Ongoing speciation within the diatom Fragilariopsis kerguelensis in the Southern Ocean?
While the identification of microbial eukaryotes using metabarcoding tools is now widespread, additional data are needed to confirm molecular observations, to mark the difference between species and population variants, and to better understand the biogeography of microbial eukaryotes. In this issue of Molecular Ecology, Postel et al not only use three molecular approaches to identify subgroups of Fragilariopsis kerguelensis but also use morphology and physiology to better understand the relationship between the three genotypes. They revealed that (a) the three genotypes of the diatom F. kerguelensis show negligible gene flux; (b) two of the genotypes are geographically isolated with different physiology but still able to crossbreed; and (c) the remaining genotype is omnipresent but reproductively isolated.


A synthesized nostocionone derivative potentiates programmed cell death in human T-cell leukemia Jurkat cells through mitochondria via the release of endonuclease G.
Nostocionone (Nost), a compound isolated from Nostoc commune, and its synthesized derivatives (NostDs) were evaluated for in vitro cytotoxicity against human T-cell leukemia Jurkat cells. NostD3 [(1E,4E)-1-(3,4-dihydroxyphenyl)-5-(2,6,6-trimethylcyclohex-1-enyl)penta-1,4-dien-3-one] inhibited cell growth more potently than Nost. To elucidate the mechanisms of NostD3-induced cell death, we examined changes in cell morphology, the loss of mitochondrial membrane potential (MMT), and DNA fragmentation. From these results, the cytotoxic effects of NostD3 were found to be mainly due to Type I programmed cell death (PCDI; i.e., apoptosis). Using caspase inhibitors, we further found that NostD-3-induced PCDI occurred through a caspase-independent pathway. Moreover, NostD3 decreased MMT and modulated multiple signaling molecules (MAPKs, Akt, Bcl-2, Bax, and c-Myc) in Jurkat cells, thereby inducing the release of endonuclease G (Endo-G) from mitochondria. The level of intracellular reactive oxygen species (ROS) in cells treated with NostD3 was elevated up to 1 h after the treatment. However, suppression of ROS by N-acetyl-l-cysteine restored Jurkat cell growth. Taken together, our data suggested that ROS production acted as a trigger in NostD3-induced PCDI in Jurkat cells through release of Endo-G from the mitochondria.


Relationship between oversulfation and conformation of low and high molecular weight fucoidans and evaluation of their in vitro anticancer activity.
Low and high molecular weight fucoidans (F(5-30K) and F(>30K)) were chemically modified through the addition of sulfate groups, and the effect of oversulfation on the in vitro anticancer activity was investigated. After the addition of sulfate groups, a considerable increase of 35.5 to 56.8% was observed in the sulfate content of the F(5-30K) fraction, while the sulfate content of the F(>30K) fraction increased to a lesser extent (from 31.7 to 41.2%). Significant differences in anticancer activity were observed between the oversulfated F(5-30K) and F(>30K) fractions, with activities of 37.3-68.0% and 20.6-35.8%, respectively. This variation in the anticancer activity of oversulfated fucoidan derivatives was likely due to differences in their sulfate content. The results suggest that the molecular conformation of these molecules is closely related to the extent of sulfation in the fucan backbones and that the sulfates are preferably substituted when the fucoidan polymers are in a loose molecular conformation.


Infrarenal abdominal aortic aneurysm with concomitant urologic malignancy: treatment results in the era of endovascular aneurysm repair.
During diagnostic workup for urologic malignancies, an abdominal aortic aneurysm (AAA) is identified in a proportion of patients. In the era of open AAA repair, these patients presented a surgical dilemma with regard to the sequence of the operations: cancer treatment first or AAA repair first? Previous assessments have concluded that irrespective of the followed strategy, the early and mediumterm mortality from the two operative procedures in this patient category was significant. With the introduction of endovascular aneurysm repair (EVAR), the mortality and morbidity associated with the treatment of both pathologic conditions may be more favorable than with open aneurysm repair. The objective of this study was to assess, in an institutional series of patients receiving EVAR, the early and long-term survival and complication rates in patients with urologic malignancies. In a series of 385 patients receiving EVAR, 14 had a concomitant urologic malignancy: renal cell carcinoma (5 patients), prostate carcinoma (6 patients), and carcinoma of the bladder (3 patients). The first-month mortality was nil. Long-term survival was 80%, 83%, and 67% for the three tumor types, respectively. EVAR offers improved treatment in patients with concomitant AAA and urologic malignancy and should be considered the first choice for these patients.


Daily consumption of ultra-processed foods and cardiometabolic risk factors in children aged 7 to 10 years in Northeast Brazil.
Background: Ultra-processed foods (UPFs) consumption is associated with pediatric overweight and obesity. Aim: To evaluate the UPFs consumption in children classified either as eutrophic or with excess weight (overweight and obesity). It was also described the fasting plasma glucose, total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL) and low-density lipoprotein (LDL) and the correlation between UPFs consumption and cardiometabolic risk factors. Methods: A total of 139 children aged 7-10years of both sexes, living in Northeast Brazil were classified as eutrophic (n = 65) or excess weight (n = 62). Waist circumference (WC), percentage of body fatness (% BF), fat-free-mass and fat mass were evaluated. Fasting blood sample were collected for biochemical analysis. Food consumption was classified according to the degree of processing. Results: Children with excess weight had a reduction in plasma HDL concentration (45.00; IQR:36.00-54.50 mg/dL vs. 40.00; IQR:35.75-45.25 mg/dL; p = 0.021) and an increase in blood glucose (82.00; IQR:79.00-86.00 mg/dL vs. 86.00; IQR:81.00-90.00 mg/dL; p < 0.001) and TG (64.00; IQR:45.00-92.50 mg/dL vs. 81.00; IQR:57.50-111.75 mg/dL; p < 0.021) when compared with the eutrophic children. UPFs accounted for 43.43% of the total calories consumed by children. Children with excess weight had higher total energy consumption resulting from consumption of UPFs (714.30 ± 26.32 kcal vs. 848.06 ± 349.46 kcal; p = 0.011). The absolute consumption of the UPFs showed a positive correlation with WC (r = 0.202; p = 0.023) and %BF (r = 0.198; p = 0.026). Conclusion: UPFs consumption was higher for children with excess weight and positively correlated with two cardiometabolic risk factors, suggesting the need for strengthening public policies that discourage the consumption of these foods.


Dynamic Surgery Scheduling Based on an Improved Genetic Algorithm.
We formulated a new stochastic programming formulation to solve the dynamic scheduling problem in a given set of elective surgeries in the day of operation. The problem is complicated by the fact that the exact surgery durations are not known in advance. Elective surgeries could be performed in parallel in a subset of operating rooms. The appointment times and assignments of surgeries were planned by an experienced nurses in advance. We present a mathematical model to capture the nature of dynamic scheduling problem. We propose an efficient solution based on an improved genetic algorithm (IGA). Our numerical results showed that dynamic scheduling with the IGA improves the resource utilization as measured by surgeon waiting time and operation room idle time.


The relationship between axial length/corneal radius of curvature ratio and stress-strain index in myopic eyeballs: Using Corvis ST tonometry.
Purpose: This study aimed to investigate the correlation of axial length/corneal radius of curvature ratio with stress-strain index (SSI). Methods: Retrospective analysis was conducted to compare the right eyes of those with high myopia (HM, n = 132; age and 10-48 years) with those without high myopia (NHM, n = 135; age and 7-48 years), where the baseline axial length, corneal radius of curvature ratio, and central corneal thickness were analyzed; the differences in two groups were compared; and the relationship of axial length and axial length/corneal radius of curvature ratio with SSI were explored. Results: Compared with AL < 26mm, SSI significantly decreased when AL ≥ 26 mm (p = 0.001), while there was no correlation with AL in the NHM group (r = -0.14, p = 0.12) or HM group (r = -0.09, p = 0.32). AL/CR was significantly associated with SSI in both the NHM (r = -0.4, p < 0.001) and HM (r = -0.18, p = 0.04) groups. In the NHM group, AL/CR was significantly associated with SSI (unstandardized beta = -0.514, se = 0.109, p < 0.001) with the adjustment of age and gender. Additionally, a significant association of SSI with AL/CR was also found after adjusting for age and gender (unstandardized beta = -0.258, se = 0.096, and p = 0.0082) in the HM group. Conclusion: SSI showed a significant negative correlation with AL/CR in patients without high myopia and in patients with high myopia. However, SSI exhibited no decrease with the worsening of myopia, but it gradually remained stable at a low level. The findings of this study validate, to some extent, the possibility of analyzing the dynamic changes in ocular wall stiffness during the development of myopia by measuring in vivo corneal biomechanical parameters.


Prophylactic use of donut-shaped cushion to reduce sacral pressure injuries during open heart surgery.
Pressure injuries are likely to develop in the operating room due to the high temperature and humidity underneath the patients. This study was designed to reduce sacral pressure injuries using donut-shaped cushions on patients undergoing open heart surgery in a supine position for more than three hours. Patients undergoing open heart surgery for more than three hours were randomly allocated. Depending on the allocation, either the donut-shaped cushion (donut group) or hydrophilic foam dressing (control group) was applied before draping. Patients were evaluated for the development of pressure injuries, National Pressure Ulcer Advisory Panel (NPUAP) stage, and injury size immediately after surgery, 48 hours, and seven days after surgery. Forty-five patients were enrolled in this study. Twenty-two were assigned to the donut group and 23 were assigned to the control group. Three patients developed pressure injuries of NPUAP stage I or higher. All injuries occurred in the control group, but there was no statistically significant difference (P = 0.083). Patients who underwent cardiac surgery for more than three hours and used a donut-shaped cushion did not develop pressure injuries, although no statistical difference was noted. Specific preventative measures in the operating room may play a crucial role in preventing pressure injuries, and further research should be pursued.


Transcranial resection of a juvenile psammomatoid ossifying fibroma of the orbit: A case report with 2-year follow-up.
Juvenile psammomatoid ossifying fibromas (JPOFs) are benign, locally invasive lesion of the craniofacial skeleton that may undergo rapid growth resulting in damage to cranial and facial structures. They usually occur before the age of 15 years and should be carefully treated as their diagnosis may be confused with other lesions such as psammomatous meningioma. A 14-year-old male presented to the clinic with a history of progressive left proptosis. Imaging studies revealed a well-circumscribed lesion involving the left orbital roof and showing internal areas of calcification and sclerosis. He underwent a transcranial resection of the lesion and follow-up imaging revealed no evidence of recurrence. JPOFs are locally invasive lesions that require careful diagnosis and meticulous excision to prevent recurrence.


