suitable model for IDDM. On the other hand, nSTZ and SH rats were hyperinsulinemic and insulin resistant and may be used as models to study insulin sensitivity. DOCA-hypertensive rat may not be a suitable model for studying the effects of various drug interventions on glucose homeostasis and insulin sensitivity as DOCA itself appears to influence these factors.


Defining Potential Overutilization of Physical Therapy Consults on Hospital Medicine Services.
Appropriate use of inpatient physical therapy services is important for preventing hospital-associated disability (HAD). We assessed potential overutilization of physical therapy consults on hospital medicine services using the Activity Measure-Post Acute Care (AM-PAC) score. Our sample included 3592 unique admissions (mean age, 66 years; 48% women) at a large academic medical center. Based on an AM-PAC cutoff of >43.63 (raw score, 18) in patients who were discharged to home, 38% of physical therapy consults were considered "potential overutilization." Combined with age <65 years, 18% of consults remained "potential overutilization." After adjustment for age, sex, and length of stay, patients admitted with high mobility scores were 5.38 times more likely to be discharged to home (95% CI, 4.36-2.89) compared with those with low mobility scores. Being more judicious with physical therapy consults and reserving skilled therapy for at-risk patients could help prevent HAD while also having a positive impact on healthcare systems.


Nuclear origin of progesterone receptor of the chick oviduct cytosol. An immunoelectron microscopic study.
Progesterone receptor (PR) was studied immunoelectron microscopically from fixed vibratome sections of the chick oviduct and biochemically from the fractionated oviduct homogenate. Immunoelectron microscopically both unoccupied and occupied PR were localized inside the nuclei. Only a few cells showed PR immunoreactivity in the endoplasmic reticulum which probably represents newly synthetized PR. Biochemically unoccupied PR was in the cytosol fraction. The cytosol and nuclear PR as well as the non-transformed 8S-form and the transformed 4S-forms of cytosol PR were recognized by the anti-PR antibody (IgG-RB). The lack of PR immunostaining in the cytoplasm is therefore not due to lack of recognition by IgG-RB. We propose that in the chick oviduct progesterone receptor is a nuclear protein but synthetized in the endoplasmic reticulum.


Use of multicompartment compliance aids for elderly patients: patient viewpoints and hospital length of stay.
To explore elderly (aged > or = 75 years) patients' views regarding the use of multicompartment compliance aids (MCAs) and determine whether MCAs would prolong their length of hospital stay. A cross-sectional, prospective study in 3 acute geriatric wards in a district general hospital in the United Kingdom. Patients admitted to the hospital who were found to be users of MCAs were interviewed about their perception of MCAs, and their length of hospital stay was monitored. A total of 1080 older patients were admitted over a 3-month period. Only 51 (4.7%) patients were users of MCAs and constituted the study group. The majority (51%) of MCAs were requested by general practitioners. Eight (16%) patients were asked whether they wished to use the MCAs and 3 (6%) had formal assessment prior to MCA start. On the patients' survey, 18 (35%) patients did not prefer the MCA if they were given the choice. This group of patients had better cognitive function assessed by the Mini-Mental State Examination (24.4 [3.6] vs 21.8 [3.6]; P = 0.02) and were less dependent on social services (39% vs 67%; P = 0.04) in comparison with patients who did prefer the MCA. They expressed a greater lack of autonomy (94% vs 52%; P = 0.002) and decision making (78% vs 49%; P = 0.04). They tended to be more informed about their medications' names (44% vs 6%; P = 0.01), indications (28% vs 9%; P = 0.02), and self-administration of medications (89% vs 39%; P = 0.01). Multicompartment compliance aids resulted in delayed discharges of 40 (78%) patients, with a mean of 1.3 days (standard deviation, 0.9 days; range, 0-3 days per patient) and a total of 65 days. The use of MCAs resulted in a lack of autonomy and decision making in older patients and a significant delay of discharges, thereby increasing hospital costs.


The role of the cytoskeleton in cell body enlargement, increased nuclear eccentricity and chromatolysis in axotomized spinal motor neurons.
When spinal motor axons are injured, the nucleolus, nucleus and cell body of the injured cell transiently increase in size, the nucleus becomes more eccentrically placed, and the organization of polyribosomes into Nissl bodies is temporarily disrupted. The mechanisms for these classical morphological responses to axotomy have not been satisfactorily explained. In this study we address the role of the cell body cytoskeleton in these structural changes. We show that the cytoskeleton of uninjured lumbar motor neuron cell bodies maintains nucleolar, nuclear and cell body size and nuclear position. When isolated, the relatively insoluble cell body cytoskeleton contains Nissl bodies and lipofuscin granules. After axotomy, protein labeling increases markedly and the cytoskeleton enlarges, increasing nucleolar, nuclear and cell body size, as well as nuclear eccentricity. Nearly all of the protein mass that accumulates in the cell body after axotomy appears to be added to the cytoskeleton. We conclude that axotomy causes the conjugate enlargement of the nucleolus, nucleus and cell body and increases nuclear eccentricity in spinal motor neurons by adding protein to the cytoskeleton. The change in nuclear position, we propose, occurs when cytoskeletal elements of the axon cannot enter the shortened axon and "dam up" between the nucleus and axon hillock. As a consequence, we suggest that Nissl body-free axonal cytoskeleton accumulates between the nucleus and axon, displaces Nissl body-containing cytoskeleton, and produces central chromatolysis in that region of the cell.


Lifelong Fitness in Ambulatory Children and Adolescents with Cerebral Palsy I: Key Ingredients for Bone and Muscle Health.
Physical activity of a sufficient amount and intensity is essential to health and the prevention of a sedentary lifestyle in all children as they transition into adolescence and adulthood. While fostering a fit lifestyle in all children can be challenging, it may be even more so for those with cerebral palsy (CP). Evidence suggests that bone and muscle health can improve with targeted exercise programs for children with CP. Yet, it is not clear how musculoskeletal improvements are sustained into adulthood. In this perspective, we introduce key ingredients and guidelines to promote bone and muscle health in ambulatory children with CP (GMFCS I-III), which could lay the foundation for sustained fitness and musculoskeletal health as they transition from childhood to adolescence and adulthood. First, one must consider crucial characteristics of the skeletal and muscular systems as well as key factors to augment bone and muscle integrity. Second, to build a better foundation, we must consider critical time periods and essential ingredients for programming. Finally, to foster the sustainability of a fit lifestyle, we must encourage commitment and self-initiated action while ensuring the attainment of skill acquisition and function. Thus, the overall objective of this perspective paper is to guide exercise programming and community implementation to truly alter lifelong fitness in persons with CP.


Smad7 is required for TGF-beta-induced activation of the small GTPase Cdc42.
Transforming growth factor beta (TGF-beta) is a potent regulator of cell growth and differentiation in many cell types. The Smad signaling pathway constitutes a main signal transduction route downstream of TGF-beta receptors. The inhibitory Smads, Smad6 and Smad7, are considered to function as negative regulators of the TGF-beta/Smad signaling cascade. In a previous study, we found that TGF-beta induces rearrangements of the actin filament system in human prostate carcinoma cells and that this response requires the small GTPases Cdc42 and RhoA. On the basis of the current view on the function of Smad7 in TGF-beta signaling, we hypothesized that Smad7 would function as a negative regulator of the TGF-beta-induced activation of Cdc42 and RhoA, but instead we found that the reverse is the case; Smad7 is required for the TGF-beta-induced activation of Cdc42 and the concomitant reorganization of the actin filament system. These observations propose a novel role for Smad7 in TGF-beta-dependent activation of Rho GTPases.


SETDB1 fuels the lung cancer phenotype by modulating epigenome, 3D genome organization and chromatin mechanical properties.
Imbalance in the finely orchestrated system of chromatin-modifying enzymes is a hallmark of many pathologies such as cancers, since causing the affection of the epigenome and transcriptional reprogramming. Here, we demonstrate that a loss-of-function mutation (LOF) of the major histone lysine methyltransferase SETDB1 possessing oncogenic activity in lung cancer cells leads to broad changes in the overall architecture and mechanical properties of the nucleus through genome-wide redistribution of heterochromatin, which perturbs chromatin spatial compartmentalization. Together with the enforced activation of the epithelial expression program, cytoskeleton remodeling, reduced proliferation rate and restricted cellular migration, this leads to the reversed oncogenic potential of lung adenocarcinoma cells. These results emphasize an essential role of chromatin architecture in the determination of oncogenic programs and illustrate a relationship between gene expression, epigenome, 3D genome and nuclear mechanics.


Designing adiabatic radio frequency pulses using the Shinnar-Le Roux algorithm.
Adiabatic pulses are a special class of radio frequency (RF) pulses that may be used to achieve uniform flip angles in the presence of a nonuniform B(1) field. In this work, we present a new, systematic method for designing high-bandwidth (BW), low-peak-amplitude adiabatic RF pulses that utilizes the Shinnar-Le Roux (SLR) algorithm for pulse design. Currently, the SLR algorithm is extensively employed to design nonadiabatic pulses for use in magnetic resonance imaging and spectroscopy. We have adapted the SLR algorithm to create RF pulses that also satisfy the adiabatic condition. By overlaying sufficient quadratic phase across the spectral profile before the inverse SLR transform, we generate RF pulses that exhibit the required spectral characteristics and adiabatic behavior. Application of quadratic phase also distributes the RF energy more uniformly, making it possible to obtain the same spectral BW with lower RF peak amplitude. The method enables the pulse designer to specify spectral profile parameters and the degree of quadratic phase before pulse generation. Simulations and phantom experiments demonstrate that RF pulses designed using this new method behave adiabatically.


