Getting Americans to buckle up: the efficacy of state seat belt laws.
Annual state observed safety belt use rates over the period 1991-2001 are examined using time-series cross-section regression analysis. It was found that seat belt laws are associated with higher use rates and that the enforcement provision matters. Primary states experience belt use rates that on average are 9.1 percentage points higher than their secondary counterparts. In addition, the level of the fine imposed by statute has an effect on safety belt use apart from that attributable to the enforcement provision. The current median fine of 25 US dollars is associated with an additional 3.8 percentage points increase in belt use. To further increase safety belt use, it is recommended that states adopt primary enforcement and impose fines of at least $50 for violating a seat belt law.


Current surgical management of endometrial cancer.
It is reasonable to perform complete lymphadenectomy in patients at significant risk of lymph node metastases, and use the results to guide adjuvant treatment decisions.(24,25) Criteria for staging based on intraoperative pathology should be determined in consultation with the pathologist, preferably with an institution-specific quality-assurance review.(34) Patients with more aggressive histologies should undergo a staging procedure including an omental biopsy whenever possible, with the understanding that most require systemic adjuvant therapy. Minimally invasive surgery is associated with shorter recovery and fewer postoperative complications than open endometrial cancer staging,(4,5,45) with preliminary data showing similar oncologic outcomes (Walker and colleagues, late breaking abstract SGO 2010 Annual Meeting). Whenever feasible, patients should be offered minimally invasive surgery for endometrial cancer staging. Retrospective data support an attempt at complete cytoreduction in patients with advanced endometrial cancer and a good performance status.(8-12) The decision to perform aggressive cytoreductive surgery should be individualized, taking into account the patient's comorbidities, her performance status, her symptoms, and the risks associated with more aggressive surgical procedures.


Accumulation of [3H]fucose-labelled glycoproteins in the Golgi apparatus of dorsal root ganglion neurons during inhibition of fast axonal transport caused by exposure of the ganglion to Co2+-containing or Ca2+-free medium.
Previous in vitro studies have established that Co2+-containing or Ca2+-free media interfere with the initiation of the fast axonal transport of proteins. The present study has used light- and electron-microscope radioautography to compare the distribution of [3H]fucose-labelled glycoproteins in neuronal cell bodies of control dorsal root ganglia and ganglia incubated for 16-17 h in Ca2+-free medium or in medium containing 0.18 mM Co2+. The radioautographic reaction in control cell bodies was diffusely scattered throughout the cytoplasm; grain counts revealed that 22% of the reaction was associated with elements of the Golgi apparatus and 78% was over other organelles and the remainder of the cytoplasm. In most experimental cell bodies, 78% of the silver grains were clustered over elements of the Golgi complex whereas other organelles and the remainder of the cytoplasm were comparatively much less labelled; structural alterations of the Golgi apparatus were also produced by the modified media. In parallel studies where the radioactivity in nerve trunks and ganglia was measured by liquid scintillation counting, it was found that the Ca2+-free medium and the Co2+-containing medium both reduced by approximately 80% the quantity of [3H]fucose-labelled glycoproteins which were carried by the fast axonal transport system; they did so without interfering with the incorporation of [3H]fucose into glycoproteins. The results indicate that in the presence of Co2+ or in the absence of Ca2+ the proteins which are destined for fast axonal transport accumulate at the Golgi apparatus of neuronal cell bodies. These results thus suggest that Ca2+ is required for proteins to leave the Golgi region in transit to the fast axonal transport system.


Inoculation of plant growth promoting bacterium Achromobacter xylosoxidans strain Ax10 for the improvement of copper phytoextraction by Brassica juncea.
In this study, a copper-resistant plant growth promoting bacterial (PGPB) strain Ax10 was isolated from a Cu mine soil to assess its plant growth promotion and copper uptake in Brassica juncea. The strain Ax10 tolerated concentrations up to 600 mg CuL(-1) on a Luria-Bertani (LB) agar medium and utilized 1-aminocyclopropane-1-carboxylic acid (ACC) as a sole N source in DF salts minimal medium. The strain Ax10 was characterized as Achromobacter xylosoxidans based on its 16S rDNA sequence homology (99%). The bacterium A. xylosoxidans Ax10 has also exhibited the capability of producing indole acetic acid (IAA) (6.4 microg mL(-1)), and solubilizing inorganic phosphate (89.6 microg mL(-1)) in specific culture media. In pot experiments, inoculation of A. xylosoxidans Ax10 significantly increased the root length, shoot length, fresh weight and dry weight of B. juncea plants compared to the control. This effect can be attributed to the utilization of ACC, production of IAA and solubilization of phosphate. Furthermore, A. xylosoxidans Ax10 inoculation significantly improved Cu uptake by B. juncea. Owing to its wide action spectrum, the Cu-resistant A. xylosoxidans Ax10 could serve as an effective metal sequestering and growth promoting bioinoculant for plants in Cu-stressed soil. The present study has provided a new insight into the phytoremediation of Cu-contaminated soil.