Microstructural Analysis of Novel Preceramic Paper-Derived SiCf/SiC Composites.
This paper presents the results of microstructural analysis of novel preceramic paper-derived SiCf/SiC composites fabricated by spark plasma sintering. The sintering temperature and pressure were 2100/2200 °C and 60/100 MPa, respectively. The content of fibers in the composites was approx. 10 wt %. The SiCf/SiC composites were analyzed by positron annihilation methods, X-ray diffraction technology, scanning electron microscopy, and Raman spectroscopy. Longer sintering time causes the proportion of the 6H-SiC composition to increase to ~80%. The increase in sintering temperature from 2100 °C to 2200 °C leads to partial transition of 4H-SiC to 6H-SiC during the sintering process, and the long-life component of positrons indicates the formation of Si vacancies. The Raman characteristic peaks of turbostratic graphite appear in the Raman spectrum of SiC fibers, this is caused by the diffusion of carbon from the surface of the SiC fiber and the preceramic paper during the high-temperature sintering process.


Thiopental versus propofol on the outcome of the newborn after caesarean section: An impact study.
In 2011, the company that produced thiopental in France and in the United States stopped its marketing. Because of limited evidences, the choice of the best induction agent for caesarean section remains controversial, especially in emergency. The objective of this study was to compare the effects of propofol versus thiopental on the Apgar score of the newborn. Newborns delivered by elective or emergency caesarean section under general anaesthesia in a university hospital were included from January 2009 to December 2013. Two periods, according to the hypnotic drug used, were compared in this before-and-after comparative study: thiopental before May 2011 and propofol after. The primary outcome was to compare the proportion of newborns with a 5-minute Apgar Score < 7 between both groups. 367 newborns were enrolled, 178 in thiopental group and 189 in propofol group. Demographic and clinical characteristics were similar in both groups. The occurrence of a 5-minute Apgar Score less than 7 was not influenced by the use of propofol (OR 1.40 [CI 95% 0.90-2.20] P = 0.135). Blood gas analyses and admission's rate in neonatal intensive care unit were similar in both groups. Thiopental and propofol do not appear to present significant difference in term of outcome of the newborn after caesarean section. In this situation, propofol may probably be a reliable alternative to the supply reduction of thiopental imposed by forces. Prospective studies are required to confirm the safety of propofol, particularly in the long term.


Fasting plasma free fatty acid concentrations and Pro12Ala polymorphism of the peroxisome proliferator-activated receptor (PPAR) gamma2 gene in healthy individuals.
The Pro12Ala polymorphism of the peroxisome proliferator-activated receptor (PPAR) gamma gene has been associated in some, but not all, studies with lower body mass index (BMI) and improved insulin sensitivity; how an altered transcriptional activity of PPARgamma2 could influence insulin sensitivity is currently unclear. The free fatty acids (FFAs) released from adipose tissue triglycerides via lipolysis are key mediators of impaired insulin sensitivity; however, no study has described the relationship of the Pro12Ala mutation with circulating levels of FFAs under physiological conditions. To investigate in a population-based sample of Caucasians the relation of the Pro12Ala polymorphism with plasma concentrations of FFAs and other markers of lipid and glucose metabolism described as components of the insulin resistance syndrome. Four hundred and thirty-eight nondiabetic employees of the Italian Telephone Company, aged 35-65 years, randomly selected from a total population of 3900 participants in a company-sponsored health screening. The Pro12Ala polymorphism of the PPARgamma was studied together with plasma FFAs, insulin, glucose, triglycerides, high density lipoprotein (HDL) cholesterol, blood pressure and anthropometry. The Homeostatic Model Assessment (HOMA) index was calculated as a measure of insulin resistance. Carriers and noncarriers of the Pro12Ala polymorphism showed very similar circulating levels of FFA (0.46 +/- 0.2 vs. 0.47 +/- 0.2, NS); plasma glucose, triglycerides, HDL cholesterol and blood pressure were also similar in the two groups with or without the polymorphism. To allow for the possible confounding effect of obesity, a separate analysis was conducted in overweight (BMI > or = 25 kg/m(2)) and normal-weight people (BMI < 25 kg/m(2)). Circulating plasma FFA concentrations, as well as triglycerides, blood pressure and HOMA, were significantly higher in overweight than normal-weight, as expected, but no significant differences were detected between carriers and noncarriers of the Pro12Ala polymorphism within each BMI group (0.49 +/- 0.2 vs. 0.48 +/- 0.2, NS, and 0.44 +/- 0.2 vs. 0.47 +/- 0.2, NS, in overweight and normal-weight, respectively). The Pro12Ala polymorphism was also analysed across increasing quartiles of FFA concentrations and no relationship was observed between the frequency of the polymorphism and FFA values (overall chi2 = 0.48, NS). This study does not show any relationship between the Pro12Ala polymorphism of the PPARgamma gene and fasting FFAs in the general population. The possibility of a different handling of FFAs under different conditions (i.e. postprandial) cannot be excluded and remains to be explored.


Vitamin K2 Can Rescue the Dexamethasone-Induced Downregulation of Osteoblast Autophagy and Mitophagy Thereby Restoring Osteoblast Function In Vitro and In Vivo.
Chronic long-term glucocorticoids (GC) use is associated with glucocorticoid-induced osteoporosis (GIOP) by inhibiting the survival and impairing the functions of osteoblasts. Autophagy and mitophagy play key roles in osteoblast differentiation, mineralization and survival, and mounting evidence have implicated osteoblast autophagy and mitophagy as a novel mechanism in the pathogenesis of GIOP. Vitamin K2 (VK2) is an essential nutrient supplement that have been shown to exert protective effects against osteoporotic bone loss including GIOP. In this study, we showed that the glucocorticoid dexamethasone (Dex) deregulated osteoblast autophagy and mitophagy by downregulating the expression of autophagic and mitophagic markers LC3-II, PINK1, Parkin. This consequently led to inhibition of osteoblast differentiation and mineralization function in vitro. Interestingly, co-treatment with VK2 significantly attenuated the Dex-induced downregulation of LC3-II, PINK1, Parkin, thereby restoring autophagic and mitophagic processes and normal osteoblastic activity. In addition, using an established rat model of GIOP, we showed that VK2 administration can protect rats against the deleterious effects of Dex on bone by reinstating autophagic and mitophagic activities in bone tissues. Collectively, our results provide new insights into the role of osteoblast autophagy and mitophagy in GIOP. Additionally, the use of VK2 supplementation to augment osteoblast autophagy/mitophagy may significantly improve clinical outcomes of GIOP patients.


Dibenzofuran 4,4a-dioxygenase from Sphingomonas sp. strain RW1: angular dioxygenation by a three-component enzyme system.
Sphingomonas sp. strain RW1 synthesized a constitutive enzyme system that oxygenated dibenzofuran (DBF) to 2,2',3-trihydroxybiphenyl (THB). We purified this dibenzofuran 4,4a-dioxygenase system (DBFDOS) and found it to consist of four components which catalyzed three activities. Two isofunctional, monomeric flavoproteins (components A1 and A2; M(r) of about 44,000) transferred electrons from NADH to the second component (B; M(r) of about 12,000), a ferredoxin, which transported electrons to the heteromultimeric (alpha 2 beta 2) oxygenase component (C; M(r) of alpha, 45,000; M(r) of beta, 23,000). DBFDOS consumed 1 mol each of NADH, O2, and DBF, which was dioxygenated to about 1 mol of THB; no intermediate was observed. The reaction was thus the dioxygenation of DBF at the 4 and 4a positions to give a diene-diol-hemiacetal which rearomatized by spontaneous loss of a phenolate group to form THB. Components A1 and A2 each reduced dichlorophenolindophenol but had negligible activity with cytochrome c; each lost the yellow color, observed to be flavin adenine dinucleotide, upon purification. Component B, which transported electrons to the oxygenase or cytochrome c, had an N-terminal amino acid sequence with high homology to the putidaredoxin of cytochrome P-450cam. The oxygenase had the UV spectrum of a Rieske iron-sulfur center. We presume DBFDOS to be a class IIA dioxygenase system (EC 1.14.12.-), functionally similar to pyrazon dioxygenase.


Wear Evolution of the Glass Fiber-Reinforced PTFE under Dry Sliding and Elevated Temperature.
The wear evolution of the glass fiber reinforced Polytetrafluoroethylene (PTFE) sliding against duplex steel at elevated temperature was investigated using the interrupted wear tests coupling with the worn surface observations. The morphological changes of the PTFE composite during the sliding were related to the variation of the tribological properties to analyze the underlying wear mechanisms. Results show that the coefficient of friction and wear rate change with the increase of temperature. During the sliding, three regions can be identified regardless of the temperature. The high temperature is beneficial to the formation of tribo-film. The sequence of wear evolution is PTFE removal, load transfer to glass fiber, and minor formation of tribo-film for the low temperature condition. For high temperatures, the wear behaviors are more complicated. The different phenomena include the third body abrasion, flake delamination of PTFE matrix, scratching and reformation of transfer film on the counterface, and the filling of the large scale PTFE groove. These behaviors may dominate the different stages in the stable region, but occur simultaneously and cause the dynamic steady wear. As a result, the wear rate at 200 °C is slightly fluctuant.


Fibromuscular elements of the right atrium: pseudomass at MR imaging.
Results of 20 random cardiac spin-echo and cine gradient-echo magnetic resonance (MR) imaging examinations were reviewed for nodular and/or linear soft-tissue structures projecting from the right atrial wall. A nodular soft-tissue structure (mean diameter, 6 mm) isointense with myocardium was observed along the posterior atrial wall in 18 of 20 patients (90%). The structure extended between the orifices of the superior and inferior venae cavae. Linear strand-like projections originating from the structure coursed across the atrial chamber in 5 of 20 patients (25%). Similar findings were present in one patient who underwent cardiac surgery for a suspected atrial mass. The region of nodular thickening was shown histologically to represent myocyte hypertrophy and fibrosis. The nodular and linear structures correlated anatomically with the crista terminalis muscle bundle and Chiari network, respectively. These structures are frequently visualized on cardiac MR images, are of variable prominence, and may closely simulate the appearance of tumor or other cardiac masses in some patients. Awareness of the location and MR imaging features of these structures will help prevent misdiagnosis.


