Sulfur oxidation of Paracoccus pantotrophus: the sulfur-binding protein SoxYZ is the target of the periplasmic thiol-disulfide oxidoreductase SoxS.
The periplasmic thiol-disulfide oxidoreductase SoxS is essential for chemotrophic growth of Paracoccus pantotrophus with thiosulfate. To trap its periplasmic partner, the cysteine residues of the CysXaaXaaCys motif of SoxS (11 kDa) were changed to alanine by site-directed mutagenesis. The disrupted soxS gene of the homogenote mutant G OmegaS was complemented with plasmids carrying the mutated soxS[C13A] or soxS[C16A] gene. Strain G OmegaS(pRD179.6[C16A](S)) displayed a marginal thiosulfate-oxidizing activity, suggesting that Cys13(S) binds the target protein. Evidence is presented that SoxS specifically binds SoxY. (i) Immunoblot analysis using non-reducing SDS gel electrophoresis and anti-SoxS and anti-SoxYZ antibodies identified the respective antigens of strain G OmegaS(pRD179.6[C16A](S)) at the 25 kDa position, suggesting an adduct of about 14 kDa, close to the value expected for SoxY migration. (ii) A mutant unable to produce SoxYZ, such as strain G OmegaX(pRD187.7[C16A](S)), did not form a SoxS(C16A) adduct, while addition of homogeneous SoxYZ resulted in the 25 kDa adduct. (iii) The SoxY and SoxZ subunits were distinguished by site-directed mutagenesis of the cysteine residue in SoxZ. SoxYZ(C53S) formed the 25 kDa adduct with SoxS(C16A). These results demonstrate that the target of SoxS is the sulfur-binding protein SoxY of the SoxYZ complex. As SoxYZ is reversibly inactivated, SoxS may activate SoxYZ as a crucial function for chemotrophy of P. pantotrophus.


Technologists'Attitudes Regarding Social Networking and Implications for Managers.
Social networking has both positive and negative implications and can be an excellent communication and networking tool or it can have detrimental consequences. Healthcare workers, including radiologic technologists, need to be aware of the possible impli- cations of their online postings. Radiologic technologists are extensively using and accessing social media sites and should have appropriate profes- sional boundaries. Radiology administrators should assure that technologists are aware of policies related to social networking. Employee education regarding negative implica- tions may prove helpful; creating a radi- ology department with sound ethical standards.


Positive and negative symptoms and the thematic organisation of schizophrenic speech.
This study questions the prevailing view that schizophrenic delusions, hallucinations and incoherence of speech (positive symptoms) reflect loss of cognitive control and that flattening of affect and poverty of speech (negative symptoms) reflect restriction of cognitive processing. The prevailing view was examined by analysing the thematic organisation of speech produced by 18 patients describing pictures. Results showed that (a) positive and negative symptom schizophrenics did not differ in the control and restriction of thematic speech organisation; (b) speech disordered schizophrenics, positive as well as negative, showed cognitive restriction, by producing fewer inferential ideas than non-speech disordered schizophrenics. The wider implications of these results are discussed, particularly the implications of (b) for the notion of concreteness in schizophrenia.


Hypermutation as a factor contributing to the acquisition of antimicrobial resistance.
Contrary to what was thought previously, bacteria seem to be, not merely spectators to their own evolution, but, through a variety of mechanisms, able to increase the rate at which mutations occur and, consequently, to increase their chances of becoming resistant to antibiotics. Laboratory studies and mathematical models suggest that, under stressful conditions, such as antibiotic challenge, selective pressure favors mutator strains of bacteria over nonmutator strains. These hypermutable strains have been found in natural bacterial populations at higher frequencies than expected. The presence of mutator strains in the clinical setting may indicate an enhanced risk of acquiring antibiotic resistance through mutational and recombinational events. In addition, some antibiotics are inducers of mechanisms that transiently increase the mutation rate, and thus probably act, not only as mere selectors of antibiotic resistant clones, but also as resistance-promoters.


Molecular probes for cellular imaging of post-translational proteoforms.
Specific post-translational modification (PTM) states of a protein affect its property and function; understanding their dynamics in cells would provide deep insight into diverse signaling pathways and biological processes. However, it is not trivial to visualize post-translational modifications in a protein- and site-specific manner, especially in a living-cell context. Herein, we review recent advances in the development of molecular imaging tools to detect diverse classes of post-translational proteoforms in individual cells, and their applications in studying precise roles of PTMs in regulating the function of cellular proteins.


Serum Copper, Ceruloplasmin and Non Ceruloplasmin Copper Levels in Hyperpigmentary Disorders.
In 50 controls and 50 patients with hyperpigmentation serum copper, ceruloplasmin and non-ceruloplasmin copper have been estimated. Significantly higher levels of serum copper and non-ceruloplasmin copper have been detected in hyperpigmentary disorders. In toxic melanodenna and in females with melasma the main rise had been in non-ceruloplasmin copper, importance of which has been high-lighted.


A rare case of acute on chronic gastric volvulus with Borchardt's triad.
Gastric volvulus is a rare condition with two forms of presentation, either acute or chronic. Since its discovery, there have been no cases of acute on chronic volvulus discussed in the literature. Its vague presentation makes diagnosis and subsequent management difficult. The diagnosis of acute gastric volvulus is made on clinical grounds via Borchardt's triad; however, barium swallow and oesophagogastroduodenoscopy have been shown to play a role. We describe a case of a 95-year-old Caucasian woman who presented with worsening dysphagia, epigastric pain, retching without vomiting and hiccups of 5 months. Initially diagnosed as a hiatus hernia, the patient subsequently died following an acute on chronic gastric volvulus. This rare, life-threatening diagnosis provides an opportunity to discuss characteristics of gastric volvulus and the difficulties in management.


Depressive and anxiety disorders and short leukocyte telomere length: mediating effects of metabolic stress and lifestyle factors.
Depressive and anxiety disorders are associated with shorter leukocyte telomere length (LTL), an indicator of cellular aging. It is, however, unknown which pathways underlie this association. This study examined the extent to which lifestyle factors and physiological changes such as inflammatory or metabolic alterations mediate the relationship. We applied mediation analysis techniques to data from 2750 participants of the Netherlands Study of Depression and Anxiety. LTL was assessed using quantitative polymerase chain reaction. Independent variables were current depressive (30-item Inventory of Depressive Symptoms - Self Report) and anxiety (21-item Beck's Anxiety Inventory) symptoms and presence of a depressive or anxiety disorder diagnosis based on DSM-IV; mediator variables included physiological stress systems, metabolic syndrome components and lifestyle factors. Short LTL was associated with higher symptom severity (B = -2.4, p = 0.002) and current psychiatric diagnosis (B = -63.3, p = 0.024). C-reactive protein, interleukin-6, waist circumference, triglycerides, high-density lipoprotein cholesterol and cigarette smoking were significant mediators in the relationship between psychopathology and LTL. When all significant mediators were included in one model, the effect sizes of the relationships between LTL and symptom severity and current diagnosis were reduced by 36.7 and 32.7%, respectively, and the remaining direct effects were no longer significant. Pro-inflammatory cytokines, metabolic alterations and cigarette smoking are important mediators of the association between depressive and anxiety disorders and LTL. This calls for future research on intervention programs that take into account lifestyle changes in mental health care settings.


Increasing cotton genome coverage with polymorphic SSRs as revealed by SSCP.
Simple sequence repeat (SSR) markers are widely used in plant genetics and breeding. However, there are many SSR markers that do not reveal polymorphism in cotton. Traditional SSR genotyping methods only provide information on product sizes. This leaves many marker polymorphism undetected, thus, lowering the utility of SSRs. In the present study, monomorphic SSRs between two mapping parents, 'Emian22' and 3-79, were subjected to single-strand conformation polymorphism (SSCP) analysis to reveal polymorphism. Of the 4194 monomorphic SSR primer pairs, 158 pairs (3.77%) showed polymorphism and revealed 174 polymorphic loci. Sequence analysis showed that the differences in PCR products between the mapping parents were solely due to base transition or transversion, which was in agreement with SSCP principles. SSCP also revealed SSRs with motifs of AT/TA and GAA/CTT were more polymorphic in dinucleotides and trinucleotides, respectively. Genetic mapping integrated 160 loci into our interspecific BC(1) linkage map, 5 of which associated with QTLs related to cotton fiber quality. The technique discussed in the present study enables us to detect polymorphism of monomorphic SSRs, and increase the utilization efficiency of the existing SSR primers.


Renal function in community-dwelling frail elderly. Comparison between measured and predicted glomerular filtration rate in the elderly and proposal for a new cystatin C-based prediction equation.
There is a great need to evaluate renal function regularly in elderly people. This study aimed at analyzing renal function in stable, community-dwelling elderly people of 75 years and over, to compare measured and predicted glomerular filtration rates (GFR) and to develop an accurate prediction equation for this age group. Forty-five ambulatory elderly people in stable health in ordinary living were randomly selected into four age-classes, aged 75-95. Demographic data, personal activities of daily living, continuous drug prescriptions, body composition, blood pressure and blood chemistry were analysed. GFR was measured as Iohexol clearance based on three time-points 3, 4 and 7 hours after Iohexol injection. Mean GFR was well preserved in all four age-classes. The GFR range was 18-83 mL/min and declined with age. The Cockcroft-Gault prediction equation systematically underestimated measured GFR. A new 'GFRA' prediction equation is presented, based on the inverse of serum cystatin C and independent of gender, body surface area, body weight, lean body mass or serum creatinine. The proposed equation underestimated measured GFR with a mean of only 0.1 mL/min, had better precision compared with the Cockcroft-Gault equation, and was evaluated by the method of cross-validation. GFR exhibits extensive heterogeneity in frail, community-dwelling elderly people. The proposed GFRA was clearly more precise than the Cockcroft-Gault prediction equation in the study group. However, it needs to be validated in a larger population of elderly subjects, including more individuals in stable health with substantially reduced renal function in whom GFR is measured by a reference method with adequate sampling time.


Detection of human papillomavirus DNA in gynaecological swabs by filter in situ hybridization.
Gynaecological smears from the endo- and ectocervix of women with and without cytological and colposcopic abnormalities of the epithelium were investigated for human papillomavirus (HPV) types 6, 11, 16, and 18 by filter in situ hybridization (FISH). The data were compared with cytological, colposcopic, and histological findings. Of the 266 gynaecological smears, HPV DNA was detected in 84 (32%); of 101 cytologically and colposcopically HPV negative cases, HPV DNA was found in 10%. Of 56 women, cytologically and colposcopically positive for HPV infection, HPV DNA was detected in 68%. The sensitivity of the method was controlled by comparing the results of FISH with those of Southern-blot analysis of five cervical tumour biopsies. The data presented demonstrate the necessity of FISH for identification of the HPV type that might be of prognostic value in cervical pathology. Cytological and colposcopic positivity is a reliable sign in about 70% of the cases where HPV infection was proved by FISH.