Machine learning highlights the deficiency of conventional dosimetric constraints for prevention of high-grade radiation esophagitis in non-small cell lung cancer treated with chemoradiation.
Radiation esophagitis is a clinically important toxicity seen with treatment for locally-advanced non-small cell lung cancer. There is considerable disagreement among prior studies in identifying predictors of radiation esophagitis. We apply machine learning algorithms to identify factors contributing to the development of radiation esophagitis to uncover previously unidentified criteria and more robust dosimetric factors. We used machine learning approaches to identify predictors of grade ≥ 3 radiation esophagitis in a cohort of 202 consecutive locally-advanced non-small cell lung cancer patients treated with definitive chemoradiation from 2008 to 2016. We evaluated 35 clinical features per patient grouped into risk factors, comorbidities, imaging, stage, histology, radiotherapy, chemotherapy and dosimetry. Univariate and multivariate analyses were performed using a panel of 11 machine learning algorithms combined with predictive power assessments. All patients were treated to a median dose of 66.6 Gy at 1.8 Gy per fraction using photon (89.6%) and proton (10.4%) beam therapy, most often with concurrent chemotherapy (86.6%). 11.4% of patients developed grade ≥ 3 radiation esophagitis. On univariate analysis, no individual feature was found to predict radiation esophagitis (AUC range 0.45-0.55, p ≥ 0.07). In multivariate analysis, all machine learning algorithms exhibited poor predictive performance (AUC range 0.46-0.56, p ≥ 0.07). Contemporary machine learning algorithms applied to our modern, relatively large institutional cohort could not identify any reliable predictors of grade ≥ 3 radiation esophagitis. Additional patients are needed, and novel patient-specific and treatment characteristics should be investigated to develop clinically meaningful methods to mitigate this survival altering toxicity.


Management of discoid lateral meniscus tears: observations in 34 knees.
The goal of this study was to evaluate arthroscopic partial resection of discoid lateral meniscus tears with an emphasis on radiographic evidence of degenerative changes after this procedure. Retrospective clinical study. Of 41 patients with an arthroscopic diagnosis of discoid meniscus over an 8-year period, 34 symptomatic lateral discoid meniscus tears in 33 patients were analyzed at an average follow-up of 5.6 years. The average age at operation was 19.8 years and most patients had vague and intermittent symptoms that caused delay in clinical diagnosis. Eight patients were lost to follow-up and were excluded from the study. Magnetic resonance imaging, performed in 12 cases, and arthroscopy in all of these patients provided the precise diagnosis. All of the knees with symptomatic torn discoid menisci underwent arthroscopic partial meniscectomy. Only 1 Watanabe Wrisberg ligament type of discoid meniscus with posterior instability was totally meniscected. Based on Ikeuchi's grading, 39% of the knees had an excellent result, 46% had a good result, and 15% had a fair result; none of the results was poor. At an average 5-year follow-up, partial meniscectomy in patients with a Watanabe complete or incomplete discoid meniscus showed 85% good or excellent clinical results. However, a significant percentage of patients show femoral condyle flattening on radiography.


Characterization and messenger activity of poly(A)-containing RNA from Chlorella.
Poly(A)-containing RNA was isolated by cellulose column chromatography from total RNA extracted from Chlorella fusca var. vacuolata 211/8p. RNA retained by the column was identified as poly(A)-containing RNA because it contained ribonuclease-resistant tracts, 25 to 55 nucleotides in length, from which not less than 80% of base was found to be adenine after acid hydrolysis. The base composition of poly(A)-containing RNA differed from that of RNA (largely ribosomal) which did not adsorb to cellulose, having a higher adenine content and a lower guanine content. Poly(A)-containing RNA was polydisperse including molecules with mobilities from 10S to 40S with a mean of about 20S. In an in vitro system derived from wheat-germ, protein synthesis was stimulated by adding poly(A)-containing RNA from Chlorella. Optimum conditions were established in this system with respect to the amount of poly(A)-containing RNA added and the concentration of KCl and Mg-2+. It is proposed that, in Chlorella, poly(A)-containing RNA includes cytoplasmic mRNA as has been shown for some other eucaryotic organisms.


Postoperative continuous paravertebral anesthetic infusion for pain control in posterior cervical spine surgery: a case-control study.
Patients who undergo posterior cervical spinal fusion procedures frequently experience significant postoperative pain. Use of a local anesthetic continuous infusion pump after surgery may improve these outcome variables. After posterior cervical spine fusion procedures, 25 consecutive patients received continuous infusion of 0.5% bupivacaine into the subfascial aspects of the wound via an elastomeric pump. Data were collected prospectively by third party assessment using standard nursing protocols. This included numeric pain scores and opiate use over the first 4 postoperative days (PODs), length of hospitalization, and complications. In a retrospective analysis, we compared each study patient to a control patient who did not receive the continuous infusion of bupivacaine. Demographic variables and surgical procedure were similar among matched cases. Patients receiving continuous local anesthetic infusion used significantly less narcotics (P < .05) during the first 4 PODs: 24.4% on day 1, 34.1% on day 2, 53.5% on day 3, and 58.1% on day 4. A lower average pain score was observed among study patients on each POD (P < .05): 31.5% less on day 1, 13.0% on day 2, 24.0% on day 3, and 35.7% on day 4. Patients with the infusion device were discharged home earlier (POD 4.9 versus 6.7; P = .024) and demonstrated improvement in time to ambulation, first bowel movement, and discontinuation of the patient-controlled analgesia machine. No complications were associated with the device. Patients with the local anesthetic continuous infusion device required less narcotics and reported lower pain scores than control patients on each of the first 4 PODs. These results suggest that continuous infusion of local anesthetic into the paravertebral tissue during the immediate postoperative period is a safe and effective technique that achieves lower pain scores and narcotic use and improves multiple postoperative outcome variables.


Modifiable risk factors in the first 1000 days for subsequent risk of childhood overweight in an Asian cohort: significance of parental overweight status.
Many studies have identified early-life risk factors for subsequent childhood overweight/obesity, but few have evaluated how they combine to influence risk of childhood overweight/obesity. We examined associations, individually and in combination, of potentially modifiable risk factors in the first 1000 days after conception with childhood adiposity and risk of overweight/obesity in an Asian cohort. Six risk factors were examined: maternal pre-pregnancy overweight/obesity (body mass index (BMI) ⩾25 kg m-2), paternal overweight/obesity at 24 months post delivery, maternal excessive gestational weight gain, raised maternal fasting glucose during pregnancy (⩾5.1 mmol l-1), breastfeeding duration <4 months and early introduction of solid foods (<4 months). Associations between number of risk factors and adiposity measures (BMI, waist-to-height ratio (WHtR), sum of skinfolds (SSFs), fat mass index (FMI) and overweight/obesity) at 48 months were assessed using multivariable regression models. Of 858 children followed up at 48 months, 172 (19%) had none, 274 (32%) had 1, 244 (29%) had 2, 126 (15%) had 3 and 42 (5%) had ⩾4 risk factors. Adjusting for confounders, significant graded positive associations were observed between number of risk factors and adiposity outcomes at 48 months. Compared with children with no risk factors, those with four or more risk factors had s.d. unit increases of 0.78 (95% confidence interval 0.41-1.15) for BMI, 0.79 (0.41-1.16) for WHtR, 0.46 (0.06-0.83) for SSF and 0.67 (0.07-1.27) for FMI. The adjusted relative risk of overweight/obesity in children with four or more risk factors was 11.1(2.5-49.1) compared with children with no risk factors. Children exposed to maternal pre-pregnancy (11.8(9.8-13.8)%) or paternal overweight status (10.6(9.6-11.6)%) had the largest individual predicted probability of child overweight/obesity. Early-life risk factors added cumulatively to increase childhood adiposity and risk of overweight/obesity. Early-life and preconception intervention programmes may be more effective in preventing overweight/obesity if they concurrently address these multiple modifiable risk factors.


New times for migrants' health in Europe.
Patterns of migration can change greatly over time, with the size and composition of migrant populations reflecting both, current and historical patterns of migration flows. The recent economic crisis has caused a decrease on migration flows towards the most affected areas, as well as cut offs in health interventions addressed to migrants. The objective of this paper is to review available data about interventions on migrants' health in Europe, and to describe changes in migrant health policies across Europe after the economic crisis, that can have a negative effect in their health status. Although migrants have the right to health care under legal settlements issued by the EU, there is no a standard European approach to offer health care to migrants, since; policies in each EU Member State are developed according to specific migrant experience, political climate, and attitudes towards migration. Migrants use to face greater health problems and major health care access barriers, compared with their counterparts from the EU. Therefore, migrant health policies should focus in protects this vulnerable group, especially during economic hardship, taking into account economic and socio-demographic risk factors. There is an especial need for research in the cost-effectiveness of investing in the health care of the migrant population, demonstrating the benefit of such, even in the health of the European native population, and the need for constant intervention despite of resource constraints.


[Uterine, adnexal and cul-de-sac masses. Comparative study by intravaginal and trans-abdominal echography].
42 female patients were selected for Trans-Vaginal Sonography (TVS) in an ultrasonographic study, after clinical examination, computed tomography or a previous study had suggested the existence of one or more lumps in the pelvic cavity. The TVS method gave higher quality diagnostic information in 55% of the cases studied, while the Trans-Abdominal method was better in 12.5% of the cases. In 79% of the cases the TVS was considered better in image quality while 11% of the cases showed the same image quality in all of the methods. The results agree with those obtained by other authors and confirm that Trans-Vaginal Sonography is of considerable value in the study of female pelvis, as an isolated exploration, complementary or otherwise with subsequent abdominal examination with or without a full bladder.


Adrenocortical responses to adrenocorticotrophin in the hypophysectomized ovine fetus.
Fetal adrenocortical responsiveness to ACTH declines during 90-120 days gestation and fetal pituitary peptides have been implicated in this refractoriness. In these studies the ACTH-induced cortisol responses were measured in 11 ovine fetuses of 114 days gestation. Five animals were hypophysectomized as evidenced by prolonged gestation, pituitary histology, TRH-testing, delayed maturation and decreasing fetal plasma prolactin concentrations (less than 1 ng.ml-1) (P less than 0.005). Resting cortisol concentrations decreased from 22.4 to 8.1 ng.ml-1 in the hypophysectomy group and were not different from the control group (19.6-14.9 ng.ml-1) over the 5 days of study. Responses measured as increments in plasma cortisol concentrations increased equally and successively in both groups. Since pituitary ablation fails to enhance fetal adrenal responsiveness to ACTH we conclude that refractoriness is unlikely to be caused by an inhibitor of pituitary origin.