The Role of Cytokines Produced via the NLRP3 Inflammasome in Mouse Macrophages Stimulated with Dental Calculus in Osteoclastogenesis.
Dental calculus (DC) is a common deposit in periodontitis patients. We have previously shown that DC contains both microbial components and calcium phosphate crystals that induce an osteoclastogenic cytokine IL-1β via the NLRP3 inflammasome in macrophages. In this study, we examined the effects of cytokines produced by mouse macrophages stimulated with DC on osteoclastogenesis. The culture supernatants from wild-type (WT) mouse macrophages stimulated with DC accelerated osteoclastogenesis in RANKL-primed mouse bone marrow macrophages (BMMs), but inhibited osteoclastogenesis in RANKL-primed RAW-D cells. WT, but not NLRP3-deficient, mouse macrophages stimulated with DC produced IL-1β and IL-18 in a dose-dependent manner, indicating the NLRP3 inflammasome-dependent production of IL-1β and IL-18. Both WT and NLRP3-deficient mouse macrophages stimulated with DC produced IL-10, indicating the NLRP3 inflammasome-independent production of IL-10. Recombinant IL-1β accelerated osteoclastogenesis in both RANKL-primed BMMs and RAW-D cells, whereas recombinant IL-18 and IL-10 inhibited osteoclastogenesis. These results indicate that DC induces osteoclastogenic IL-1β in an NLRP3 inflammasome-dependent manner and anti-osteogenic IL-18 and IL-10 dependently and independently of the NLRP3 inflammasome, respectively. DC may promote alveolar bone resorption via IL-1β induction in periodontitis patients, but suppress resorption via IL-18 and IL-10 induction in some circumstances.


Innovative partnerships to advance public health training in community-based academic residency programs.
Collaborative partnerships between community-based academic residency training programs and schools of public health, represent an innovative approach to training future physician leaders in population management and public health. In Kaiser Permanente Northern California, development of residency-Masters in Public Health (MPH) tracks in the Internal Medicine Residency and the Pediatrics Residency programs, with MPH graduate studies completed at the University of California Berkeley School of Public Health, enables physicians to integrate clinical training with formal education in epidemiology, biostatistics, health policy, and disease prevention. These residency-MPH programs draw on more than 50 years of clinical education, public health training, and health services research - creating an environment that sparks inquiry and added value by developing skills in patient-centered care through the lens of population-based outcomes.


[Response of the hypothalamo-corticotropic system to metyrapone in pigeons].
Chronic catheterization and miniature recording device allowed plasma corticosterone (B) and hypothalamic multiunit activity (MUA) to be simultaneously obtained from freely behaving, awake pigeons, before and for 4 hrs after intravenous injection of metyrapone. Injection of vehicle (tartric acid : 100 mg/4 ml/kg) led to MUA and B profiles quite similar to stress-induced responses, i.e., a rapid and sustained rebounding increase in hypothalamic firing rate and, shifted by 5-10 min, in plasma B. These responses were progressively attenuating for 90-120 mn. Metyrapone administration induced first a rapid and short MUA and B increase. Then both parameters drastically decreased near zero for about 2 hrs and were slowly restored to initial values within 3-4 hrs. It is suggested that metyrapone treatment inhibited both peripheral (B synthesis) and central (hypothalamic neurons) levels of the corticotropic axis.


Cloning and expression of a Na(+), K(+)-ATPase alpha-subunit from Taenia solium (TNaK1alpha).
The Na(+), K(+)-ATPase are membrane-associated enzymes that transport Na(+) and K(+) across the membrane generating chemical and electrical gradients, essential to maintain the resting potential for the excitation of myocytons and neurons and for transport of nutrients. The cDNA encoding a full-length isoform of Taenia solium Na(+), K(+)-ATPase alpha-subunit (TNaK1alpha) was isolated from a cysticercal cDNA library. TNaK1alpha has 1014 amino acids and a predicted molecular mass of 111,989Da. The protein displays strong sequence homology and conserved motifs typical of Na(+), K(+)-ATPase alpha-subunits. Northern and Southern hybridizations reveal a TNaK1alpha mRNA of about 3.7kb, which is encoded by a single gene. Polyclonal antibodies raised against a synthetic peptide corresponding to the NH(2)-terminal sequence of TNaK1alpha recognized a 100-kDa polypeptide in the membrane fraction of adult and larval stages of T. solium and other Taenia species. Immunolocalization studies using the same antibodies revealed that the TNaK1 is preferentially localized in muscle cells and protonephridial ducts, and in small quantities in the tegument of T. solium cysticerci.


[Technique for automating HLA-DR typing].
Two types of anti-class II coated magnetic beads were compared for the use in isolation of B lymphocytes from whole blood. The HLA DR typing was performed in parallel after separation of the cells by the rosette technique. The depletion was monitored by Flow cytometry using CD2 and CD20 antibodies. Typing was performed using classic lymphocytotoxicity test of Propidium-Iodide-Carboxyfluorescein diacetate fluorescence. The results were scored with an ordinary microscope or by photometric evaluation. These techniques lead to simplification in cell isolation from small amounts of blood with an important gain of time and a less subjective interpretation of DR phenotyping was until now long and difficult.


MiR-766-3p Suppresses Malignant Behaviors and Stimulates Apoptosis of Colon Cancer Cells via Targeting TGFBI.
MicroRNAs (miRNAs) can affect the progression of colon cancer cells. A variety of miRNAs, especially miR-766-3p, are proved to be abnormally expressed in colon cancer, but the molecular mechanism of miR-766-3p in this cancer has not yet been fully defined. Differentially expressed genes in the TCGA-COAD dataset were searched through bioinformatics analysis. MiR-766-3p and TGFBI mRNA levels were measured by qRT-PCR. TGFBI protein expression was measured via Western blot. Targeting relation between miR-766-3p and TGFBI was investigated by dual-luciferase reporter gene assay. Cell proliferation, invasion migration, and apoptosis were detected by cell functional assays. MiR-766-3p was less expressed, while TGFBI was conspicuously highly expressed in colon cancer. MiR-766-3p high expression suppressed cell malignant behaviors and induced cell apoptosis in colon cancer. MiR-766-3p had a targeting relation with TGFBI verified by dual-luciferase assay. The cancer-suppressive impact of miR-766-3p overexpression was attenuated by overexpressing TGFBI. MiR-766-3p/TGFBI axis suppressed malignant behaviors and facilitated apoptosis of colon cancer cells. MiR-766-3p may be an underlying target for colon cancer.


Potential Link between Gut Microbiota and Deoxynivalenol-Induced Feed Refusal in Weaned Piglets.
This study investigated the potential link between gut microbiota and deoxynivalenol (DON)-induced feed refusal. A total of 24 barrows were randomly divided into one of three diets containing 0.61 (control diet), 1.28, or 2.89 mg DON/kg feed for 28 days. Dietary exposure to DON at 2.89 mg/kg significantly decreased the relative abundances of unclassified_f_Lachnospiraceae, Phascolarctobacterium and Ruminococcaceae_UCG-014, whereas it increased Prevotella_9 and norank_f_Prevotellaceae in the cecal digesta. Moreover, the decreased relative abundance of unclassified_f_Lachnospiraceae induced by DON exposure was positively correlated with average daily feed intake. Exposure to DON increased the serum concentrations of glucagon-like peptide-1 and peptide YY but reduced the levels of serum growth hormone and insulin-like growth factor 1. In summary, these findings suggest that chronic dietary exposure to DON induces disturbances of intestinal microbiota. Disturbed appetite-regulating hormones and somatotropic-axis-hormone secretion induced by negative microbial changes could be the potential mechanisms for DON-induced anorexia.


Beclin 1-independent autophagy induced by a Bcl-XL/Bcl-2 targeting compound, Z18.
Inhibitors of Bcl-XL/Bcl-2 can induce autophagy by releasing the autophagic protein Beclin 1 from its complexes with these proteins. Here we report a novel compound targeting the BH3 binding groove of Bcl-XL/Bcl-2, Z18, which efficiently induces autophagy-associated cell death in HeLa cells, without apparent apoptosis. Unexpectedly, the inhibition of Beclin 1 and phosphatidylinositol 3-kinase have no obvious effect on Z18-induced autophagy in HeLa cells, implying that it is a non-canonical Beclin 1-independent autophagy. Meanwhile, the accumulation of autophagosomes is positively correlated with Z18-induced cell death and the full flux of autophagy is not necessary.


Day-night differences in mucosal plasma proteins in common cold.
Aggravation of symptoms in inflammatory airway diseases is common in the early morning hours, but little is known about day-night differences in the occurrence of plasma exudate on the airway surface. We have therefore examined the plasma macromolecules on the nasal mucosa at different time points. The study comprised 20 subjects who had been inoculated (day 0) with coronavirus intranasally. Ten subjects remained healthy and 10 developed common cold with significant symptoms from day 2 to day 6. Starting on day 3 at 8.00 h and repeated at 4 h intervals until 4.00 h on day 4, nasal lavages were carried out by employment of a nasal pool-device which fills the entire unilateral nasal cavity and gently but effectively irrigates its surface. Lavage fluid levels of albumin (Mw 69,000 D) and fibrinogen (Mw 340,000 D) were determined. In the healthy subjects the levels of albumin and fibrinogen remained low throughout the experiment, however, with mean peak values of the two proteins occurring at 4.00 h (p < 0.05 compared to daytime nadir at 16.00 h). In subjects with common cold both albumin (p < 0.05) and fibrinogen (p < 0.01) exhibited marked variation with individual and mean peak levels recorded at 8.00 h day 3, and 4.00 h day 4. These mean peak values were 5-20 times higher (p < 0.01 - p < 0.05) than the mean levels recorded in these subjects at the other time periods. The present data indicate a marked day-night difference in the occurrence of plasma proteins on the airway surface in common cold, whereas in health the difference is much less. We conclude that different-sized plasma proteins may accumulate on the mucosa in healthy airways during late night hours and that in common cold this nocturnal accumulation may be considerably increased.


[Role of interferons in the treatment of hepatitis B and hepatitis C virus infections].
Since the discovery of hepatitis C (HCV), the efficacy of treatment has significantly progressed using standard mono-therapy: with Interferon alpha (IFN) during six months we obtained approximately 10% sustained response and currently with the association of pegylated IFN and Ribavirin a 55% sustained response was achieved. HCV infection continues to present therapeutic problems which have not entirely been solved, mainly related to clinical and biological tolerance, and non-responders. Moreover, the care of patients with extra-hepatic localization, cirrhotic patients, as well as therapeutic problems of co-infected HIV-HCV patients. As regards hepatitis B (HBV) new effective treatments against this virus have appeared, IFN then nucleoside analogs, some of which are available in France (i.e. lamivudine, adefovir, dipovoxil). The main objective of chronic hepatitis B treatment is to obtain the complete inhibition of the HBV virus by Hbe-antigen antibody seroconversion which would therefore significantly increase patient survival. In this article the advantages and disadvantages of the different treatments are assessed. Despite the considerable and rapid progress obtained in the therapeutic treatment of infection due to HCV and HBV a number of unknown factors remain, which warrants further trials, in particular to evaluate the efficacy as well as the tolerance of the antiviral agent association.