Primary Pulmonary Malignant Melanoma: Report of an Important Entity and Literature Review.
Malignant melanoma involving the respiratory tract is nearly always metastatic in origin, and primary tumors are extremely rare. Published data on primary pulmonary malignant melanomas are limited. Up to now 40 relevant cases have been reported in the English literature. Herein, we report a case of a 56-year-old female patient who presented with intracranial metastases due to primary pulmonary melanoma. She underwent bronchoscopy and died 5 months after the initial diagnosis despite the administered biochemotherapy and subsequent immunotherapy. To establish the diagnosis of primary pulmonary malignant melanoma, any extrapulmonary origin was excluded by detailed examination and radiographic imaging. Moreover, an extensive review of the literature regarding this rare entity has been performed.


Inhibition of cerebral ischemia/reperfusion injury-induced apoptosis: nicotiflorin and JAK2/STAT3 pathway.
Nicotiflorin is a flavonoid extracted from Carthamus tinctorius. Previous studies have shown its cerebral protective effect, but the mechanism is undefined. In this study, we aimed to determine whether nicotiflorin protects against cerebral ischemia/reperfusion injury-induced apoptosis through the JAK2/STAT3 pathway. The cerebral ischemia/reperfusion injury model was established by middle cerebral artery occlusion/reperfusion. Nicotiflorin (10 mg/kg) was administered by tail vein injection. Cell apoptosis in the ischemic cerebral cortex was examined by hematoxylin-eosin staining and terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Bcl-2 and Bax expression levels in ischemic cerebral cortex were examined by immunohistochemial staining. Additionally, p-JAK2, p-STAT3, Bcl-2, Bax, and caspase-3 levels in ischemic cerebral cortex were examined by western blot assay. Nicotiflorin altered the shape and structure of injured neurons, decreased the number of apoptotic cells, down-regulates expression of p-JAK2, p-STAT3, caspase-3, and Bax, decreased Bax immunoredactivity, and increased Bcl-2 protein expression and immunoreactivity. These results suggest that nicotiflorin protects against cerebral ischemia/reperfusion injury-induced apoptosis via the JAK2/STAT3 pathway.


Synchrony of bone marrow proliferation and maturation as the origin of cyclic haemopoiesis.
Cyclic haemopoiesis in Grey Collie dogs is characterized by stable oscillations in all haemopoietic lineages. It is proposed that in these animals, in contrast to normal animals, the maturation process of haemopoietic (in particular granuloid) cells from the primitive progenitors to the functional cells is characterized by an abnormally strong synchrony. It is conjectured that the marrow maturation time has a very small variance compared with non-cyclic normal dogs. With a mathematical model of haemopoiesis it is shown that small fluctuations are amplified via regular feedback processes such that stable granuloid oscillations are established. Erythroid oscillations are induced indirectly by granuloid feedback to the stem cell pool. The model calculations further show that the synchrony hypothesis of bone marrow maturation can quantitatively explain the following experimental results: (1) the maintenance of stable cycles of granuloid and erythroid bone marrow and blood cells with a period of approximately 14 d; (2) the disappearance of granuloid and erythroid cycles during the administration of the colony stimulating factor rhG-CSF; (3) the reappearance of oscillations when the administration of CSF is discontinued; (4) the cessation of cycles during endotoxin application; and (5) the persistence of cycles during erythroid manipulations (bleeding anaemia, hypoxia, hypertransfusion). We therefore conclude that cyclic haemopoiesis is not caused by a defect in the regulatory control system but by an unusual maturation process.


Manageable microsurgical technique for creating an opening in small vessels for end-to-side anastomosis.
The end-to-side anastomosis is one of the most useful techniques in microsurgery. It creates a recipient opening for the donor, keeps the donor vessel intact, and does not interrupt distal blood flow, compared to the end-to-end anastomosis technique. The end-to-side anastomosis is consequently becoming more acceptable in reconstructive microsurgery. The author describes a manageable microsurgical technique for creating recipient vessel openings in small vessels for end-to-side anastomoses.


Stenting of a large thrombus-containing subclavian artery stenosis using a distal protection device.
Atheromatous obstructive lesions of the arch vessels that contain thrombi are at high risk for distal embolization during angioplasty. This can lead to catastrophic neurological complications. We report a case of acute-on-chronic ischemia of the left upper limb due to thrombus-containing subclavian artery stenosis. After placement of an intravascular filter device, angioplasty and stent implantation successfully relieved the stenosis without any complications.


Do we have to hyperventilate during laparoscopic surgery?
The purpose of this study was to assess the effects of hyperventilation on patients undergoing laparoscopic surgeries on haemodynamics, partial pressure of carbon dioxide and acid base status. 60 patients undergoing laparoscopic surgeries under General Anaesthesia were randomized into two groups, "control group" ventilated with tidal volume of 10 ml/kg and respiratory rate of 12/minute and "study group" same tidal volume with respiratory rate of 15/ minute. Hemodynamic variables (heart rate and mean arterial pressure) recorded and End tidal C02, PaC02, pH and Bicarbonate estimation done before, during and after C02 pneumoperitoneum and analyzed. There was no significant difference in hemodynamic variables but there was linear increase in ETC02 and PaC02 measurements in higher normal levels in control group (ETC02 33.3+/-3.20, 37.93+/-3.95 and 43.20+/-3.40; PaC02 30.08+/-2.35, 34.80+/-4.01 and 41.94+/-3.66 mmHg before, during, and after pneumoperitoneum respectively) compared to study group in which these parameters were in lower normal levels (ETC02 33.33+/-4.11, 28.00+/-4.10 and 36.73+/-2.49 mmHg and PaC02 31.80+/-2.73, 29.36+/-3.16 and 35.15+/-1.32 mmHg before, during, and after pneumoperitoneum respectively). There was highly significant difference in these parameters when intergroup comparison was done during and after pneumoperitoneum period. pH and bicarbonate levels were within normal limits but there was decreasing tendency towards acidosis side in control group. 10-15% increment in Minute Volume is beneficial during C02 pneumoperitoneum to prevent adverse effects of hypercarbia and acidosis.


Inverse design and implementation of a wavelength demultiplexing grating coupler.
Nanophotonics has emerged as a powerful tool for manipulating light on chips. Almost all of today's devices, however, have been designed using slow and ineffective brute-force search methods, leading in many cases to limited device performance. In this article, we provide a complete demonstration of our recently proposed inverse design technique, wherein the user specifies design constraints in the form of target fields rather than a dielectric constant profile, and in particular we use this method to demonstrate a new demultiplexing grating. The novel grating, which has not been developed using conventional techniques, accepts a vertical-incident Gaussian beam from a free-space and separates O-band (1300 nm) and C-band (1550 nm) light into separate waveguides. This inverse design concept is simple and extendable to a broad class of highly compact devices including frequency filters, mode converters, and spatial mode multiplexers.


Rove beetles collected with carrion traps (Coleoptera: Staphylinidae) in Quercus forest of Cerro de García, Jalisco and Quercus, Quercus-pine, and pine forests in other jurisdictions of Mexico.
We present the species diversity of rove beetles (Coleoptera: Staphylinidae) collected with carrion baited traps in Quercus forests of Cerro de García, Jalisco, and provide a compilation of published species records in Quercus, Quercus-pine and pine forests in other jurisdictions of Mexico. This work includes taxonomic notes, information on species phenology, distribution, and their occurrence in Cerro de García (if applicable), and other jurisdictions of Mexico. In Cerro de García, 75 species were collected in total, of which 16 are shared with other Quercus forests in different locations, and 9 species are provided with new habitat data. The remaining individuals were only determined to morphospecies. In Mexico, there are 77 known species of rove beetles collected with carrion traps (determined to species or near species) and recorded from Quercus, Quercus-pine and pine forests. These species belong to 30 genera, 11 tribes and 10 subfamilies. This study provides biological information on Mexican rove beetles captured with carrion traps and highlights the importance of rove beetles as indicator species of habitat change for conservation analysis, forestry, agronomy and forensic sciences studies.


[Successful treatment with rituximab in a patient with refractory thrombotic thrombocytopenic purpura refractory to plasma exchange].
We report a patient with refractory idiopathic thrombotic thrombocytopenic purpura (TTP) who was successfully treated with rituximab. A 50-year-old woman was referred to our hospital with progressive psychoneurotic symptoms, hemolytic anemia and thrombocytopenia. The diagnosis of TTP was confirmed by the absence of ADAMTS13 activity with the presence of circulating ADAMTS13 inhibitor. High-dose steroid therapy and plasma exchange were performed. Despite 21 sessions of plasma exchange, however, there was no remarkable improvement. We then administered rituximab. Fifteen days after the first infusion of rituximab, she achieved complete remission and ADAMTS13 activity increased up to 14%. The patient has remained in remission for more than 9 months.


Alcanivorax sediminis sp. nov., isolated from deep-sea sediment of the Pacific Ocean.
A taxonomic study was carried out on strain PA15-N-34T, which was isolated from deep-sea sediment of Pacific Ocean. The bacterium was Gram-stain-positive, oxidase- and catalase-positive and rod-shaped. Growth was observed at salinity of 0-15.0% NaCl and at temperatures of 10-45 °C. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain PA15-N-34T belonged to the genus Alcanivorax, with the highest sequence similarity to Alcanivorax profundi MTEO17T (97.7 %), followed by Alcanivorax nanhaiticus 19 m-6T (97.3 %) and 12 other species of the genus Alcanivorax (93.4 %-97.0 %). The average nucleotide identity and DNA-DNA hybridization values between strain PA15-N-34T and type strains of the genus Alcanivorax were 71.46-81.78% and 18.7-25.2 %, respectively. The principal fatty acids (>10 %) were summed feature 8 (C18 : 1 ω7c and/or C18 : 1 ω6c; 31.2 %), C16 : 0 (25.0 %) and summed feature 3 (14.6 %). The DNA G+C content was 57.15 mol%. The polar lipids were phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, four unidentified aminolipids and three unidentified lipids. The novel strain can be differentiated from its closest type strain by a negative test for urease and the presence of diphosphatidylglycerol and aminolipid. The combined genotypic and phenotypic data show that strain PA15-N-34T represents a novel species within the genus Alcanivorax, for which the name Alcanivorax sediminis sp. nov. is proposed, with the type strain PA15-N-34T (=MCCC 1A14738T=KCTC 72163T).