Efficacy of reciprocating and rotary systems for removing root filling material: a micro-computed tomography study.
This study aimed to use micro-computed tomography (micro-CT) imaging to evaluate the efficacy of the reciprocating and rotary systems for the removal of root filling materials in comparison with hand files. Thirty maxillary incisor teeth were prepared with ProTaper Universal (PTU) system, filled using cold lateral condensation and randomly divided into three groups of ten teeth each. The root fillings were removed with WaveOne Reciprocating and ProTaper Universal Re-treatment (PTU-R) systems and hand files. Micro-CT was used to scan the specimens before and after each treatment step. Percentage of volume of residual root filling was measured. The operating time was recorded. PTU-R instruments yielded better results for removing filling material, even though there was no statistically significant difference between PTU-R and WaveOne groups. Reciprocating and rotary systems showed similar performances in terms of efficacy and operating time for root filling removal.


Short-term clinical outcomes for intermittent cold versus intermittent warm blood cardioplegia in 2200 adult cardiac surgery patients.
Aim of the present study was to compare clinical outcome of intermittent cold (ICC) versus intermittent warm (IWC) blood cardioplegia in different cardiosurgical procedures. Two thousand one hundred and eighty-eight patients were retrospectively divided into 5 groups: isolated coronary artery bypass surgery (CABG; N.=1203), isolated aortic valve surgery (AVR; N.=374), isolated mitral valve surgery (MVR; N.=151), combined AVR+CABG (N.=390), and combined MVR+CABG (N.=70). Myocardial protection was performed by ICC (N.=1578) or IWC (N.=610) blood cardioplegia. In logistic regression models the effect of cardioplegia on 30-day mortality, IABP/ECLS (intraaortic balloon-pump/extracorporal life support) implantation, transient neurological deficit, stroke, renal failure, new-onset atrial fibrillation, and troponin T release was estimated. Potential modifications of the effect of cardioplegia by logistic EuroSCORE, cross-clamping time, ejection fraction, and op-status elective versus urgent/emergent were investigated. There were no statistically significant differences between ICC and IWC regarding 30-day mortality (odds ratio [OR]=0.70; 95% CI: 0.39-1.23; P=0.219), IABP/ECLS support (OR=0.60; 95% CI: 0.23-1.55; P=0.294), transient neurological deficit (OR=0.90; 95% CI: 0.65-1.24; P=0.541), stroke (OR=0.79; 95% CI: 0.40-1.54; P=0.495), renal failure (OR=1.07; 95% CI: 0.57-1.99; P=0.825), and atrial fibrillation (OR=0.96; 95% CI: 0.77-1.18; P=0.713) across all 5 groups. Troponin t release was significantly higher in ICC compared to IWC (by 0.029±0.015 ng/mL; P=0.046) in univariate analysis; this effect was lowered by risk-factor adjustment and lost statistical significance. The effect of cardioplegia was not significantly different between groups. In urgent/emergent surgery ICC resulted in a significantly higher 30-day mortality (OR=3.03; P=0.024) compared to IWC. The comparison of IWC and ICC blood cardioplegia in different cardiosurgical procedures showed no statistical significant difference in myocardial protection. The use of ICC, however, appeared overall associated with a slightly better clinical outcome except in patients undergoing urgent/emergent CABG where IWC led to a reduction in 30-day-mortality.


Arthrobacter silviterrae sp. nov., isolated from forest soil.
A novel actinomycete strain, designated KIS14-16T, was isolated from forest soil in Ongjin county, South Korea and characterized using polyphasic taxonomy. The cells are aerobic, Gram-stain-positive, non-flagellated and short rods. The strain grew in a temperature range of 4-33 °C (optimum, 28-30 °C) and pH range of 5.0-10.0 (optimum, 7.0) and in the presence of 0-5 % (w/v) NaCl (optimum, 0 %). Comparison of 16S rRNA gene sequences showed that strain KIS14-16T is a member of the genus Arthrobacter exhibiting high sequence similarity with A. livingstonensis LI2T (97.7 %), A. cryoconiti Cr6-08T (97.6 %), A. psychrochitiniphilus GP3T (97.4 %), A. stackebrandtii CCM 2783T (97.1 %) and A. globiformis DSM 20124T (96.3 %). DNA-DNA relatedness and phenotypic data distinguished strain KIS14-16T from phylogenetically related type strains. The peptidoglycan type of strain KIS14-16T was A3α, with an interpeptide bridge comprising l-Lys, l-Thr, Gly and l-Ala4. Strain KIS14-16T contained a large amount of MK-9(H2) and relatively small amounts of MK-10(H2) and MK-8(H2). The main polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol and dimannosylglyceride. The major fatty acids (>10 %) were anteiso-C15 : 0 and anteiso-C17 : 0. The genomic DNA G+C content was 63.9 mol%. On the basis of these phenotypic, chemotaxonomic and phylogenetic data, strain KIS14-16T should be designated as a representative novel species of the genus Arthrobacter, for which the name Arthrobacter silviterrae sp. nov. is proposed. The type strain is KIS14-16T (=KACC 17303T=DSM 27180T=NBRC 109660T).


Plate fixation or intramedullary fixation of humeral shaft fractures.
The optimal approach to operative treatment of humeral shaft fractures remains debatable. Previously published trials have been limited in size and have been inconclusive regarding important patient outcome variables following treatment with either intramedullary nails or plates. We conducted a meta-analysis of available trials comparing treatment of humeral shaft fractures. We performed a literature search from 1967 to November 2007 in the main medical search engines and selected 4 randomized trials that compared nails and plates in patients with humeral shaft fractures and that reported on complications due to surgery. We statistically pooled patient data using standard meta-analytic approaches. Our primary outcome was the total complication rate, comprised of all complications listed in the articles included. Secondary outcomes included non-union, infection, nerve palsy, and reoperation rate. Methodology was assessed using the CLEAR NPT. When pooling the data of the 4 trials (n = 203 patients), we did not find a statistically significant difference between implants in the rate of total complications, non-union, infection, nerve-palsy, or the need for reoperation. The studies included were small and had methodological limitations. Our meta-analysis suggests stastistically insignificant differences between plates and nails in the treatment of humeral shaft fractures. Small sample sizes, study heterogeneity, and methodological limitations argue strongly for a definitive, large trial. We recommend that this trial should be a randomized controlled trial with appropriate allocation of patients and blinding of patients and care providers and outcome assessors, and that it should include patient-important outcomes.


Ex vivo evaluation of the effect of various surgical procedures on blood delivery to the patellar tendon of dogs.
OBJECTIVE To determine the effect of arthrotomy alone or in combination with osteotomy of the proximal portion of the tibia on blood delivery to the patellar tendon of dogs. SAMPLE 24 canine cadavers. PROCEDURES One hind limb from each cadaver was assigned to 1 of 4 treatment groups: medial arthrotomy (MA; MA group), lateral arthrotomy (LA; LA group), MA and LA with tibial tuberosity transposition (MALA group), and MA with tibial plateau leveling osteotomy (TPLO; TPLO group). The contralateral hind limb served as the control sample. Contrast solution (barium [33%], India ink [17%], and saline [0.9% NaCl] solution [50%]) was injected through an 8F catheter inserted in the caudal portion of the abdominal aorta. Limbs were radiographed to allow examination of vascular filling. The patella, patellar tendon, and tibial crest were harvested, radiographed to allow examination of tissue vascular filling, and fixed in 4% paraformaldehyde. Vessels perfused with contrast solution were counted in sections obtained from the proximal, middle, and distal regions of each patellar tendon. RESULTS Vessel counts did not differ significantly among the 3 tendon regions. Compared with results for the control group, delivery of contrast solution to the patellar tendon was significantly decreased in the MALA and TPLO groups but was not changed in the MA or LA groups. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that surgical procedures used to treat cranial cruciate injuries (ie, TPLO) and patellar luxation decreased blood delivery to the patellar tendon of canine cadavers, at least acutely.


Success of Pulpal Anesthesia Following Buccal Infiltration of the Maxillary First Molar With 1.8 mL and 3.6 mL of 4% Articaine With 1:100,000 Epinephrine: A Prospective, Randomized Crossover Study.
The purpose of this prospective, randomized crossover study was to compare the peak incidence of success, onset, and incidence over time of pulpal anesthesia in maxillary first molars following a buccal infiltration of 1.8 mL or 3.6 mL of 4% articaine with 1:100 000 epinephrine. A total of 118 adults received 1.8 mL or 3.6 mL of 4% articaine with 1:100 000 epinephrine via buccal infiltration of the maxillary first molar at 2 separate appointments. Electric pulp testing (EPT) of the maxillary first molar was performed over 68 minutes. There was no significant difference in the peak incidence of anesthetic success (85% and 92%, respectively) in the maxillary first molar between 1.8 mL and 3.6 mL. The difference in onset times (4.5 min for 1.8 mL vs 4.4 min for 3.6 mL) was not statistically significant. However, the 3.6-mL volume did produce a significantly higher incidence of pulpal anesthesia from minutes 48 to 68 compared with the 1.8-mL volume. There was no significant difference in peak incidence or onset of pulpal anesthesia in the maxillary first molar between 1.8 mL and 3.6 mL of articaine with epinephrine. The incidence of pulpal anesthesia was significantly higher with 3.6 mL of articaine at 48 minutes and beyond, but neither volume provided complete pulpal anesthesia for all subjects that lasted at least 60 minutes.


Ni-Catalyzed 1,2-Alkyl Borylation and Silylation of Allenes En Route to [1,3]-Bis-Organometallic Reagents.
A nickel-catalyzed multicomponent reaction that rapidly and reliably accesses [1,3]-bis-organometallic reagents from allenes is reported. The protocol exhibits a predictable regioselectivity pattern that enables the incorporation of B,B(Si) fragments across the allene backbone under mild conditions, thus offering a complementary platform for accessing polyorganometallic reagents possessing both sp2 and sp3 hybridization from readily available precursors.