Use of Standard Reference Material 2242 (Relative Intensity Correction Standard for Raman Spectroscopy) for microarray scanner qualification.
As a critical component of any microarray experiment, scanner performance has the potential to contribute variability and bias, the magnitude of which is usually not quantified. Using Standard Reference Material (SRM) 2,242, which is certified for Raman spectral correction, for monitoring the microarray fluorescence at the two most commonly used wavelengths, our team at the National Institute of Standards and Technology (NIST) has developed a method to establish scanner performance, qualifying signal measurement in microarray experiments. SRM 2,242 exhibits the necessary photostability at the excitation wavelengths of 635 nm and 532 nm, which allows scanner signal stability monitoring, although it is not certified for use in this capacity. In the current study, instrument response was tracked day to day, confirming that changes observed in experimental arrays scanned are not due to changes in the scanner response. Signal intensity and signal-to-noise ratio (S/N) were tracked over time on three different scanners, indicating the utility of the SRM for scanner qualification.


Effect of Ethrel and Ceratocystis fimbriata on the Synthesis of Fatty Acids and 6-Methoxy Mellein in Carrot Root.
The rate of incorporation of (14)C from acetate-1-(14)C into fatty acids by carrot root discs, 18 hours after inoculation with Ceratocystis fimbriata, was 9-fold greater than that in freshly cut discs. The rate in discs treated with water or Ethrel was 3-fold greater. The rate of incorporation of (14)C from glucose-U-(13)C into fatty acids was 3-fold greater 18 hours after any of the above treatments. The rate of (14)C incorporation from malonate-2-(14)C into fatty acids 24 hours after inoculation with C. fimbriata or treatment with water was 25 and 60%, respectively, of that in freshly cut discs. Linoleic acid was the principal fatty acid in carrot root, but incorporation of (14)C from acetate-1-(14)C into the acid was low until 18 hours after inoculation with C. fimbriata or treatment with Ethrel. Turnover rates of the fatty acids appeared low and were similar for all treatments.There was little or no incorporation of (14)C from acetate or malonate into 3-methyl-6-methoxy-8-hydroxy-3,4-dihydroisocoumarin (6-methoxy mellein) in fresh carrot discs or in discs treated with water, but label was incorporated rapidly in discs inoculated with C. fimbriata or treated with Ethrel. The rate of incorporation of label from acetate into fatty acids was severalfold higher than into 6-methoxy mellein, but the rate of incorporation of label from malonate was approximately equal into fatty acids and 6-methoxy mellein 24 hours after inoculation. The rate of fatty acid synthesis does not appear directly related to the accumulation of 6-methoxy mellein.


Cu and Ag catalyzed oxidative arylthiation of terminal acetylenes.
A mild Cu or Ag catalyzed oxidative arylthiation of terminal acetylenes is introduced. The process, featuring metal catalyzed C-H bond activation as a key step, leads to the formation of highly substituted mercaptoacetylenes under unprecedented neutral conditions.


Reductive-Delay Heck 1,1-Diarylation of Terminal Alkenes.
Pd-catalyzed chemo- and regiocontrollable 1,1-diarylation of unactivated aliphatic alkenes with two aryl halides was developed. Under the cationic reductive-delay Heck pathway, the first aryl insertion is followed by β-H elimination, while the second aryl insertion is terminated by C-H bond formation.


[Genetic cancer syndromes and reproductive choice: dialogue between parents and politicians on preimplantation genetic diagnosis].
Genetic cancer syndromes have identical clinical severity, limited therapeutic options, reduced life expectancy, and risks of genetic transmission, as do other genetic or congenital diseases for which prenatal genetic diagnosis or preimplantation genetic diagnosis (PGD) is allowed in the Netherlands. That was implied in the certification of one Dutch PGD centre at Maastricht University Hospital by the Dutch Ministry of Health, Welfare and Sport in 2003. A report by the Health Council of the Netherlands in 2006 confirmed this view with scientific and ethical evaluation. However, in 2006 the State Secretary for Health strongly objected to PGD for cancer, and disease risks of 50-100% for gene carriers, i.e. for highly, but not always fully penetrant genes. In 2006, the Maastricht centre discontinued PGD for cancer and couples were referred to other countries; prenatal genetic diagnosis remained available, however. On 26 May 2008, the present State Secretary proposed to parliament that the Health Council of the Netherlands report from 2006 be followed. This once again clashed with the fears of some Christian parties for a slippery slope and embryo selection for 'only a risk and not certainty of disease'. Yet no firm evidence for the existence of such a slope has been found. The Dutch framework for handling the ethical and medical evaluation of new reproductive and genetic technologies by the Health Council of the Netherlands Advisory Committees, professional and patient organisations, and the Ministry, has functioned for over 30 years without leading to any wrongdoing. There is no actual need for a new government body to license genetic tests on a case-by-case or per disease basis.


[Thrombophilia and pregnancy].
The incidence of venous thromboembolism is increased five to six times in pregnancy; and it is estimated that thromboembolic episodes- superficial and deep venous thromboembolism and pulmonary embolism occur in 1:1000 to 1:1500 pregnancies. These complications during pregnancy and puerperium, are not common but serious and leading cause of maternal morbidity and mortality. Thrombophilias--acquired or inherited, result of anticoagulant regulatory proteins deficiency, could compromise normal pregnancy by increasing the risk of developing first or recurrent thromboembolic incidents and adverse obstetric events.


Myelodysplastic syndrome and acquired factor VIII inhibitor with severe subcutaneous haemorrhage.
A case of acquired haemophilia A presenting with extensive spontaneous bruising and anaemia is reported. The anaemia was due to myelodysplastic syndrome (FAB: refractory anaemia with ringed sideroblasts). A factor-VII:C-specific inhibitor was also found. Prednisone and pyridoxine were given, and the inhibitor became undetectable after 4 weeks of therapy, but the abnormal ringed sideroblasts still persisted on repeated bone marrow biopsy.


Thiazolidinediones and fatty acids convert myogenic cells into adipose-like cells.
Fatty acids and thiazolidinediones act as potent activators of the adipose differentiation program in established preadipose cell lines. In this report, the effects of these agents on the differentiation pathway of myoblasts have been investigated. Exposure of C2C12N myoblasts (a subclone of the C2C12 cell line) to thiazolidinediones or fatty acids prevents the expression of myogenin, alpha-actin, and creatine kinase, thus abolishing the formation of multinucleated myotubes. These treatments lead in parallel to the expression of a typical adipose differentiation program including acquisition of adipocyte morphology and activation of adipose-related genes. A similar transition toward the adipose differentiation pathway also occurs in mouse muscle satellite cells maintained in primary culture. Thiazolidinediones exert their adipogenic effects only in non-terminally differentiated myoblasts; myotubes are insensitive to the compounds. Continuous exposure to inducers after growth arrest is not required to maintain the adipose phenotype, but proliferation of adipose-like C2C12N cells leads to a complete reversion toward undifferentiated cells able to undergo either myogenic or adipogenic differentiation depending on the composition of culture medium. These results indicate that adipogenic inducers, such as thiazolidinediones or fatty acids, specifically convert the differentiation pathway of myoblasts into that of adipoblasts.


Association of postoperative delirium with markers of neurodegeneration and brain amyloidosis: a pilot study.
The aim of the study was to investigate the association between postoperative delirium (POD) and in vivo markers of Alzheimer's disease pathology in nondemented hip fracture surgery patients. POD was assessed with the Confusion Assessment Method. Amyloid load was quantified on 18F-Flutemetamol positron emission tomography images as standardized uptake value ratio. Secondary outcome measures were gray matter volumes, white matter integrity, and functional connectivity at rest. All the patients with POD (POD+, N = 5) were amyloid negative (standardized uptake value ratio <0.59), whereas 6 out of 11 patients without POD (POD-) showed brain amyloid positivity. POD+ compared to POD- displayed: lower gray matter volumes in the amygdala (p = 0.003), in the middle temporal gyrus and in the anterior cingulate cortex (p < 0.001), increased diffusivity in the genu of the corpus callosum and in the anterior corona radiata (p < 0.05), and higher functional connectivity within the default mode network (p < 0.001). POD patients showed altered gray and white matter integrity in the fronto-limbic regions in absence of brain amyloidosis. Based on this preliminary investigation, delirium pathophysiology might be independent of Alzheimer's disease. Future studies on larger samples are needed to confirm this hypothesis.


Genetics and biochemistry of seed flavonoids.
Flavonoids are secondary metabolites that accumulate in most plant seeds and are involved in physiological functions such as dormancy or viability. This review presents a current view of the genetic and biochemical control of flavonoid metabolism during seed development. It focuses mainly on proanthocyanidin accumulation in Arabidopsis, with comparisons to other related metabolic and regulatory pathways. These intricate networks and their fine-tuned regulation, once they are determined, should contribute to a better understanding of seed coat development and the control of PA and flavonol metabolism. In addition, flavonoids provide an interesting model to study various biological processes and metabolic and regulatory networks.


Presence and identification of polyamines in xylem and Phloem exudates of plants.
Polyamines were identified by high performance liquid chromatography (benzoylation) and by thin layer chromatography (dansylation) in xylem exudates from stems of sunflowers (Helianthus annuus [L.]), mung bean (Vigna radiata [L.] Wilczek), grapevine (Vitis vinifera [L.] cv Grenache), and orange (Citrus sinensis [L.] Osbeck, cv Valencia), as well as in phloem sap (using elution into EDTA) of sunflower and mung bean plants. Putrescine was the major polyamine detected, ranging in concentrations of 150 to 9200 picomoles per milliliter exudate, whereas only trace amounts of spermine were detected. High amounts of putrescine and spermidine were found in EDTA eluates (possibly phloem sap) as compared with elution into water. Concentrations of putrescine and spermidine in xylem exudates were related to the physiological conditions of the plants prior to exudate collection. More putrescine was found in exudates of older than in younger sunflower plants, and salt stress applied to sunflower plants resulted in a higher concentration of putrescine and spermidine in the exudate. The presence and abundance of putrescine and spermidine in xylem and phloem exudates indicate that polyamines may be translocated in plants. This long-distance translocation further supports the hypothesis that polyamines have a regulatory role in plant growth and response to stress.


Molecular basis for oligomeric-DNA binding and episome maintenance by KSHV LANA.
LANA is the KSHV-encoded terminal repeat binding protein essential for viral replication and episome maintenance during latency. We have determined the X-ray crystal structure of LANA C-terminal DNA binding domain (LANADBD) to reveal its capacity to form a decameric ring with an exterior DNA binding surface. The dimeric core is structurally similar to EBV EBNA1 with an N-terminal arm that regulates DNA binding and is required for replication function. The oligomeric interface between LANA dimers is dispensable for single site DNA binding, but is required for cooperative DNA binding, replication function, and episome maintenance. We also identify a basic patch opposite of the DNA binding surface that is responsible for the interaction with BRD proteins and contributes to episome maintenance function. The structural features of LANADBD suggest a novel mechanism of episome maintenance through DNA-binding induced oligomeric assembly.