Birth Outcomes after the Fukushima Daiichi Nuclear Power Plant Disaster: A Long-Term Retrospective Study.
Changes in population birth outcomes, including increases in low birthweight or preterm births, have been documented after natural and manmade disasters. However, information is limited following the 2011 Fukushima Daiichi Nuclear Power Plant Disaster. In this study, we assessed whether there were long-term changes in birth outcomes post-disaster, compared to pre-disaster data, and whether residential area and food purchasing patterns, as proxy measurements of evacuation and radiation-related anxiety, were associated with post-disaster birth outcomes. Maternal and perinatal data were retrospectively collected for all live singleton births at a public hospital, located 23 km from the power plant, from 2008 to 2015. Proportions of low birthweight (<2500 g at birth) and preterm births (<37 weeks gestation at birth) were compared pre- and post-disaster, and regression models were conducted to assess for associations between these outcomes and evacuation and food avoidance. A total of 1101 live singleton births were included. There were no increased proportions of low birthweight or preterm births in any year after the disaster (merged post-disaster risk ratio of low birthweight birth: 0.98, 95% confidence interval (CI): 0.64-1.51; and preterm birth: 0.68, 95% CI: 0.38-1.21). No significant associations between birth outcomes and residential area or food purchasing patterns were identified, after adjustment for covariates. In conclusion, no changes in birth outcomes were found in this institution-based investigation after the Fukushima disaster. Further research is needed on the pathways that may exacerbate or reduce disaster effects on maternal and perinatal health.


Supporting communication in semantic dementia: clinical consensus from expert practitioners.
The purpose of this paper is to gain consensus regarding the clinical priorities and tasks required in supporting communication needs in those living with semantic dementia and their families, by specialist speech and language therapists (SLTs), working in clinical practice within dementia care settings in the UK. A nominal group technique was used, followed by further exploration and refinement of issues using a modified Delphi technique with a group of six SLTs who specialised in dementia care and who had experience of working with individuals with semantic dementia and their families. The findings in the study demonstrate a broader scope of practice than is evident within the research literature with this client group. Therapists identified a range of psychosocial issues for both the person with semantic dementia and their family, in particular finding ways to support activity and participation in conversation and explore barriers and facilitators within the communication environment. This represents the first study to explore everyday practice in this rarer dementia and the information gathered here will be of use to a variety of health and social care professions interested in supporting those with semantic dementia and their families.


Vestibular schwannoma surgical treatment.
Neurosurgical intervention remains the main step in the effective management of vestibular schwannomas. Extensive studies on vestibular schwannoma treatment have placed emphasis on preserving quality of life and neurological functions, particularly of the facial and vestibulocochlear nerves. Facial nerve preservation and hearing preservation have been achieved by significant advances in skull base microsurgical techniques and intraoperative neuromonitoring. Diffusion tensor imaging is a powerful and accurate method for preoperatively identifying the facial nerve in relation to vestibular schwannomas. Endoscopy offers excellent illumination of the anatomical structures and provides panoramic vision inside the surgical area. In this report, we focused on facial nerve and vestibulocochlear nerve preservation and analyzed the major techniques used for identifying the nerve-tumor relationship.


SVM Based Descriptor Selection and Classification of Neurodegenerative Disease Drugs for Pharmacological Modeling.
Systems pharmacological modeling of drug mode of action for the next generation of multitarget drugs may open new routes for drug design and discovery. Computational methods are widely used in this context amongst which support vector machines (SVM) have proven successful in addressing the challenge of classifying drugs with similar features. We have applied a variety of such SVM-based approaches, namely SVM-based recursive feature elimination (SVM-RFE). We use the approach to predict the pharmacological properties of drugs widely used against complex neurodegenerative disorders (NDD) and to build an in-silico computational model for the binary classification of NDD drugs from other drugs. Application of an SVM-RFE model to a set of drugs successfully classified NDD drugs from non-NDD drugs and resulted in overall accuracy of ∼80 % with 10 fold cross validation using 40 top ranked molecular descriptors selected out of total 314 descriptors. Moreover, SVM-RFE method outperformed linear discriminant analysis (LDA) based feature selection and classification. The model reduced the multidimensional descriptors space of drugs dramatically and predicted NDD drugs with high accuracy, while avoiding over fitting. Based on these results, NDD-specific focused libraries of drug-like compounds can be designed and existing NDD-specific drugs can be characterized by a well-characterized set of molecular descriptors.


Sedentary Behavior in Preschoolers: How Many Days of Accelerometer Monitoring Is Needed?
The reliability of accelerometry for measuring sedentary behavior in preschoolers has not been determined, thus we determined how many days of accelerometry monitoring are necessary to reliably estimate daily time spent in sedentary behavior in preschoolers. In total, 191 and 150 preschoolers (three to five years) wore ActiGraph accelerometers (15-s epoch) during the in-school (≥4 days) and the total-day (≥6 days) period respectively. Accelerometry data were summarized as time spent in sedentary behavior (min/h) using three different cutpoints developed for preschool-age children (<37.5, <200, and <373 counts/15 s). The intraclass correlations (ICCs) and Spearman-Brown prophecy formula were used to estimate the reliability of accelerometer for measuring sedentary behavior. Across different cutpoints, the ICCs ranged from 0.81 to 0.92 for in-school sedentary behavior, and from 0.75 to 0.81 for total-day sedentary behavior, respectively. To achieve an ICC of ≥0.8, two to four days or six to nine days of monitoring were needed for in-school sedentary behavior and total-day sedentary behavior, respectively. These findings provide important guidance for future research on sedentary behavior in preschool children using accelerometry. Understanding the reliability of accelerometry will facilitate the conduct of research designed to inform policies and practices aimed at reducing sedentary behavior in preschool children.


Stepwise Targeted Matching Strategy for Comprehensive Profiling of Xanthohumol Metabolites In Vivo and In Vitro Using UHPLC-Q-Exactive Orbitrap Mass Spectrometer.
Xanthohumol (XN), a natural prenylated flavonoid extracted and isolated from the hop plant (Humulus lupulus), possesses diverse pharmacological activities. Although the metabolites of XN have been investigated in the previous study, a comprehensive metabolic profile has been insufficient in vivo or in vitro until now. The current study was aimed at systematically elucidating the metabolic pathways of XN after oral administration to rats. Herein, a UHPLC-Q-Exactive Orbitrap MS was adopted for the potential metabolites detection. A stepwise targeted matching strategy for the overall identification of XN metabolites was proposed. A metabolic net (53 metabolites included) on XN in vivo and in vitro, as well as the metabolic profile investigation, were designed, preferably characterizing XN metabolites in rat plasma, urine, liver, liver microsomes, and feces. On the basis of a stepwise targeted matching strategy, the net showed that major in vivo metabolic pathways of XN in rats include glucuronidation, sulfation, methylation, demethylation, hydrogenation, dehydrogenation, hydroxylation, and so on. The proposed metabolic pathways in this research will provide essential data for further pharmaceutical studies of prenylated flavonoids and lay the foundation for further toxicity and safety studies.


Negative sonographic findings followed by rapid cervical dilatation due to cervical incompetence.
A case of rapid cervical dilatation due to cervical incompetence within 20 minutes of a negative sonogram is presented. Patients with a history of cervical incompetence should not be followed by sonography to determine which ones require therapy.


Aberrant function of myeloid-derived suppressor cells (MDSCs) in experimental colitis and in inflammatory bowel disease (IBD) immune responses.
Myeloid-derived suppressor cells (MDSCs) encompass a novel population of suppressor cells and a potential candidate for cell-based therapies in inflammatory diseases. Herein, we investigated their immunomodulatory properties in experimental inflammatory colitis and T cell-mediated immune responses in inflammatory bowel disease (IBD) patients. MDSCs (defined as CD14-HLA-DR-/lowCD33+CD15+) numbers were determined in peripheral blood (PB) from IBD patients. PB MDSC function was assessed in vitro. Experimental colitis was induced upon 2,4,6-trinitrobenzene sulfonic acid (TNBS) treatment and MDSCs were characterized by flow cytometry. The in vivo suppressive potential of bone marrow (BM)-derived MDSCs (BM-MDSCs) was tested by using both depleting and adoptive transfer strategies. MDSCs were enriched in the periphery of IBD patients during active disease. TNBS colitis induced amplification of MDSCs, particularly of the granulocytic (Ly6G+) subset during the effector phase of disease. Of interest, BM-MDSCs potently suppressed CD4+ T cell responses under steady state but failed to control colitis-associated immune responses in vivo. Mechanistically, under the colonic inflammatory milieu MDSCs switched phenotype (decreased proportion of Gr1high and increased numbers of Gr1low) and downregulated CCAAT/enhancer-binding protein beta (CEBPβ) expression, a critical transcription factor for the suppressive function of MDSCs. In accordance with the murine data, human CD33 + CD15+ MDSCs from peripheral blood of IBD patients not only failed to suppress autologous T cell responses but instead enhanced T cell proliferation in vitro. Our findings demonstrate an aberrant function of MDSCs in experimental inflammatory colitis and in IBD-associated immune responses in vitro. Delineation of the mechanisms that underlie the loss of MDSCs function in IBD may provide novel therapeutic targets.


Poverty, economic growth, deprivation, and water: the cases of Cambodia and Vietnam.
Poverty reduction decorates all development agendas, but the complexity of the poverty issue is too often hidden behind simplistic indicators and development goals. Here, a closer look is taken at the concepts of "deprivation" and "vulnerability" as outcomes of poverty. Deprivation leads typically to social exclusion and marginalization; such groups are particularly weak in getting themselves out of poverty by "self-help," and economic growth does not trickle down to these people. When looking at the connections between poverty reduction and economic growth, special emphasis should be put on the differences between modern and more traditional sectors: development of the modern sector should not marginalize and exclude those dependent on more traditional livelihoods. Two case studies--The Tonle Sap area, Cambodia, and the Mekong Delta, Vietnam--reveal that investment in education, empowerment of small-scale entrepreneurship and other means of microeconomic environment, along with good governance, infrastructure, and income distribution can ensure that economic growth includes the poorer echelons of society.


Relationship Between Synaptic AMPAR and Spine Dynamics: Impairments in the FXS Mouse.
Structural dynamics of dendritic spines are important for memory and learning and are impaired in neurodevelopmental disorders such as fragile X syndrome. Spine dynamics are regulated by activity-dependent mechanisms that involve modulation of AMPA receptors (AMPAR); however, the relationship between AMPAR and spine dynamics in vivo and how these are altered in FXS mouse model is not known. Here, we tracked AMPAR and spines over multiple days in vivo in the cortex and found that dendritic spines in the fmr1 KO mouse were denser, smaller, had higher turnover rates and contained less sGluA2 compared to littermate controls. Although, KO spines maintained the relationship between AMPAR and spine stability, AMPAR levels in the KO were more dynamic with larger proportion of spines showing multiple dynamic events of AMPAR. Directional changes in sGluA2 were also observed in newly formed and eliminated spines, with KO spines displaying greater loss of AMPAR before elimination. Thus, we demonstrate that AMPAR levels within spines not are only continuously dynamic, but are also predictive of spine behavior, with impairments observed in the fmr1 KO mice.


