The pathway for serial proton supply to the active site of nitrogenase: enhanced density functional modeling of the Grotthuss mechanism.
Nitrogenase contains a well defined and conserved chain of water molecules leading to the FeMo cofactor (FeMo-co, an [Fe7MoCS9] cluster with bidentate chelation of Mo by homocitrate) that is the active site where N2 and other substrates are sequentially hydrogenated using multiple protons and electrons. The function of this chain is proposed to be a proton wire, serially translocating protons to triply-bridging S3B of FeMo-co, where, concomitant with electron transfer to FeMo-co, an H atom is generated on S3B. Density functional simulations of this proton translocation mechanism are reported here, using a large 269-atom model that includes all residues hydrogen bonded to and surrounding the water chain, and likely to influence proton transfer: three carboxylate O atoms of obligatory homocitrate are essential. The mechanism involves the standard two components of the Grotthuss mechanism, namely H atom slides that shift H3O(+) from one water site to the next, and HOH molecular rotations that convert backward (posterior) OH bonds in the water chain to forward (anterior) OH bonds. The topography of the potential energy surface for each of these steps has been mapped. H atom slides pass through very short (ca. 2.5 Å) O-H-O hydrogen bonds, while HOH rotations involve the breaking of O-HO hydrogen bonds, and the occurrence of long (up to 3.6 Å) separations between contiguous water molecules. Both steps involve low potential energy barriers, <7 kcal mol(-1). During operation of the Grotthuss mechanism in nitrogenase there are substantial displacements of water molecules along the chain, occurring as ripples. These characteristics of the 'Grotthuss two-step', coupled with a buffering ability of two carboxylate O atoms of homocitrate, and combined with density functional characterisation of the final proton slide from the ultimate water molecule to S3B (including electron addition), have been choreographed into a complete mechanism for serial hydrogenation of FeMo-co. The largest potential barrier is estimated to be 14 kcal mol(-1). These results are discussed in the context of reactivity data for nitrogenase, and the occurrence of a comparable water chain in cytochrome-c oxidase. Further investigation of the low-frequency conformational dynamics of the nitrogenase proteins, coupling proton transfer with other events in the nitrogenase cycle, is briefly canvassed.


Vitamin D receptor gene silencing effects on differentiation of myogenic cell lines.
The active form of vitamin D (1,25-dihydroxy-vitamin D3) is known to increase fast-type myosin heavy chain expression in differentiated myogenic cell lines. The mechanisms for this effect are not fully understood. The aim of this study was to determine the role of signals transmitted through the vitamin D receptor (VDR) during differentiation of myoblasts. Electroporation was used to introduce VDR siRNA molecules into C2C12 and G8 murine myoblast cell lines. Gene and protein expression profiles of VDR-gene silenced cells were analyzed in vitro. Suppressing VDR expression by RNA interference resulted in inhibition of myogenic differentiation of C2C12 and G8 cell lines at both mRNA and protein levels. Our results suggest that myoblasts require signals transmitted through VDR for differentiation into myocytes and emphasize the importance of VDR expression in skeletal muscles for maintaining muscle volume in the elderly.


The use of Section 136 (Mental Health Act 1983) in Gloucestershire.
The small number of published studies on the use of Section 136 (S136) of the Mental Health Act 1983 may reflect neither the current situation nor the true national picture as most of the research comes from large urban centres and was published before 1997. We studied the use of S136 between 2002 and 2006 in Gloucestershire, a rural English county with a population of approximately 585,000, by analysing data held by the police and local mental health services. On average 192 subjects (range 176-203) were detained each year under S136, equating to a population rate of 32.8 S136 detentions per 100,000 per year in Gloucestershire. In contrast to other published studies, ethnic minorities, particularly Afro-Caribbean males, were overrepresented only in a minor way. Of those individuals detained, about a third were admitted, a lower rate than in other studies. Acts or threats of self-harm were common (55%), but acts or threats of violence (28%) and evidence of intoxication (16%) were present in a minority, suggesting that detainees are more likely to pose a risk to themselves than others.


Proteoglycans in Leiomyoma and Normal Myometrium: Abundance, Steroid Hormone Control, and Implications for Pathophysiology.
Uterine leiomyoma are a common benign pelvic tumors composed of modified smooth muscle cells and a large amount of extracellular matrix (ECM). The proteoglycan composition of the leiomyoma ECM is thought to affect pathophysiology of the disease. To test this hypothesis, we examined the abundance (by immunoblotting) and expression (by quantitative real-time polymerase chain reaction) of the proteoglycans biglycan, decorin, and versican in leiomyoma and normal myometrium and determined whether expression is affected by steroid hormones and menstrual phase. Leiomyoma and normal myometrium were collected from women (n = 17) undergoing hysterectomy or myomectomy. In vitro studies were performed on immortalized leiomyoma (UtLM) and normal myometrial (hTERT-HM) cells with and without exposure to estradiol and progesterone. In leiomyoma tissue, abundance of decorin messenger RNA (mRNA) and protein were 2.6-fold and 1.4-fold lower, respectively, compared with normal myometrium. Abundance of versican mRNA was not different between matched samples, whereas versican protein was increased 1.8-fold in leiomyoma compared with myometrium. Decorin mRNA was 2.4-fold lower in secretory phase leiomyoma compared with proliferative phase tissue. In UtLM cells, progesterone decreased the abundance of decorin mRNA by 1.3-fold. Lower decorin expression in leiomyoma compared with myometrium may contribute to disease growth and progression. As decorin inhibits the activity of specific growth factors, its reduced level in the leiomyoma cell microenvironment may promote cell proliferation and ECM deposition. Our data suggest that decorin expression in leiomyoma is inhibited by progesterone, which may be a mechanism by which the ovarian steroids affect leiomyoma growth and disease progression.


Create Fat Substitute From Soybean Protein Isolate/Konjac Glucomannan: The Impact of the Protein and Polysaccharide Concentrations Formulations.
In this study, soybean protein isolate (SPI) and coconut oil were emulsified and konjac flour was added to prepare the protein/polysaccharide composite emulsion gel. The SPI/polysaccharide compound fat substitute was obtained by vacuuming. The effects of protein and konjac flour addition on the gel system of the mixed emulsion were explored. Sensory evaluation experiments showed that the overall acceptability of fat substitutes added with 1% SPI was higher. With the increase of protein and konjac content, the juiciness of the samples decreased gradually. The increase of konjac content reduced the brightness of compound fat substitutes, and the yellowness of compound fat substitute increases significantly with the increase of protein content. The rheological results showed that the G' and loss modulus (G″) increased with the increase of protein and konjac content, forming a rigid elastic gel matrix, which provided a basis for the preparation of fat substitutes. Texture profile analysis (TPA) results showed that the springiness of all samples was similar to the natural fat after 20 min of heating. With the increase of protein and konjac content, the hardness of the samples increased gradually. The results of oral tribology showed that the friction coefficients of all samples were very small. The friction behavior of the samples with SPI content of 1% was similar to that of natural fat, which could better simulate the swallowing feeling and lubricity of natural fat. To sum up, the appearance of solid fat substitutes prepared with SPI and konjac flour is similar to pork fat. They show ideal functional characteristics in mechanical properties and oral tribology. Among them, the fat substitute with the protein content of 1% and konjac content of 4% is the most popular among consumers.


Accurate calibration of a molecular beam time-of-flight mass spectrometer for on-line analysis of high molecular weight species.
Time-of-Flight (TOF) Mass Spectrometry is a powerful analytical technique, provided that an accurate calibration by standard molecules in the same m/z range of the analytes is performed. Calibration in a very large m/z range is a difficult task, particularly in studies focusing on the detection of high molecular weight clusters of different molecules or high molecular weight species. External calibration is the most common procedure used for TOF mass spectrometric analysis in the gas phase and, generally, the only available standards are made up of mixtures of noble gases, covering a small mass range for calibration, up to m/z 136 (higher mass isotope of xenon). In this work, an accurate calibration of a Molecular Beam Time-of Flight Mass Spectrometer (MB-TOFMS) is presented, based on the use of water clusters up to m/z 3000. The advantages of calibrating a MB-TOFMS with water clusters for the detection of analytes with masses above those of the traditional calibrants such as noble gases were quantitatively shown by statistical calculations. A comparison of the water cluster and noble gases calibration procedures in attributing the masses to a test mixture extending up to m/z 800 is also reported. In the case of the analysis of combustion products, another important feature of water cluster calibration was shown, that is the possibility of using them as "internal standard" directly formed from the combustion water, under suitable experimental conditions. The water clusters calibration of a MB-TOFMS gives rise to a ten-fold reduction in error compared to the traditional calibration with noble gases. The consequent improvement in mass accuracy in the calibration of a MB-TOFMS has important implications in various fields where detection of high molecular mass species is required. In combustion products analysis, it is also possible to obtain a new calibration spectrum before the acquisition of each spectrum, only modifying some operative conditions. Copyright © 2016 John Wiley & Sons, Ltd.


Short-term psychotherapeutic interventions for somatizing patients in the general hospital: a randomized controlled study.
Treatment acceptance and motivation for psychotherapy of somatizing patients in the general hospital is low. Patients (n = 91) fulfilling the criteria for somatization were randomized into an intervention group (n = 49) and a control group (n = 42). The patients in the intervention group attended 5 psychotherapeutic sessions based on the modified reattribution model. The patients in the control group received psychoeducational reading material. The primary outcomes were motivation for psychotherapy and contacting a psychotherapist after discharge. The secondary outcomes consisted of changes regarding somatoform symptoms, emotional distress and quality of life. Patients from the intervention group were significantly more motivated for psychotherapy (p = 0.001) than patients from the control group. At the 3-month follow-up, 42% of the patients from the intervention group had contacted a psychotherapist, compared to 20% of the patients from the control group (p = 0.045). At the 6-month follow-up, however, the ratio of patients having contacted a psychotherapist had changed to 44 and 29%, respectively, and was no longer significant. The intensity of somatoform symptoms and the anxiety symptoms decreased and mental functioning improved significantly over time for patients from both groups. Short-term psychotherapeutic interventions for somatizing patients in general hospitals have a moderately better effect on motivation for psychotherapy and contacting a psychotherapist than psychoeducational reading material alone. Future studies should attempt to prove the effectiveness of short-term psychoeducational interventions for somatizing patients in the general hospital.