Multifaceted effects of hydroxychloroquine in human disease.
Hydroxychloroquine (HCQ) is a widely used medication for the treatment of rheumatoid arthritis and systemic lupus erythematosus. An increasing body of evidence supports actions of this drug that are not directly related to its immunosuppressive or anti-rheumatic properties. The objective of this systematic review is to characterize the spectrum of conditions that might be responsive to treatment with HCQ. PubMed was searched using the MeSH for HCQ with relevant subheadings and the limits of human topics and English language. Four-hundred and fifty-six abstracts from this search were examined individually to exclude those that were not focused on the objectives of this review. The resulting 76 articles were grouped according to topic areas and reviewed in detail. HCQ has been reported to have therapeutic effects in a wide array of conditions, including diabetes mellitus, dyslipidemias, coagulopathies, infectious diseases and malignancies. Mechanisms of action responsible for these effects likely include altered signaling through cellular receptors, post-glycosylation modifications of infectious agents, changes in levels of inflammatory mediators and inhibition of autophagy. Many of the pathways are likely dependent on drug-induced changes in intra-endosomal acidity. The use of, and interest in, HCQ has spread into many areas of medicine. Actions of this drug may be directly beneficial to patients with non-rheumatic conditions such as diabetes mellitus or viral infections. Further understanding of underlying mechanisms has potential to reveal modifiable pathogenic pathways that might elucidate approaches to the design of more effective therapeutics for many chronic diseases.


Turning dread into capital: South Africa's AIDS diplomacy.
In much of the world, President George W. Bush was not admired for his foreign policy and diplomacy. It is therefore ironic that Bush's single most uncontested foreign policy triumph was an instance of what has now become known as "health diplomacy". In 2003 Bush launched the President's Emergency Plan for AIDS Relief, a five-year $15 billion initiative to fight HIV/AIDS, mostly in Africa. The president's pragmatic health diplomacy may well save his foreign policy legacy. This article argues that a middle power such as South Africa should consider a similar instrumental AIDS diplomatic strategy, to rehabilitate its public health as well as foreign policy images. This article reflects on the emergence and contemporary practice of health diplomacy. In particular, it explores the potential of niche areas within health diplomacy to become constructive focal points of emerging middle powers' foreign policies. Middle powers often apply niche diplomacy to maximise their foreign policy impact, particularly by pursuing a multilateral agenda. The literature on middle powers indicates that such foreign policy ambitions and concomitant diplomacy mostly act to affirm the global status quo. Instead, this paper argues that there may well be niches within health diplomacy in particular that can be used to actually challenge the existing global order. Emerging middle powers in particular can use niche areas within health diplomacy in a critical theoretical manner, so that foreign policy and diplomacy become a project of emancipation and transformation, rather than an affirmation of the world as it is. The article first describes the emergence and contemporary practice of health diplomacy; this is followed by a discussion of niche diplomacy, in particular as it applies to the foreign policy agendas of emerging middle powers. It then reviews South African foreign policy and diplomacy, before situating these policies within the context of emerging mechanisms of south-south multilateralism. The article concludes by synthesizing these elements and advocating for a South African AIDS diplomacy, emphasizing its potential to galvanize a global project of emancipation.


Cationic and anionic detergent buffers in sequence yield high-quality genomic DNA from diverse plant species.
Because of the heterogeneity among seedlings of outbreeding species, the use of seedling tissues as a source of DNA is unsuitable for the genomic characterization of elite germplasms. High-quality DNA, free of RNA, proteins, polysaccharides, secondary metabolites, and shearing, is mandatory for downstream molecular biology applications, especially for next-generation genome sequencing and pangenome analysis aiming to capture the complete genetic diversity within a species. The study aimed to accomplish an efficient protocol for the extraction of high-quality DNA suitable for diverse plant species/tissues. We describe a reliable, and consistent protocol suitable for the extraction of DNA from 42 difficult-to-extract plant species belonging to 33 angiosperm (monocot and dicot) families, including tissues such as seeds, roots, endosperm, and flower/fruit tissues. The protocol was first optimized for the outbreeding recalcitrant trees viz., Prosopis cineraria, Conocarpus erectus, and Phoenix dactylifera, which are rich in proteins, polysaccharides, and secondary metabolites, and the quality of the extracted DNA was confirmed by downstream applications. Nine procedures were attempted to extract high-quality, impurities-free DNA from these three plant species. Extraction of the ethanol-precipitated DNA from cetyltrimethylammonium bromide (CTAB) protocol using sodium dodecyl sulfate (SDS) buffer, i.e., the extraction using a cationic (CTAB) detergent followed by an anionic (SDS) detergent was the key for high yield and high purity (1.75-1.85 against A260/280 and an A260/230 ratio of >2) DNA. A vice versa extraction procedure, i.e., SDS buffer followed by CTAB buffer, and also CTAB buffer followed by CTAB, did not yield good-quality DNA. PCR (using different primers) and restriction endonuclease digestion of the DNA extracted from these three plants validated the protocol. The accomplishment of the genome of P. cineraria using the DNA extracted using the modified protocol confirmed its applicability to genomic studies. The optimized protocol successful in extracting high-quality DNA from diverse plant species/tissues extends its applicability and is useful for accomplishing genome sequences of elite germplasm of recalcitrant plant species with quality reads.


Malaria in injection drug abusers in Vietnam.
A prospective case-control study was conducted in a referral hospital in Ho Chi Minh City, Vietnam, to compare the clinical and laboratory features and outcome of severe falciparum malaria in injection drug abusers (IDAs) with those of patients who had acquired malaria by mosquito bite. From 1991 to 1996, 70 IDAs were admitted to the hospital, of whom at least 32 had acquired malaria by needle sharing. Although IDAs were more likely than control patients with severe malaria to be malnourished and to have coincident hepatitis B, hepatitis C, and human immunodeficiency virus infections, the overall rates of mortality, complications, and recovery were similar in the 2 groups. The route of malaria acquisition did not affect the outcome of severe malaria. The management of severe malaria in IDAs is similar to that for other patients.


Targeting MAPK/NF-κB Pathways in Anti-Inflammatory Potential of Rutaecarpine: Impact on Src/FAK-Mediated Macrophage Migration.
Studies have discovered that different extracts of Evodia rutaecarpa and its phytochemicals show a variety of biological activities associated with inflammation. Although rutaecarpine, an alkaloid isolated from the unripe fruit of E. rutaecarpa, has been exposed to have anti-inflammatory properties, the mechanism of action has not been well studied. Thus, this study investigated the molecular mechanisms of rutaecarpine (RUT) in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. RUT reserved the production of nitric oxide (NO) and the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor (TNF-α), and interleukin (IL)-1β in the LPS-induced macrophages. RUT showed an inhibitory effect on the mitogen-activated protein kinases (MAPKs), and it also inhibited nuclear transcription factor kappa-B (NF-κB) by hindering IκBα and NF-κB p65 phosphorylation and p65 nuclear translocation. The phospho-PI3K and Akt was concentration-dependently suppressed by RUT. However, RUT not only suggestively reduced the migratory ability of macrophages and their numbers induced by LPS but also inhibited the phospho-Src, and FAK. Taken together, these results indicate that RUT participates a vital role in the inhibition of LPS-induced inflammatory processes in RAW 264.7 macrophages and that the mechanisms involve PI3K/Akt and MAPK-mediated downregulation of NF-κB signaling pathways. Notably, reducing the migration and number of cells induced by LPS via inhibiting of Src/FAK pathway was also included to the anti-inflammatory mechanism of RUT. Therefore, RUT may have potential benefits as a therapeutic agent against chronic inflammatory diseases.


ATG-Fresenius increases the risk of red blood cell transfusion after kidney transplantation.
In sensitized deceased donor kidney allograft recipients, the most frequent induction therapy is anti-thymocyte globulins (ATG), including Thymoglobulin® (Thymo) and ATG-Fresenius (ATG-F). We conducted a 3-year monocentric observational study to compare the impact of ATGs on hematological parameters. We included adult kidney transplant recipients treated with ATG induction therapy, either Thymo or ATG-F, on a one-in-two basis. The primary endpoint was red blood cell (RBC) transfusions within 14 days after transplantation. Among 309 kidney allograft recipients, 177 (57.2%) received ATG induction, 90 (50.8 %) ATG-F, and 87 (49.2%) Thymo. The ATG-F group received significantly more RBC transfusions (63.3% vs. 46% p = 0.02) and in bigger volumes (p = 0.01). Platelet transfusion was similar in both groups. Within 14 and 30 days after transplantation, older age, ATG-F induction, and early surgical complication were independently associated with RBC transfusion. Patient survival rate was 95%, and the death-censored kidney allograft survival rate was 91.5% at 12 months post-transplantation. There was no difference in the incidence of acute rejection and infections or in the prevalence of anti-HLA donor-specific antibodies. In conclusion, after kidney transplantation, ATG-F is an independent risk factor for early RBC transfusion and early thrombocytopenia without clinical and biological consequences. These new data should be clinically considered, and alternatives to ATG should be further explored.


Another flame retardant, tris-(1,3-dichloro-2-propyl)-phosphate, and its expected metabolites are mutagens.
A flame retardant used in children's sleepwear, tris-(1,3-dichloro-2-propyl)phosphate (Fyrol FR2) is a mutagen in the Salmonella-mammalian tissue homogenate test after it has been activated by mouse or rat liver homogenate. The expected enzymatic hydrolysis product, 1,3-dichloro-2-propanol, is similarly a mutagen after activation by liver homogenate. A proposed metabolite of the flame retardant, 1,3-dichloro-2-propanone, is a potent mutagen in the absence of such activation. A flame retardant with similar structure, tris-(2,3-dibromopropyl)phosphate (tris-BP), was shown previously to be a mutagen, to cause sterility in animals, to be a carcinogen, and to be absorbed through human skin. These and other flame retardants have characteristic nuclear magnetic resonance spectra that can be used to determine which flame retardant is present in commercially purchased sleepwear. Sleepwear treated with tris-BP, Fyrol FR2, and other chemical additives was being sold in late 1977.