Blockade of LOX-1 prevents endotoxin-induced acute lung inflammation and injury in mice.
Lectin-like oxidized low-density lipoprotein (LDL) receptor-1 (LOX-1), a cell surface receptor expressed in endothelial cells, is known to mediate oxidized LDL-induced vascular inflammation and atherogenesis. Although the role of LOX-1 in vascular inflammation has been well established, its involvement in acute lung inflammation and injury remains unclear. In the present study, we examined the effects of a LOX-1-blocking antibody on lung inflammation in a mouse endotoxin lipopolysaccharide (LPS)-induced acute lung injury model. We demonstrated that intraperitoneal challenge with LPS induced a rapid and robust increase in LOX-1 expression in mouse lung. Pre-treatment of mice with anti-LOX-1-blocking antibody significantly inhibited LPS-induced lung inflammation as indicated by decreased neutrophil accumulation in the lung. Furthermore, anti-LOX-1 was capable of inhibiting LPS-induced inflammatory responses, including NF-kappaB activation, ICAM-1 expression and apoptotic signaling, in mouse lung. Collectively, these results indicate that LOX-1 may serve as a valuable therapeutic target in the prevention of acute lung inflammation and injury in sepsis.


Inhibitory effect of jujuboside A on glutamate-mediated excitatory signal pathway in hippocampus.
Jujuboside A (JuA) is a main component of jujubogenin extracted from the seed of Ziziphus jujuba Mill var spinosa (Bunge) Hu ex H F Chou (Ziziphus), which is widely used in Chinese traditional medicine for the treatment of insomnia and anxiety. Previously, we reported the inhibitory effects of JuA on hippocampal formation in vivo and in vitro, the present study was carried out to examine the effects of JuA on glutamate (Glu)-mediated excitatory signal pathway in hippocampus. Microdialysis coupled with high-performance liquid chromatography (HPLC) was used to monitor the changes of Glu levels in the hippocampus induced by penicillin sodium, or a mixture of penicillin sodium and JuA. The results showed that penicillin increased the hippocampal Glu concentration (p < 0.01) and a high dose of JuA (0.1 g/L) significantly blocked penicillin-induced Glu release (p < 0.05). Moreover, the effect of JuA on intracellular Ca2+ changes after the stimulation by Glu was studied in cultured hippocampal neurons with confocal laser scanning microscope (CLSM). It was found that Glu (0.5 mM) induced an intracellular [Ca2+]i increase (p < 0.01), and JuA significantly inhibited the Glu-induced Ca2+ increase. The calmodulin (CaM) antagonist trifluoperazine (TFP) showed a similar inhibitory effect as JuA. These observations suggested that JuA has inhibitory effects on Glu-mediated excitatory signal pathway in hippocampus and probably acts through its anti-calmodulin action.


Evaluation of the Effect Coronavirus Lockdown had on Chronic Disease Management Care in Pediatrics: A Survey of Jordanian Pediatricians.
The outbreak of the COVID-19 pandemic puts a great strain on the healthcare system, as the national and global infection rates increased rapidly. Efforts were devoted to minimizing the effects of the spreading pandemic without overwhelming the already stretched healthcare system. The study objective was to establish how coronavirus lockdown was affecting chronic disease care among pediatric patients admitted to hospitals in developing countries. For that purpose, a cross-sectional survey of registered pediatricians was carried out. Findings showed that the mortality rate from COVID-19 in children seemed to be low. However, children with chronic illnesses were likely to be gravely affected by the disturbance of repetitive healthcare services. About 79% of pediatricians treated a child with a chronic condition during the lockdown. Furthermore, 15% of patients with chronic diseases visiting pediatricians exhibited uncontrolled emerging complications. In addition, 9% of pediatricians reported one to five fatalities among children under their care due to delay or lack of appropriate medical care in the period of the lockdown. Residents (48.9%) reported a significantly (p < 0.001) higher proportion of providing face-to-face services compared with consultants (17.9%) and specialists (13.6%). In conclusion, the care of chronically ill children should be taken into consideration when implementing lockdown and/or social distancing, thus minimizing the negative effects of lockdown and/or social distancing on children with chronic diseases.


Altering adenoviral tropism via click modification with ErbB specific ligands.
Methods for targeting oncolytic viruses can increase efficacy and accelerate development. Genetic engineering, the predominant method for changing vector tropism, is limited in scope and often represents the bottleneck for vector development. Metabolic incorporation of an unnatural azido sugar, O-GlcNAz, at a specific site on the adenoviral surface allows chemoselective attachment of affibodies for Her2 or EGF receptors. Modification with these high-affinity, high-selectivity proteins is straightforward and readily generalizable, demonstrates minimal impact on virus physiology, and affords significant increases in gene delivery to cancer cells. As a result, this method has significant potential to increase the efficacy of next-generation viral vectors.


Hepatitis B surface antigen predicts recurrence after radiofrequency ablation in patients with low hepatitis B virus loads.
Radiofrequency ablation (RFA) is a first-line option for the treatment of small liver cancers, but the recurrence remains a problem affecting long-term survival. Hepatitis B virus (HBV) activity is associated with the prognosis of hepatocellular carcinoma (HCC). We investigated the significance of hepatitis B surface antigen (HBsAg) in HCC recurrence after curative RFA treatment in HBV-related small HCC.We enrolled 404 HBV-related patients with small HCC (≤3 cm) who underwent curative RFA. We used univariate and multivariate analyses to investigate the baseline levels of HBsAg, in addition to other known risk factors for HCC recurrence, for association with HCC tumor recurrence after curative RFA.The overall 1-, 2-, and 3-year recurrence-free survival (RFS) rates were 75%, 50%, and 34%, respectively. The median recurrence-free time was 25 months. The level of HBsAg was an independent risk factor for recurrence in patients with lower HBV-DNA levels. In hepatitis Be antigen (HBeAg)-negative patients, the 1-, 2-, and 3-year RFS rates were 79%, 64%, and 44%, respectively, for that with low HBsAg levels, compared with 73%, 50%, and 37%, respectively, for that with high HBsAg levels (P = .039).HBsAg might serve as a valuable marker to evaluate the risk of HCC recurrence in HBeAg-negative patients with low HBV viral load.


Significant pharmacokinetic differences of berberine are attributable to variations in gut microbiota between Africans and Chinese.
We investigated the influence of gut microbiotal metabolism on the pharmacokinetics of berberine in healthy male Africans and Chinese. The Cmax and AUC in the Africans were 2.67-fold and 2.0-fold higher than the Chinese, respectively. Microbiotal compositions by 16S rRNA pyrosequencing showed higher abundance of the genera Prevotella, Bacteroides, and Megamonas (34.22, 13.88, and 10.68%, respectively) in the Chinese than the Africans (30.08, 9.43, and 0.48%, respectively). Scatter plot showed a strong negative correlation between the microbiotal abundance and the berberine AUC, especially for the genus Prevotella (r = -0.813) and its species. A more extensive metabolism was observed in Chinese with 1.83-fold higher metabolites, possibly contributing to the lower AUC than the Africans. In conclusion, significant PK differences of berberine were observed between Africans and Chinese, which is partly attributable to variations in gut microbiota and its corresponding metabolic capacity.


Epidemiology of Nontuberculous Mycobacterial Infection in Tuberculosis Suspects.
Nontuberculosis mycobacteria (NTM) are opportunistic pathogens that cause a wide range of illnesses. Here, the species distribution and prevalence of NTM infections in tuberculosis suspects was analyzed. A total of 7,073 specimens from pulmonary and extrapulmonary sites were analyzed, and 709 (10%) were found to be culture positive for mycobacteria. Of these, 85.2% were identified as Mycobacterium tuberculosis complex and 14.8% as NTM (65.7% rapid growers and 34.3% slow growers). Speciation of the NTM isolates (n = 69) identified 19 NTM species. M. abscessus (33.3%) and M. fortuitum (24.6%) were the most dominant NTM species isolated from the patients, followed by M. porcinum (5.8%) and M. parascrofulaceum (4.3%). We also report peritonitis caused by rapidly growing NTM among the patients undergoing continuous ambulatory peritoneal dialysis and a case of M. senegalense peritonitis. A low prevalence but high species diversity of NTM was detected in our study. The high species diversity of NTM necessitates the need to unequivocally identify mycobacterial isolates for appropriate treatment.


Size and stability of reconstituted sesame oil bodies.
Oil bodies of sesame seeds comprise a triacylglycerol matrix, which is surrounded by a monolayer of phospholipids embedded with unique proteins, mainly structural proteins termed oleosins. Artificial oil bodies were successfully reconstituted with various compositions of triacylglycerols, phospholipids, and oil-body proteins. The sizes of reconstituted oil bodies displayed a normal distribution with an average size proportional to the ratio of triacylglycerols to oil-body proteins. Both thermostability and structural stability of reconstituted oil bodies decreased as their sizes increased, and vice versa. Proteinase K digestion indicated that oleosins anchored both native and reconstituted oil bodies via their central hydrophobic domains. The stability of reconstituted oil bodies, as well as the purified ones from sesame seeds, could be substantially enhanced after their surface proteins were cross-linked by glutaraldehyde or genipin.


[Bilateral adrenal lymphoma. A case report].
A rare case of malignant non-Hodgkin lymphoma of the adrenal gland in a 59-year-old male is reported. This patient, completely healthy, observed for a routine check after a laparoscopic cholecystectomy performed one year before, underwent an explorative laparatomy for getting information about a retroperitoneal mass, ultrasound scan observed. A CT guided needle biopsy was inconclusive to clarify this rare haematological diagnosis.


Photocontrol over cucurbit[8]uril complexes: stoichiometry and supramolecular polymers.
Herein we report the photocontrol of cucurbit[8]uril (CB[8])-mediated supramolecular polymerization of azobenzene-containing monomers. The CB[8] polymers were characterized both in solution and in the solid state. These host-guest complexes can be reversibly switched between highly thermostable photostationary states. Moreover, a remarkable stabilization of Z-azobenzene was achieved by CB[8] complexation, allowing for structural characterization in the solid state.