Predictors of diagnostic delay in amyotrophic lateral sclerosis: a cohort study based on administrative and electronic medical records data.
Objectives: To characterize the timing and pathway of amyotrophic lateral sclerosis (ALS) diagnosis and to identify predictors of delayed diagnosis in a retrospective cohort. Methods: The cohort included all patients with incident ALS between 2010 and 2014 in Friuli-Venezia Giulia (FVG) region, Italy, admitted to two University Hospitals. Information on demographics, clinical presentation, and healthcare use was obtained from health databases and electronic medical records (EMRs). Total diagnostic time (TDT), the interval between ALS symptoms onset and diagnosis, was compared between patient groups through Wilcoxon-Mann-Whitney test. The adjusted odds ratio (aOR), with 95% confidence interval (95% CI), of having a TDT ≥12 months was estimated using unconditional logistic regression. Results: Among 134 patients, median TDT (interquartile range [IQR]) was 11.5 months (7.1-18.3), shorter in those aged <60 years vs. ≥60 years (8.1; 5.1-11.1 vs. 12.4; 7.4-21.5; p = 0.0064), first referred to a neurologist vs. other specialist (10.2; 6.1-16.3 vs. 13.2; 8.1-24.5; p = 0.0386) and without neurologic comorbidities (11.1; 7.1-16.5 vs. 19.7; 8.8-33.7; p = 0.0243). TDT was ≥12 months in 64 (48.5%) patients and was predicted by male sex (aOR: 2.47; 95% CI: 1.06-5.75), age at onset ≥60 years (11.46; 3.13-41.9), spinal onset (2.04; 1.00-5.93), and prior therapies or first referral to a non-neurologist (3.15; 1.36-7.29). Conclusions: In this cohort, delayed diagnosis was common, particularly in older patients and in those with neurological comorbidities. Timely referral to a neurologist may improve diagnostic timing.


Impact of Subsequent Biopsies on Comprehensive Health Related Quality of Life in Patients with and without Prostate Cancer.
The aim of this study was to identify the effects of subsequent prostate needle biopsies after the baseline biopsy on health related quality of life with time. We compared men with and without prostate cancer, and men who did and did not undergo followup prostate needle biopsy. Included in analysis were patients enrolled in the Center for Prostate Disease Research Multicenter National Database between 2007 and 2015 who had low or favorable intermediate risk prostate cancer, were on active surveillance and underwent prostate needle biopsy for suspicion of prostate cancer. Patients completed the EPIC (Expanded Prostate Cancer Index Composite) and the RAND SF-36 (36-Item Short Form Health Survey) after baseline biopsy and at regular followup intervals. Mean health related quality of life was compared with time between patients who did and did not undergo subsequent prostate needle biopsies following baseline. Of the 637 patients included in study 129 (20.3%) with prostate cancer were on active surveillance and 508 (79.7%) were in the noncancer group. In the cancer and noncancer groups mean ± SD followup was 34.7 ± 16.9 and 31.6 ± 14.6 months, respectively. Of the patients with prostate cancer 54 (60.7%) underwent subsequent prostate needle biopsies compared with 114 (27.1%) without cancer. No significant impact on health related quality of life was observed in men who underwent subsequent prostate needle biopsies during a 5-year period. A subsequent prostate needle biopsy is required in most active surveillance protocols and in men with persistent suspicion of prostate cancer. Our analysis shows that subsequent prostate needle biopsies do not significantly impact health related quality of life.


E-cigarette Solvent Ratio and Device Power Influence Ambient Air Particulate Matter.
Electronic cigarette (ECIG)-generated aerosol contains particulate matter with a diameter less than 2.5 microns (PM2.5). Particles of this size may be injurious to the health of those who inhale them. Few studies have assessed the relationship between ECIG aerosol PM2.5 and ECIG liquid ingredients or ECIG device power. Two studies were conducted in which participants generated aerosols with ECIGs: in one, ECIG liquids contained various vegetable glycerin/propylene glycol ratios and in the other, ECIG devices varied by electrical power output. Results indicate that, in general, PM2.5 increases as the ratio of vegetable glycerin to propylene glycol increases, or as device power increases. Regulating ECIG PM2.5 emissions to protect non-users requires an understanding of all the factors that influence these emissions.


In situ detection of sequence-specific DNA binding activity specified by a recombinant bacteriophage.
We have used a recombinant bacteriophage that expresses the DNA-binding domain of C/EBP to optimize conditions for a screening technique that may facilitate the cloning of genes that encode sequence-specific DNA-binding proteins. The method relies on the expression of cDNA inserts in bacteriophage lambda gt11. Fusion protein adsorbed onto nitrocellulose filters is probed with radioactive, double-stranded DNA as a ligand. Two procedures greatly increase the level of binding between ligand and recombinant fusion protein. First, nitrocellulose filters are processed through a denaturation/renaturation regimen using 6 M guanidine hydrochloride. Second, synthetic DNA corresponding to the specific binding site is catenated extensively using DNA ligase. The combination of these procedures leads to remarkably strong detection signals. Specific DNA-binding signals can be detected on duplicate filters, and filters can be washed and reused by repeating the cycle of denaturation/renaturation.


Neuroglian stabilizes epithelial structure during Drosophila oogenesis.
The vertebrate L1 family of cell adhesion molecules (CAMs) and their fly homolog, Neuroglian, are members of the immunoglobulin (Ig) superfamily of CAMs. In general, Ig CAMs have been found to play critical roles in mediating axon guidance. One Ig CAM, NCAM, has also been implicated in maintaining epithelial integrity and suppressing metastatic dissemination of tumor cells. Other Ig CAMs, such as Nrg, are also expressed in epithelia. We thus tested the hypothesis that, like NCAM, Nrg might also be required for maintaining epithelial integrity and for inhibiting tumor invasion. We used the Drosophila follicular epithelium to determine the function of Nrg in vivo in maintaining epithelial structure, and in regulating the motility of migrating border cells and invasive tumorous follicle cells. Nrg(167) is expressed on the lateral membrane of follicle cells. Loss of Nrg(167) causes border cells to delay delamination and causes other follicle cells to delaminate inappropriately. The delaminated cells have aberrant epithelial polarity manifested as severe mislocalization of apical and basal membrane proteins, and uniform localization of lateral membrane proteins. Furthermore, loss of Nrg(167) dramatically enhances the invasive phenotype associated with loss of Discs Large, a neoplastic tumor suppressor. These results indicate that Nrg(167) stabilizes epithelial polarity by regulating junctional adhesion and function in normal and tumorous epithelia. Our data also suggest that Ig superfamily members have significant functional redundancy in maintaining epithelial polarity, with individual members playing subtle, unique roles during epithelial morphogenesis.


Biofilm research using calorimetry--a marriage made in heaven?
Aggregated bacteria growing on a surface, so-called biofilms, play an important role in technical processes like wastewater treatment, bioremediation, or bioprocessing. In contrast, problems arise when biofilm growth results in undesired processes that may cause huge financial losses, e.g., clogged pipes, microbially influenced corrosion or pathogenic contamination. For observation purposes and to develop efficient control strategies, real-time monitoring tools for biofilms are required. Among the large variety of tools used in biofilm research, calorimetry is rarely applied, even though many characteristics qualify it for biofilm investigation and monitoring. Calorimetric measurements are non-invasive and non-destructive, and can be applied to nearly any kind of samples (including heterogeneous or turbid solutions) without the need of special sample preparation. Online and real-time data acquisition reduces the labor and facilitates high-throughput measurements. The following article is meant to introduce and promote calorimetry as a future tool in biofilm research. It attempts an assessment of common, existent monitoring tools and specifically addresses the potential of calorimetry in this field.


Genetic characterization of suspected MODY patients in Tunisia by targeted next-generation sequencing.
Maturity Onset Diabetes of the Young (MODY) is a monogenic form of diabetes with autosomal dominant inheritance pattern. The diagnosis of MODY and its subtypes is based on genetic testing. Our aim was investigating MODY by means of next-generation sequencing in the Tunisian population. We performed a targeted sequencing of 27 genes known to cause monogenic diabetes in 11 phenotypically suspected Tunisian patients. We retained genetic variants passing filters of frequency in public databases as well as their probable effects on protein structures and functions evaluated by bioinformatics prediction tools. Five heterozygous variants were found in four patients. They include two mutations in HNF1A and GCK that are the causative genes of the two most prevalent MODY subtypes described in the literature. Other possible mutations, including novel frameshift and splice-site variants were identified in ABCC8 gene. Our study is the first to investigate the clinical application of targeted next-generation sequencing for the diagnosis of MODY in Africa. The combination of this approach with a filtering/prioritization strategy made a step towards the identification of MODY mutations in the Tunisian population.


The importance of microscopic examination in the management of desquamative diseases of the scalp.
After determining the usual malassezic biota of the scalp in adult, normal persons, 259 patients with different desquamative diseases were studied by a simple adhesive tape technique. The main purpose of this study was to investigate the utility of this technique to improve the diagnosis and treatment of patients. Most patients with seborrhoeic dermatitis and sebopsoriasis demonstrated large numbers of Malassezia spp. cells corresponding to the so called "pityrosporosis". Only 43.6% of patients with pityriasis capitis (dandruff) presented with such a diagnosis. Symptomatic pityrosporosis of the scalp should be treated with imidazolic derivatives or other antifungal substances. Patients with psoriasis of the scalp showed a typical microscopic picture represented by parakeratosic (nucleated) keratinocytes with absence of lipophilic yeasts which should be attributed to the usual dryness of the scales Microbial epidermitis (eczema) of the scalp revealed another characteristic picture constituted by abundant leukocytes and bacteria without the presence of yeasts. The different microscopic pictures seen with this simple technique for diseases of the scalp, offer an adjunct to make a proper diagnosis and to establish a convenient treatment in cases which are not clinically well defined.


Effects of lithium carbonate on human calcium metabolism.
Serum calcium and immunoreactive parathyroid hormone levels increase within the normal range in 80% of patients during the first four weeks of lithium carbonate administration and may rise above normal in 10% after long-term therapy. Since the lithium ion in vitro makes the parathyroid cell less sensitive to calcium, and since several lithium carbonate-treated patients with parathyroid adenomas have been described, it has been suggested that the lithium ion can stimulate parathyroid growth. The data are inconclusive, however, since the adenomas could be sporadic and there has been no direct proof of increased parathyroid mass or biologic activity. Based on the available studies, we have formulated a reasonable scheme for monitoring calcium metabolism during lithium carbonate treatment. Proper treatment of hypercalcemic lithium carbonate-treated patients remains uncertain, but we have outlined some tentative management guidelines.