The urea cycle as a source of nitric oxide implicated in the pathogenesis of insulin-dependent diabetes mellitus.
Diabetes mellitus has long been considered an autoimmune disorder whereby the immune system attacks pancreatic tissue, destroying the insulin-producing cells of the pancreas. In this way, diabetes mellitus may be the only metabolic disorder in which the disease state is in no way related to any metabolic pathway. The specific role that nitric oxide plays in the pathogenesis of diabetes mellitus has yet to be established. However, researchers have shown that nitric oxide will independently destroy the beta cells (insulin-producing cells) of the pancreas in the absence of any pathogenic mediators. It is my hypothesis that a breakdown in the urea cycle (via activation of nitric oxide synthase (NOS)), a primary metabolic pathway, whereby nitric oxide production is competitively favored over urea production, is responsible for generating the major source of pathogenic nitric oxide resulting in the death of the beta cells of the pancreas.


Apparent volumes of distribution and drug binding to plasma proteins and tissues.
A pharmacokinetic model that incorporates linear binding of drug to plasma proteins and tissue indicates the same relationship between apparent volume of distribution and drug binding as that proposed by Gillette (1971) based on a simple distribution model. Apparent volume of distribution (V) is directly proportional to free fraction of drug in plasma (fp) and indirectly proportional to free fraction of drug in tissue (fT). In the case of a constant fT, a plot of V versus fp will be linear with an intercept equal to plasma volume (Vp). If fT changes with fp, an apparently linear plot may result but the intercept will exceed Vp. An approach to the calculation of fT, a composite binding parameter, is presented and illustrated by comparing the tissue binding of tolbutamide in patients during acute viral hepatitis and upon recovery.


Marked gender differences in progression of mild cognitive impairment over 8 years.
This study examined whether, among subjects with mild cognitive impairment (MCI), women progressed at faster rates than men. We examine longitudinal rates of change from baseline in 398 MCI subjects (141 Females, 257 Males) in the Alzheimer's Disease Neuroimaging Initiative-1 (ADNI-1), followed for up to 8 years (mean 4.1±2.5 years) using mixed effects models incorporating all follow ups (mean 8±4 visits). Women progressed at faster rates than men on ADAS-Cog (p=0.001) and CDR-SB (p=0.003). Quadratic fit for change over time was significant for both ADAS-Cog (p=0.001) and CDR-SB (p=0.004), and the additional acceleration in women was 100% for ADAS-Cog and 143% for CDR-SB. The variability of change was greater in women. The gender effect was greater in ApoE4 carriers. Women with MCI have greater longitudinal rates of cognitive and functional progression than men. Studies to confirm and uncover potential mechanisms appear to be warranted.


Polymorphisms of interferons and their receptors in the genetics of severe RSV-associated diseases.
Because of their important role in the pathophysiology of severe RSV infection, IFNs represent an ideal group of candidate genes for determining RSV disease severity. We studied 14 polymorphisms within 7 genes involved in IFNs signalling. Our study populations consisted of 156 infants with severe RSV infection and 296 healthy control children. None of the genes showed association with severe RSV infection in children. Thus, despite the involvement of different IFNs in the pathophysiology of RSV infection, genetic variants in IFNG and related genes might not alter the risk for the development of severe RSV-associated diseases.


Serum-cholesterol: sex specific psychological correlates during rest and stress.
In the present study an attempt was made to assess whether male and female students differ in their cholesterol and catecholamine reaction to examination stress. An answer was also sought to the question of whether cholesterol level and reactivity could be predicted from behavioral traits and mood. In 29 male and 23 female students, cholesterol and urine-catecholamines were measured on an examination day and on a control day. Cholesterol level was found to be higher on the examination day, in both males and females. Although males showed a larger adrenaline reaction than females, their cholesterol reaction did not differ from that of the females. Specifically with regard to males, 62% of the variance in cholesterol base level and 40% of the variance of the stress induced cholesterol rise, were explained by the psychological variables measured. Achievement motivation and depression contributed to both predictions. No significant predictions could be made in the female group. This demonstrates the necessity of taking sex differences into account in psychophysiological studies. It is suggested to pay greater attention in future research to the mediating role that blood lipids play in the relationship between psychological factors and the risk of coronary heart disease.