In vitro susceptibility of the seven Malassezia species to ketoconazole, voriconazole, itraconazole and terbinafine.
Fifty-five strains, either authentic or ex-type, of seven Malassezia species were investigated for in vitro susceptibility to various concentrations (0.03-64.0 microg/mL) of three azole drugs, ketoconazole, voriconazole and itraconazole, as well as the allylamine terbinafine, using the agar dilution method. All strains of the seven Malassezia species were susceptible to the three azole drugs at low concentrations. M. furfur, M. sympodialis, M. slooffiae, M. pachydermatis, M. globosa, M. obtusa and M. restricta were most sensitive to ketoconazole and itraconazole, with minimum inhibitory concentrations (MICs) ranging from < or = 0.03 to 0.125 microg/mL. The recently introduced antifungal, voriconazole, was also very effective, with MIC80 values < or = 0.03 microg/mL for 80% of strains. MICs of terbinafine against the seven Malassezia species ranged from </= 0.03 to 64.0 microg/mL. There were variations in susceptibility of the seven Malassezia species to ketoconazole, voriconazole, itraconazole and terbinafine. Strains of M. furfur, M. globosa and M. obtusa were more tolerant to terbinafine than the remaining Malassezia species; M. sympodialis was highly susceptible. M. furfur strains tested with terbinafine ranged from highly susceptible to relatively resistant. Correct identification of Malassezia species could facilitate selection of appropriate antifungal therapy.


[Assessment of fetal circulation in the late first trimester--preliminary study].
to confirm that fetal echocardiography is indeed possible in late first trimester and that it improves the standard of the so-called "genetic" ultrasound scan. Early echocardiography was performed in 75 fetuses from high and low risk pregnancies. All fetuses underwent echocardiography examination in 18-22 weeks of gestation and established follow up. The most suitable method of visualization seems to be transabdominal examination, between 13.0-13.6 weeks of gestation, an transvaginal one, between 12.0-12.6 weeks of gestation, with 90% effectiveness. In researched group of 75 fetuses (with established follow up) there were four heart defects (5.3%). Three of them were diagnosed before 14th week of gestation. One case (tetralogy of Fallot) was overlooked. There were two false positive diagnosis verified at 20th week of gestation. Early echocardiography, especially between 12.0-13.6 weeks of gestation, is a possible and valuable method of diagnosis. Reference evaluation should be performed between 18 and 22 weeks of gestation. In cases with suspected anomalies karyotyping is recommended. Congenital heart disease diagnosed at late first trimester should be treated as the next potential marker of genetic disorder.


Deposition and early disposition of inhaled 233UO2(NO3)2 and 232UO2(NO3)2 in the rat.
Little information exists on the metabolism and potential health effects of 233U and 232U, high-specific-activity U isotopes associated with Th breeder systems. This paper describes the distribution and retention of the two isotopes following inhalation of uranyl nitrate, a simulated process solution. The lungs of rats exposed to 233UO2(NO3)2 and 232UO2(NO3)2 aerosols contained from 7 to 23% of the total amount of U retained in the rat after a 30-min inhalation exposure. Uranium was translocated rapidly from the lung and was retained mainly in skeleton, kidney and liver. Amounts equivalent to from one-quarter to one-half the initial lung burden (ILB) of U were excreted in urine the first day after inhalation. Radiation dose estimates based on 233U and 232U retention kinetics indicate that lung and skeleton would be the target organs for delayed radiation effects.


An experience of qualified preventive screening: shiraz smart screening software.
Computerized preventive screening software is a cost effective intervention tool to address non-communicable chronic diseases. Shiraz Smart Screening Software (SSSS) was developed as an innovative tool for qualified screening. It allows simultaneous smart screening of several high-burden chronic diseases and supports reminder notification functionality. The extent in which SSSS affects screening quality is also described. Following software development, preventive screening and annual health examinations of 261 school staff (Medical School of Shiraz, Iran) was carried out in a software-assisted manner. To evaluate the quality of the software-assisted screening, we used quasi-experimental study design and determined coverage, irregular attendance and inappropriateness proportions in relation with the manual and software-assisted screening as well as the corresponding number of requested tests. In manual screening method, 27% of employees were covered (with 94% irregular attendance) while by software-assisted screening, the coverage proportion was 79% (attendance status will clear after the specified time). The frequency of inappropriate screening test requests, before the software implementation, was 41.37% for fasting plasma glucose, 41.37% for lipid profile, 0.84% for occult blood, 0.19% for flexible sigmoidoscopy/colonoscopy, 35.29% for Pap smear, 19.20% for mammography and 11.2% for prostate specific antigen. All of the above were corrected by the software application. In total, 366 manual screening and 334 software-assisted screening tests were requested. SSSS is an innovative tool to improve the quality of preventive screening plans in terms of increased screening coverage, reduction in inappropriateness and the total number of requested tests.


An Atypical Presentation of Mevalonate Kinase Deficiency in Response to Colchicine Treatment.
Mevalonate kinase deficiency (MKD) is a periodic fever syndrome. Nonsteroidal anti-inflammatory drugs, corticosteroids, and anakinra are the most common treatments. However, colchicine is considered insufficient in disease control. In this case report, we present an 8-month-old infant with an atypical presentation of MKD. She had recurrent fever episodes, diarrhea, and lethargy. Elevated mevalonic acid was not detected in the urine. However, the genetic investigation showed a novel pathogenic heterozygous c.925G>C (p.Gly309Arg) variant and a heterozygous c.1129G>A (p.Val377Ile) mutation in the MVK gene. The patient was treated with colchicine for 8 months. During treatment, no further fever episode had been observed. It should be kept in mind that mevalonic acid excretion may not be present in the urine with mild MKD. Colchicine may be a reasonable option in mild MKD patients for a longer duration of treatment due to favorable adverse event profiles.


Fine-mapping at the HTR2A locus reveals multiple episodic memory-related variants.
A functional polymorphism (His452Tyr) in the gene encoding the serotonin 2A receptor (HTR2A) has been previously associated with human episodic memory performance and with differences in brain volume in memory-related brain regions. Here we present data obtained through imputation and fine-mapping showing that multiple loci within HTR2A are significantly associated with human memory performance independently of the His452Tyr polymorphism. Our data support the existence of multiple memory-related loci within HTR2A.


Nutrition facts and functional potential of quinoa (Chenopodium quinoa willd.), an ancient Andean grain: a review.
Quinoa, Chenopodium quinoa Willd., is an Amaranthacean, stress-tolerant plant cultivated along the Andes for the last 7000 years, challenging highly different environmental conditions ranging from Bolivia, up to 4.500 m of altitude, to sea level, in Chile. Its grains have higher nutritive value than traditional cereals and it is a promising worldwide cultivar for human consumption and nutrition. The quinoa has been called a pseudo-cereal for botanical reasons but also because of its unusual composition and exceptional balance between oil, protein and fat. The quinoa is an excellent example of 'functional food' that aims at lowering the risk of various diseases. Functional properties are given also by minerals, vitamins, fatty acids and antioxidants that can make a strong contribution to human nutrition, particularly to protect cell membranes, with proven good results in brain neuronal functions. Its minerals work as cofactors in antioxidant enzymes, adding higher value to its rich proteins. Quinoa also contains phytohormones, which offer an advantage over other plant foods for human nutrition.


Functional and Structural Variation among Sticholysins, Pore-Forming Proteins from the Sea Anemone Stichodactyla helianthus.
Venoms constitute complex mixtures of many different molecules arising from evolution in processes driven by continuous prey-predator interactions. One of the most common compounds in these venomous cocktails are pore-forming proteins, a family of toxins whose activity relies on the disruption of the plasmatic membranes by forming pores. The venom of sea anemones, belonging to the oldest lineage of venomous animals, contains a large amount of a characteristic group of pore-forming proteins known as actinoporins. They bind specifically to sphingomyelin-containing membranes and suffer a conformational metamorphosis that drives them to make pores. This event usually leads cells to death by osmotic shock. Sticholysins are the actinoporins produced by Stichodactyla helianthus. Three different isotoxins are known: Sticholysins I, II, and III. They share very similar amino acid sequence and three-dimensional structure but display different behavior in terms of lytic activity and ability to interact with cholesterol, an important lipid component of vertebrate membranes. In addition, sticholysins can act in synergy when exerting their toxin action. The subtle, but important, molecular nuances that explain their different behavior are described and discussed throughout the text. Improving our knowledge about sticholysins behavior is important for eventually developing them into biotechnological tools.


A bibliometric analysis of publication output in selected South American countries.
Research output provides an insight into the development of the scientific capability of a country. Budget allocation for research and development (R&D) is directly proportional to the research output of a country. Bibliometric analysis of South American countries has not been done in many studies. The purpose of this paper was to analyse research outputs from South American countries on various metrics. An analysis was done for a period of 11 years from 2010 to 2020. The analysis revealed that Brazil with highest percentage of research spend has lowest Field Weighted Citation Impact (FWCI). This contrasts with Uruguay, whose FWCI is high despite comparatively lower spend on R&D and lower publication output. Although Argentina has the highest percentage of researchers per million population (1202), it has the least papers per researchers (0.3 per year) among the countries studied. A huge disparity in terms of percentage of research spent, research output, papers per researcher, and output with national and international co-authorship was observed.


Craniofacial allometry in the OIM-/- mouse model of osteogenesis imperfecta.
Osteogenesis imperfecta (OI) is a skeletal disorder characterized by the impaired synthesis of type I collagen (Col1). This study tests the hypothesis that the craniofacial phenotype of severe OI is linked to an overall reduction in body size. 3D landmark data were collected from µCT scans of adult OIM-/- and wild-type (WT) mice and used to calculate centroid sizes (CS) and interlandmark distances (ILDs). To remove the effect of body size, ILDs were scaled against craniomandibular lengths and CS. Mann-Whitney U tests were used to compare CS and absolute/scaled ILDs between genotypes. OIM-/- mice are smaller than their WT littermates in body mass, craniomandibular CS, and absolute ILDs including skull, basicranial, palatal, mandibular, and toothrow lengths. When linear distances are scaled to CS, OIM-/- mice have a relatively short midface, short nasal bones, tall mandibular corpora, and long mandibular toothrows. Results underscore the importance of size and scaling in morphometric analyses. The deleterious effect of Col1 mutations on global skeletal dimensions combined with localized morphometric changes may underlie the facial phenotype seen in human patients with severe OI. Attempts to identify these localized changes should first account for the restricted growth and small body sizes present in individuals with OI.