Differences in Outcomes in Prenatally Diagnosed Congenital Diaphragmatic Hernia Compared to Postnatal Detection: A Single-Center Experience.
To compare outcomes in pregnancies with a prenatal detection of congenital diaphragmatic hernia (CDH) with children diagnosed after birth, treated at the same institution, and to determine the ability to predict prognosis through measurements of the observed to expected lung-to-head ratio (O/E LHR). This is a retrospective review of all children with CDH treated at our institution during 2006-2014. We compared outcomes of infants referred for surgery after postnatal diagnosis with outcomes of infants with prenatally diagnosed CDH. In the prenatal group, O/E LHR was significantly different between survivors and deceased patients, with a cutoff at 35% O/E LHR. Survival to discharge and 1-year survival were significantly higher in the postnatal group that required intubation within 24 h; i.e., 92 and 89% versus 85 and 73% in the prenatal group (p < 0.05). There was less need for extracorporeal membrane oxygenation (ECMO), 41 versus 60%, and patch, 41 versus 75% (p < 0.001), in the postnatal group with early diagnosis compared with the prenatal group, respectively. Children with prenatally diagnosed CDH represent a population with a more severe condition compared to infants diagnosed after birth. They have poorer outcomes with higher needs for ECMO or use of patch, and lower survival rates were observed at an O/E LHR below 35%.


[INITIAL EXPERIENCE OF TRANSVAGINAL EXTRACTION OF THE KIDNEY FOLLOWING LAPAROSCOPIC NEPHRECTOMY IN OUR DEPARTMENT].
We report the detailed technique and results of transvaginal extraction of the kidney following laparoscopic nephrectomy. From August 2013 onward, we planned to perform transvaginal extraction of the kidney following laparoscopic nephrectomy in a total of 6 female patients. Of the 6 patients, 5 underwent the procedure. After completion of the primary laparoscopic nephrectomy and entrapping the removed kidney, the patients were placed in the supine lithotomy position. A transverse posterior colpotomy was created transvaginally at the apex of the posterior fornix. An opening was made in the peritoneum bluntly with the fingers under laparoscopic view. After the drawstring of the entrapped specimen was delivered into the vagina, the specimen was extracted intact via the vagina. When the vaginal wall was too tight for a large specimen, the incision was extended on the affected side. After removal of the specimen, the peritoneum was sutured laparoscopically, and the posterior colpotomy incision was repaired transvaginally. Transvaginal extraction was successful in 5 patients. The mean operative time for the vaginal extraction procedure was 59 minutes. Blood loss was minimal. The mean specimen weight was 447 g (range 271 to 655 g). No intraoperative complications occurred. Postoperatively, one case needed intermittent catheterization for a few days because of temporal dysfunction of the bladder. Transvaginal extraction is an efficacious and minimally morbid technique for removing the intact kidney after laparoscopic nephrectomy.


Detection of morphine-3-sulfate and morphine-6-sulfate in human urine and plasma, and formation in liver cytosol.
Morphine is still the mainstay in treatment of severe pain and is metabolized in the liver mainly by glucuronidation, partly to the pharmacologically active morphine-6-glucuronide (M6G). The sulfation pathway has attracted much less attention but may also form active metabolites. The aim of the present study was to study two sulfate metabolites of morphine in humans. Urine and plasma from newborns, adult heroin addicts, and terminal cancer patients was analyzed for the presence of morphine-3-sulfate (M3S) and morphine-6-sulfate (M6S) by a new liquid chromatography - tandem mass spectrometry (LC-MS/MS) method. In addition, morphine sulfation was studied in vitro in human liver cytosol preparations. M3S was present in urine and plasma from all study groups although at lower concentrations than morphine-3-glucuronide (M3G). The plasma M3S/M3G ratio was 30 times higher in newborns than in adults indicating that the relative sulfation is more important at early stage of life. M6S was measurable in only one plasma sample from a newborn patient, and in one of the urine sample from the drug testing group. The incubation of morphine with liver cytosol extracts resulted in approximately equal rate of formation of both M3S and M6S. In conclusion, sulfation of morphine is catalyzed in human liver but this minor metabolic pathway probably lacks clinical significance. The M6S metabolite is formed at a low rate, making it undetectable in most individuals.


Isolation and heterologous expression of a gene encoding 4-hydroxyphenylpyruvate dioxygenase from the wheat leaf-spot pathogen, Mycosphaerella graminicola.
We describe the isolation and sequence of a gene encoding 4-hydroxyphenylpyruvate dioxygenase (HPPD) (EC 18.104.22.168)) from the wheat leaf-spot fungal pathogen Mycosphaerella graminicola (Septoria tritici), that directs the synthesis of 2,5-dihydroxyphenylacetate (homogentisic acid, HGA). The sequence of the deduced peptide showed homology to HPPDs from other organisms; the greatest identity was to a T-cell reactive protein, also identified as HPPD, from the human fungal pathogen Coccidioides immitis. As observed for HPPD from other sources, expression of the M. graminicola HPPD gene in Escherichia coli cells could be detected by the gradual development of a brown pigment in cultures as a result of the spontaneous oxidation and polymerisation of HGA. Pigment development in these cultures was prevented by the HPPD inhibitor sulcotrione.


Amino Acid Catabolism in Alzheimer's Disease Brain: Friend or Foe?
There is a dire need to discover new targets for Alzheimer's disease (AD) drug development. Decreased neuronal glucose metabolism that occurs in AD brain could play a central role in disease progression. Little is known about the compensatory neuronal changes that occur to attempt to maintain energy homeostasis. In this review using the PubMed literature database, we summarize evidence that amino acid oxidation can temporarily compensate for the decreased glucose metabolism, but eventually altered amino acid and amino acid catabolite levels likely lead to toxicities contributing to AD progression. Because amino acids are involved in so many cellular metabolic and signaling pathways, the effects of altered amino acid metabolism in AD brain are far-reaching. Possible pathological results from changes in the levels of several important amino acids are discussed. Urea cycle function may be induced in endothelial cells of AD patient brains, possibly to remove excess ammonia produced from increased amino acid catabolism. Studying AD from a metabolic perspective provides new insights into AD pathogenesis and may lead to the discovery of dietary metabolite supplements that can partially compensate for alterations of enzymatic function to delay AD or alleviate some of the suffering caused by the disease.


Relation of JAGGED 1 and collagen type 1 alpha 1 polymorphisms with bone mineral density in Chinese postmenopausal women.
Osteoporosis is a complex disease characterized by low bone mineral density (BMD), which is determined by an interaction of genetics and environmental factors. Collagen type alpha 1 (COL1A) and JAGGED (JAG1) genes have been implicated in relation to BMD. The aim of this study was to investigate possible association among BMD and rs2273061 of JAG1, rs1107946 and rs1800012 of Col1A1 polymorphisms, as well as their haplotypes with BMD in postmenopausal Chinese women. A structured questionnaire for risk factors was recorded and BMD in lumbar spine and total hip was measured by dual-energy X-ray absorptiomety. Genomic DNA was obtained from 367 postmenopausal Chinese women. Genomic DNA was extracted from EDTA-preserved peripheral venous blood by phenol-chloroform extraction method and analyzed by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). As a result, the rs1800012 polymorphism of COL1A1 showed an association with BMD of the lumbar spine under a dominant model. Besides, haplotype analysis of COL1A1 gene showed that G-G haplotype presented higher BMD in lumbar spine. No significant association between genotypes and alleles distributions of the rs1107946 polymorphism of COL1A1 and rs2273061 polymorphism of the JAG1 was found. In conclusion, our results suggest that the rs1800012 polymorphism of the COL1A1 and one haplotype were significantly associated with lumbar spine BMD variations in Chinese postmenopausal women.


Resistance of Aspergillus fumigatus to Micafungin is Increased by Exogenous β-glucan.
Aspergillus species are ubiquitous in the environment and Aspergillus fumigatus can cause life-threatening infections in immunocompromised patients. β-1,3-/1,6-glucan is a major fungal cell wall polysaccharide that has various biological effects on the infected host, but little is known about the influence of β-glucan on the fungus itself. In a previous study, we demonstrated that the cell wall β-glucan content could be increased in Aspergillus spp. by addition of β-glucan to the culture medium. In this study, we investigated the influence of β-glucan on the susceptibility of A. fumigatus to antifungal agents. A. fumigatus was cultured in the presence or absence of β-glucan for antifungal susceptibility testing based on changes of the growth rate and morphology. Susceptibility to micafungin, a β-glucan synthase inhibitor, was about 10-fold lower when β-glucan was added to the culture medium. On the other hand, susceptibility to amphotericin B and voriconazole was similar in either the presence or absence of β-glucan. These results strongly suggest that β-glucan has an important physiological role in Aspergillus spp.


Tailoring anti-TNF therapy in IBD: drug levels and disease activity.
The treatment of IBD with anti-TNF agents has substantially evolved since their first introduction more than a decade ago. The robust efficacy witnessed in many patients has raised new questions pertaining to the observation of subgroups of patients who fail to respond or who lose response to these otherwise very effective drugs. Conversely, the exorbitant cost of biologic agents coupled with their efficacy in inducing lasting remission has introduced new concepts addressing the possibility of therapy cessation in some patients after deep remission has been achieved. Measuring drug and anti-drug antibody (ADA) levels which develop in some patients has emerged as a valuable tool in understanding the mechanisms responsible for some of these clinical scenarios. However, knowledge on how to use these measurements to guide clinical decisions in daily practice is still in its nascency and awaits prospective validation trials. Furthermore, as described in this Review, knowledgeable interpretation of drug and ADA test results mandates understanding the interplay between the technical profile of the assay used, the timing of the measurement in the drug cycle, assessment of disease activity, and the profoundly different pharmaco-clinical scenarios that can culminate in a similar test result.