Tungsten carbide revisited: New anion photoelectron spectrum and density functional theory calculations.
A new anion photoelectron (PE) spectrum of WC(-) is presented and analyzed using existing and new calculations. This spectrum is different from the PE spectrum previously published [X. Li et al., J. Chem. Phys. 111, 2464 (1999)], which we suggest was actually the PE spectrum of W(-). The ground anion state is determined by calculations and comparison with spectral features to be the (2)Delta(32) state. The (3)Delta(1)-(2)Delta(32) transition is observed at an electron binding energy of 2.155 eV, which corresponds to the adiabatic electron affinity of WC. The bond length of the anion is determined to be 1.771(5) A. A number of spectral assignments corresponding to both excited anion and neutral states are made based on previously obtained fluorescence spectra [S. M. Sickafoose et al., J. Chem. Phys. 116, 993 (2002)] and density functional theory calculations.


Skeletal muscle capillarity during hypoxia: VEGF and its activation.
Long-term exposure of humans and many mammals to hypoxia leads to the activation of several cellular mechanisms within skeletal muscles that compensate for a limited availability of cellular oxygen. One of these cellular mechanisms is to increase the expression of a subset of hypoxia-inducible genes, including the expression of vascular endothelial growth factor (VEGF). The VEGF promoter contains a hypoxic response element (HRE) that can bind the transcription factor, hypoxia-inducible factor-1alpha; (HIF-1alpha), and initiate transcriptional activation of the VEGF gene. VEGF gene expression is critically important for skeletal muscle angiogenesis and VEGF gene deletion in the mouse has been shown to greatly reduce skeletal muscle capillarity. However, HIF-1alpha-dependent transcriptional activation of the VEGF gene may not be the only signaling pathway that leads to increased or maintained VEGF levels under conditions of acute or long-term hypoxia. Additional mechanisms, induced during hypoxic exposure that could signal skeletal muscle VEGF activation include inflammation, possibly linked to reactive O(2) species generation, or a change in cellular energy status as reflected by AMP kinase activity. These pathways may provide quite different mechanisms for VEGF upregulation in the context of muscular activity during long-term exposure to a hypoxic environment such as occurs at high altitude. This review will accordingly discuss the potential cellular signals or stimuli resulting from hypoxic exposure that could increase myocyte VEGF expression. These cellular signals include 1) a decrease in intracellular P(O(2)), 2) skeletal muscle inflammation, associated cytokines and oxidative stress, and 3) an increase in AMP kinase activity and adenosine accompanying a reduction in cellular energy potential.


Characterization of Danon disease in a male patient and his affected mother.
Danon disease, primary lysosome-associated membrane protein-2 (LAMP-2) deficiency, is histologically characterized by unusual vacuoles bound by membranes with sarcolemmal features in skeletal muscle. We studied skeletal muscle specimens from a male patient with genetically confirmed Danon disease who had two muscle biopsies, at age 20 months and 16 years, and from his mother with cardiomyopathy but without clinically apparent skeletal myopathy. In the patient, the number of vacuoles increased over the 14-year interval between biopsies, suggesting that the number of vacuolated fibers increases with age, and correlates with the development of muscle symptoms. In contrast, in the muscle biopsy from the mother there were no vacuoles even though she had decreased LAMP-2.


Synthesis of Fluorine-Containing Phosphodiesterase 10A (PDE10A) Inhibitors and the In Vivo Evaluation of F-18 Labeled PDE10A PET Tracers in Rodent and Nonhuman Primate.
A series of fluorine-containing PDE10A inhibitors were designed and synthesized to improve the metabolic stability of [(11)C]MP-10. Twenty of the 22 new analogues had high potency and selectivity for PDE10A: 18a-j, 19d-j, 20a-b, and 21b had IC50 values <5 nM for PDE10A. Seven F-18 labeled compounds [(18)F]18a-e, [(18)F]18g, and [(18)F]20a were radiosynthesized by (18)F-introduction onto the quinoline rather than the pyrazole moiety of the MP-10 pharmacophore and performed in vivo evaluation. Biodistribution studies in rats showed ~2-fold higher activity in the PDE10A-enriched striatum than nontarget brain regions; this ratio increased from 5 to 30 min postinjection, particularly for [(18)F]18a-d and [(18)F]20a. MicroPET studies of [(18)F]18d and [(18)F]20a in nonhuman primates provided clear visualization of striatum with suitable equilibrium kinetics and favorable metabolic stability. These results suggest this strategy may identify a (18)F-labeled PET tracer for quantifying the levels of PDE10A in patients with CNS disorders including Huntington's disease and schizophrenia.


Influenza vaccination during pregnancy and risk of selected major structural noncardiac birth defects, National Birth Defects Prevention Study 2006-2011.
To assess associations between influenza vaccination during etiologically-relevant windows and selected major structural non-cardiac birth defects. We analyzed data from the National Birth Defects Prevention Study, a multisite, population-based case-control study, for 8233 case children diagnosed with a birth defect and 4937 control children without a birth defect with delivery dates during 2006-2011. For all analyses except for neural tube defects (NTDs), we classified mothers who reported influenza vaccination 1 month before through the third pregnancy month as exposed; the exposure window for NTDs was 1 month before through the first pregnancy month. For defects with five or more exposed case children, we used logistic regression to estimate propensity score-adjusted odds ratios (aORs) and 95% confidence intervals (CIs), adjusting for estimated delivery year and season; plurality; maternal age, race/ethnicity, smoking and alcohol use, low folate intake; and, for NTDs, folate antagonist medications. There were 334 (4.1%) case and 197 (4.0%) control mothers who reported influenza vaccination from 1 month before through the third pregnancy month. Adjusted ORs ranged from 0.53 for omphalocele to 1.74 for duodenal atresia/stenosis. Most aORs (11 of 19) were ≤1 and all adjusted CIs included the null. The unadjusted CIs for two defects, hypospadias and craniosynostosis, excluded the null. These estimates were attenuated upon covariate adjustment (hypospadias aOR: 1.25 (95% CI 0.89, 1.76); craniosynostosis aOR: 1.23 (95% CI: 0.88, 1.74)). Results for several non-cardiac major birth defects add to the existing evidence supporting the safety of inactivated influenza vaccination during pregnancy. Under-reporting of vaccination may have biased estimates downward.


Alpha thalassemia/mental retardation syndrome X-linked gene product ATRX is required for proper replication restart and cellular resistance to replication stress.
Alpha thalassemia/mental retardation syndrome X-linked (ATRX) is a member of the SWI/SNF protein family of DNA-dependent ATPases. It functions as a chromatin remodeler and is classified as an SNF2-like helicase. Here, we showed somatic knock-out of ATRX displayed perturbed S-phase progression as well as hypersensitivity to replication stress. ATRX is recruited to sites of DNA damage, required for efficient checkpoint activation and faithful replication restart. In addition, we identified ATRX as a binding partner of MRE11-RAD50-NBS1 (MRN) complex. Together, these results suggest a non-canonical function of ATRX in guarding genomic stability.


Coenzyme Q10 Supplementation Improves Adipokine Levels and Alleviates Inflammation and Lipid Peroxidation in Conditions of Metabolic Syndrome: A Meta-Analysis of Randomized Controlled Trials.
Evidence from randomized controlled trials (RCTs) suggests that coenzyme Q10 (CoQ10) can regulate adipokine levels to impact inflammation and oxidative stress in conditions of metabolic syndrome. Here, prominent electronic databases such as MEDLINE, Cochrane Library, and EMBASE were searched for eligible RCTs reporting on any correlation between adipokine levels and modulation of inflammation and oxidative stress in individuals with metabolic syndrome taking CoQ10. The risk of bias was assessed using the modified Black and Downs checklist, while the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool was used to evaluate the quality of evidence. Results from the current meta-analysis, involving 318 participants, showed that CoQ10 supplementation in individuals with metabolic syndrome increased adiponectin levels when compared to those on placebo (SMD: 1.44 [95% CI: -0.13, 3.00]; I2 = 96%, p < 0.00001). Moreover, CoQ10 supplementation significantly lowered inflammation markers in individuals with metabolic syndrome in comparison to those on placebo (SMD: -0.31 [95% CI: -0.54, -0.08]; I2 = 51%, p = 0.07). Such benefits with CoQ10 supplementation were related to its ameliorative effects on lipid peroxidation by reducing malondialdehyde levels, concomitant to improving glucose control and liver function. The overall findings suggest that optimal regulation of adipokine function is crucial for the beneficial effects of CoQ10 in improving metabolic health.


HIV-1 Nef promotes infection by excluding SERINC5 from virion incorporation.
HIV-1 Nef, a protein important for the development of AIDS, has well-characterized effects on host membrane trafficking and receptor downregulation. By an unidentified mechanism, Nef increases the intrinsic infectivity of HIV-1 virions in a host-cell-dependent manner. Here we identify the host transmembrane protein SERINC5, and to a lesser extent SERINC3, as a potent inhibitor of HIV-1 particle infectivity that is counteracted by Nef. SERINC5 localizes to the plasma membrane, where it is efficiently incorporated into budding HIV-1 virions and impairs subsequent virion penetration of susceptible target cells. Nef redirects SERINC5 to a Rab7-positive endosomal compartment and thereby excludes it from HIV-1 particles. The ability to counteract SERINC5 was conserved in Nef encoded by diverse primate immunodeficiency viruses, as well as in the structurally unrelated glycosylated Gag from murine leukaemia virus. These examples of functional conservation and convergent evolution emphasize the fundamental importance of SERINC5 as a potent anti-retroviral factor.


HLA restriction of secondary mumps-specific cytotoxic T lymphocytes.
Mumps virus-specific cytotoxic T lymphocytes (CTL) were induced by incubating peripheral lymphocytes from healthy blood donors with autologous mumps virus-infected stimulator cells. Maximum cytotoxicity was generated after 5 to 7 days in culture. No cytotoxic activity was induced in the absence of viral antigens. The cytotoxicity induced in vitro was a secondary immune response, because no specific lytic activity could be generated in lymphocyte cultures from mumps seronegative donors. The effector cells were restricted by the HLA complex in a "hierarchical" pattern. The major restriction antigens for secondary CTL were certain HLA B determinants such as B18, B27, Bw25, Bw62, and Bw63. Mumps responses in spite of high [3H]-thymidine uptake in sensitized cultures. The present data suggest that mumps virus-specific CTL may be directly regulated by certain genes of the HLA B locus.