How loneliness linked to anxiety and depression: a network analysis based on Chinese university students.
There is conclusive evidence of a multifaceted and bidirectional relationship between loneliness and depression and anxiety. Nonetheless, more extensive research is needed to examine their relationships at a more granular level. This study employed a network analysis approach to identify the pathological mechanisms underpinning those relationships and to identify important bridge nodes as potential targets for intervention. 941 University students were included in this study. The ULS-6 (the short-form UCLA Loneliness Scale) was used to assess loneliness, the PHQ-9 (Patient Health questionnaire-9) and GAD-7 (Generalized anxiety disorder 7-item) scales were used to assess the symptoms of depression and anxiety. We constructed two network structures of loneliness-anxiety and loneliness-depression and computed bridge expected influence for each symptom. In addition, we showed a flow network of "Suicide" containing symptoms of depression and loneliness. All edges were positive in both networks constructed and the strongest edges were present within disorder communities. The overall connection between loneliness and depression was stronger compared to anxiety. The results demonstrated that the loneliness item "People are around me but not with me" was identified as bridge symptom in both networks. Furthermore, "Suicide" was directly connected to five symptoms of depression and four items of loneliness, with the strongest connections being between it and "Feeling of worthlessness" and "Psychomotor agitation/retardation". Our findings provide a more nuanced explanation of the link between loneliness and depression and anxiety. The results identified the bridge symptom "People are around me but not with me", which had the strongest effect on enhancing symptoms of depression and anxiety. Clinical improvements based on the findings of this study and the impact of the intervention are discussed.


Resistance training with interval blood flow restriction effectively enhances intramuscular metabolic stress with less ischemic duration and discomfort.
Increases in muscle size and strength similar to those obtained with high resistance load can be achieved by combining lower loads with continuous blood flow restriction (BFR). However, high ratings for distress have been reported for continuous BFR. Therefore, we investigated the efficacy (metabolic stress) of BFR applied only during intervals in resistance exercise. Seven healthy men performed three 1-min sets of plantar flexion (30 reps/min) with 1-min rest intervals under 4 conditions: low-load resistance exercise (L, 20% 1-repetition maximum (1RM)) without BFR (L-noBFR), L with BFR during exercise sets (L-exBFR), L with BFR during rest intervals (L-intBFR), and L with continuous BFR during both exercise and rest intervals (L-conBFR). Based on the results of the first experiment, we performed additional protocols using a moderate load (M, 40% 1RM) with intermittent (exercise or rest intervals) BFR (M-exBFR and M-intBFR). Intramuscular metabolic stress, defined as decreases in phosphocreatine and intramuscular pH, was evaluated by 31P magnetic resonance spectroscopy. Rated perceived exertion (RPE) was also assessed. At the end of exercise, total decreases in phosphocreatine and intramuscular pH were similar among L-noBFR, L-intBFR, and L-exBFR and significantly less than those in L-conBFR (p < 0.05). In contrast, changes in these variables in M-intBFR but not in M-exBFR were similar to those in L-conBFR. Nevertheless, RPE was lower in M-intBFR than in both M-exBFR and L-conBFR (p < 0.05). The effect of intermittent BFR during exercise might be insufficient to induce metabolic stress when using a low load. However, effective metabolic stress for muscle adaptation could be obtained by moderate-load resistance exercise with BFR during intervals with less ischemic duration and discomfort.


High-performance liquid chromatography of selenoamino acids and organo selenium compounds. Speciation by inductively coupled plasma mass spectrometry.
As part of an ongoing study to identify selenium compounds with cancer chemopreventive activity, extracts of selenium-enriched samples were analyzed by HPLC-inductively coupled plasma (ICP)-MS. Ion-exchange, ion pair and derivatization methods for reversed-phase HPLC were considered and advantages and disadvantages for each compared. Anion exchange allows separation of selenite and selenate, but otherwise provides poor separation. Pre-column derivatization and reversed-phase chromatography provides separation of compounds with terminal amine functionalities, but many other species elute in the void volume. The ion pair method gave optimal separation and was compatible with standard ICP-MS operating conditions.


Occurrences and removal of pharmaceuticals and personal care products (PPCPs) in drinking water and water/sewage treatment plants: A review.
In recent years, many of micropollutants have been widely detected because of continuous input of pharmaceuticals and personal care products (PPCPs) into the environment and newly developed state-of-the-art analytical methods. PPCP residues are frequently detected in drinking water sources, sewage treatment plants (STPs), and water treatment plants (WTPs) due to their universal consumption, low human metabolic capability, and improper disposal. When partially metabolized PPCPs are transferred into STPs, they elicit negative effects on biological treatment processes; therefore, conventional STPs are insufficient when it comes to PPCP removal. Furthermore, the excreted metabolites may become secondary pollutants and can be further modified in receiving water bodies. Several advanced treatment systems, including membrane filtration, granular activated carbon, and advanced oxidation processes, have been used for the effective removal of individual PPCPs. This review covers the occurrence patterns of PPCPs in water environments and the techniques adopted for their treatment in STP/WTP unit processes operating in various countries. The aim of this review is to provide a comprehensive summary of the removal and fate of PPCPs in different treatment facilities as well as the optimum methods for their elimination in STP and WTP systems.


Mechanisms for endotoxin-induced disruption of ovarian cyclicity: observations in sheep.
This review summarizes a series of experiments that address mechanisms by which endotoxin, a commonly used model of immune/inflammatory challenge, disrupts the oestrous cycle of the ewe. Initial studies in ovariectomized ewes demonstrated that endotoxin inhibits pulsatile LH secretion and that this suppression is achieved in two ways: (i) decreased episodic secretion of GnRH and (ii) reduced pituitary responsiveness to GnRH. These findings led to the hypothesis that the inhibition of pulsatile LH secretion can account for the disruptive effects of endotoxin on the oestrous cycle. Follow-up studies to test this hypothesis revealed that suppression of LH pulsatility during the follicular phase is clearly one means by which endotoxin disrupts the oestrous cycle. However, these studies also provided evidence that endotoxin can impair ovarian follicular responsiveness to gonadotrophin stimulation and inhibit the oestradiol-induced preovulatory LH surge. Collectively, these disturbances in hypothalamo-hypophyseal-ovarian function interrupt the preovulatory chain of events and thereby contribute to disruption of the ovarian cycle in response to this immune/inflammatory challenge.


Cell to cell interaction in the immune response. V. Target cells for tolerance induction.
Collaboration between thymus-derived lymphocytes, and nonthymus-derived antibody-forming cell precursors occurs during the immune response of mice to sheep erythrocytes (SRBC). The aim of the experiments reported here was to attempt to induce tolerance in each of the two cell populations to determine which cell type dictates the specificity of the response. Adult mice were rendered specifically tolerant to SRBC by treatment with one large dose of SRBC followed by cyclophosphamide. Attempts to restore to normal their anti-SRBC response by injecting lymphoid cells from various sources were unsuccessful. A slight increase in the response was, however, obtained in recipients of thymus or thoracic duct lymphocytes and a more substantial increase in recipients of spleen cells or of a mixture of thymus or thoracic duct cells and normal marrow or spleen cells from thymectomized donors. Thymus cells from tolerant mice were as effective as thymus cells from normal or cyclophosphamide-treated controls in enabling neonatally thymectomized recipients to respond to SRBC and in collaborating with normal marrow cells to allow a response to SRBC in irradiated mice. Tolerance was thus not achieved at the level of thelymphocyte population within the thymus, perhaps because of insufficient penetration of the thymus by the antigens concerned. By contrast, thoracic duct lymphocytes from tolerant mice failed to restore to normal the response of neonatally thymectomized recipients to SRBC. Tolerance is thus a property that can be linked specifically to thymus-derived cells as they exist in the mobile pool of recirculating lymphocytes outside the thymus. Thymus-derived cells are thus considered capable of recognizing and specifically reacting with antigenic determinants. Marrow cells from tolerant mice were as effective as marrow cells from cyclophosphamide-treated or normal controls in collaborating with normal thymus cells to allow a response to SRBC in irradiated recipients. When a mixture of thymus or thoracic duct cells and lymph node cells was given to irradiated mice, the response to SRBC was essentially the same whether the lymph node cells were derived from tolerant donors or from thymectomized irradiated, marrow-protected donors. Attempts to induce tolerance to SRBC in adult thymectomized, irradiated mice 3-4 wk after marrow protection, by treatment with SRBC and cyclophosphamide, were unsuccessful: after injection of thoracic duct cells, a vigorous response to SRBC occurred. The magnitude of the response was the same whether or not thymus cells had been given prior to the tolerization regime. The various experimental designs have thus failed to demonstrate specific tolerance in the nonthymus-derived lymphocyte population. Several alternative possibilities were discussed. Perhaps such a population does not contain cells capable of dictating the specificity of the response. This was considered unlikely. Alternatively, tolerance may have been achieved but soon masked by a rapid, thymus-independent, differentiation of marrow-derived lymphoid stem cells. On the other hand, tolerance may not have occurred simply because the induction of tolerance, like the induction of antibody formation, requires the collaboration of thymus-derived cells. Finally, tolerance in the nonthymus-derived cell population may never be achieved because the SRBC-cyclophosphamide regime specifically eliminates thymus-derived cells leaving the antibody-forming cell precursors intact but unable to react with antigen as there are no thymus-derived cells with which to interact.