Improved glycemic control with insulin glargine versus pioglitazone as add-on therapy to sulfonylurea or metformin in patients with uncontrolled type 2 diabetes mellitus.
To compare glycemic control with add-on insulin glargine versus pioglitazone treatment in patients with type 2 diabetes. This 48-week, multicenter, parallel-group, open-label study randomized 389 adults with poorly controlled type 2 diabetes (glycated hemoglobin A1c [A1C], 8.0% to 12.0%), despite > or =3 months of sulfonylurea or metformin monotherapy, to receive add-on therapy with insulin glargine or pioglitazone. Outcomes included A1C change from baseline to end point (primary), percentage of patients achieving A1C levels < or =7.0%, and changes from baseline in fasting plasma glucose, body mass index, weight, and serum lipids. The safety analysis included incidence of adverse events and rates of hypoglycemia. At end point, insulin glargine yielded a significantly greater reduction in A1C in comparison with pioglitazone (-2.48% versus -1.86%, respectively; 95% confidence interval, -0.93 to -0.31; P = .0001, 48-week modified intent-to-treat population). Insulin glargine also yielded significantly greater reductions in fasting plasma glucose at all time points (end point difference, -34.9 mg/dL; 95% confidence interval, -47.6 to -22.2; P<.0001). In comparison with pioglitazone, insulin glargine resulted in a lower overall incidence of possibly related treatment-emergent adverse events (12.0% versus 20.7%) and fewer study discontinuations (2.2% versus 9.1%), but a higher rate (per patient-year) of confirmed clinically relevant hypoglycemic episodes (blood glucose <70 mg/dL and all severe hypoglycemia) (4.97 versus 1.04; P<.0001) and severe hypoglycemia (0.07 versus 0.01; P = .0309). Weight and body mass index changes were similar between the 2 treatment groups. The addition of insulin glargine early in the diabetes treatment paradigm in patients for whom sulfonylurea or metformin monotherapy had failed resulted in significantly greater improvements in glycemic control in comparison with the addition of pioglitazone. Although severe hypoglycemia was more frequent in patients with insulin glargine therapy, hypoglycemic events occurred in <5% of patients in the insulin glargine treatment group.


Determinants of spacing contraceptive use among couples in Mumbai: a male perspective.
This study aimed to determine the factors influencing the use of spacing contraceptive methods in India, particularly from men's perspective. Data were obtained through a semi-structured interview schedule from 2,687 married men aged between 18 and 40 years from central Mumbai City, India, during 1999. Chi-squared tests and binary logistic regression analysis was carried out to determine the relationship between various variables and the likelihood of a couple using spacing contraceptive methods. Of the 2,687 couples, 1,395 (51.9%) were using one or other method of spacing contraceptives and 1,292 (48.1%) were not using any method at the time of survey. Male participation in contraceptive use was 23% (condom and withdrawal). The results indicate that the use of spacing contraceptive methods was significantly higher among those couples where the men desired one or two children (OR=4.3), had knowledge of five or more contraceptive methods (OR=1.9) and discussed with their wives obtaining family planning information (OR=3.2), spacing (OR=2.7) and permanent (OR=2) contraceptive methods. Age, income, desired number of children, knowledge of a greater number of contraceptive methods, inter-spouse communication regarding obtaining family planning information, spacing and permanent methods were found to be strong predictors of the use of spacing contraceptive methods. The study underlines the importance of intervention programmes aimed at promoting a small family norm, increasing the number of contraceptive choices available and encouraging inter-spouse communication. Hence, policymakers and programme managers should encourage interventions in this direction, targeting couples to enhance the use of spacing contraceptive methods.


Human p32, interacts with B subunit of the CCAAT-binding factor, CBF/NF-Y, and inhibits CBF-mediated transcription activation in vitro.
To understand the role of the CCAAT-binding factor, CBF, in transcription, we developed a strategy to purify the heterotrimeric CBF complex from HeLa cell extracts using two successive immunoaffinity chromatography steps. Here we show that the p32 protein, previously identified as the ASF/SF2 splicing factor-associated protein, copurified with the CBF complex. Studies of protein-protein interaction demonstrated that p32 interacts specifically with CBF-B subunit and also associates with CBF-DNA complex. Cellular localization by immunofluorescence staining revealed that p32 is present in the cell throughout the cytosol and nucleus, whereas CBF is present primarily in the nucleus. A portion of the p32 colocalizes with CBF-B in the nucleus. Interestingly, reconstitution of p32 in an in vitro transcription reaction demonstrated that p32 specifically inhibits CBF-mediated transcription activation. Altogether, our study identified p32 as a novel and specific corepressor of CBF-mediated transcription activation in vitro.


Secretion of endogenous and exogenous proteins from polarized MDCK cell monolayers.
Confluent monolayers of MDCK (Madin-Darby canine kidney) cells provide a widely used system to study the biogenesis of epithelial cell polarity. We now report that these cells are also capable of the vectorial constitutive secretion of a major endogenous product, a glycoprotein of 81 kDa, which is released into the medium from the apical surface within 30 min of its synthesis. This release represents a bona fide exocytotic secretory process and is not the result of proteolytic cleavage of a plasma membrane-associated precursor since, in cells treated with chloroquine, a protein indistinguishable from the mature secretory product accumulated intracellularly. In contrast to the vectorial secretion of the endogenous product, a variety of exogenous exocrine and endocrine proteins synthesized in MDCK cells transfected with the corresponding genes were secreted from both the apical and basolateral surfaces. These included proteins such as rat growth hormone, chicken oviduct lysozyme, bovine gastric prochymosin, and rat salivary gland alpha 2u-globulin, which in their cells of origin are secreted via a regulated pathway, as well as the liver form of the alpha 2u-globulin and the immunoglobulin kappa chain, which are normally released constitutively. These results demonstrate the existence of secretory pathways that lead to both surfaces of MDCK cells and are accessible to the foreign secretory products. They are consistent with the operation of a sorting mechanism in which the polarized secretion of the endogenous product is effected through the recognition of signals that prevent its random distribution within the fluid phase in the cellular endomembrane system.


Heterodimerization of substance P and mu-opioid receptors regulates receptor trafficking and resensitization.
The micro-opioid receptor (MOR1) and the substance P receptor (NK1) coexist and functionally interact in nociceptive brain regions; however, a molecular basis for this interaction has not been established. Using coimmunoprecipitation and bioluminescence resonance energy transfer (BRET), we show that MOR1 and NK1 can form heterodimers in HEK 293 cells coexpressing the two receptors. Although NK1-MOR1 heterodimerization did not substantially change the ligand binding and signaling properties of these receptors, it dramatically altered their internalization and resensitization profile. Exposure of the NK1-MOR1 heterodimer to the MOR1-selective ligand [D-Ala2,Me-Phe4,Gly5-ol]enkephalin (DAMGO) promoted cross-phosphorylation and cointernalization of the NK1 receptor. Conversely, exposure of the NK1-MOR1 heterodimer to the NK1-selective ligand substance P (SP) promoted cross-phosphorylation and cointernalization of the MOR1 receptor. In cells expressing MOR1 alone, beta-arrestin directs the receptors to clathrin-coated pits, but does not internalize with the receptor. In cells expressing NK1 alone, beta-arrestin internalizes with the receptor into endosomes. Interestingly, in cells coexpressing MOR1 and NK1 both DAMGO and SP induced the recruitment of beta-arrestin to the plasma membrane and cointernalization of NK1-MOR1 heterodimers with beta-arrestin into the same endosomal compartment. Consequently, resensitization of MOR1-dependent receptor functions was severely delayed in coexpressing cells as compared with cells expressing MOR1 alone. Together, our findings indicate that MOR1 by virtue of its physical interaction with NK1 is sequestered via an endocytotic pathway with delayed recycling and resensitization kinetics.


Effects of anti-vertigo drugs on medial vestibular nucleus neurons activated by horizontal rotation.
The effects of anti-vertigo drugs on medial vestibular nucleus (MVN) neurons were examined to assess the site and mode of action using cats anesthetized with alpha-chloralose. Single neuron activity in the MVN was extracellularly recorded using a silver wire microelectrode attached along a seven-barreled micropipette, each of which was filled with diphenhydramine, diphenidol, betahistine, glutamate or NaCl. Type I of the MVN neurons were identified according to the responses obtained when the animal placed on a turn-table was rotated sinusoidally. The effects of the drugs were examined on type I neurons which received impulses primarily from the labyrinth and sent them to the oculomotor nuclei. The microiontophoretic application of diphenhydramine, diphenidol and betahistine inhibited rotation-induced firing of type I MVN neurons. Diphenhydramine and diphenidol were more potent than betahistine. These results suggest that these drugs directly act on MVN neurons to reduce the responsiveness to rotatory stimulation.


King's Sarcoidosis Questionnaire (KSQ) - Validation study in Serbian speaking population of sarcoidosis patients.
Sarcoidosis is a multiorgan, multisystem chronic disease of unknown etiology and unpredictable course. Health status is reduced in sarcoidosis and assessing it is a difficult multitask effort due to many faces this disease might have. Recently, a new questionnaire for assessing health status in sarcoidosis was developed by a group of authors from England-King's Sarcoidosis Questionnaire (KSQ). The benefit of KSQ is the ability to develop the best care plan for the patient, as well as to differentiate the efficacy of the administered treatment. The aim of this study was to validate the KSQ in Serbian speaking population of sarcoidosis patients. The test itself is a modular, multi-organ health status measure for patients with sarcoidosis for use in clinic and the evaluation of therapies. The correlation of KSQ with different clinical course of sarcoidosis (acute vs chronic disease) and with the clinical outcome status (COS) in sarcoidosis was also investigated. A total of 159 biopsy positive sarcoidosis patients participated in this study. The average age of the participants was 49.67, majority was female (67.3%) and majority had only pulmonary form of sarcoidosis (71.7%). KSQ - new disease-specific health status instrument, was compared with 5 other already existing instruments already used and validated in sarcoidosis (Saint George Respiratory Questionnaire- SGRQ, Daily Activity List -DAL, Fatigue Assessment Scale- FAS, Medical Research Council dyspnea scale-MRC, Borg Dyspnea Scale and 15D as general questionnaire. KSQ has significant correlation with other quality of life questionnaires already used in sarcoidosis. Translated version of KSQ shows significant internal reliability, similar to the original KSQ. Serbian version of KSQ has significant correlation with different clinical course of sarcoidosis and with COS as well. The translated version of KSQ is reliable sarcoidosis specific instrument for assessing health status in these patients.


Mindfulness-based cognitive therapy in obsessive-compulsive disorder: protocol of a randomized controlled trial.
Obsessive-compulsive disorder (OCD) is a very disabling condition with a chronic course, if left untreated. Though cognitive behavioral treatment (CBT) with or without selective serotonin reuptake inhibitors (SSRI) is the method of choice, up to one third of individuals with obsessive-compulsive disorder (OCD) do not respond to treatment in terms of at least 35% improvement of symptoms. Mindfulness based cognitive therapy (MBCT) is an 8-week group program that could help OCD patients with no or only partial response to CBT to reduce OC symptoms and develop a helpful attitude towards obsessions and compulsive urges. This study is a prospective, bicentric, assessor-blinded, randomized, actively-controlled clinical trial. 128 patients with primary diagnosis of OCD according to DSM-IV and no or only partial response to CBT will be recruited from in- and outpatient services as well as online forums and the media. Patients will be randomized to either an MBCT intervention group or to a psycho-educative coaching group (OCD-EP) as an active control condition. All participants will undergo eight weekly sessions with a length of 120 minutes each of a structured group program. We hypothesize that MBCT will be superior to OCD-EP in reducing obsessive-compulsive symptoms as measured by the Yale-Brown-Obsessive-Compulsive Scale (Y-BOCS) following the intervention and at 6- and 12-months-follow-up. Secondary outcome measures include depressive symptoms, quality of life, metacognitive beliefs, self-compassion, mindful awareness and approach-avoidance tendencies as measured by an approach avoidance task. The results of this study will elucidate the benefits of MBCT for OCD patients who did not sufficiently benefit from CBT. To our knowledge, this is the first randomized controlled study assessing the effects of MBCT on symptom severity and associated parameters in OCD. German Clinical Trials Register DRKS00004525 . Registered 19 March 2013.