Multiple muscular variations including tenuissimus and tensor fasciae suralis muscles in the posterior thigh of a human case.
The posterior thigh muscles on the right side of an 81-year-old male cadaver had multiple variations, denoted muscles I-IV. Muscle I originated from the posteromedial surface of the greater trochanter and divided into two muscle bellies. These muscle bellies fused with the long head of the biceps femoris and were innervated by two branches from muscular branches of the semitendinosus and the long head of the biceps. Muscle II separated from the medial surface of the long head of the biceps in the proximal third and fused with the semitendinosus in the distal fourth. Muscle III was a biventer muscle. Its superior belly separated from the medial surface of the long head of the biceps in the distal third. The inferior belly of this muscle fused with the posterior surface of the crural fascia and was innervated by the tibial nerve. Muscle IV separated from the adductor magnus muscle, passed between the long and short heads of the biceps, fused with the inferior belly of muscle III, and was innervated by the muscular branch of the common fibular nerve to the short head of the biceps. Peeling off the epineurium of the muscular branches to the inferior belly of muscle III showed that this nerve fascicle divided from the common trunk with branches to the gastrocnemius and soleus muscles. The inferior bellies of muscle III and muscle IV were thought to be equivalent to the tensor fasciae suralis and tenuissimus muscles, respectively.


Combination chemotherapy for advanced squamous cell carcinoma of the head and neck.
Fifty-one patients (32 previously untreated, 19 previously treated) with advanced squamous cell carcinoma of the head and neck received a single course of combination chemotherapy consisting of high dose cis-platinum (DDP), bleomycin (Bleo), +/- high dose methotrexate (MTX). Thirty-three (65%) patients responded to therapy; 5 (10%) of these patients had a complete response. Previously untreated patients and those who received the three drugs (DDP, Bleo and MTX) had the highest response rates. The duration of response was 8 to 12 weeks. Seven (15%) patients showed a two-year survival rate. All nonresponders were dead of disease within two years. Three (56%) of the five complete-response patients and 4 (21%) of the partial-response patients survived for two years. The role of preoperative chemotherapy in head and neck cancer is yet to be conclusively defined.


Conceptualization of disease timeline predicts posttreatment distress in breast cancer patients.
A sample of 69 breast cancer patients was assessed before and after cessation of treatment to determine the predictors of posttreatment distress. Patients were assessed approximately 6 weeks before completing chemotherapy treatment, 1 month after completing treatment, and 3 months after completing treatment. Results indicate that timeline beliefs are related to distress: Patients who conceptualize their cancer as a chronic or cyclic illness are more anxious, depressed, and worried about a recurrence than patients who conceptualize their cancer as an acute illness. These findings hold true even while controlling for disease stage. The way patients conceptualize their illness appears to be more influential in determining levels of posttreatment distress than objective indicators of the likelihood of recurrence.


Recent resurgence of measles in a community with high vaccination coverage.
Even though 2-dose measles vaccination coverage rate was maintained at more than 95%, the largest measles outbreaks since 1996 still occurred in Wuhu city, P R China. A total of 916 cases were reported during 2005-2010. The annual incidence was 6.7 cases per 100,000 population with the peak incidence of 17.6 cases per 100,000 population in 2008. The highest age-specific incidence rate was 222.1 per 100,000 population and occurred in infants aged between 8 and 12 months; the second was 151.9 per 100,000 population in infants aged <8 months. Also, 200 cases occurred in those aged to 22 to 30 years old, accounting for 21.8% of total cases, with the age-specific incidence being 12.8 per 100,000 population. The characteristics related to age distribution have changed in recent measles outbreaks. It underlines the need for vaccination of susceptible young adults and timely administration of the first dose of the measles vaccine.


Model-based Cost-effectiveness of State-level Latent Tuberculosis Interventions in California, Florida, New York, and Texas.
Targeted testing and treatment (TTT) for latent tuberculosis (TB) infection (LTBI) is a recommended strategy to accelerate TB reductions and further TB elimination in the United States. Evidence on cost-effectiveness of TTT for key populations can help advance this goal. We used a model of TB transmission to estimate the numbers of individuals who could be tested by interferon-γ release assay and treated for LTBI with 3 months of self-administered rifapentine and isoniazid (3HP) under various TTT scenarios. Specifically, we considered rapidly scaling up TTT among people who are non-US-born, diabetic, living with human immunodeficiency virus (HIV), homeless or incarcerated in California, Florida, New York, and Texas-states where more than half of US TB cases occur. We projected costs (from the healthcare system perspective, in 2018 dollars), 30-year reductions in TB incidence, and incremental cost-effectiveness (cost per quality-adjusted life-year [QALY] gained) for TTT in each modeled population. The projected cost-effectiveness of TTT differed substantially by state and population, while the health impact (number of TB cases averted) was consistently greatest among non-US-born individuals. TTT was most cost-effective among persons with HIV (from $2828/QALY gained in Florida to $11 265/QALY gained in New York) and least cost-effective among people with diabetes (from $223 041/QALY gained in California to $817 753/QALY in New York). The modeled cost-effectiveness of TTT for LTBI varies across states but was consistently greatest among people with HIV; moderate among people who are non-US-born, incarcerated, or homeless; and least cost-effective among people with diabetes.


Effective isolation of bacterioplankton genus Polynucleobacter from freshwater environments grown on photochemically degraded dissolved organic matter.
Effective isolation of freshwater bacterioplankton belonging to genus Polynucleobacter from a shallow eutrophic lake and its tributary was achieved by size-selective filtration with a 0.7-mum pore filter and cultivation on R2A agar medium. Partial 16S rRNA gene analysis showed that over 80% of all the strains were highly similar to the Polynucleobacter cluster. Essential medium components for effective cultivation are pyruvate, yeast extract and peptone, whereas soluble starch and glucose are not necessary. Isolate KF001 (affiliated with Polynucleobacter subcluster D) has a strict requirement for organic acids as carbon sources, and we hypothesize that the Polynucleobacter cluster of bacteria could utilize compounds formed via photochemically dissolved organic matter (DOM) degradation for growth. Because organic acids form from solar radiation of DOM in aquatic environments, carbon sources that are typical products of DOM photochemical degradation were added to the medium. These compounds were readily utilized by KF001 in this study. Finally, we observed the stimulation of strain KF001 activity by photochemical degradation of natural lake water. Our findings suggest a carbon flow of DOM photoproducts to Polynucleobacter in the freshwater microbial loop.


High-fat diet reduces novelty-induced expression of activity-regulated cytoskeleton-associated protein.
Chronic high-fat-diet (HFD) consumption can lead to the development of brain insulin resistance, which then exerts deleterious effects on learning and memory. Activity-regulated cytoskeleton-associated protein (Arc) is a memory-related protein, and its expression can be induced by insulin stimulation. In HFD-fed animals, their basal Arc protein levels in cerebral cortex and hippocampus are reduced. However, the effects of HFD on novelty-induced Arc protein expression that is important for cognitive function is still unknown. In the present study, after feeding HFD (60% kcal from fat) for 5 weeks, mice developed brain insulin resistance and had a significant reduction in the novelty-induced but not the basal Arc protein levels in their hippocampi. Further experiments were performed in primary rat hippocampal neurons. The results show that, under the condition of neuronal insulin resistance, acute insulin stimulation induced less activation of the phosphatidylinositol 3-kinase/protein kinase B/p70 ribosomal S6 kinase (PI3K/Akt/p70S6K) pathway, resulting in reduced induction of Arc protein expression. Accordingly, it is suggested that following HFD feeding, the reduction in novelty-induced Arc protein expression in animal's hippocampus is probably related to a suppressed activation of the PI3K/Akt/p70S6K pathway due to the existence of brain insulin resistance.


Cardiovascular effects of nicotine, chlorisondamine, and mecamylamine in the pigeon.
Chlorisondamine and mecamylamine are nicotinic antagonists that produce both ganglionic and central blockade. Chlorisondamine, when administered as a large systemic dose, produces a persistent central block, despite being charged. The present study evaluated the cardiovascular effects of chlorisondamine. Shortly after administration, chlorisondamine (0.10, 1, and 10 mg/kg i.m.) lowered blood pressure significantly and decreased heart rate at the low dose (0.1 mg/kg i.m.) and increased heart rate at the high dose (10 mg/kg i.m.). Mecamylamine (1 and 10 mg/kg i.m.) also lowered blood pressure and heart rate. After both antagonists, heart rate returned to baseline values within 90 min and blood pressure within 24 h. Low doses of nicotine (0.01-0.03 mg/kg i.m.) lowered blood pressure but did not affect heart rate. Higher doses (0.10-3.2 mg/kg i.m.) transiently increased blood pressure and heart rate. Subsequent to antagonist administration, nicotine was administered to determine whether either drug blocked the cardiovascular effects of nicotine. Chlorisondamine (0.1, 1, and 10 mg/kg i.m.) administered 30 min before nicotine blocked the increases in blood pressure and heart rate. Only the high dose (10 mg/kg i.m.) of chlorisondamine administered 24 h before nicotine produced a blockade of nicotine's pressor effect. This block diminished within 3 days. Mecamylamine (1 mg/kg i.m.) antagonized only nicotine's tachycardic effect. Longer pretreatment with mecamylamine (10 mg/kg, 24 h before nicotine challenge) did not antagonize the cardiovascular effects of nicotine. Thus, chlorisondamine produces a longer lasting blockade of nicotine's cardiovascular effects than mecamylamine.


Biochemical and biophysical characterization of the transmissible gastroenteritis coronavirus fusion core.
Transmissible gastroenteritis coronavirus (TGEV) is one of the most destructive agents, responsible for the enteric infections that are lethal for suckling piglets, causing enormous economic loss to the porcine fostering industry every year. Although it has been known that TGEV spiker protein is essential for the viral entry for many years, the detail knowledge of the TGEV fusion protein core is still very limited. Here, we report that TGEV fusion core (HR1-SGGRGG-HR2), in vitro expressed in GST prokaryotic expression system, shares the typical properties of the trimer of coiled-coil heterodimer (six alpha-helix bundle), which has been confirmed by a combined series of biochemical and biophysical evidences including size exclusion chromatography (gel-filtration), chemical crossing, and circular diagram. The 3D homologous structure model presents its most likely structure, extremely similar to those of the coronaviruses documented. Taken together, TGEV spiker protein belongs to the class I fusion protein, characterized by the existence of two heptad-repeat (HR) regions, HR1 and HR2, and the present knowledge about the truncated TGEV fusion protein core may facilitate in the design of the small molecule or polypeptide drugs targeting the membrane fusion between TGEV and its host.