Statin induces inhibition of triple negative breast cancer (TNBC) cells via PI3K pathway.
Primary TNBCs are treated as if they were a single disease entity, yet it is clear they do not behave as a single entity in response to current therapies. Recently, we reported that statins might have a potential benefit for TNBCs associated with ets-1 overexpression. The aim of this study is to investigate the role of PTEN loss in the effects of statin on TNBC cells. In addition, we analyze the relationship between AKT downstream pathways and the effects of statin on TNBC cells. We investigated the effect of a statin on TNBC cells and analyzed the association of PI3K pathways using various TNBC cells in terms of PTEN loss and AKT pathways. Simvastatin treatments resulted in decreased cell viabilities in various TNBC cell lines. Compared with PTEN wild-type TNBC cells, PTEN mutant-type TNBC cells showed a decreased response to simvastatin. Expressions of phosphorylated Akt and total Akt showed an inverse relationship with PTEN expression. The TNBC cell lines, which showed increased expression of p-Akt, appeared to attenuate the expression of p-Akt by PTEN loss in simvastatin-treated TNBC cells. The Akt inhibitor, LY294002, augmented the effect of simvastatin on PTEN wild-type TNBC cells. Simvastatin induces inhibition of TNBC cells via PI3K pathway activation.


Efficacy of daptomycin combined with rifampicin for the treatment of experimental meticillin-resistant Staphylococcus aureus (MRSA) acute osteomyelitis.
Daptomycin exhibits rapid bactericidal activity against Gram-positive organisms, including meticillin-resistant Staphylococcus aureus (MRSA). Daptomycin in combination with rifampicin needs to be assessed in bone infection. An MRSA acute osteomyelitis model was used. Daptomycin and vancomycin were compared, alone or in combination with rifampicin, over 4 days. Surviving bacteria were counted in bone, bone marrow and joint fluid. Vancomycin and daptomycin as single therapies were ineffective, but both combinations were significantly more effective than the corresponding monotherapy. Combination of daptomycin and rifampicin could prevent S. aureus from developing resistance. This combination could be a useful alternative to treat MRSA osteomyelitis at an early stage.


Extracellular vesicles released by hair follicle and adipose mesenchymal stromal cells induce comparable neuroprotective and anti-inflammatory effects in primary neuronal and microglial cultures.
Despite intensive research, to date, there is no effective treatment for neurodegenerative diseases. Among the different therapeutic approaches, recently, the use of extracellular vesicles (EVs) derived from mesenchymal stromal cells (MSCs) has gained attention. In the present work, we focused on medium/large extracellular vesicles (m/lEVs) derived from hair follicle--derived (HF) MSCs, comparing their potential neuroprotective and anti-inflammatory effect against adipose tissue (AT)-MSC-derived m/lEVs. The obtained m/lEVs were similar in size with comparable expression of surface protein markers. The neuroprotective effect of both HF-m/lEVs and AT-m/lEVs was statistically significant in dopaminergic primary cell cultures, increasing cell viability after the incubation with 6-hidroxydopamine neurotoxin. Moreover, the administration of HF-m/lEVs and AT-m/lEVs counteracted the lipopolysaccharide-induced inflammation in primary microglial cell cultures, decreasing the levels of pro-inflammatory cytokines, tumor necrosis factor-α and interleukin-1β. Taken together, HF-m/lEVs demonstrated comparable potential with that of AT-m/lEVs as multifaceted biopharmaceuticals for neurodegenerative disease treatment.