Essential oil of lavender inhibited the decreased attention during a long-term task in humans.
This study examined the effects of odors on sustained attention during a vigilance task. Two essential oils (lavender and eucalyptus) and two materials (l-menthol and linalyl acetate) were compared with a control. The increase in reaction time was significantly lower with lavender than with the control. The results suggest that the administration of lavender helped to maintain sustained attention during the long-term task.


Skeletal response to teriparatide in real-life setting: effects of age, baseline bone density and prior denosumab use.
Teriparatide (TPD) is an osteoanabolic agent used in patients with high osteoporotic fracture risk. Predictors of therapeutic response to TPD in real-life setting are not well characterised. This study investigated the influence of previous antiresorptive therapy, age and other patient characteristics on the skeletal response to TPD. Retrospective study at the metabolic bone clinic, University Hospitals Leuven, Belgium. Patients with osteoporosis and a high fracture burden received TPD for 9-18 months. Bone mineral density (BMD) was measured at baseline, 9 and 18 months at lumbar spine (LS), femoral neck (FN) and total hip (TH). BMD at LS increased at 9 months (change mean (standard error) 6.8 % (0.7) p < 0.001) and at 18 months (8.0 % (0.9) p < 0.001), while BMD at FN and TH did not change significantly. Non-response in BMD change at the LS was seen with prior denosumab use (odds ratio 0.21, 95% confidence interval (CI) 0.049-0.912, p = 0.037). Changes in BMD at TH were significantly greater in younger patients and in patients with a lower baseline BMD. TPD-induced changes in BMD at TH might depend on age and baseline BMD and at LS on prior denosumab use. The results suggest that these factors may be relevant for clinical decision making when initiating TPD treatment, although larger studies are needed to confirm these findings.


Comparison of tetrodotoxin and procaine in internally perfused squid giant axons.
Squid giant axons were internally perfused with tetrodotoxin and procaine, and excitability and electrical properties were studied by means of current-clamp and sucrose-gap voltage-clamp methods. Internally perfused tetrodotoxin was virtually without effect on the resting potential, the action potential, the early transient membrane ionic current, and the late steady-state membrane ionic current even at very high concentrations (1,000-10,000 nM) for a long period of time (up to 36 min). Externally applied tetrodotoxin at a concentration of 100 nM blocked the action potential and the early transient current in 2-3 min. Internally perfused procaine at concentrations of 1-10 mM reversibly depressed or blocked the action potential with an accompanying hyperpolarization of 2-4 mv, and inhibited both the early transient and late steady-state currents to the same extent. The time to peak early transient current was increased. The present results and the insolubility of tetrodotoxin in lipids have led to the conclusion that the gate controlling the flow of sodium ions through channels is located on the outer surface of the nerve membrane.


A model for continuous fermentations with amylolytic yeasts.
A two-stage, associative fermentation process is more effective for continuous yeast biomass production from starch than a single-stage mixed culture fermentation process. By operating two stages, competition for the same growth limiting substrate is reduced leading to efficient starch utilization. In this article, a mathematical model has been proposed for continuous, two-stage fermentation with a pure culture, amylolytic yeast in the first stage and a mixed culture second stage with a faster growing, nonamylolytic yeast. The model parameters were determined for Saccharomycopsis fibuligera and Candida utilis in continuous, single-stage, pure cultures. In the two-stage model, the effects of changes in dilution rate on biomass, amylase, reducing sugar, and starch concentration, and ratio of stage volumes on microbial composition are discussed and compared with experimental data.


[Analyzing variations and clinical significance of perioperative serum inflammatory indicators in patients undergoing acute aortic dissection repair].
To study perioperative inflammatory response status in patients with acute aortic dissection. To analyze the reason and outcome of the inflammatory activation. Between August 2011 and December 2011, 30 patients (22 male and 8 female, mean aged (43 ± 9) years) had undergone open repairs of aortic dissection or aneurysm with deep hypothermic circulatory arrest. Indications for surgical intervention were type A aortic dissection in 26 patients and aortic aneurysm in 4 patients. In detail, ascending aorta and arch replacement combined with stent elephant trunk were done in 29 patients, arch replacement combined with stent elephant trunk in 1 patient. According to the time from clinical onset of the dissection to operation, acute group (less than 7 days, group A) 20 patients, chronic group (more than 30 days and aortic aneurysm, group C) 10 patients. White blood cell, C-reactive protein and procalcitonin were assayed before and after operation. These valuables were recorded and compared statistically between two groups. There were no significant differences in age, operation time, and blood transfusion volume (P > 0.05). Preoperative serum level of inflammatory indicators in group A were significant higher than in group C (t > 3, P < 0.05). Postoperative serum peak level of these indicators were significant higher than preoperative level in both groups (t > 4, P < 0.05). There were much more complications occurred on patients in group A (21 cases) than in group C (0 cases). The occurrence of early postoperative complications in group A was much higher than group C (χ(2) = 12.209, P = 0.000). Mechanic ventilation time in group A and group C were (35 ± 58) hours and (18 ± 9) hours respectively. ICU length of stay in two group were (49 ± 61) hours and (33 ± 12) hours, respectively. The patients with mechanic ventilation time more than 24 h, ICU length of stay more than 5 days in group A was more than in group C significantly (χ(2) = 5.161, P = 0.010; χ(2) = 3.657, P = 0.024). Acute aortic dissection and surgical procedure induce an acute phase inflammatory reaction. The patients with acute aortic dissection involved more serious organic injury and worse outcome following surgery compared with chronic aortic dissection.


Anosmia and dysgeusia in COVID-19: A systematic review.
Background: This systematic review had three aims: i) to determine the frequency of anosmia (or other smell disorders) and dysgeusia (or other taste disorders) in COVID-19 patients; ii) to determine whether anosmia or dysgeusia are independently associated with COVID-19 diagnosis; and iii) to determine whether anosmia or dysgeusia are prognostic factors for impaired outcomes among COVID-19 patients. Methods: On April 20 th, 2020, we search MEDLINE, Embase, Global Health, Scopus, Web of Science and MedXriv. We used terms related to COVID-19, smell and taste disorders. We selected case series, cross-sectional, case-control and cohort studies. We included studies with COVID-19 patients describing their symptoms; studies that compared smell and taste disorders between COVID-19 patients and otherwise healthy subjects; and studies comparing smell and taste disorders between COVID-19 severe and mild/moderate cases. Because of methodological heterogeneity and the limited number of results, a qualitative synthesis is presented. Results: From 31 reports, we selected six (n=2,757). Six studies reported the proportion of smell and taste disorders among COVID-19 patients. Two reports studied whether smell and taste disorders were independently associated with COVID-19 diagnosis. No reports studied the association with impaired outcomes among COVID-19 patients. The frequency of anosmia ranged between 22%-68%. The definition of taste disorders varied greatly, with dysgeusia present in 33% and ageusia in 20%. People who reported loss of smell and taste had six-fold higher odds of being COVID-19 positive; similarly, anosmia and ageusia were associated with 10-fold higher odds of COVID-19 diagnosis. Conclusions: The frequency of smell and taste disorders is as high as other symptoms, thus, at least anosmia for which the definition was more consistent, could be included in lists of COVID-19 symptoms. Although there is promising evidence, it is premature to conclude that smell and taste disorders are strongly associated with COVID-19 diagnosis. Registration: PROSPERO CRD42020181308.


[Identification of a novel HLA allele HLA-DRB1*09:01:07].
To identify and confirm a novel HLA allele in a Chinese Han individual. HLA typing was performed by polymerase chain reaction-sequence specific oligonucleotide probes (PCR-SSOP) for HLA-A, -B and -DRB1 in a registered donor of China Marrow Donor Program(CMDP). Sequencing-based typing (SBT) was carried out to further confirm the novel allele of HLA-DRB1. The SSOP result showed HLA-DRB1*09:03,15GEP, but an unusual pattern that could not be defined indicated potential presence of a novel allele. The SBT result showed the novel sequence has 1nt change from its closest allele DRB1*09:01:02 at nt306 where C to T(codon 73 GCC to GCT) resulting in no amino acid change. 73A was not changed. A novel HLA allele, HLA-DRB1*09:01:07, has been identified and named officially by WHO Nomenclature Committee for Factors of the HLA System.


A content analysis of the portrayal of alcohol in televised music videos in New Zealand: changes over time.
We aimed to: (i) document the extent and nature of alcohol portrayal in televised music videos in New Zealand in 2010; and (ii) assess trends over time by comparing with a similar 2005 sample. We undertook a content analysis for references to alcohol in 861 music videos shown on a youth-orientated television channel in New Zealand. This was compared with a sample in 2005 (564 music videos on the same channel plus sampling from two other channels). The proportion of alcohol content in the music videos was slightly higher in 2010 than for the same channel in the 2005 sample (19.5% vs. 15.7%) but this difference was not statistically significant. Only in the genre 'Rhythm and Blues' was the increase over time significant (P = 0.015). In both studies, the portrayal of alcohol was significantly more common in music videos where the main artist was international (not from New Zealand). Furthermore, in the music videos with alcohol content, at least a third of the time, alcohol was shown being consumed and the main artist was involved with alcohol. In only 2% (in 2005) and 4% (in 2010) of these videos was the tone explicitly negative towards alcohol. In both these studies, the portrayal of alcohol was relatively common in music videos. Nevertheless, there are various ways that policy makers can denormalise alcohol in youth-orientated media such as music videos or to compensate via other alcohol control measures such as higher alcohol taxes.