Impact of DARC rs12075 Variants on Liver Fibrosis Progression in Patients with Chronic Hepatitis C: A Retrospective Study.
: The Duffy antigen receptor for chemokines (DARC) rs12075 polymorphism regulates leukocyte trafficking and proinflammatory chemokine homeostasis. Hepatitis C virus (HCV)-mediated liver fibrosis is associated with an uncontrolled inflammatory response. In this study, we evaluate the association between the DARC rs12075 polymorphism and liver stiffness progression in HCV-infected patients. We carried out a retrospective cohort study (repeated measures design) in 208 noncirrhotic patients with chronic hepatitis C (CHC) who had at least two liver stiffness measurements (LSM) with a separation of at least 12 months. We used generalized linear models to analyze the association between DARC rs12075 polymorphism and outcome variables. During a follow-up of 46.6 months, the percentage of patients with stages of fibrosis F0/F1 decreased (p < 0.001), while LSM values and the percentage of patients with cirrhosis increased (p < 0.001). This pattern of changes was maintained in each of the groups of patients analyzed according to their rs12075 genotypes (AA or AG/GG). However, the variations in liver stiffness characteristics were lower in patients with the rs12075 AG/GG genotype (AG/GG versus AA). Thereby, in the adjusted analysis, patients with the rs12075 AG/GG genotype had a lower risk of an increased value of LSM2/LSM1 arithmetic mean ratio (AMR = 0.83; p = 0.001) and of an increase in LSM ≥ 5 kPa (odds ratio (OR) = 0.28; p = 0.009). Besides, patients with rs12075 AG/GG had a lower risk of cirrhosis progression (OR = 0.24; p = 0.009). No significant associations were found for an increase in LSM ≥ 10 kPa. We found an association between the DARC rs12075 single nucleotide polymorphism (SNP) and CHC progression. Specifically, patients with the DARC rs12075 AG/GG genotype had a lower risk of liver fibrosis progression and development of cirrhosis.


Adaptation of the osteoarthritis-specific quality of life scale (the OAQoL) for use in Germany, Hungary, Italy, Spain and Turkey.
The Osteoarthritis Quality of Life scale (OAQoL) is specific to individuals with osteoarthritis. The present study describes the adaptation of the OAQoL for use in the following five European languages: German, Hungarian, Italian, Spanish and Turkish. The study involved three stages in each language; translation, cognitive debriefing (face and content validity) and validation. The validation stage assessed internal consistency (Cronbach's alpha), reproducibility (test-retest reliability using Spearman's rank correlations), convergent and divergent validity (correlations with the Health Assessment Questionnaire, The Western Ontario and McMaster Universities Index of osteoarthritis and Nottingham Health Profile) and known group validity. The OAQoL was successfully translated into the target languages with minimal problems. Cognitive debriefing interviewees found the measures easy to complete and identified few problems with content. Internal consistency ranged from 0.94 to 0.97 and test-retest reliability (reproducibility) from 0.87 to 0.98. These values indicate that the new language versions produce very low levels of measurement error. Median OAQoL scores were higher for patients reporting a current flare of osteoarthritis in all countries. Scores were also related, as expected, to perceived severity of osteoarthritis. The OAQoL was successfully adapted for use in Germany, Hungary, Italy, Spain and Turkey. The addition of these new language versions will prove valuable to multinational clinical trials and to clinical practice in the respective countries.


Is protein disulfide isomerase a redox-dependent molecular chaperone?
Protein disulfide isomerase (PDI) is a multifunctional protein catalysing the formation of disulfide bonds, acting as a molecular chaperone and being a component of the enzymes prolyl 4-hydroxylase (P4H) and microsomal triglyceride transfer protein. The role of PDI as a molecular chaperone or polypeptide-binding protein is mediated primarily through an interaction of substrates with its b' domain. It has been suggested that this binding is regulated by the redox state of PDI, with association requiring the presence of glutathione, and dissociation the presence of glutathione disulfide. To determine whether this is the case, we investigated the ability of PDI to bind to a folding polypeptide chain within a functionally intact endoplasmic reticulum and to be dissociated from the alpha-subunit of P4H in vitro in the presence of reducing or oxidizing agents. Our results clearly demonstrate that binding of PDI to these polypeptides is not regulated by its redox state. We also demonstrate that the dissociation of PDI from substrates observed in the presence of glutathione disulfide can be explained by competition for the peptide-binding site on PDI.


Platelet reactivity in patients with venous thrombosis who use rosuvastatin: a randomized controlled clinical trial.
Essentials Statins, especially rosuvastatin, may reduce venous thrombosis risk, but the mechanism is unclear. We performed a randomized trial investigating the effect of rosuvastatin on platelet reactivity. Thromboxane-A2 mediated platelet aggregation was measured before and after rosuvastatin therapy. Rosuvastatin did not inhibit thromboxane-mediated platelet aggregation in venous thrombosis patients. Background Statins may exert a protective effect against the risk of venous thrombosis (VT), but the mechanism is unclear. Objectives In this open-label, randomized clinical trial (www.clinicaltrials.gov NCT01613794), we aimed to determine the ex vivo effect of rosuvastatin on platelet reactivity in patients with a history of VT. Methods Platelet reactivity, in platelet reaction units (PRUs), was measured at baseline and after 28 days with VerifyNow, which uses arachidonic acid to determine thromboxane-mediated platelet aggregation, in 50 consecutive patients included in our study (25 receiving rosuvastatin and 25 without intervention). Results Forty-seven of 50 (94.0%) consecutively enrolled patients had two valid PRU measurements. The mean PRUs in rosuvastatin users were 609 at baseline and 613 at the end of the study (mean change 5; 95% confidence interval [CI] - 18 to 27). The mean PRUs in non-users were 620 at baseline and 618 at the end of the study (mean change - 2; 95% CI - 15 to 12). The mean difference in PRU change between users and non-users was 6 (95% CI - 20 to 33). After exclusion of patients who used antiplatelet medication, or had thrombocytopenia, similar results were obtained, i.e. no apparent effect of rosuvastatin on PRUs, with a mean difference in PRU change between users and non-users of - 1 (95% CI - 20 to 19). Conclusions Rosuvastatin does not affect platelet reactivity when arachidonic acid is used as an agonist in patients with a history of VT.


Refinement of thalamocortical arbors and emergence of barrel domains in the primary somatosensory cortex: a study of normal and monoamine oxidase a knock-out mice.
In the rodent primary somatosensory cortex, the thalamocortical axons (TCAs) are organized into clusters that correspond to functional units in the periphery. Around these axons, neurons in layer IV aggregate as barrels. To understand how this organization emerges, we analyzed TCA development in mice that do not form barrels, the monoamine oxidase A knock-out (MAOA-KO), and in MAOA/5-HT(1B) receptor double-KO mice, which have a restored barrel field. We show that TCAs already attain cortical layer IV on the day of birth. They are uniformly distributed in this layer from postnatal day 0 (P0) to P2 and secondarily coalesce into barrel domains in layer IV, over a 3 d period (P3-P5), with no prepatterning in the deeper layers. In MAOA-KO mice, the uniform distribution of the TC projection is maintained, and no axon clusters emerge. Individual TCA arbors were traced after carbocyanine injections. At P1, TCAs were poorly branched and covered variable tangential widths, encompassing one to two prospective barrels. At P7 the number of TCA branches increased 10-fold in layer IV and became restricted to one barrel. In MAOA-KO mice, there was a 50% reduction of the TCA terminal branches in layer IV, with a 40% increase in their tangential extent. These defects were corrected in the MAOA/5-HT(1B) double knock-out mice, indicating an effect of the presynaptic 5-HT(1B) receptor on axon branching. Our results indicate that the barrel-deficient phenotype of MAOA-KO mice results from an altered refinement of the TCA arbors in their target layer IV, involving branch elaboration and collateral retraction during early postnatal life.


Age-related changes in male skin: quantitative evaluation of one hundred and fifty male subjects.
Modern men have changed their beauty and grooming habits, which has resulted in an increasing demand for cosmetics for men. However, very little information is available about the dermatological needs of male skin. Therefore, the aim of this present clinical study was to conduct the first systematic assessment of the skin physiology of men with special attention to lifetime changes. A total of 150 healthy male subjects (aged 20-70 years) were selected following strict criteria, including age, sun behavior and smoking habits. Transepidermal water loss (TEWL), hydration level, sebum production and pH values were measured with worldwide-acknowledged biophysical measuring methods at the forehead, cheek, neck, volar forearm and dorsum of hand. TEWL and sebum production vary by localization, but generally not with increasing age, whereas stratum corneum (SC) hydration decreases significantly at the face and neck. The greatest decrease was assessed at the forehead. Skin surface pH significantly increases with aging in the face. The present study assigns for the first time systematic reference values for standardized biophysical measuring methods and localizations reflecting the skin physiology of men in relation to age. The results show that the physiology of male skin partly changes with aging. While SC hydration and skin surface pH are affected by the subject's age, TEWL and sebum production show only minor variations.


Attention deficit hyperactivity disorder and substance use disorders: Is there a causal link?
Attention-deficit hyperactivity disorder (ADHD), characterized by restless, inattentive and hyperactive behaviours, is a relatively common childhood disorder that affects approximately 5% of the general population. There has been controversy about whether ADHD increases risks of developing substance use disorders. The available evidence suggests that, in the absence of conduct disorder, ADHD is not associated with an increased risk of substance use problems in males. There is only limited evidence on the role of ADHD in the aetiology of substance use disorders among females. While ADHD has traditionally been considered as a childhood disorder, it may also occur in adults; research needs to examine the extent to which ADHD in adulthood increases the risk of substance use disorders.


Ways of coping in survivors of suicide.
The purpose of this pilot study was to describe ways in which survivors cope after a death by suicide of a family member or significant other and to explore the psychometric properties of the Ways of Coping Questionnaire (WoCQ). An examination of inter-item correlations indicated that subscales were unidimensional and reliabilities ranged from α = .57 to α = .82. Construct validity was established by correlating the WoCQ subscales with other established instruments. Females used Seeking Social Support and Positive Reappraisal significantly more than males (p < .05). Interventions to enhance positive coping strategies may assist future survivors in managing the death of a significant other by suicide.


[Laparoscopic and open subtotal colectomy for inflammatory bowel disease].
Studies have shown that laparoscopic colectomy (LC) for inflammatory bowel disease (IBD) is just as safe as open colectomy. Some of the short-term advantages of laparoscopy are faster recovery, less pain, shorter hospital stay and fewer complications. The long-term advantages include superior cosmetic result, reduced intra abdominal adhesion formation, less frequent hospitalization due to small bowel obstruction and fewer incisional hernias. Cost-benefit analyses also favour laparoscopic surgery for IBD.