Hypersensitivity to Febuxostat in a Patient with a Previous Allopurinolinduced Steven-Johnson Syndrome: A Case Report of Treatment with a Slow Desensitization Protocol.
We report the case of a 43-year-old Chinese male with Tophaceous gout who had been living in Italy for some years. Previous treatments with allopurinol had induced Steven Johnson syndrome, dictating a switch to febuxostat 80 mg daily. After two years of treatment with febuxostat, he developed a diffuse maculopapular rash with severe itching. Rheumatologists stopped febuxostat; however, gout worsened over the following years despite treatment with kalnicitrate and colchicine. Therefore, an allergy consultation was called for. A slow desensitization protocol with febuxostat was started, with a low oral dosage scheme to be increased up to 80 mg/day. Febuxostat was prepared in a solid formulation by the consultation pharmacist as pills instead of the more frequently used liquid suspension. The patient is currently receiving febuxostat 80 mg, and he has shown no side effects as of now, while his gout has improved. This is the first reported example and he has shown no side effect till now, while his gout improved of a successful desensitization protocol using a solid preparation of diluted febuxostat given as pills.


Differences between rodents and humans in the metabolic toxification of N,N-dimethylformamide.
The widely used industrial solvent N,N-dimethylformamide (DMF) causes liver damage in occupationally exposed persons and is suspected of involvement in the generation of certain occupational malignancies. Here the extent of the biotransformation of DMF to three urinary metabolites has been compared in humans and rodents. The metabolites, which were quantified by gas chromatography (GC) are N-(hydroxymethyl)-N-methylformamide (HMMF), which yielded N-methylformamide on GC analysis, a species which decomposed to formamide on GC analysis, and N-acetyl-S-(N-methylcarbamoyl) cysteine (AMCC), measured after derivatization with ethanol to give ethyl N-methylcarbamate. Ten volunteers who absorbed between 28 and 60 mumol/kg DMF during an 8-hr exposure to DMF in the air at 60 mg/m3 excreted in the urine within 72 hr between 16.1 and 48.7% of the dose as HMMF, between 8.3 and 23.9% as formamide, and between 9.7 and 22.8% as AMCC. AMCC, together with HMMF, was also detected in the urine of workers after occupational exposure to DMF. The portion of the dose (0.1, 0.7, or 7.0 mmol/kg given ip) which was metabolized in mice, rats, or hamsters to HMMF varied between 8.4 and 47.3% of the dose; between 7.9 and 37.5% were excreted as formamide and only between 1.1 and 5.2%, as AMCC. The results suggest that there is a quantitative difference between the metabolic pathway of DMF to AMCC in humans and rodents. It is argued that the hepatotoxic potential of DMF may be linked to the extent of its metabolic conversion to AMCC.


Fitting Marginal Structural and G-Estimation Models Under Complex Treatment Patterns: Investigating the Association Between De Novo Vitamin D Supplement Use After Breast Cancer Diagnosis and All-Cause Mortality Using Linked Pharmacy Claim and Registry Data.
Studies have shown that accounting for time-varying confounding through time-dependent Cox proportional hazards models may provide biased estimates of the causal effect of treatment when the confounder is also a mediator. We explore 2 alternative approaches to addressing this problem while examining the association between vitamin D supplementation initiated after breast cancer diagnosis and all-cause mortality. Women aged 50-80 years were identified in the National Cancer Registry Ireland (n = 5,417) between 2001 and 2011. Vitamin D use was identified from linked prescription data (n = 2,570). We sought to account for the time-varying nature of vitamin D use and time-varying confounding by bisphosphonate use using 1) marginal structural models (MSMs) and 2) G-estimation of structural nested accelerated failure-time models (SNAFTMs). Using standard adjusted Cox proportional hazards models, we found a reduction in all-cause mortality in de novo vitamin D users compared with nonusers (hazard ratio (HR) = 0.84, 95% confidence interval (CI): 0.73, 0.99). Additional adjustment for vitamin D and bisphosphonate use in the previous month reduced the hazard ratio (HR = 0.45, 95% CI: 0.33, 0.63). Results derived from MSMs (HR = 0.44, 95% CI: 0.32, 0.61) and SNAFTMs (HR = 0.45, 95% CI: 0.34, 0.52) were similar. Utilizing MSMs and SNAFTMs to account for time-varying bisphosphonate use did not alter conclusions in this example.


Component processes underlying future thinking.
This study sought to investigate the component processes underlying the ability to imagine future events, using an individual-differences approach. Participants completed several tasks assessing different aspects of future thinking (i.e., fluency, specificity, amount of episodic details, phenomenology) and were also assessed with tasks and questionnaires measuring various component processes that have been hypothesized to support future thinking (i.e., executive processes, visual-spatial processing, relational memory processing, self-consciousness, and time perspective). The main results showed that executive processes were correlated with various measures of future thinking, whereas visual-spatial processing abilities and time perspective were specifically related to the number of sensory descriptions reported when specific future events were imagined. Furthermore, individual differences in self-consciousness predicted the subjective feeling of experiencing the imagined future events. These results suggest that future thinking involves a collection of processes that are related to different facets of future-event representation.