Mutations in ribosomal protein L3 and 23S ribosomal RNA at the peptidyl transferase centre are associated with reduced susceptibility to tiamulin in Brachyspira spp. isolates.
The pleuromutilin antibiotic tiamulin binds to the ribosomal peptidyl transferase centre. Three groups of Brachyspira spp. isolates with reduced tiamulin susceptibility were analysed to define resistance mechanisms to the drug. Mutations were identified in genes encoding ribosomal protein L3 and 23S rRNA at positions proximal to the peptidyl transferase centre. In two groups of laboratory-selected mutants, mutations were found at nucleotide positions 2032, 2055, 2447, 2499, 2504 and 2572 of 23S rRNA (Escherichia coli numbering) and at amino acid positions 148 and 149 of ribosomal protein L3 (Brachyspira pilosicoli numbering). In a third group of clinical B. hyodysenteriae isolates, only a single mutation at amino acid 148 of ribosomal protein L3 was detected. Chemical footprinting experiments show a reduced binding of tiamulin to ribosomal subunits from mutants with decreased susceptibility to the drug. This reduction in drug binding is likely the resistance mechanism for these strains. Hence, the identified mutations located near the tiamulin binding site are predicted to be responsible for the resistance phenotype. The positions of the mutated residues relative to the bound drug advocate a model where the mutations affect tiamulin binding indirectly through perturbation of nucleotide U2504.


[Application of the molecular test PCR multiplex for identification of Mycobacterium bovis BCG strains].
In our last paper (18) we described the problem of proper microbiological identification of BCG strains and how important is distinguishing vaccine strain from virulent strains of Mycobacterium tuberculosis complex. We have suggested the modern algorithm of BCG strains identification including mycolic acids profile by HPLC and 14C PZA resistance methods. These methods allowed us to made fast and accurate microbiological identification of side effects of BCG vaccine in the children. Identification of BCG by HPLC is possible within one working day compared with 3-4 weeks required for conventional methods. However both methods need very expensive instruments like HPLC and/or Bactec-460 Tb radiometric system. Presently we have evaluated molecular test based on the analyzis of the region RD1 encoding a 9.5-kb fragment. This fragment is deleted in all BCG substrains (6) and present in all human and bovine virulent strains. To evaluate this method for the rapid and specific detection of BCG, a large strain collection (32 strains) representating M. bovis BCG (vaccine strains and strains isolated from the children in case of adverse reactions after vaccination) M. bovis and M. tuberculosis from own collection was analyzed. RD1 was present in all 15 M. tuberculosis and M. bovis tested strains and deleted in 17 of 18 BCG strains. The multiplex PCR method was 100% sensitive and specific for the identification of BCG among strains of the Mycobacterium tuberculosis complex. Multiplex PCR can be used as a diagnostic test and has significant advantages over existing methods.


Impairments in muscle shape changes affect metabolic demands during in-vivo contractions.
The uncoupling behaviour between muscle belly and fascicle shortening velocity (i.e. belly gearing), affects mechanical output by allowing the muscle to circumvent the limits imposed by the fascicles' force-velocity relationship. However, little is known about the 'metabolic effect' of a decrease/increase in belly gearing. In this study, we manipulated the plantar flexor muscles' capacity to change in shape (and hence belly gearing) by using compressive multidirectional loads. Metabolic, kinetic, electromyography activity and ultrasound data (in soleus and gastrocnemius medialis) were recorded during cyclic fixed-end contractions of the plantar flexor muscles in three different conditions: no load, +5 kg and +10 kg of compression. No differences were observed in mechanical power and electrophysiological variables as a function of compression intensity, whereas metabolic power increased as a function of it. At each compression intensity, differences in efficiency were observed when calculated based on fascicle or muscle behaviour and significant positive correlations (R2 range: 0.7-0.8 and p > 0.001) were observed between delta efficiency (ΔEff: Effmus-Efffas) and belly gearing (Vmus/Vfas) or ΔV (Vmus-Vfas). Thus, changes in the muscles' capacity to change in shape (e.g. in muscle stiffness or owing to compressive garments) affect the metabolic demands and the efficiency of muscle contraction.


Self-heterodyne interference spectroscopy using a comb generated by pseudo-random modulation.
We present an original instrument designed to accomplish high-speed spectroscopy of individual optical lines based on a frequency comb generated by pseudo-random phase modulation of a continuous-wave (CW) laser. This approach delivers efficient usage of the laser power as well as independent control over the spectral point spacing, bandwidth and central wavelength of the comb. The comb is mixed with a local oscillator generated from the same CW laser frequency-shifted by an acousto-optic modulator, enabling a self-heterodyne detection scheme. The current configuration offers a calibrated spectrum every 1.12 µs. We demonstrate the capabilities of the spectrometer by producing averaged, as well as time-resolved, spectra of the D1 transition of cesium with a 9.8-MHz point spacing, a 50-kHz resolution and a span of more than 3 GHz. The spectra obtained after 1 ms of averaging are fitted with complex Voigt profiles that return parameters in good agreement with expected values.


Multidimensional analysis of metabolism contributions involved in running track tests.
It is difficult to interpret the training induced changes in middle-distance running, since numerous aerobic and anaerobic determinants of the performance are interdependent. Several aerobic and anaerobic tests are available but their results, particularly those from anaerobic tests, may be discordant, not providing univocal interpretation of training. The purpose of this study is to use a multidimensional approach to distinguish aerobic and anaerobic capacities assessed by two running tests on a track: the maximal anaerobic running test (MART) and V(O2max) tests. Eleven runners carried out two maximal tests on a synthetic track before and after a 4-week training period: (i) a maximal test to determine V(O2max), the velocity associated with V(O2max) (vV(O2max)) and the velocity at the lactate threshold (v(LT)), (ii) a maximal anaerobic running test to estimate anaerobic capacity. An all-out test run at v(LT)+50% of the difference between v(LT) and vV(O2max), known to be affected by both aerobic and anaerobic energy production, was used to test this approach. A principal components analysis (PCA) shows that two components (i.e., aerobic and anaerobic) explained 79% of the variation in the physiological variables. The PCA suggests that V(O2max) and MART tests assess the aerobic and the anaerobic capacities, respectively. In contrast, the performance in the all-out test is affected by both aerobic and anaerobic energy production. The PCA shows that v(LT) and DeltaP (difference between the maximal power of the MART and V(O2max)) are clear markers of the long-term endurance and the anaerobic capacity, respectively. This multidimensional approach can be a useful way to disentangle the aerobic and anaerobic components of track tests.


Granulocyte colony-stimulating factor induces osteoblast apoptosis and inhibits osteoblast differentiation.
Long-term treatment of mice or humans with granulocyte colony-stimulating factor (G-CSF) is associated with a clinically significant osteopenia characterized by increased osteoclast activity and number. In addition, recent reports have observed a decrease in number of mature osteoblasts during G-CSF administration. However, neither the extent of G-CSF's suppressive effect on the osteoblast compartment nor its mechanisms are well understood. Herein, we show that short-term G-CSF treatment in mice leads to decreased numbers of endosteal and trabecular osteoblasts. The effect is specific to mature osteoblasts, because bone-lining cells, osteocytes, and periosteal osteoblasts are unaffected. G-CSF treatment accelerates osteoblast turnover in the bone marrow by inducing osteoblast apoptosis. In addition, whereas G-CSF treatment sharply increases osteoprogenitor number, differentiation of mature osteoblasts is impaired. Bone marrow transplantation studies show that G-CSF acts through a hematopoietic intermediary to suppress osteoblasts. Finally, G-CSF treatment, through suppression of mature osteoblasts, also leads to a marked decrease in osteoprotegerin expression in the bone marrow, whereas expression of RANKL remains relatively constant, suggesting a novel mechanism contributing to the increased osteoclastogenesis seen with long-term G-CSF treatment. In sum, these findings suggest that the hematopoietic system may play a novel role in regulating osteoblast differentiation and apoptosis during G-CSF treatment.


Diel activity patterns of two distinct populations of Aedes aegypti in Miami, FL and Brownsville, TX.
The diel biting activity of Aedes (Stegomyia) aegypti (L) populations was extensively investigated in the early 1900s to gain more information on the biology of Ae. aegypti, and this information was used to devise effective approaches to controlling populations of this species and protect the human population from widespread arbovirus outbreaks. However, few contemporary studies are available regarding the diel activity patterns of Ae. aegypti. To assess the diel activity patterns of Ae. aegypti in southern Florida and Texas, we conducted 96-h uninterrupted mosquito collections once each month from May through November 2019 in Miami, Florida, and Brownsville, Texas, using BG-Sentinel 2 Traps. The overall diel activity pattern in both cities was bimodal with morning and evening peak activity between 7:00 and 8:00 and between 19:00 and 20:00. There were significant daily, monthly, seasonal, and site-specific differences in activity patterns, but these differences did not affect the overall peak activity times. These differences suggest daily, monthly, seasonal, and site-specific variations in human exposure to Ae. aegypti. Our observations can be used in planning and executing Ae. aegypti vector control activities in southern Florida and southern Texas, specifically those targeting the adult mosquito populations.


Understanding the pathophysiology of postpartum psychosis: Challenges and new approaches.
Postpartum psychosis is a severe psychiatric condition which affects 1-2 of every 1000 mothers shortly after childbirth. Whilst there is convincing evidence that the condition is precipitated by a complex combination of biological and environmental factors, as yet the pathophysiological mechanisms remain extremely poorly defined. Here, I critically review approaches that have been, or are being, employed to identify and characterise such mechanisms; I also review a recent animal model approach, and describe a novel biological risk model that it suggests. Clarification of biological risk mechanisms underlying disorder risk should permit the identification of relevant predictive biomarkers which will ensure that "at risk" subjects receive prompt clinical intervention if required.


[Effects of scale-like pit and mulching measures on soil moisture of dryland jujube orchard in North Shaanxi Province, China].
Soil moisture is a key factor affecting jujube growth in the semiarid Northern Shaanxi Province. The impacts of different engineering and mulching measures on soil moisture were investigated via in situ measurements in a typical dryland jujube orchard. The results showed that the mean soil moistures (0-180 cm) of scale-like pit + branch mulching, scale-like scale + straw mulching, and soil moisture of scale-like pit with no mulching were increased by 14.2%, 9.4%, and 4.8% than control, respectively. Different measures, especially for the scale-like pit + branch mulching, significantly increased the soil moisture in the soil surface (0-20 cm) and the main root zone layer (20-100 cm) during the jujube growth stage. Individual precipitation events had great impacts on soil moisture in the 0-100 cm, while its effect on soil moisture in deep layers was not apparent. There was no significant difference among the soil moistures in different soil depths of scale-like pit with no mulching when compared with the control under high, medium, and low soil humidity conditions. This study indicated that using the clipped jujube branches as mulching could both save materials cost and achieve the goal of reserving more water in dryland jujube orchard in north Shaanxi Province.