The Influence of Flow Velocity in the Feeding Vessel on Flap Perfusion in Deep Inferior Epigastric Artery Perforator Flap.
Contralateral perfusion of zones II and IV is critical to estimate the amount of fat necrosis and determine intraoperative flap sacrifice during autologous breast reconstruction. We aimed to determine whether perfusion of the contralateral side was affected by the peak flow velocity in the feeding vessels in the deep inferior epigastric artery (DIEA) perforator free flap reconstructions. This was a retrospective review of patients who received DIEA perforator flap for autologous breast reconstruction from February to July 2020. Intraoperative indocyanine green (ICG) angiography and measurement software (Image J) were used to validate the perfusion of the contralateral side of the flap. Peak flow in the vessels was measured with duplex color Doppler and linear correlation was used to analyze the association between perfusion and blood flow velocity. Forty-two patients received a DIEP flap. The average age of the patients was 48.5 years, and body mass index was 23.84 kg/m2. Peak flow velocity of the internal mammary artery (IMA) was significantly higher than that of the DIEA (p <0.05). Contralateral perfusion confirmed by ICG angiography was higher in the IMA than in the DIEA (p <0.05). A linear correlation was found between peak speed (p = 0.045) and ICG perfusion length (p = 0.00003). The status of flap perfusion depends on the feeding vessel. The velocity of blood flow between IMA and DIEA is different, and the flap perfusion varies accordingly. Therefore, ICG angiography should be performed after anastomosis at the recipient site for an accurate assessment.


Aldehyde dehydrogenase 2 partly mediates hypotensive effect of nitrite on L-NAME-induced hypertension in normoxic rat.
Nitrite has become a topic of interest in the field of medical research because of its potential therapeutic role as an alternative source of nitric oxide (NO). While the bioconversion of nitrite to NO occurs via either nonenzymatic or enzymatic reduction under acidic or hypoxic conditions, little is known about its conversion to NO under normoxic conditions. Because of a recent report of aldehyde dehydrogenase 2 (ALDH2)-catalyzed glyceryl trinitrate (GTN) vasorelaxation by denitration of GTN to 1,2-glyceryl dinitrate (1,2-GDN) and nitrite, we therefore investigated a catalytic activity of ALDH2 for nitrite reduction and subsequent effect on N(ω)-nitro-l-arginine methyl ester (l-NAME)-induced hypertension in normoxic rat. Male Sprague-Dawley rats treated with l-NAME in drinking water for 3 weeks developed hypertension with significantly reduced plasma levels of nitrite and nitrate. The intravenous injection of sodium nitrite lowered the arterial pressure in a dose-dependent manner (17, 50 and 150 μmol/kg). Pretreatment with ALDH2 inhibitors (cyanamide and chloral hydrate) partially inhibited the hypotensive responses to sodium nitrite. In addition, cyanamide significantly delayed the nitrite clearance from plasma and most of the organs examined during the experimental period. These results suggest that ALDH2 may be at least in part involved in nitrite-mediated hypotensive effects and nitrite catalysis in many organs of normoxic rats.


5-[2-(4-Acetyl-oxyphen-yl)ethen-yl]benzene-1,3-diyl diacetate.
The title compound, C(20)H(18)O(6), was prepared from resveratrol {systematic name: 5-[(E)-2-(4-hy-droxy-phen-yl)ethen-yl]ben-z-ene-1,3-diol}, which can be isolated from grapes, through triacetyl-ation with using acetic anhydride in pyridine. The two benzene rings are approximately coplanar, making a dihedral angle of 6.64 (14)°, and the three acet-oxy group are located on the same side of the plane. The skeleton of the compound resembles a table with three legs. In the crystal, mol-ecules are linked via C-H⋯O interactions, forming inversion dimers. These dimers are further linked via C-H⋯O interactions, forming a three-dimensional structure.


Can the three-phase bone scan differentiate osteomyelitis from metabolic or metastatic bone disease?
The three-phase bone scan has been reported of value in the diagnosis of osteomyelitis. The use of a radionuclide angiogram, an immediate postinjection "blood pool" image, and 2 to 3 hour delayed image have been useful in separating nonosseous inflammatory disease from osteomyelitis. However, dependence on increased blood flow and focal hyperemia for this diagnosis may limit the use of the study if other processes are shown to produce similar results. To identify limitations of the three-phase bone scan we studied 14 patients with metastatic bone disease and nine patients with Paget's disease. Blood flow results showed no increase in three of 14 patients with metastases, intermediate increase in seven of 14 patients with metastases and two of nine patients with Paget's, and intense increase in four of 14 patients with metastases and seven of nine patients with Paget's. All patients showed increased focal activity in the immediate "blood pool" and delayed images. We conclude that because of increased flow Paget's disease may be difficult to separate from osteomyelitis. However, metastatic disease can often be differentiated on the basis of quantitative focal hyperemia. The three-phase bone scan remains of value in the diagnosis of osteomyelitis, but other diseases of bone must be included in the differential diagnosis.


Oculo-palato-cerebral syndrome: a third case supporting autosomal recessive inheritance.
In 1985, Frydman et al. [1985: Clin Genet 27:414-419] described a syndrome characterized by growth failure, microcephaly, persistent hyperplastic primary vitreous (PHPV) with microphthalmia, cleft palate, connective tissue abnormality, mental retardation, and spastic quadriplegia. The syndrome was termed as oculo-palato-cerebral dwarfism. The first patients described were offsprings of a consanguineous couple of Moroccan Jewish descent, suggesting autosomal recessive inheritance. An additional case was reported by Pellegrino et al. [2001: Am J Med Genet 99:200-203] in 2001. The clinical features were milder than the original cases, and there was no consanguinity. We report a third patient with oculo-palato-cerebral syndrome, supporting autosomal recessive inheritance, and a detailed comparison with the previous cases. This article contains supplementary material, which may be viewed at the American Journal of Medical Genetics website at http://www.interscience.wiley.com/jpages/0148-7299/suppmat/index.html.


[Analysis of quality of life. Development of an evaluation instrument].
To develop a questionnaire about quality of life (QV) suitable for Intensive Care Unit (ICU) patients. Two prospective studies by direct interviews; in the first one the questionnaire was answered before and after surgical intervention and in the second during ICU stay and six months after hospital discharge. Surgical ward and surgical-medical ICU. Adult, co-operative patients, resident near the hospital, who gave informed consent have been interviewed. The following items of QOL were investigated: residence, physical activity, social life, perceived QV, oral communication and functional limitation, considering age. The last two items were assessed by the interviewer. Inter-observer reliability on oral communication and functional limitation, assessed by two interviewers in 87 surgical patients, was good (p = 0.68 and p = 0.72 respectively). Validation of the questionnaire in 37 surgical cases showed worsening in all the items, consistent with theoretical prediction. In the 152 ICU consecutively admitted eligible patients, physical activity, social life, functional limitation and global QV (sum of all the investigated items) significantly changed. Residence, perceived QV and oral communication did not change. Internal consistency of the instrument was good (p < 0.05). The evaluative instrument studied shows good reliability and validity. The authors suggest a shorter questionnaire could be tested in future investigations.


A non-dimensional parameter for classification of the flow in intracranial aneurysms. II. Patient-specific geometries.
A simple parameter, called the Aneurysm number (An) which is defined as the ratio of transport to vortex time scales, has been shown to classify the flow mode in simplified aneurysm geometries. Our objective is to test the hypothesis that An can classify the flow in patient-specific intracranial aneurysms (IA). Therefore, the definition of this parameter is extended to anatomic geometries by using hydraulic diameter and the length of expansion area in the approximate direction of the flow. The hypothesis is tested using image-based flow simulations in five sidewall and four bifurcation geometries, i.e., if An ≲ 1 (shorter transport time scale), then the fluid is transported across the neck before the vortex could be formed, creating a quasi-stationary shear layer (cavity mode). By contrast, if An ≳ 1 (shorter vortex time scale), a vortex is formed. The results show that if An switches from An ≲ 1 to An ≳ 1, then the flow mode switches from the cavity mode to the vortex mode. However, if An does not switch, then the IAs stay in the same mode. It is also shown that IAs in the cavity mode have significantly lower An, temporal fluctuations of wall shear stress and oscillatory shear index (OSI) compared to the vortex mode (p < 0.01). In addition, OSI correlates with An in each flow mode and with pulsatility index in each IA. This suggests An to be a viable hemodynamic parameter which can be easily calculated without the need for detailed flow measurements/ simulations.


[Mechanism of transcriptional regulation by Runx2 in osteoblasts].
Runt-related transcription factor 2 (Runx2) is an essential transcription factor for osteoblast differentiation, and the expression is regulated by many factors including bone morphogenetic protein (BMP). Core binding factorbeta (Cbf beta) is required for DNA binding of Runx2 and Runx2-dependent transcription, and Cbf beta regulates Runx2 function isoform-dependently. Further, ability of Runx2 for transcriptional activation is regulated by many molecules. Phosphoinositide 3-kinase (PI3K)-Akt signaling enhances DNA binding of Runx2 and Runx2-dependent transcription, and Runx2 upregulates PI3K subunits (p85 and p110 beta) and Akt. Therefore, Runx2 and PI3K-Akt signaling are mutually dependent each other in the regulation of osteoblast and chondrocyte differentiation and their migration.


Prevalence and risk factors of diarrheal diseases in Sierra Leone, 2019: a cross-sectional study.
many studies have shown that unimproved water sources, inadequate sanitation facilities and poor hygiene are the main causes of diarrheal diseases, especially in developing countries. The aim of this study was to determine the prevalence and risk factors associated with diarrheal diseases in Sierra Leone. a cross-sectional study was conducted in March 2019. We used a questionnaire to collect data from study participants. Descriptive statistical analysis was followed to determine frequencies and percentages. Univariate analysis was used to find any association between dependent variable and independent variables. Independent variables that had an association in univariate were included in the multivariate model. we surveyed 1,002 households (516 in rural and 486 in urban), and 2,311 respondents in four districts. The main source of income was farming 437 (43.6%). A total of 49 (54.2%) households earned below the national minimum wage per month. Females represented 61.9% of respondents. A total of 242 (32.2%) households had one to five household members and 229 (30.5%) households had more than ten members. Around 88.9% of households in urban, and 42.2% rural areas use improved water sources. The prevalence of diarrheal diseases was 12.3%. Multivariate analysis showed that using of unimproved water sources (aOR=1.9; 95% CI, 1.01 to 3.63, p=0.045), and large family size (aOR= 2.5; 95% CI, 1.18 to 5.35, p=0.017) were associated with diarrheal disease. we concluded that the risk factors associated with diarrheal diseases included unimproved water sources and large family size. More efforts required to improve water resources, adequate sanitation, and hygiene, particularly in rural areas.