Singing from the grave: DNA from a 180 year old type specimen confirms the identity of Chrysoperla carnea (Stephens).
Historically serving as repositories for morphologically-based taxonomic research, natural history collections are now increasingly being targeted in studies utilizing DNA data. The development of advanced molecular techniques has facilitated extraction of useable DNA from old specimens, including type material. Sequencing diagnostic molecular markers from type material enables accurate species designation, especially where modern taxonomic hypotheses confirm morphologically cryptic species complexes. One such example is Chrysoperla carnea (Stephens), which belongs to a complex of about 20 cryptic species, most of which can only be reliably distinguished by their pre-mating courtship songs or by DNA analysis. The subtle morphological variation in the group has led to disagreement over the previous designation of the lectotype for C. carnea, an issue that has been further compounded because Chrysoperla carnea is a highly valued biological control agent in arable crops. Archival DNA extraction and sequencing from the 180 year old lectotype specimen, combined with Bayesian and Likelihood based phylogenetic analyses of modern specimens from the entire complex, were used to establish unambiguously the true identity of Chrysoperla carnea.


Computation-Aided Engineering of Cytochrome P450 for the Production of Pravastatin.
CYP105AS1 is a cytochrome P450 from Amycolatopsis orientalis that catalyzes monooxygenation of compactin to 6-epi-pravastatin. For fermentative production of the cholesterol-lowering drug pravastatin, the stereoselectivity of the enzyme needs to be inverted, which has been partially achieved by error-prone PCR mutagenesis and screening. In the current study, we report further optimization of the stereoselectivity by a computationally aided approach. Using the CoupledMoves protocol of Rosetta, a virtual library of mutants was designed to bind compactin in a pro-pravastatin orientation. By examining the frequency of occurrence of beneficial substitutions and rational inspection of their interactions, a small set of eight mutants was predicted to show the desired selectivity and these variants were tested experimentally. The best CYP105AS1 variant gave >99% stereoselective hydroxylation of compactin to pravastatin, with complete elimination of the unwanted 6-epi-pravastatin diastereomer. The enzyme-substrate complexes were also examined by ultrashort molecular dynamics simulations of 50 × 100 ps and 5 × 22 ns, which revealed that the frequency of occurrence of near-attack conformations agreed with the experimentally observed stereoselectivity. These results show that a combination of computational methods and rational inspection could improve CYP105AS1 stereoselectivity beyond what was obtained by directed evolution. Moreover, the work lays out a general in silico framework for specificity engineering of enzymes of known structure.


Type III and I interferons increase HIV uptake and replication in human cells that overexpress CD4, CCR5, and CXCR4.
The newly discovered type III interferon lambda (IFN-lambda) has antiviral activity against a broad spectrum of viruses and potent immune-related activities. Its major producers are peripheral blood mononuclear cells (PBMCs) and dendritic cells. The above functions and cells are deeply involved in AIDS pathogenesis, but there is no information so far on IFN-lambda effects on HIV. Therefore we addressed the sensitivity of HIV-1 replication to cell exposure to human IFN-lambda2. Human PBMCs and C8166 T cells were treated with human Type III or Type I IFNs, and the ability of HIV-1 to bind and replicate in untreated and IFN-treated cells was investigated. Virus amounts were quantified by infectivity and p24 assays. In parallel, we evaluated the possible antiproliferative effects of IFN-lambda2 and the expression of CD4, CXCR4, and CCR5 genes, whose transcripts were quantified by real time RT-PCR. Data showed increased adsorption of HIV to IFN-treated cells in a dose-dependent fashion. Virus yields increased accordingly. In both systems the accumulation of CD4, CXCR4, and CCR5 transcripts was increased, particularly in PBMCs. Antiproliferative activity and classical antiviral state were instead detected on PBMCs, but not on C8166 cells. We concluded that pretreatment of PBMCs and C8166 cells with Type III and Type I IFNs causes increased HIV binding and replication. These effects are likely to be due to increased expression of HIV receptors and coreceptors on the plasma membrane. These findings indicate another mechanism utilized by HIV for subversion of host defenses.


Reflection filter multilayers of metallic and dielectric thin films.
Narrowband spectral filters operating in reflection and consisting of multilayers containing both dielectric and metallic films are of interest for fiber-optical communication systems at wavelengths from 1250 to 1600 nm. Formulas are derived which relate the potential transmittances of the main metallic film to important specifications of the filter, namely, bandwidth and rejection, and it is shown how the parameters of the layers are chosen to meet these and other requirements such as free spectral range. Monitoring procedures are discussed, and the results of photometric observations on five filters are compared to theoretical predictions.


[The effect of vasopressin on the excretion of magnesium and other electrolytes].
In dogs, i.v. administration of pituitrin (0.5-0.8;5.0-8.0; 50.0-80.0 med/kg) in conditions of spontaneous and water diuresis increases the renal excretion of Mg, Ca and Na. This is due to the vasopressin fraction of pituitrin as the synthetic vasopressin exerted the same effect. An increase in Mg excretion after i.p.-administration of pituitrin (1 med/100 g) was noted in rats too. In 2 week puppies administration of 1 med pituitrin did not change the urine excretion of Mg or Ca. Vasopressin is supposed to participate in the Mg metabolism regulation.


A Hybrid Model for the Population Dynamics of Periodical Cicadas.
In addition to their unusually long life cycle, periodical cicadas, Magicicada spp., provide an exceptional example of spatially synchronized life stage phenology in nature. Within regions ("broods") spanning 50,000-500,000 km[Formula: see text], adults emerge synchronously every 13 or 17 years. While satiation of avian predators is believed to be a key component of the ability of these populations to reach high densities, it is not clear why populations at a single location remain entirely synchronized. We develop nonlinear Leslie matrix-type models of periodical cicadas that include predation-driven Allee effects and competition in addition to reproduction and survival. Using both analytical and numerical techniques, we demonstrate the observed presence of a single brood critically depends on the relationship between fecundity, competition and predation. We analyze the single-brood, two-brood and all-brood equilibria in the large life span limit using a tractable hybrid approximation to the Leslie matrix model with continuous time competition in between discrete reproduction events. Within the hybrid model, we prove that the single-brood equilibrium is the only stable equilibrium. This hybrid model allows us to quantitatively predict population sizes and the range of parameters for which the stable single-brood and unstable two-brood and all-brood equilibria exist. The hybrid model yields a good approximation to the numerical results for the Leslie matrix model for the biologically relevant case of a 17-year life span.


Differences in clinical outcomes among hepatitis C genotype 1-infected patients treated with peginterferon alpha-2a or peginterferon alpha-2b plus ribavirin: a meta-analysis.
With the development of new direct acting antiviral (DAA) therapy for hepatitis C, the backbone peginterferon alpha used may be of importance in maximizing treatment outcomes. To this end, the rates of sustained virologic response (SVR), relapse, and treatment discontinuation among hepatitis C genotype 1-infected patients given peginterferon alpha-2a plus ribavirin or peginterferon alpha-2b plus ribavirin were determined using a meta-analysis. Randomized trials examining peginterferon alpha-2a or peginterferon alpha-2b co-administered with ribavirin for 48 weeks were included. Data were extracted on SVR, relapse, and treatment discontinuations for treatment-naïve and treatment-experienced patients. Pooled proportions using fixed and random effects meta-analysis were calculated. Twenty-six trials provided data on patients treated with peginterferon alpha-2a plus ribavirin, and 19 trials provided data on patients treated with peginterferon alpha-2b plus ribavirin. Five trials were direct head-to-head evaluations. In the subset of trials that included head-to-head evaluations, no significant differences were observed between the two treatments for treatment-naïve (relative risk [RR]: 1.07, 95% confidence intervals [CI]: 0.97-1.18) and treatment-experienced patients (RR: 1.27, 95% CI: 0.58-2.77). Using only active trial arms, a larger proportion of the treatment- naïve patients who were provided peginterferon alpha-2a plus ribavirin achieved a SVR (47%), which is greater than that of treatment-naïve patients who were provided peginterferon alpha- 2b plus ribavirin (40% SVR achievement); however, a larger proportion of treatment- experienced patients who were provided peginterferon alpha-2b plus ribavirin achieved a SVR (16%) when compared with treatment-experienced patients given peginterferon alpha-2a plus ribavirin (12% SVR achievement). A larger proportion of relapses occurred among both treatment-naïve and treatment-experienced patients given peginterferon alpha-2a plus ribavirin, when compared with treatment-naïve and treatment-experienced patients taking peginterferon alpha-2b plus ribavirin. The proportion of patients discontinuing treatment was greater among treatment-naïve patients taking peginterferon alpha-2a plus ribavirin, but smaller among treatment-experienced patients. There are small differences in treatment outcomes for different types of peginterferon- alpha. Patient status and complexity of administration may differentiate clinical outcomes.


Problem gambling and family violence: Findings from a population-representative study.
Few studies have investigated the association between problem gambling (PG) and violence extending into the family beyond intimate partners. This study aimed to explore the association between PG and family violence (FV) in a population-representative sample. It was hypothesized that: (a) PG would be positively associated with FV, even after adjusting for sociodemographic variables and comorbidities and (b) these relationships would be significantly exacerbated by substance use and psychological distress. A secondary aim was to explore whether gender moderated these relationships. Computer-assisted telephone interviews were conducted with a population-representative sample of 4,153 Australian adults. Moderate-risk (MR)/problem gamblers had a 2.73-fold increase in the odds of experiencing FV victimization (21.3%; 95% CI: 13.1-29.4) relative to non-problem gamblers (9.4%; 95% CI: 8.5-10.4). They also had a 2.56-fold increase in the odds of experiencing FV perpetration (19.7%; 95% CI: 11.8-27.7) relative to non-problem gamblers (9.0%; 95% CI: 8.0-10.0). Low-risk gamblers also had over a twofold increase in the odds of experiencing FV victimization (20.0%; 95% CI: 14.0-26.0) and perpetration (19.3%; 95% CI: 13.5-25.1). These relationships remained robust for low-risk gamblers, but were attenuated for MR/problem gamblers, after adjustment for substance use and psychological distress. MR/problem gamblers had a greater probability of FV victimization, if they reported hazardous alcohol use; and low-risk gamblers had a greater probability of FV perpetration if they were female. These findings provide further support for routine screening, highlight the need for prevention and intervention programs, and suggest that reducing alcohol use may be important in these efforts.