Mn-Modified ZnO Nanoflakes for Optimal Photoelectrochemical Performance Under Visible Light: Experimental Design and Theoretical Rationalization.
Doping of zinc oxide (ZnO) with manganese (Mn) tunes midbandgap states of ZnO to enhance its optical properties and makes it into an efficient photoactive material for photoelectrochemical water splitting, waste removal from water, and other applications. We demonstrate that ZnO modified with 1 at. % Mn exhibits the best performance, as rationalized by experimental, structural, and optical characterization and theoretical analysis. ZnO doped with the optimal Mn content possesses improved light absorption in the visible region and minimizes charge carrier recombination. The doping is substitutional and creates midgap states near the valence band. Mn atoms break localized charge traps at oxygen vacancy sites and eliminate photoluminescence peaks associated with oxygen vacancies. The optimal performance of Mn-modified ZnO is demonstrated with the photodegradation of Congo red and photoelectrochemical water splitting.


Contact Dermatitis to Diabetes Medical Devices.
Skin adverse reactions to diabetes medical devices have been reported frequently over recent years. Adhesives attaching glucose sensors and continuous insulin infusion sets to the skin are proven to cause both allergic contact dermatitis and irritant contact dermatitis in patients with diabetes mellitus. Several allergens contained in adhesives and/or parts of medical devices are documented to cause allergic contact dermatitis, with acrylate chemicals being the most common culprit-especially isobornyl acrylate (IBOA), but also 2,2'-methylenebis(6-tert-butyl-4-methylphenol) monoacrylate or cyanoacrylates. Epoxy resin, colophonium and nickel were also identified as causative allergens. However, repetitive occlusion, maceration of the skin and resulting disruption of the skin barrier seem to have an impact on the development of skin lesions as well. The purpose of this study is to highlight the burden of contact dermatitis triggered by diabetes medical devices and to show possible mechanisms responsible for the development of contact dermatitis in a group of diabetic patients.


Seasonality of delusions of parasitosis.
Delusions of parasitosis (DOP) is an emotional disorder in which patients are convinced that they are infested with tiny, almost invisible, mites or insects. Despite sample examination by entomologists and repeated doctor visits, no evidence of a real infestation can be found. Previous studies of DOP patients have described epidemiological features such as age, race, and gender. This is the first report of an apparent link between season of the year and DOP.


The application of crystallization in the presence of additives to enable drug-in-capsule technology.
Crystallization in the presence of additives such as surfactants, polymers or impurities has been widely investigated in the pharmaceutical and chemical industries in order to change the crystal habit or to obtain a more desirable polymorph, affect crystal growth and influence dissolution. However, in this study, we investigated the concept of crystallization in the presence of surfactants in order to incorporate into the crystal lattice, a small amount (less than 1% w/w) of surfactant, sodium lauryl sulfate (SLS). The resulting crystals were further compared to crystals coated with SLS using a washing procedure; in order to assess whether either procedure generates improvements in the apparent solubility and dissolution of a poorly soluble drug so it can be filled directly into a capsule without the need of a complex formulation process.


Medical decision support for remote general practitioners using telemedicine.
A telemedicine link was set up between the casualty department of a remote community hospital and the accident and emergency department of a large urban hospital. The telemedicine link comprised teleradiology, videoconferencing and telepresence. The system was connected by ISDN (128 kbit/s) and also by a satellite link (64 kbit/s). During a one-year clinical trial, 120 teleconsultations took place between the community hospital and the specialist trauma centre, 110 using ISDN and 10 using the satellite link. Teleradiology was used in 116 teleconsultations, videoconferencing in 76, and telepresence in four. Survey results indicated that both the general practitioners running the community hospital and accident and emergency consultants felt that teleconsultation had improved patient care. Communication between clinicians using the telemedicine link avoided the transfer of 70 patients, representing an estimated cost saving of Pounds 65,000.


Induced abortion is not a cause of subsequent preterm delivery in teenage pregnancies.
To examine the possible impact of previous induced abortion on the occurrence of preterm delivery in the subsequent pregnancy in teenage women, a retrospective case-control study was performed on mothers aged 13-19 years who delivered in one tertiary hospital over a 4 year period. Those who had a history of induced abortion prior to the index pregnancy were identified from the records and compared with a control group without previous induced abortion and who were matched for maternal age and parity. Of the 118 cases thus identified, 28 (23.7%) had more than one induced abortions and 18 (15.3%) had one or more induced abortions in the second trimester. There were 10 (8.5%) para 1 cases. No significant differences could be demonstrated between the study and control groups in the maternal demographics, major pregnancy complications, or perinatal outcome, except for the incidence of smokers which was significantly higher (39.0 versus 14.4%, P < 0.02) in the study group. The number of previous induced abortions did not appear to be related to the incidence of preterm labour, which was 10.2 and 8.5% in the study and control groups respectively. Our findings indicate that previous induced abortion is not a significant cause of preterm labour and delivery in teenage pregnancies.


Predicting Intermittent Atrial Fibrillation in Outpatient Clinics.
Palpitations are the most common complaint in cardiology outpatient clinics. These palpitations may be derived from paroxysmal atrial fibrillation (AF) and can be easily overlooked. It is unclear whether inter-atrial conduction time (ICT) may predict the paroxysmal AF in out-patients that present with palpitations. We evaluated the ability of the ICT to predict paroxysmal AF in these patients. The study group consisted of 199 patients (110 female). All patients underwent 24-hour Holter electrocardiogram (ECG) monitoring (total of 327 Holter ECG monitorings, mean: 1.64 times per patient). Brief episodes of AF were documented in 35 patients (20 female, Group 1). The remaining patients without AF were designated as Group 2 (90 female). All patients underwent routine transthoracic echocardiographic examination. ICT was also measured by echocardiography. The mean age in Group 1 was greater than in Group 2 (63.02±14 vs. 51.27±16 years, p<0.001). The left atrium was larger in Group 1 than in Group 2 (39.7±3.4 vs. 37.29±4.3 mm, p<0.001). The other echocardiographic variables were comparable between the two groups. The mean ICT was significantly higher in Group 1 than in Group 2 (138±14 vs. 114±12 msn, p<0.001). The ICT of 127 ms was predictive for AF with a sensitivity of 86% and specificity of 87% (p<0.001). Our findings show that ICT was prolonged in patients with palpitations who developed a brief episode of AF in Holter ECG monitoring. ICT prolongation may be used to identify patients with palpitation that are at risk of an AF episode. Holter ECG monitoring should be repeated to detect AF episodes in patients with prolonged ICT.


Evaluation of multiple ancillary therapies used in combination with an antimicrobial in newly received high-risk calves treated for bovine respiratory disease.
Ancillary therapy (ANC) is commonly provided in conjunction with an antimicrobial when treating calves for suspected bovine respiratory disease (BRD) in an attempt to improve the response to a suspected BRD challenge. The first experiment evaluated the effects of 3 ANC in combination with an antimicrobial in high-risk calves treated for BRD during a 56-d receiving period. Newly received crossbred steers (n = 516; initial BW = 217 ± 20 kg) were monitored by trained personnel for clinical signs of BRD. Calves that met antimicrobial treatment criteria (n = 320) were then randomly assigned to experimental ANC treatment (80 steers/experimental ANC treatment): intravenous flunixin meglumine injection (NSAID), intranasal viral vaccination (VACC), intramuscular vitamin C injection (VITC), or no ANC (NOAC). Animal served as the experimental unit for all variables except DMI and G:F (pen served as the experimental unit for DMI and G:F). Within calves treated 3 times for BRD, those receiving NOAC had lower (P < 0.01) clinical severity scores (severity scores ranged from 0 to 4 on the basis of observed clinical signs and severity) and heavier (P = 0.01) BW than those receiving NSAID, VACC, or VITC at the time of third treatment. Between the second and third BRD treatments, calves receiving NOAC had decreased (P < 0.01) daily BW loss (−0.13 kg ADG) compared with those receiving NSAID, VACC, or VITC (−1.30, −1.90, and −1.41 kg ADG, respectively). There were no differences in rectal temperature, combined mortalities and removals, or overall performance among the experimental ANC treatments. Overall, morbidity and mortality attributed to BRD across treatments were 66.5% and 13.2%, respectively. After the receiving period, a subset of calves (n = 126) were allocated to finishing pens to evaluate the effects ANC administration on finishing performance, carcass characteristics, and lung scores at harvest. Ultrasound estimates, BW, and visual appraisal were used to target a common physiological end point for each pen of calves. There were no differences among the experimental ANC observed during the finishing period (P ≥ 0.11). In summary, the use of NSAID, VACC, and VITC do not appear to positively impact clinical health and could potentially be detrimental to performance during the receiving period in high-risk calves receiving antimicrobial treatment for suspected BRD.


Inhibition of diacylglycerol acyltransferase by alkamides isolated from the fruits of Piper longum and Piper nigrum.
Pharmacological inhibition of acyl CoA:diacylglycerol acyltransferase (DGAT, EC 126.96.36.199) has emerged as a potential therapy for the treatment of obesity and type 2 diabetes. Bioassay-guided isolation of CHCl3 extracts of the fruits of Piper longum and Piper nigum (Piperaceae), using an in vitro DGAT inhibitory assay, lead to isolation of a new alkamide named (2E,4Z,8E)-N-[9-(3,4-methylenedioxyphenyl)-2,4,8-nonatrienoyl]piperidine (2), together with four known alkamides: retrofractamide C (1), pipernonaline (3), piperrolein B (4), and dehydropipernonaline (5). Compounds 2-5 inhibited DGAT with IC50 values of 29.8 (2), 37.2 (3), 20.1 (4), and 21.2 (5) microM, respectively, but the IC50 value for 1 was more than 900 microM. This finding indicates that compounds possessing piperidine groups (2-5) can be potential DGAT inhibitors.