Air suctioning during colon biopsy forceps removal reduces bacterial air contamination in the endoscopy suite.
Bacterial contamination of endoscopy suites is of concern; however studies evaluating bacterial aerosols are lacking. We aimed to determine the effectiveness of air suctioning during removal of biopsy forceps in reducing bacterial air contamination. This was a prospective single-blinded trial involving 50 patients who were undergoing elective nontherapeutic colonoscopy. During colonoscopy, endoscopists removed the biopsy forceps first without and then with suctioning following contact with the sigmoid mucosa. A total of 50 L of air was collected continuously for 30 seconds at 30-cm distance from the biopsy channel valve of the colonoscope, with time starting at forceps removal. Airborne bacteria were collected by an impactor air sampler (MAS-100). Standard Petri dishes with CNA blood agar were used to culture Gram-positive bacteria. Main outcome measure was the bacterial load in endoscopy room air. At the beginning and end of the daily colonoscopy program, the median (and interquartile [IQR] range) bioaerosol burden was 4 colony forming units (CFU)/m (3) (IQR 3 - 6) and 16 CFU/m (3) (IQR 13 - 18), respectively. Air suctioning during removal of the biopsy forceps reduced the bioaerosol burden from a median of 14 CFU/m (3) (IQR 11 - 29) to a median of 7 CFU/m (3) (IQR 4 - 16) ( P = 0.0001). Predominantly enterococci were identified on the agar plates. The bacterial aerosol burden during handling of biopsy forceps can be reduced by applying air suction while removing the forceps. This simple method may reduce transmission of infectious agents during gastrointestinal endoscopies.


Patient recall of receiving lifestyle advice for overweight and hypertension from their General Practitioner.
Overweight, obesity and hypertension can be prevented through improvements in lifestyle including nutrition and physical activity. General practitioners (GPs) in Australia have access to over 90% of the population in the course of a year and therefore, the general practice setting may be ideal to assist patients with lifestyle change for weight management and hypertension. The present study aimed to determine the proportion of overweight/obese patients that recalled receiving advice by their GP to make lifestyle changes for weight loss. Recall of advice received by hypertensive patients to reduce salt intake was also measured. A face to face survey was conducted on a representative sample (urban, suburban and rural) of South Australian residents. Respondents provided information on height and weight (self-report), whether they had received lifestyle advice from their GP for weight loss, and for those with self reported hypertension if they had received advice to reduce dietary salt. The sample included 2947 South Australian adult residents (58% female; BMI (mean (SD)), 26.6 (5.3) kg/m2; age, 50.7 (18.0) years). Ninety-six percent had visited their GP in the past 12 months. Forty-one percent of males and 25% of females were overweight and 19% of males and 20% of females were obese. Twenty-seven percent of overweight/obese respondents reported receiving lifestyle advice for weight loss purposes. Of the 33% who reported they had hypertension, 34% reported receiving advice to reduce salt intake. Less than 1/3 of overweight/obese patients reported that they had received lifestyle advice that could assist with weight loss from their GP. About a third of respondents with hypertension reported that they received advice to reduce salt intake. There are potentially missed opportunities in which GPs could provide re-enforcement of benefits of lifestyle changes with respect to weight and blood pressure control.


Formant frequency analysis of children's spoken and sung vowels using sweeping fundamental frequency production.
High-pitched productions present difficulties in formant frequency analysis due to wide harmonic spacing and poorly defined formants. As a consequence, there is little reliable data regarding children's spoken or sung vowel formants. Twenty-nine 11-year-old Swedish children were asked to produce 4 sustained spoken and sung vowels. In order to circumvent the problem of wide harmonic spacing, F1 and F2 measurements were taken from vowels produced with a sweeping F0. Experienced choir singers were selected as subjects in order to minimize the larynx height adjustments associated with pitch variation in less skilled subjects. Results showed significantly higher formant frequencies for speech than for singing. Formants were consistently higher in girls than in boys suggesting longer vocal tracts in these preadolescent boys. Furthermore, formant scaling demonstrated vowel dependent differences between boys and girls suggesting non-uniform differences in male and female vocal tract dimensions. These vowel-dependent sex differences were not consistent with adult data.


ATPase activity of the type IC restriction-modification system EcoR124II.
We have investigated the ATPase activity of the type IC restriction-modification (R-M) system EcoR124II. As with all type I R-M systems EcoR 124II requires ATP hydrolysis to cut DNA. We determined the KM for ATP to be 10(-5) to 10(-4) M. By measuring ATP hydrolysis under different conditions and by simultaneously monitoring DNA restriction, methylation and ATP hydrolysis we propose that the order of events during restriction is: (1) binding of EcoR124II to a non-methylated recognition sequence, (2) start of DNA-dependent ATP hydrolysis which continues even after restriction is complete, (3) restriction of DNA, (4) methylation of the product. Non-cleavable DNA substrates, such as recognition site containing oligonucleotides, also support ATP hydrolysis. Methylation can also occur prior to ATP hydrolysis and prevent DNA degradation.


Efficacy and safety of apatinib monotherapy in metastatic renal cell carcinoma (mRCC) patients: A single-arm observational study.
Antiangiogenic treatments play an important role in the therapeutic strategy for metastatic renal cell carcinoma. Apatinib is an oral tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor-2. We aimed to assess the efficacy and safety of apatinib therapy in metastatic renal cell carcinoma patients. Between January 2018 and November 2018, we enrolled 53 metastatic renal cell carcinoma patients. Apatinib was administered at an initial dose of 500 mg once daily. The disease control rate, objective response rate, progression-free survival, and adverse events were reviewed and evaluated. Among the 53 patients, 14 achieved partial response and 31 achieved stable disease. Thus, the disease control rate was 84.9% and the objective response rate was 26.4%. The median progression-free survival was 11.2 months (95% confidence interval: 9.884-12.574). Most of the adverse events (AEs) were at grade 1 or 2, and the main grade 3 AEs were hypertension (5.7%), anemia (3.8%), and thrombocytopenia (3.8%). Apatinib showed promising efficacy and manageable toxicity in metastatic renal cell carcinoma patients, giving potent evidence to conduct further clinical trials.


Investigation of circadian rhythms in peak power and mean power of female physical education students.
The aim of this investigation was to establish if there were characteristic circadian rhythms in peak power and mean power. Thirteen female physical education undergraduate students, aged from 18-21 years, were measured for peak power and mean power (Wingate Anaerobic Test) at four time points: 0300, 0900, 1500, and 2100 hours. Peak power was defined as the highest mechanical power that is elicited during a 5-sec period and mean power was defined as the average power that is sustained throughout a 30-s period. A significant circadian rhythm was found for the peak power (F = 3.22, p = 0.030). The mean peak power at 1500 h was about 7% higher (p < .05) than at 0300 h. Also a tendency to circadian rhythm was observed in mean power (F = 3.99, p = 0.01) being about 16% and 15% higher respectively (p < 0.05) at 1500 h and 2100 h than at 0300 h. Based upon the particular protocol used, it was concluded that there are characteristic circadian rhythms in peak power and mean power.


Thoracic full-endoscopic unilateral laminotomy with bilateral decompression for treating ossification of the ligamentum flavum with myelopathy.
The aim of the present study was to evaluate the curative effect and safety of thoracic full-endoscopic unilateral laminotomy with bilateral decompression (TE-ULBD) for treating ossification of the ligamentum flavum (OLF) with myelopathy. Between January 2015 and December 2018, 23 consecutive patients with symptomatic thoracic OLF were treated with TE-ULBD. Of these, 21 (13 women and 8 men, aged 49-75 years) were included in the study and followed up for a minimum of 1 year. The mean blood loss was 15.48 mL (10-30 mL), operative duration was 78.86 min (55-115 min), and hospitalization was 5.05 days (3-15 days). The Japanese Orthopaedic Association (JOA) was used to evaluate spinal cord function, and the curative effect was defined by the JOA improvement rate. The area of OLF (AOLF), the maximum spinal cord compression (MSCC), and the area of spinal cord (ASC) were used to evaluate OLF clearance and spinal cord decompression status. At the final follow up,the JOA score was 8.33 points (5-11 points), which was a significant improvement from the preoperative 5.33 points (3-9 points, P<0.01). The excellent and good rate was 76.19% (16/21). The average preoperative AOLF and AOLF ratio were 85.27±23.66 mm2 and 57.86%±11.86%, respectively, and the postoperative AOLF and AOLF ratio were 16.27±11.75 mm2 and 8.13%±5.38%, respectively. The MSCC increased from 27.99%±13.51% preoperatively to 48.02%±6.66% postoperatively. The ASC was 42.90±10.60 mm2 preoperatively and 64.54±21.36 mm2 postoperatively. There were statistically significant differences in all parameters preoperatively and postoperatively (P<0.01). One case had postoperative hematoma, and the symptoms gradually eased after 3 weeks of conservative treatment. There were no other complications. No recurrence of OLF was detected during the follow-up period. TE-ULBD is safe and effective for thoracic OLF with the advantages of reduced trauma and bleeding, and faster recovery.


Molecular Characterization of Distinct Fungal Communities in the Soil of a Rare Earth Mining Area.
The exploitation of ion-absorbed rare earth elements (REEs) has caused serious ecological destruction and environmental pollution. Effects on soil fungal structure and diversity exerted by mining activities are usually ignored, although fungus is one of the most important components in soil ecosystems. In the present research, quantitative polymerase chain reaction (qPCR) and high-throughput Illumina MiSeq sequencing were conducted to characterize fungal community composition and structure in soil of a rare earth mining area after in situ leaching. Statistical analyses, network, and FUNGuild were used to conduct in-depth analyses. Ascomycota, Basidiomycota, and Glomeromycota were the most abundant phyla in the mining soils. Fungal community structures were stable after leaching practice, but nutrition contents (organic matter, TC, and TN) significantly and positively contributed to fungal abundances and diversities. Saprotrophs in phyla Ascomycota and Basidiomycota were the dominant fungal trophic mode, and they played critical roles in nutrient cycling, transformation processes, and reducing REE toxicity. Symbiotrophs of phyla Glomeromycota contributed to soil aggregation and slowing down nutrient losses after in situ leaching practice. In addition, fungi could regulate the interactions between species to resist the harsh environment of REE toxicity or ammonium caused by in situ leaching practice.


Adaptive single replica multiple state transition interface sampling.
The multiple state transition path sampling method allows sampling of rare transitions between many metastable states, but has the drawback that switching between qualitatively different pathways is difficult. Combination with replica exchange transition interface sampling can in principle alleviate this problem, but requires a large number of simultaneous replicas. Here we remove these drawbacks by introducing a single replica sampling algorithm that samples only one interface at a time, while efficiently walking through the entire path space using a Wang-Landau approach or, alternatively, a fixed bias. We illustrate the method on several model systems: a particle diffusing in a simple 2D potential, isomerization in a small Lennard Jones cluster, and isomerization of the alanine dipeptide in explicit water.