Pregnancy-specific protein B and progesterone concentrations in French Alpine goats throughout gestation.
The 34 French Alpine dairy goats originated from a single flock and were artificially inseminated 44 h after synchronization of oestrus. They were bled daily at the jugular vein from 15 to 27 days after AI. An early pregnancy diagnosis by RIA of progesterone concentration was performed 21 days after AI. In pregnant goats (greater than 1.5 ng progesterone/ml) daily sampling was extended until 30 days after AI and, from those, 9 were bled every 2 weeks until the end of pregnancy and at 50 and 63 days post partum. Pregnancy-specific protein B (PSPB) was also assayed. The kidding rate was 67.6% (23/34). PSPB concentrations (ng/ml) in pregnant goats were significantly different from those of non-pregnant goats at 24 days after AI (0.82 +/- 0.18 vs 1.78 +/- 0.19; mean +/- s.e.m.) and rose to 40 ng/ml at the end of pregnancy. From Day 25 and throughout gestation, females with 2 fetuses had higher PSPB concentrations than did those with a single fetus (P less than 0.05). In the 2 goats exhibiting late embryonic mortality according to progesterone concentrations, one had a PSPB profile very similar to those of pregnant goats until 30 days while the other did not show any elevation of PSPB concentration. It is concluded that PSPB profiles in goats are similar to those found in cows throughout pregnancy and that PSPB RIA may be useful for pregnancy diagnosis or diagnosis of late embryonic mortality.


Lasting associations between early-childhood temperament and late-adolescent reward-circuitry response to peer feedback.
Behavioral inhibition, a temperament identifiable in infancy, is associated with heightened withdrawal from social encounters. Prior studies raise particular interest in the striatum, which responds uniquely to monetary gains in behaviorally inhibited children followed into adolescence. Although behavioral manifestations of inhibition are expressed primarily in the social domain, it remains unclear whether observed striatal alterations to monetary incentives also extend to social contexts. In the current study, imaging data were acquired from 39 participants (17 males, 22 females; ages 16-18 years) characterized since infancy on measures of behavioral inhibition. A social evaluation task was used to assess neural response to anticipation and receipt of positive and negative feedback from novel peers, classified by participants as being of high or low interest. As with monetary rewards, striatal response patterns differed during both anticipation and receipt of social reward between behaviorally inhibited and noninhibited adolescents. The current results, when combined with prior findings, suggest that early-life temperament predicts altered striatal response in both social and nonsocial contexts and provide support for continuity between temperament measured in early childhood and neural response to social signals measured in late adolescence and early adulthood.


Ru-Ni bimetallic catalysts for steam reforming of xylene: effects of active metals and calcination temperature of the support.
A series of Ru and Ni supported catalysts were prepared and their catalytic performance was evaluated in the steam reforming of xylenes. The effects of active metals, active metal loading sequence, and the calcination temperature of the support on the catalyst activity and stability were investigated. The bimetallic 2Ru → 15Ni catalyst shows much higher activity and stability than the monometallic 2Ru and 15Ni catalyst owing to the synergic effect of Ni and Ru. The 2Ru → 15Ni catalyst has the least coke deposition owing to its high conversion performance and much less coke precursor being formed on the catalyst surface. After decoking, most of the small-sized pores cannot be recovered because of the pore collapse under severe hydrothermal conditions. o-Xylene has the lowest reactivity due to electronic and steric effects. Besides the steam reforming reaction, demethylation and C-C cracking are also observed, forming benzene and toluene. The catalyst with a loading sequence of 15Ni → 2Ru shows high activity at low temperatures (550-600 °C), but undergoes an activity drop at high temperatures (625-650 °C) because the Ni sintering at high temperatures greatly affects the state of Ru on the catalyst. The catalyst with a loading sequence of 2Ru → 15Ni has an advantage at high temperatures owing to its better sintering resistance. The simultaneously loaded 2Ru ↔ 15Ni catalyst shows the lowest activity. The high calcination temperature of the support enhances the catalyst stability by eliminating the small-sized pores before reaction; on the other hand, the elimination of pores decreases the dispersion of the active metals. The 2Ru → 15Ni catalyst calcined at 1000 °C balances the active metal dispersion and resistance to sintering under severe hydrothermal conditions, showing the best activity and stability. The catalyst calcined at 1000 °C has the best coke resistance with only 0.166 g gcat -1 of coke formation after the 24 h durability test. The DTG results indicate that the carbon formed on the catalysts is mainly graphitic carbon.


A new 3D luminescent Zn(ii)-organic framework containing a quinoline-2,6-dicarboxylate linker for the highly selective sensing of Fe(iii) ions.
A new 3D zinc-organic framework [Zn(QDA)]·0.5H2O·0.7DMF (1, H2QDA = quinoline-2,6-dicarboxylic acid, DMF = N,N-dimethylformamide) was synthesized under solvothermal conditions. The single crystal X-ray diffraction analysis reveals that the 3D framework structure of 1 has a PtS topology and contains Zn(ii) ions having distorted square pyramidal geometry with ZnO4N configuration. The phase purity of the bulk sample was characterized by X-ray powder diffraction (XRPD), thermogravimetric analysis (TGA) and Fourier transform infrared (FT-IR) spectroscopy. The as-synthesized sample (1) was activated by stirring with acetone for 24 h, followed by heating under vacuum for 24 h at 120 °C. The TGA experiment indicated that both 1 and its activated form (1') are stable up to 380 °C. The crystalline structure of the compound was retained after immersion in water, 1 M HCl, acetic acid and NaOH (at pH = 10) solutions. Compound 1' exhibited very quick fluorescence quenching response after the addition of Fe3+ solution. This quenching was not affected by the presence of other competitive metal cations. A very low detection limit of 9.2 ppb was observed for Fe3+ ions, which is among the lowest values documented in the literature for MOF based fluorescent probes. Both fluorescence resonance energy transfer (FRET) and photo-induced electron transfer (PET) processes play major roles in the selective detection of Fe3+ ions. The recyclability experiment suggested that 1' can be used for the long-term detection of Fe3+ ions.


Tissue-specific Gene Expression in Rat Hearts and Aortas in a Model of Vascular Nitrate Tolerance.
Nitroglycerin exerts a direct myocardial anti-ischemic effect even in the state of vascular nitrate tolerance. To examine the potentially diverse molecular responses in vascular and cardiac tissues, we investigated the gene expression profile of the heart and the aorta by DNA microarray in male Wistar rats that were previously made tolerant to the vascular effects of nitroglycerin. The blood pressure-lowering effect of nitroglycerin (1-100 μg/kg) was markedly attenuated in rats pretreated for 3 days with 3 × 100 mg/kg nitroglycerin. Nitric oxide content was significantly elevated in the heart but not in the aorta of nitrate-tolerant animals, which indicated tissue-specific differences in nitroglycerin bioconversion. Of 7742 genes analyzed by DNA microarray, we found that although the expression of 25 genes changed significantly in the heart (increased: Tas2r119, Map6, Cd59, Kcnh2, Kcnh3, Senp6, Mcpt1, Tshb, Haus1, Vipr1, Lrn3, Lifr; decreased: Ihh, Fgfr1, Cryge, Krt9, Agrn, C4bpb, Fcer1a, Csf3, Hsd17b11, Hsd11b2, Ctnnbl1, Prpg1, Hsf1), only 14 genes were altered in the aorta (increased: Tas2r119, Ihh, Rrad, Npm1, Snai1; decreased: Tubb2b, Usp15, Sema6c, Wfdc2, Rps21, Ramp2, Galr1, Atxn1, Lhx1) in vascular nitrate tolerance. Quantitative reverse transcription polymerase chain reaction analysis of genes related to oxidative/nitrative/nitrosative stress also showed differential expression pattern in the heart and aorta. This is the first pharmacogenomic analysis showing that nitroglycerin treatment leading to vascular nitrate tolerance differentially impacts gene expression in vascular and cardiac tissues, which indicates different tissue-specific downstream signaling pathways.


A CHEK2 genetic variant contributing to a substantial fraction of familial breast cancer.
CHEK2 (previously known as "CHK2") is a cell-cycle-checkpoint kinase that phosphorylates p53 and BRCA1 in response to DNA damage. A protein-truncating mutation, 1100delC in exon 10, which abolishes the kinase function of CHEK2, has been found in families with Li-Fraumeni syndrome (LFS) and in those with a cancer phenotype that is suggestive of LFS, including breast cancer. In the present study, we found that the frequency of 1100delC was 2.0% among an unselected population-based cohort of 1,035 patients with breast cancer. This was slightly, but not significantly (P=.182), higher than the 1.4% frequency found among 1,885 population control subjects. However, a significantly elevated frequency was found among those 358 patients with a positive family history (11/358 [3.1%]; odds ratio [OR] 2.27; 95% confidence interval [CI] 1.11-4.63; P=.021, compared with population controls). Furthermore, patients with bilateral breast cancer were sixfold more likely to be 1100delC carriers than were patients with unilateral cancer (95% CI 1.87-20.32; P=.007). Analysis of the 1100delC variant in an independent set of 507 patients with familial breast cancer with no BRCA1 and BRCA2 mutations confirmed a significantly elevated frequency of 1100delC (28/507 [5.5%]; OR 4.2; 95% CI 2.4-7.2; P=.0002), compared with controls, with a high frequency also seen in patients with only a single affected first-degree relative (18/291 [6.2%]). Finally, tissue microarray analysis indicated that breast tumors from patients with 1100delC mutations show reduced CHEK2 immunostaining. The results suggest that CHEK2 acts as a low-penetrance tumor-suppressor gene in breast cancer and that it makes a significant contribution to familial clustering of breast cancer-including families with only two affected relatives, which are more common than families that include larger numbers of affected women.


The use of the pectoralis major myocutaneous island flap for reconstruction after major ablative head and neck surgery.
The anatomy of the pectoralis major myocutaneous island flap and the technique and history of its use in reconstruction after major ablative head and neck surgery are described. Twelve cases illustrating the indications for use of the flap and the surgical applications, complications and results are reported. In the future we may expect great advances in this field due to the versatility and reliability of the flap.