Subspecies-level systematics and affinities of Cheimas Thieme-an endemic genus of the subparamo of the Venezuelan Cordillera de Mérida (Lepidoptera: Nymphalidae, Satyrinae).
The validity of the monobasic neotropical butterfly genus Cheimas Thieme (Nymphalidae, Satyrinae, Satyrini, Pronophilina) is discussed, and confirmed based on morphological and molecular data. Cheimas opalinus (Staudinger), endemic to the Venezuelan Cordillera de Mérida, and considered prior to this study to be monotypic and restricted to the central part of the range, is demonstrated to be polytypic and more widely distributed. Five subspecies are recognised, differing mostly in their dorsal patterns, in particular the shape and colour of hindwing greenish-blue patch. Mitochondrial DNA sequences (COI) were obtained for three of them. The nominate subspecies is found in the central part of the range, in the Sierra Nevada and La Culata. The other subspecies are found as follows: C. opalinus dominici n. ssp.; in the Santo Domingo valley in the centre-north; C. opalinus cristalinus n. ssp. in the north; C. opalinus iosephi n. ssp. on the eastern slopes, and C. opalinus rosalinus n. ssp. in the southern Páramo El Batallón massif. A hybrid zone between the latter two subspecies was detected in the northern part of the Batallón massif based on unusual individual variation and intermediate phenotypes. All the populations of Cheimas opalinus occur in the forest-paramo ecotone at 2800-3400 m a.s.l., with the notable exception of C. opalinus cristalinus n. ssp. found also in mid-elevation forests down to 2300 m a.s.l.


Portal hypertension: Imaging of portosystemic collateral pathways and associated image-guided therapy.
Portal hypertension is a common clinical syndrome, defined by a pathologic increase in the portal venous pressure. Increased resistance to portal blood flow, the primary factor in the pathophysiology of portal hypertension, is in part due to morphological changes occurring in chronic liver diseases. This results in rerouting of blood flow away from the liver through collateral pathways to low-pressure systemic veins. Through a variety of computed tomographic, sonographic, magnetic resonance imaging and angiographic examples, this article discusses the appearances and prevalence of both common and less common portosystemic collateral channels in the thorax and abdomen. A brief overview of established interventional radiologic techniques for treatment of portal hypertension will also be provided. Awareness of the various imaging manifestations of portal hypertension can be helpful for assessing overall prognosis and planning proper management.


[Evaluating type I interferon-inducible gene expression in patients with systemic lupus erythematosus.].
To explore the expression levels of interferon-inducible genes in patients with systemic lupus erythematosus (SLE), and to validate these gene expressions as potential biomarkers for the differentiation of disease flare and infection. Peripheral blood was obtained from 48 SLE, 16 rheumatoid arthritis (RA) patients and 26 normal controls, and total RNA was extracted and reverse transcribed into complementary DNA. Real-time PCR technique was used to determine the gene expressions of MX1, OASL, OAS1, ISG15 and LY6E at transcription level. Univariate logistic regression analysis and multivariate conditional logistic regression model were applied to analyze 5 related factors for infection or activity. (1) The expression levels of MX1, OASL, OAS1, ISG15, and LY6E mRNA in SLE patients were significantly increased as compared with normal controls (P all < 0.01), while the expression levels of OASL, OAS1, ISG15 and LY6E mRNA in SLE patients were also higher than those in RA patients (P all < 0.05). (2) There were no significant difference between male and female patients of the 5 gene expression in SLE patients. (3) By logistic regression analysis, ISG15 and LY6E were independent risk factors for active SLE patients (P < 0.01), OASL expression was an independent risk factor for SLE patients with infection (P = 0.003). All the 5 interferon inducible genes are highly expressed in SLE patients, in which ISG15 and LY6E are independently associated with disease flare, while OASL may be helpful for the evaluation of infection in SLE patients.


The effect of grape products on liver enzymes: A systematic review and meta-analysis of randomized controlled trials.
The favorable influence of grape consumption on metabolic diseases has previously been shown in studies. We sought to assess the effects of grape intake on liver enzymes, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP), in adults. We performed literature search in online databases, to find eligible randomized controlled trials (RCTs). we considered RCTs that met the following criteria: RCTs consisted of use of grape products on ALT, AST, and ALP in adults (≥18 years) with at least 2 weeks intervention duration. Pooling data from 11 trials showed that grape products intake significantly reduced ALP (p = .010), without any significant changes in ALT (p = .234) and AST (p = .300). In subgroup analysis, we found a significant reduction in ALP, ALT, and AST when the duration of intervention was ≥12 weeks, and when grape seed extract (GSE) was administered. The variable duration and dosage of intervention was one of the sources of bias in our meta-analysis. Additionally, participants involved in included studies had different physiological status and various age groups. Grape products administration may significantly improve ALT, AST, and ALP in adults in long-term interventions and/or when GSE is administered. It should be noted that the favorable effects of grape consumption were small and may not reach clinical importance.


Preparing the work force for retirement--the role of occupational health nurses.
As baby boomers reach retirement, the need to develop realistic plans is pressing. Recent political and social developments involving Social Security, savings accounts, and pensions indicate a need for greater self-sufficiency. The greatest challenges facing retirees are maintenance of self-sufficiency, productivity, generativity, and social satisfaction. Employers can optimize the investment in their work force by implementing policies and work practices that take advantage of the improved cognitive functions of aging workers despite their declining physical abilities. Occupational health nurses have the skills in policy development, regulatory issues, and ergonomic principles to advise corporate leaders. Occupational health nurses can organize and present retirement planning skills to the work force in a variety of formats and with targeted content.


Chemometric Analysis Of Inter- And Intra-Molecular Diversification Factors By A Machine Learning Simplex Approach. A Review And Research On Astragalus Saponins.
Metabolisms represent highly organized systems characterized by strong regulations satisfying the mass conservation principle. This makes a whole chemical resource to be competitively shared between several ways at both intra-and inter-molecular scales. Whole resource sharing can be statistically associated with a constant sum-unit constraint which represents the basis of simplex mixture rule. In this work, a new simplex-based simulation approach was developed to learn scaffold information on metabolic processes controlling molecular diversity from a wide set of observed chemical structures. Starting from a dataset of chemical structures classified into p clusters, a machine learning process was applied by linearly combining the p clusters j and randomly sampling a constant number (n) of molecules according to different clusters' weights (wj/w) given by Scheffé's mixture matrix. At the output of mixture design, molecular linear combinations lead to calculate barycentric molecules integrating the characteristics of the different weighted clusters. The N mixtures-design was iterated by bootstrap technique leading to extensive exploration of chemical variability between and within clusters. Finally, the K response matrices issued from K iterated mixture designs were averaged to calculate a smoothed matrix containing scaffold information on regulation processes responsible for molecular diversification at inter- and intra-molecular (atomic) scales. This matrix was used as a backbone for graphical analysis of positive and negative trends between atomic characteristics (chemical substitutions) at both mentioned scales. This new simplex approach was illustrated by cycloartane-based saponins of Astragalus genus by combining three desmosylation clusters characterized by relative glycosylation levels of different aglycones' carbons.


Whole Genome Sequencing of Sunflower Root-Associated Bacillus cereus.
In recent times, diverse agriculturally important endophytic bacteria colonizing plant endosphere have been identified. Harnessing the potential of Bacillus species from sunflower could reveal their biotechnological and agricultural importance. Here, we present genomic insights into B. cereus T4S isolated from sunflower sourced from Lichtenburg, South Africa. Genome analysis revealed a sequence read count of 7 255 762, a genome size of 5 945 881 bp, and G + C content of 34.8%. The genome contains various protein-coding genes involved in various metabolic pathways. The detection of genes involved in the metabolism of organic substrates and chemotaxis could enhance plant-microbe interactions in the synthesis of biological products with biotechnological and agricultural importance.


Association Between Serum Uric Acid and Intracranial Arterial Stenosis in a Korean Population: A Secondary Analysis Based on a Cross-Sectional Study.
Intracranial arterial stenosis (ICAS) is a common cause of cerebrovascular disease. Studies have shown that the disease may be associated with elevated serum uric acid. However, the results remain inexact and controversial. To provide theoretical support for clinical practice, we assessed the relationship between uric acid and ICAS based on previous literature. A total of 1,011 samples were included in the secondary cross-sectional study we investigated. We evaluated the relationship between uric acid level and ICAS using multivariable logistic regression analysis. The mean age of patients was 64.16 ± 9.13 years, and 35.51% (n = 359) were male in the study. One hundred and one (10%) of the included participants had ICAS. In the unadjusted model, uric acid level was positively associated with ICAS [odds ratio (OR) = 1.23, 95% confidence interval (CI): 1.07-1.42, p < 0.01]. After adjusting for potential confounders (sex, age, diabetes mellitus, coronary artery occlusive disease, hyperlipidemia, statin medication, hypertension, and fasting glucose), a positive relationship was observed between uric acid and ICAS (OR = 1.26, 95% CI: 1.08-1.47, p < 0.05). There was a positive relationship between uric acid levels and ICAS in neurologically healthy Korean participants.


Calorie restriction in biosphere 2: alterations in physiologic, hematologic, hormonal, and biochemical parameters in humans restricted for a 2-year period.
Four female and four male crew members, including two of the present authors (R. Walford and T. MacCallum)--seven of the crew being ages 27 to 42 years, and one aged 67 years--were sealed inside Biosphere 2 for two years. During seven eighths of that period they consumed a low-calorie (1750-2100 kcal/d) nutrient-dense diet of vegetables, fruits, nuts, grains, and legumes, with small amounts of dairy, eggs, and meat (approximately 12% calories from protein, approximately 11% from fat, and approximately 77% from complex carbohydrates). They experienced a marked and sustained weight loss of 17 +/- 5%, mostly in the first 8 months. Blood was drawn before entry into Biosphere 2, at many time-points inside it, and four times during the 30 months following exit from it and return to an ad libitum diet. Longitudinal studies of 50 variables on each crew member compared outside and inside values by means of a Bayesian statistical analysis. The data show that physiologic (e.g., body mass index, with a decrease of 19% for men and 13% for women; blood pressure, with a systolic decrease of 25% and a diastolic decrease of 22%), hematologic (e.g., white blood cell count, decreased 31%), hormonal (e.g., insulin, decreased 42%; T3, decreased 19%), biochemical (e.g., blood sugar, decreased 21%; cholesterol, decreased 30%), and a number of additional changes, including values for rT3, cortisol, glycated hemoglobin, plus others, resembled those of rodents or monkeys maintained on a calorie-restricted regime. Significant variations in several substances not hitherto studied in calorie-restricted animals are also reported (e.g., androstenedione, thyroid binding globulin, renin, and transferrin). We conclude that healthy nonobese humans on a low-calorie, nutrient-dense diet show physiologic, hematologic, hormonal, and biochemical changes resembling those of rodents and monkeys on such diets. With regard to the health of humans on such a diet, we observed that despite the selective restriction in calories and marked weight loss, all crew members remained in excellent health and sustained a high level of physical and mental activity throughout the entire 2 years.