Neuroimaging biomarkers in mild traumatic brain injury (mTBI).
Reviewed herein are contemporary neuroimaging methods that detect abnormalities associated with mild traumatic brain injury (mTBI). Despite advances in demonstrating underlying neuropathology in a subset of individuals who sustain mTBI, considerable disagreement persists in neuropsychology about mTBI outcome and metrics for evaluation. This review outlines a thesis for the select use of sensitive neuroimaging methods as potential biomarkers of brain injury recognizing that the majority of individuals who sustain an mTBI recover without neuroimaging signs or neuropsychological sequelae detected with methods currently applied. Magnetic resonance imaging (MRI) provides several measures that could serve as mTBI biomarkers including the detection of hemosiderin and white matter abnormalities, assessment of white matter integrity derived from diffusion tensor imaging (DTI), and quantitative measures that directly assess neuroanatomy. Improved prediction of neuropsychological outcomes in mTBI may be achieved with the use of targeted neuroimaging markers.


Electricity generation from rapeseed straw hydrolysates using microbial fuel cells.
Rapeseed straw is an attractive fuel material for microbial fuel cells (MFCs) due to its high content of carbohydrates (more than 60% carbohydrates). This study has demonstrated that reducing sugars can be efficiently extracted from raw rapeseed straw by combination of hydrothermal pretreatment and enzymatic hydrolysis followed by utilization as a fuel in two-chamber MFCs for electrical power generation. The most efficient method of saccharification of this lignocellulosic biomass (17%) turned out hydrothermal pretreatment followed by enzymatic hydrolysis. Electricity was produced using hydrolysate concentrations up to 150 mg/dm(3). The power density reached 54 mW/m(2), while CEs ranged from 60% to 10%, corresponding to the initial reducing sugar concentrations of 10-150 mg/dm(3). The COD degradation rates based on charge calculation increased from 0.445 g COD/m(2)/d for the hydrolysate obtained with the microwave treatment to 0.602 g COD/m(2)/d for the most efficient combination of hydrothermal treatment followed by enzymatic hydrolysis.


Membrane-associated lymphotoxin expression and functional analysis of lymphokine-activated killer cells derived from tumor-infiltrating lymphocytes.
The expression of a membrane-associated lymphotoxin molecule (mLT) on lymphokine-activated killer (LAK) cells obtained from 18 patients with malignant tumors and its role in the tumor cell killing mechanisms were investigated. LAK cells from tumor-infiltrating lymphocytes (TIL-LAK cells) were mainly composed of CD3-positive cells, whereas LAK cells from peripheral blood lymphocytes (PBL-LAK cells) were mainly composed of CD16- and CD56-positive cells. However, mLT was found to be expressed on TIL-LAK cells as well as PBL-LAK cells. The degree of mLT expression correlated with the killing activity of LAK cells towards L929 cells (r = 0.806, P < 0.01, n = 15), but not with that towards Daudi or K562 cells. Although the degree of mLT expression correlated with the amount of secreted lymphotoxin (LT) in the supernatant of LAK cell culture, the secreted LT itself could not account for the tumor cell killing activity of LAK cells. Polyclonal rabbit anti-LT antibody partially inhibited the killing activities of LAK cells towards L929 cells and this inhibition was found in the combination of autologous tumor cells and PBL-LAK cells. These findings suggest the possibility that the mLT-related cytotoxicity is involved in the tumor cell killing mechanisms of TIL-LAK cells as well as PBL-LAK cells.