Quality of pharmaceutical care in hospitals.
The objective of this study was to measure the quality of pharmaceutical services provided to hospital inpatients. Using Donabedian's model, normative standards from the Joint Commission on Accreditation of Hospitals and the American Society of Hospital Pharmacists were used to develop a personal interview schedule to access the structure and process components of pharmaceutical services. To determine the effect of bed size, rural vs. urban, and presence of a full- or part-time pharmacist on the quality of pharmaceutical services, three samples of short-term hospitals were drawn: a random sample of Mississippi hospitals with less than 100 beds; all Mississippi hospitals of 100 or more beds; and a sample of hospitals in Philadelphia, Pennsylvania. In each of the 112 hospitals a personal interview was conducted with either the chief pharmacist or the administrator responsible for the pharmaceutical service. The responses to the items were then tabulated and a structure and a process score were obtained for each hospital. The following conclusions can be made: (1) The quality of the "structural" components is positively related to the bed size and not to whether the hospital is located in a rural or urban setting; (2) the quality of the "process" components is related to both the bed size and the location of the hospital--hospitals having 100 or more beds or located in an urban area have a higher process quality than those having less than 100 beds or located in a rural area; and (3) hospitals employing a full-time pharmacist have a higher quality of care than those who do not.


Comparative pharmacokinetics of four major compounds after oral administration of Mori Cortex total flavonoid extract in normal and diabetic rats.
Introduction: Mori Cortex has been used in traditional Chinese Medicine as an antidiabetic agent. The aim of this study was to establish a UPLC-MS/MS method for simultaneous determination of morin, morusin, umbelliferone and mulberroside A in rat plasma and investigate the pharmacokinetics differences between normal and diabetic rats following oral administration of Mori Cortex total flavonoid extract. Methods: Samples were pre-treated by protein precipitation and genkwanin was used as internal standard. Chromatographic separation was performed using a Hypersil GOLD C18 column (50 mm × 2.1 mm, 3 μm). The mobile phase consisted of acetonitrile and water (containing 0.1% formic acid) in gradient mode at a flow rate of 0.5 ml/min. The transitions of m/z 300.9→107.1, m/z 419.3→297.1, m/z 160.9→77.0, m/z 567.1→243.2 and m/z 283.1→268.2 were selected for morin, morusin, umbelliferone, mulberroside A and internal standard, respectively. Results: The intra- and inter-day precision for analytes were less than 12.5% and the accuracy ranged from -8.1% to 3.5%. The extraction recovery was >88.5% and no obvious matrix effect was observed. The AUC (0-t) and C max of morin were 501.3 ± 115.5 ng/mL*h and 127.8 ± 56.0 ng/mL in normal rats and 717.3 ± 117.4 ng/ml*h and 218.6 ± 33.5 ng/ml in diabetic rats. Meanwhile, the AUC (0-t) and C max of morusin were 116.4 ± 38.2 ng/ml*h and 16.8 ± 10.1 ng/mL in normal rats and 325.0 ± 87.6 ng/mL*h and 39.2 ± 5.9 ng/ml in diabetic rats. For umbelliferone and mulberroside A, the AUC (0-t) and C max also increased significantly in diabetic rats (p < 0.05). Discussion: The validated method was successfully applied to the pharmacokinetic study in normal and diabetic rats.


Pyogenic granuloma over the venous component of a mixed vascular malformation.
A 52-year-old man presented with a rapidly growing red tumor on the central neckline. It had appeared over a congenital flat and pinkish vascular lesion that involved the shoulder and the upper anterior area of his chest. Intermingled with the pinkish stain, there were also some blue nodules several millimeters in diameter. Histopathologic examination revealed that the full lesion was a mixed venous-capillary malformation. The red tumor was excised and diagnosed as a pyogenic granuloma developing over the venous component of the vascular malformation. To our knowledge, a pyogenic granuloma growing over a venous malformation has not been previously described.


Development of a macroarray to specifically analyze immunological gene expression in swine.
DNA arrays are useful tools for simultaneously studying the expressions of a large number of genes. Herein, we describe the construction and the optimization of conditions for a low-density DNA macroarray specific for the porcine immune system. This specific DNA macroarray contains 63 gene products, including 20 cytokines, 11 chemokines, and 12 immunologically relevant receptors. It was constructed by designing gene-specific oligonucleotide primers from porcine sequences available in the EMBL or TIGR expressed sequence tag data bank and using primers from conserved regions of aligned sequences from other species for sequences unavailable for swine. Amplicons produced by reverse transcription-PCR were cloned, sequenced, and spotted onto nylon filters. A trial DNA array was first produced to optimize the intensity, specificity, and variability of signals from amplicons amplified with either gene-specific or universal primers. The DNA macroarray was then validated by comparing the gene expression profile of nonstimulated peripheral blood mononuclear cells (PBMCs) to that of phorbol 12-myristate 13-acetate and ionomycin (PMA-Iono)-stimulated PBMCs from three different animals over a 48-h time period. As already described for more conventional techniques, we showed that certain genes, such as those for CD40, gamma interferon, interleukin 2 (IL-2), the IL-2 receptor, and tumor necrosis factor alpha, were upregulated in PMA-Iono-stimulated PBMCs. A detailed analysis also indicated a downregulation of several genes which are expressed mainly by macrophages (IL-1, IL-8, AMCF-1, natural-resistance-associated macrophage protein, neutrophil chemotactic protein, DAP-12, and monocyte chemoattractant protein) in samples stimulated for 24 h with PMA-Iono compared to their levels of expression in control samples. These results indicate that the DNA macroarray that we constructed can be a useful tool for simultaneously monitoring the mRNA expression of immunologically relevant genes in different porcine samples.


An Exploratory Study of Online Early Sexual Initiation through Pressured and Unwanted Sexting.
Sexting in young adolescents may be an online form of early sexual debut. We assess the link between potentially problematic sexting (i.e., pressured and receiving unwanted sexts) with known risky behaviors (i.e., substance use and early sexual behavior) among middle school students aged 12 and under. The ethnically diverse sample consisted of 1131 youth (53% female) enrolled in the 7th grade in one of 24 schools in southeast Texas. Participants self-identified as 31% Hispanic, 9% White, 24% Black, 19% Asian, 11% other, and 6% unknown. Participants self-reported pressured sexting, receiving unwanted sexts, history of sexual activity, and substance use. Two-point-one percent of adolescents reported sending a sext under pressure and 13.7% reported having received an unwanted sexting image. Participants with a history of sexual intercourse, relative to their non-sexually experienced counterparts, reported higher rates of being pressured into sexting and receiving unwanted sexts. Further, a portion of youth who experienced pressured or unwanted sexting also reported the use of various substances, relative to their non-sexting counterparts. Our study underscores the need for comprehensive sex education to begin at an early age and include age-appropriate information on sexting, digital citizenship, relationships, and substance use.


Children with cough.
Most children with a cough have recurrent acute viral bronchitis or asthma. For both, the natural history is progressive improvement through childhood. An unrelenting cough with purulent sputum suggests suppurative lung disease and must not be dismissed lightly. In most cases the cause of cough can be determined by careful clinical history, physical examination and chest X-ray. Other laboratory investigations can be useful when underlying asthma is suspected.


The population genomic basis of geographic differentiation in North American common ragweed (Ambrosia artemisiifolia L.).
Common ragweed (Ambrosia artemisiifolia L.) is an invasive, wind-pollinated plant nearly ubiquitous in disturbed sites in its eastern North American native range and present across growing portions of Europe, Africa, Asia, and Australia. Phenotypic divergence between European and native-range populations has been described as rapid evolution. However, a recent study demonstrated major human-mediated shifts in ragweed genetic structure before introduction to Europe and suggested that native-range genetic structure and local adaptation might fully explain accelerated growth and other invasive characteristics of introduced populations. Genomic differentiation that potentially influenced this structure has not yet been investigated, and it remains unclear whether substantial admixture during historical disturbance of the native range contributed to the development of invasiveness in introduced European ragweed populations. To investigate fine-scale population genetic structure across the species' native range, we characterized diallelic SNP loci via a reduced-representation genotyping-by-sequencing (GBS) approach. We corroborate phylogeographic domains previously discovered using traditional sequencing methods, while demonstrating increased power to resolve weak genetic structure in this highly admixed plant species. By identifying exome polymorphisms underlying genetic differentiation, we suggest that geographic differentiation of this important invasive species has occurred more often within pathways that regulate growth and response to defense and stress, which may be associated with survival in North America's diverse climatic regions.


Hybrid normal metal/ferromagnetic nanojunctions for domain wall tracking.
Hybrid normal metal/ferromagnetic, gold/permalloy (Au/Py), nanojunctions are used to investigate magnetoresistance effects and track magnetization spatial distribution in L-shaped Py nanostructures. Transversal and longitudinal resistances are measured and compared for both straight and 90° corner sections of the Py nanostructure. Our results demonstrate that the absolute change in resistance is larger in the case of longitudinal measurements. However, due to the small background resistance, the relative change in the transversal resistance along the straight section is several orders of magnitude larger than the analogous longitudinal variation. These results prove that hybrid nanojunctions represent a significant improvement with respect to previously studied all-ferromagnetic crosses, as they also reduce the pinning potential at the junction and allow probing the magnetization locally. In addition, unusual metastable states with longitudinal domain walls along Py straight sections are observed. Micromagnetic simulations in combination with a magnetotransport model allow interpretation of the results and identification of the observed transitions.


Alterations in Blood Coagulation and Viscosity Among Young Male Cigarette Smokers of Al-Jouf Region in Saudi Arabia.
Hemorheology, a measure of rheological properties of blood, is often correlated with cerebral blood flow and cardiac output; an increased blood viscosity may increase the risk of thrombosis or thromboembolic events. Previous studies have reported a large variation in hemorheological properties of blood among smokers. This prompted us to conduct coagulation experiments to evaluate the effect of cigarette smoking on hematological parameters, like cell counts, and coagulation parameters among young males in Al-Jouf region, Saudi Arabia. The hematological and coagulation parameters were used to relate the changes in viscosity and coagulation to smoking. A total of 321 male participants (126 nonsmokers and 195 smokers) were enrolled into the study as randomized sample. Complete blood count was measured by hematology analyzer, and coagulation tests were performed by coagulation analyzer. Thettest analysis was performed to compare the relationships of variables between the 2 groups. The results confirmed that smoking alters some hematology parameters leading to significant deterioration in blood flow properties. Smoking also increased the hematocrit (HCT), whole blood viscosity (WBV), and plasma viscosity (PV) but decreased the international normalized ratio (INR). The decrease in INR was found to be associated with the increase in WBV, PV, and HCT. Further investigations are necessary to assess the reversibility of such changes in cessation of smoking or other elements of influence.