A case of brucellar spondylodiscitis involving the cervical spine.
We have presented a patient of 71-year-age with brucellar spondylodiscitis, involving the cervical spine, especially the C3-C4 segment. The patient had painful percussion of the cervical spine and passive mobilization of the neck, decreased range of motion, and cervical paravertebral tenderness; but no abnormalities observed on neurological examination. Wright agglutination test for brucella was positive at 1/320. Cervical localization for brucellar spondylodiscitis is an unusual case and should be detected and treated as early as possible. In endemic regions, spinal involvement of brucellosis should be considered in cases with fever, neck and low back pain.


Angiotensin converting enzyme inhibitors and angiotensin receptor (AT1) antagonists: either or both for primary renal disease?
At the present time we cannot assume that the proven benefits of ACEI on renal disease will be reproduced by using AT1-ra. With potentially differing modes of activity of these drugs, they cannot be seen as interchangeable and ACEI should remain the drug of choice in patients with progressive renal disease unless they are not tolerated. It is possible that AT1-ra may offer additional advantages in some patients or that synergy exists between the two agents, but this view will remain entirely speculative unless proper trials are conducted. Despite the results of the ELITE study [22], the uncertainty regarding the use AT1-ra in cardiovascular disease mirrors that of renal disease. This issue is obviously of relevance to the nephrologist in view of the spectrum of cardiac disease that accompanies chronic renal failure, such as left ventricular hypertrophy and cardiac failure, which provide multiple indications for manipulation of RAS. Despite their renoprotective effect, previous studies on ACEI [3,4] have not shown an overall reduction in mortality and this issue needs to be addressed in addition to renoprotection in studies comparing AT1-ra and ACEI.


Coordinated seasonal regulation of metabolic and reproductive hypothalamic peptides in the desert jerboa.
Jerboa (Jaculus orientalis) is a semi-desert rodent displaying strong seasonal variations in biological functions in order to survive harsh conditions. When environmental conditions become unfavorable in early autumn, it shuts down its reproductive axis, increases its body weight, and finally hibernates. In spring, the jerboa displays opposite regulations, with a reactivation of reproduction and reduction in body weight. This study investigated how genes coding for different hypothalamic peptides involved in the central control of reproduction (Rfrp and Kiss1) and energy homeostasis (Pomc, Npy, and Somatostatin) are regulated according to seasons in male jerboas captured in the wild in spring or autumn. Remarkably, a coordinated increase in the mRNA level of Rfrp in the dorso/ventromedial hypothalamus and Kiss1, Pomc, and Somatostatin in the arcuate nucleus was observed in jerboas captured in spring as compared to autumn animals. Only Npy gene expression in the arcuate nucleus displayed no significant variations between the two seasons. These variations appear in line with the jerboa's seasonal physiology, since the spring increase in Rfrp and Kiss1 expression might be related to sexual reactivation, while the spring increase in genes encoding anorexigenic peptides, POMC, and somatostatin may account for the reduced body weight reported at this time of the year. J. Comp. Neurol. 524:3717-3728, 2016. © 2016 Wiley Periodicals, Inc.


Design guidelines for perovskite/silicon 2-terminal tandem solar cells: an optical study.
Perovskite/silicon 2-terminal tandem cells have made significant advances towards >25% efficiency. Despite this, there is limited understanding of how the optical properties of the materials affect the optical losses within the tandem cell. Using an accurate optical model, we investigate, identify and propose solutions to the optical loss mechanisms inherent in a typical perovskite/silicon 2-terminal tandem cell. The results highlight, firstly, the requirement for low absorption in all layers above the perovskite film, and secondly, the importance of the proper choice of refractive index and thickness of charge transport layers of the perovskite cell, in order to minimize reflection at the interfaces formed by these layers. We demonstrate that the proper choice of these parameters is based on, and can be guided by, basic optics principles which serve as design guidelines. With careful selection of charge transport materials, optimization of the perovskite absorber thickness and the introduction of light trapping within the silicon cell, a matched current of over 20 mA/cm2 can be realized, enabling efficiencies greater than 30% using currently available cell processing methods and materials.


Chiral mixed ligand Co(II) and Ni(II) complexes: synthesis and biological activity.
Chiral mixed ligand (CML) transition metal complexes of the type MQL.2H2O, where M is Co(II)/Ni(II), Q is deprotonated 8-hydroxyquinoline and L is a deprotonated chiral saccharide such as (+)-glucose and (-)-fructose, have been synthesized. The metal complexes have been characterized on the basis of elemental analysis and various physicochemical techniques such as molar conductance, specific rotation measurements, magnetic, spectral and thermal studies. The cup-plate method has been used to study the antibacterial activity of the compounds against some of the pathogenic bacteria such as C. diphtheriae, E. coli, S. typhi, S. dysenteriae, S. aureus and V. cholerae. The antifungal activity of the complexes against some of the pathogenic fungi such as Candida albicans and Aspergillus niger has been studied by the tube dilution method. The results have been compared against those of controls, which were screened simultaneously. The complexes have been screened for acute oral toxicity in albino rats. The method of Litchfield and Wilcoxon has been used to determine the LD50 values.


Repurposing of High-Dose Erythropoietin as a Potential Drug Attenuates Sepsis in Preconditioning Renal Injury.
Due to (i) the uremia-enhanced sepsis severity, (ii) the high prevalence of sepsis with pre-existing renal injury and (iii) the non-erythropoiesis immunomodulation of erythropoietin (EPO), EPO was tested in sepsis with pre-existing renal injury models with the retrospective exploration in patients. Then, EPO was subcutaneously administered in mice with (i) cecal ligation and puncture (CLP) after renal injury including 5/6 nephrectomy (5/6Nx-CLP) and bilateral nephrectomy (BiNx-CLP) or sham surgery (sham-CLP) and (ii) lipopolysaccharide (LPS) injection, along with testing in macrophages. In patients, the data of EPO administration and the disease characteristics in patients with sepsis-induced acute kidney injury (sepsis-AKI) were evaluated. As such, increased endogenous EPO was demonstrated in all sepsis models, including BiNx-CLP despite the reduced liver erythropoietin receptor (EPOR), using Western blot analysis and gene expression, in liver (partly through hepatocyte apoptosis). A high-dose EPO, but not a low-dose, attenuated sepsis in mouse models as determined by mortality and serum inflammatory cytokines. Furthermore, EPO attenuated inflammatory responses in LPS-activated macrophages as determined by supernatant cytokines and the expression of several inflammatory genes (iNOS, IL-1β, STAT3 and NFκB). In parallel, patients with sepsis-AKI who were treated with the high-dose EPO showed favorable outcomes, particularly the 29-day mortality rate. In conclusion, high-dose EPO attenuated sepsis with preconditioning renal injury in mice possibly through the macrophage anti-inflammatory effect, which might be beneficial in some patients.


Osgood-schlatter disease: review of literature and physical therapy management.
Osgood-Schlatter disease is a traction apophysitis of the tibial tubercle, the weakest link of the extensor mechanism of the adolescent. Conventional medical treatment includes plaster casting, injections of various anti-inflammatories, and surgical removal of painful ossicles in resistant cases. While not a very common condition, Osgood-Schlatter disease is being seen with increasing frequency in teenage athletes, especially basketball players (Antich, Lombardo, J Orthop Sports Phys Ther 7: 1-4, 1985.) With a focus on muscular tightness as a possible causative factor, physical therapy evaluation is outlined, followed by techniques for pain control and stretching exercises for the quadriceps and hamstrings. Ice massage is advocated as a way for the athlete to treat postexertional discomfort in the area of the tubercle. The patient and his or her parents must be assured that while residual deformity may remain, disappearance of symptoms coinciding with closure of the apophyseal plate is often the end result.J Orthop Sports Phys Ther 1985;7(1):5-10.


The promising potential of piperlongumine as an emerging therapeutics for cancer.
In spite of the immense advancement in the diagnostic and treatment modalities, cancer continues to be one of the leading causes of mortality across the globe, responsible for the death of around 10 million patients every year. The foremost challenges faced in the treatment of this disease are chemoresistance, adverse effects of the drugs, and the high cost of treatment. Though scientific studies over the past few decades have foreseen and are focusing on the cancer-preventive and therapeutic potential of natural products and their underlying mechanism of action, many more of these agents are not still explored. Piperlongumine (PL), or piplartine, is one such alkaloid isolated from Piper longum Linn., which is shown to be safe and has significant potential in the prevention and therapy of cancer. Numerous shreds of evidence have established the ability of this alkaloid and its analogs and nanoformulations in modulating various complex molecular pathways such as phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin, nuclear factor-kappa B, Janus kinases/signal transducer and activator of transcription 3, etc. and inhibit different hallmarks of cancer such as cell survival, proliferation, invasion, angiogenesis, epithelial-mesenchymal-transition, metastases, etc. In addition, PL was also shown to inhibit radioresistance and chemoresistance and sensitize the cancer cells to the standard chemotherapeutic agents. Therefore, this compound has high potential as a drug candidate for the prevention and treatment of different cancers. The current review briefly reiterates the anti-cancer properties of PL against different types of cancer, which permits further investigation by conducting clinical studies.


An explanation for the disparate effects of synthetic peptides corresponding to human follicle-stimulating hormone beta-subunit receptor binding regions (33-53) and (81-95) and their serine analogs on steroidogenesis in cultured rat Sertoli cells.
We have recently reported that synthetic peptide amides corresponding to regions of human FSH beta-subunit, hFSH-beta-(33-53) and hFSH-beta-(81-95), bind to receptor and stimulate estradiol biosynthesis by cultured rat Sertoli cells. Because of experimental difficulties caused by the presence of free sulfhydryl groups in these peptides, synthetic analogs were prepared in which all Cys residues were replaced with Ser. These analogs, [Ser-51]-hFSH-beta-(33-53) and [Ser-82, 84, 87, 94]-hFSH-beta- (81-95), also bound to receptor but did not stimulate estradiol biosynthesis by cultured rat Sertoli cells. In order to explain this observation, we compared the effects of hFSH-beta-(33-53) and hFSH-beta-(81-95) and their Ser analogs on another recently recognized effect of FSH in Sertoli cells, namely its ability to promote influx of extracellular calcium. We and others have shown that estradiol biosynthesis by these cells is markedly decreased in the presence of high intracellular calcium. Cys-containing hFSH-beta-(33-53) and hFSH-beta-(81-95) did not increase influx of extracellular calcium over basal levels, whereas [Ser-51]-hFSH-beta-(33-53) and [Ser-82, 84, 87, 94]-hFSH-beta-(81-95) induced 2.8- and 1.8-fold increases, respectively. Cellular cAMP and estradiol biosynthesis in response to each Ser-substituted peptide were not significantly different from basal levels. Thus, the explanation for the observed disparate effects of Cys and Ser analog peptides on estradiol biosynthesis may be related to the ability of the Ser peptides to stimulate calcium entry but not cAMP accumulation in cultured rat Sertoli cells.