Endogenous and synthetic inhibitors of the Src-family protein tyrosine kinases.
Src-family kinases (SFKs) are protooncogenic enzymes controlling mammalian cell growth and proliferation. The activity of SFKs is primarily regulated by two tyrosine phosphorylation sites: autophosphorylation of a conserved tyrosine (Y(A)) in the kinase domain results in activation while phosphorylation of the regulatory tyrosine (Y(T)) near the C-terminus leads to inactivation. The phosphorylated Y(T) (pY(T)) engages in intramolecular interactions that stabilise the inactive conformation of SFKs. These inhibitory intramolecular interactions include the binding of pY(T) to the SH2 domain and the binding of the SH2-kinase linker to the SH3 domain. Thus, SFKs are active upon (i) disruption of the inhibitory intramolecular interactions, (ii) autophosphorylation of Y(A) and/or (iii) dephosphorylation of pY(T). Since aberrant activation of SFKs contributes to cancer, SFKs in normal cells are kept inactive by multiple endogenous inhibitors classified as catalytic and non-catalytic inhibitors. The catalytic inhibitors include C-terminal Src kinase (CSK) and CSK-homologous kinase (CHK) that phosphorylate Y(T) of SFKs, as well as the protein tyrosine phosphatases that dephosphorylate pY(A) of the activated SFKs. The non-catalytic inhibitors inactivate SFKs by direct binding. CHK is unique among these inhibitors because it employs both catalytic and non-catalytic mechanisms to inhibit SFKs. Other known non-catalytic inhibitors include WASP, caveolin and RACK1, which function to down-regulate SFKs in specific subcellular locations. This review discusses how the various endogenous SFK inhibitors cooperate to regulate SFKs in normal cells. As chemical compounds that can selectively inhibit SFKs in vivo are potential anti-cancer therapeutics, this review also discusses how investigation into the inhibitory mechanisms of the endogenous inhibitors will benefit the design and screening of these compounds.


LR-90 prevents dyslipidaemia and diabetic nephropathy in the Zucker diabetic fatty rat.
Previous studies have shown that LR-90, a new inhibitor of AGE formation, prevented the development of experimental type 1 diabetic nephropathy. In this study, we examined the effects of LR-90 in the Zucker diabetic fatty (ZDF) rat, a model of type 2 diabetes and metabolic syndrome, and investigated the mechanisms by which it may protect against renal injury. Male ZDF rats were treated without or with LR-90 from age 13 to 40 weeks. Metabolic and kidney functions and renal histology were evaluated. AGE accumulation and the production of the receptor for AGE (AGER) were measured. Profibrotic growth factors, extracellular matrix proteins and intracellular signalling pathways associated with glomerular and tubular damage were also analysed. LR-90 dramatically reduced plasma lipids in ZDF rats, with only modest effects on hyperglycaemia. Renal AGE, AGER and lipid peroxidation were all attenuated by LR-90. LR-90 significantly retarded the increase in albuminuria and proteinuria. This was associated with reduction in glomerulosclerosis and tubulointerstitial fibrosis, concomitant with marked inhibition of renal overproduction of TGF-beta1, connective tissue growth factor, fibronectin and collagen IV. Additionally, LR-90 downregulated the activation of key mitogen-activated protein kinases (MAPKs) and nuclear factor kappa B (NF-kappaB) in the renal cortex. These results support our earlier studies on the renoprotective effects of LR-90 on type 1 diabetic nephropathy and provide further evidence that LR-90, an AGE inhibitor with pleiotrophic effects, may also be beneficial for the prevention of type 2 diabetic nephropathy, where multiple risk factors, such as hyperglycaemia, dyslipidaemia, obesity, insulin resistance and hypertension, contribute to renal injury.


SemanticGO: a tool for gene functional similarity analysis in Arabidopsis thaliana and rice.
Gene or pathway functional similarities are important information for researchers. However, these similarities are often described sparsely and qualitatively. The latent semantic analysis of Arabidopsis thaliana (Arabidopsis) Gene Ontology (GO) data produced a set of 200-dimension feature vectors for each gene. Pathways were represented by summing the vectors of the pathway member genes. Thus, the similarities between genes and pathways were assessed. Additionally, the gene feature vectors were correlated with external gene data, including gene expression and gene network connectivity, to elucidate the associated functions. The gene feature vectors were decoded, and their applications were demonstrated. A simple online tool, SemanticGO (http://bioinformatics.fafu.edu.cn/semanticGO/), is herein provided to enable researchers to explore the similarities between genes and pathways in both Arabidopsis and rice.