Effect of alendronate treatment on bone mineral density in male patients with osteoporosis.
To assess the efficacy of alendronate therapy on bone mineral density (BMD) at the lumbar spine and hip in men with osteoporosis. Medical records of male patients with osteoporosis, who had undergone follow-up in the Endocrinology Clinic at the National Naval Medical Center, were reviewed, and nine patients treated with alendronate for at least 1 year were identified. Patients were excluded from analysis if they had evidence of osteomalacia or if baseline and follow-up BMD results on the same dual-energy x-ray absorptiometry (DEXA) densitometer, at least 10 months apart, were not available. DEXA BMD results at the lumbar spine and hip, before and after at least 10 months of alendronate treatment, were analyzed for significant differences. Patients were also receiving calcium supplementation (1,000 to 1,500 mg/day), and all but one patient received vitamin D (400 to 800 U/day). Lumbar spine BMD increased by 6.4 +/- 1.8% per year with alendronate treatment (P = 0.008). A mean absolute gain of 0.052 +/- 0.010 g/cm 2 (P = 0.005) in lumbar spine BMD was noted for the entire study group (N = 9), after a mean duration of treatment of 14 +/- 1 months. The mean lumbar spine BMD Z score improved by 0.40 +/- 0.09 (P = 0.002) with alendronate therapy. The femoral neck BMD also increased by 4.5 +/- 1.4% per year with alendronate treatment (P = 0.013). The mean absolute gain in femoral neck BMD was 0.028 +/- 0.009 g/cm 2 (P = 0.013) for the study group (N = 9) after 14 +/- 1 months of therapy. The mean femoral neck BMD Z score improved 0.30 +/- 0.08 (P = 0.005) with treatment. BMD gains at the greater trochanter of 3.2 +/- 1.5% per year (P = 0.067) and at Ward's triangle of 9.1 +/- 4.2% per year (P = 0.061) were not statistically significant. Two patients discontinued alendronate treatment after 1 year because of epigastric or retrosternal pain. Oral alendronate treatment, given in combination with calcium supplementation and physiologic doses of vitamin D, resulted in significant improvements in lumbar spine and femoral neck BMD after a 14-month period in this small group of men with osteoporosis. Although controlled, prospective trials involving larger numbers of male patients with fracture incidence data are needed before definitive conclusions can be made, alendronate treatment seems to be effective in improving BMD in men with osteoporosis, similar to its efficacy in women.


Percutaneous flexible bipolar epidural neuroelectrode for spinal cord stimulation. Technical note.
This article describes a new flexible bipolar neuroelectrode which is inserted percutaneously into the epidural space for segmental spinal cord stimulation. This electrode was used in experiments with dogs and monkeys for recording cortical somatosensory evoked potentials in order to identify intraoperative spinal cord ischemia during periods of aortic occlusion.


Phenotypic heterogeneity of Streptococcus mutans in dentin.
Information concerning phenotypic heterogeneity of Streptococcus mutans in carious dentin is sparse. Matrix-assisted laser-desorption/ionization-time-of-flight mass-spectrometry (MALDI-TOF-MS) facilitates the phenotypic differentiation of bacteria to the subspecies level. To verify a supposed influence of restorative treatment on the phenotypic heterogeneity of S. mutans, we isolated and compared a total of 222 S. mutans strains from dentin samples of 21 human deciduous molars during caries excavation (T(1)) and 8 wks (T(2)) after removal of the temporary restoration. Phenotypic heterogeneity was determined by MALDI-TOF-MS and hierarchical clustering. Thirty-six distinct S. mutans phenotypes could be identified. Although indistinguishable phenotypes were found in the same teeth at T(1) and T(2), as well as in different teeth of individual participants, the phenotypic heterogeneity increased significantly, from 1.4 phenotypes per S. mutans-positive dentin sample at T(1) to 2.2 phenotypes at T(2). We attribute this to an adaptation of S. mutans to the modified environment under the restoration following caries excavation.


Trajectories of cognitive and perceived functional decline in people with dementia: Findings from the IDEAL programme.
Impaired cognition and instrumental activities of daily living (iADL) are key diagnostic features of dementia; however, few studies have compared trajectories of cognition and iADL. Participants from the IDEAL study comprised 1537, 1183, and 851 people with dementia, and 1277, 977, and 749 caregivers at baseline, 12 and 24 months, respectively. Addenbrooke's Cognitive Examination-III and Functional Activities Questionnaire were used to measure cognition and iADL, respectively. Scores were converted to deciles. Self-rated iADL declined on average by -0.08 (-0.25, 0.08) decile points per timepoint more than cognition. Informant-rated iADL declined on average by -0.31 (-0.43, -0.18) decile points per timepoint more than cognition. Cognition and self-rated iADL declined at a similar rate. Informant-rated iADL declined at a significantly greater rate than cognition. Therefore, either cognition and perceived iADL decline at different rates or informants overestimate increasing iADL difficulties compared to both cognition and self-ratings. Self-ratings of the degree of functional difficulties were consistent with cognition Decline in self-rated everyday activities was consistent with cognitive decline Informant-ratings of everyday activities declined more than cognition.


Bonfils assisted double lumen endobronchial tube placement in an anticipated difficult airway.
The role of various airway adjuncts in the management of difficult airway has been described in the literature. Bonfils rigid fiberscope is one of the airway assist devices widely used for endotracheal intubation in the individuals with cervical instability warranting limited neck movements. With our experience in the utilization of Bonfils for single lumen endotracheal tube placement, we are increasingly using for double lumen endobronchial (DLT) intubation as well. We would like to describe our experience in the use of Bonfils for DLT placement and outline the merits and limitations of the other suitable airway assist devices in this report. The double lumen tube has to be modified by decreasing the length of DLT to accommodate the Bonfils fiberscope and this is applicable only in certain type of double lumen tubes for e.g. Bronchocath.


Microglia Express Mu Opioid Receptor: Insights From Transcriptomics and Fluorescent Reporter Mice.
Background: Microglia activation contributes to chronic pain and to the adverse effects of opiate use such as analgesic tolerance and opioid-induced hyperalgesia. Both mu opioid receptor (MOR) encoded by Oprm1/OPRM1 gene and toll like receptor 4 (TLR4) have been reported to mediate these morphine effects and a current question is whether microglia express the Oprm1 transcript and MOR protein. The aim of this study was to characterize Oprm1-MOR expression in naive murine and human microglia, combining transcriptomics datasets previously published by other groups with our own imaging study using the Cx3cr1-eGFP-MOR-mCherry reporter mouse line. Methods: We analyzed microglial Oprm1/OPRM1 expression obtained from transcriptomics datasets, focusing on ex vivo studies from adult wild-type animals and adult post-mortem human cerebral cortex. Oprm1, as well as co-regulated gene sets were examined. The expression of MOR in microglia was also investigated using our novel fluorescent Cx3cr1-eGFP-MOR-mcherry reporter mouse line. We determined whether CX3cR1-eGFP positive microglial cells expressed MOR-mCherry protein by imaging various brain areas including the Frontal Cortex, Nucleus Accumbens, Ventral Tegmental Area, Central Amygdala, and Periaqueductal Gray matter, as well as spinal cord. Results: Oprm1 expression was found in all 12 microglia datasets from mouse whole brain, in 7 out of 8 from cerebral cortex, 3 out of 4 from hippocampus, 1 out of 1 from striatum, and 4 out of 5 from mouse or rat spinal cord. OPRM1 was expressed in 16 out of 17 microglia transcriptomes from human cerebral cortex. In Cx3cr1-eGFP-MOR-mCherry mice, the percentage of MOR-positive microglial cells ranged between 35.4 and 51.6% in the different brain areas, and between 36.8 and 42.4% in the spinal cord. Conclusion: The comparative analysis of the microglia transcriptomes indicates that Oprm1/OPRM1 transcripts are expressed in microglia. The investigation of Cx3cr1-eGFP-MOR-mCherry mice also shows microglial expression of MOR proteinin the brain and spine. These results corroborate functional studies showing the actions of MOR agonists on microglia and suppression of these effects by MOR-selective antagonists or MOR knockdown.


The topology and dynamics of protein complexes: insights from intra- molecular network theory.
Intra-molecular interactions within complex systems play a pivotal role in the biological function. They form a major challenge to computational structural proteomics. The network paradigm treats any system as a set of nodes linked by edges corresponding to the relations existing between the nodes. It offers a computationally efficient tool to meet this challenge. Here, we review the recent advances in the use of network theory to study the topology and dynamics of protein- ligand and protein-nucleic acid complexes. The study of protein complexes networks not only involves the topological classification in term of network parameters, but also reveals the consistent picture of intrinsic functional dynamics. Current dynamical analysis focuses on a plethora of functional phenomena: the process of allosteric communication, the binding induced conformational changes, prediction and identification of binding sites of protein complexes, which will give insights into intra-protein complexes interactions. Furthermore, such computational results may elucidate a variety of known biological processes and experimental data, and thereby demonstrate a huge potential for applications such as drug design and functional genomics. Finally we describe some web-based resources for protein complexes, as well as protein network servers and related bioinformatics tools.


Evaluation of a new enzyme-linked immunosorbent assay to detect keratan sulfate in equine serum.
This study aimed to evaluate a system that identifies cartilage turn over and/or degradation through measurement of a new keratan sulfate (KS) epitope concentration in equine sera. Blood samples were collected from 30 horses, 1 (n = 15) and 2 year-olds (n = 15). Serum samples were analyzed for an epitope of keratan sulfate by 1/20/5D4 (KS5D4) and new epitopes of keratan sulfate using high sensitive keratan sulfate (HSKS), measured by two respective enzyme-linked immunosorbant assays (ELISAs). There was no correlation in serum concentration of KS evaluated using 5D4 and HSKS. Age had no significant effect on concentrations of KS measured with KS5D4 while 1 year-old horses showed significantly higher amounts than 2 year-olds with HSKS. Results suggest that HSKS could detect early signs of cartilage metabolic changes.


Synthesis and Configuration of Neomaclafungin A.
The relative and absolute configuration of neomaclafungins were impossible to establish by spectroscopic analyses alone because of the lack of exploitable 1 H-1 H couplings and nOes between the upper and the lower subunits. This very difficult task now is finally completed by an enantioselective total synthesis of neomaclafungin A (revised) and its diastereomer (reported). The results also provided a key reference for the complete structures for other neomaclafungins and the long-known closely related natural product maclafungin.


New bone formation after ligation of the external carotid artery and resection of a large aneurysmal bone cyst of the mandible with reconstruction: a case report.
The aneurysmal bone cyst (ABC) is a benign cystic and expanding osteolytic lesion consisting of bone-filled spaces of variable size, separated by connective tissue containing trabeculae of bone or osteoid tissue and osteoclast giant cells. Radiographic findings may vary from unicystic or moth-eaten radiolucencies to extensive multilocular lesions with bilateral expansion and destruction of mandibular cortices. Treatment modalities include curettage (with reported recurrences) and resection with immediate reconstruction. The main arterial and feeder vessels may be embolized to prevent profuse intraoperative blood loss and achieve a bloodless surgical field. Failed embolization may necessitate ligation of the external carotid artery of the affected side.