"Posture first": Interaction between posture and locomotion in people with low back pain during unexpectedly cued modification of gait initiation motor command.
The ability to adapt anticipatory postural adjustments (APAs) in response to perturbations during single-joint movements is altered in people with chronic low back pain (LBP), but a comprehensive analysis during functional motor tasks is still missing. This study aimed to compare APAs and stepping characteristics during gait initiation between people with LBP and healthy controls, both in normal (without cue occurrence) condition and when an unexpected visual cue required to switch the stepping limb. Fourteen individuals with LPB and 10 healthy controls performed gait initiation in normal and switch conditions. The postural responses were evaluated through the analysis of center of pressure, propulsive ground reaction forces, trunk and whole-body kinematics, and activation onsets of leg and back muscles. During normal gait initiation, participants with LBP exhibited similar APAs and stepping characteristics to healthy controls. In the switch condition, individuals with LBP were characterized by greater mediolateral postural stability but decreased forward body motion and propulsion before stepping. The thorax motion was associated with forward propulsion parameters in both task conditions in people with LBP but not healthy controls. No between-group differences were found in muscle activation onsets. The results suggest that postural stability is prioritized over forward locomotion in individuals with LBP. Furthermore, the condition-invariant coupling between thorax and whole-body forward propulsion in LBP suggests an adaptation in the functional use of the thorax within the postural strategy, even in poor balance conditions.


Studies of Bolivian Ptiliidae (Coleoptera) 2: The subfamily Acrotrichinae including two new genera Petrotrichis and Microtrichis, and eight new species of Acrotrichis.
This is the second report on a collection of Ptiliidae from Bolivian forest leaf litter made by Dr Petr Baňař of the Brno Museum (Czech Republic) in 2013. A small collection of Bolivian Acrotrichis in the Natural Museum, London, made by H. Mendel and M.V.L. Barclay in 2004 is also included. Two new monotypic genera are described Petrotrichis gen. n. (Acrotrichini), type species P. rotundata sp. n., and Microtrichis gen. n. (Nephanini), type species M. pectana sp. n., together with eight new species of Acrotrichis: A. armillata sp. n., A. cincinna sp. n., A. cornuta sp. n., A. corpulenta sp. n., A. inlecebrosa sp. n., A. linea sp. n., A. nashi sp. n. and A. segmenta sp. n..


MR Imaging-Guided Partial Volume Correction of PET Data in PET/MR Imaging.
Partial volume effects are caused by the limited spatial resolution of the PET system. There is increasing evidence that partial volume correction (PVC) is necessary to guarantee quantitative accuracy in PET; however, there is reluctance to apply PVC routinely in clinical practice, partly because of uncertainty regarding the method of choice. To perform accurate PVC, it is necessary to introduce information from high-resolution anatomic images, such as MR imaging. All the methods rely on accurate coregistration between the anatomic image and the PET image. PET/MR imaging offers clear advantages for PVC and can help alleviate the image registration issues.


Crossed Regio- and Enantioselective Iron-Catalyzed [4+2]-Cycloadditions of Unactivated Dienes.
The cyclohexene motif is ubiquitous in nature and specialty chemicals. A straightforward selective access to chiral cyclohexenes from unactivated dienes and dienophiles is not feasible by classical Diels-Alder reaction and constitutes an unsolved synthetic challenge. We report a mild and enantioselective iron-catalyzed cross-[4+2]-cycloaddition of unactivated dienes providing access to chiral 1,3-substituted vinyl-cyclohexenes. The development of bis-dihydroisoquinoline ligands was vital to obtain iron complexes that display high reactivities and excellent chemo-, regio- and enantioselectivities towards the targeted cyclohexenes. A range of diene substrates is well accommodated including feedstocks like butadiene, isoprene and myrcene. The structures of different iron complexes are mapped by X-ray crystallographic analysis and linked to their performance.


The reverse LICAP flap: A laterally based submammary perforator flap for breast reconstruction.
The traditional donor sites for autologous breast reconstruction include the abdomen, thigh, buttock, and posterior thorax. Herein, we describe the use of the reverse lateral intercostal perforator (LICAP) flap originating from the submammary region as an option for breast reconstruction. Fifteen patients (30 breasts) were included in this retrospective review. The procedure was performed for immediate reconstruction following a nipple sparing mastectomy utilizing an inframammary incision or an inverted T pattern with preservation of the fifth anterior intercostal perforator (n = 8), volume replacement after implant explantation (n = 5), and partial lower pole resurfacing with exteriorization of a portion of the LICAP skin paddle (n = 2). Flap survival was achieved in all patients. Three flaps (10%) had 1-2 cm of intraoperative distal tip ischemia, which was managed by excision prior to inset and closure. At the 12-month postoperative follow-up, stable results with good nipple position, breast shape, and projection were achieved in all patients. The reverse LICAP flap is a safe, effective, and reliable option for breast reconstruction following mastectomy.


t(6;9) in bone marrow cells in two patients with sarcoidosis and acute myeloid leukemia.
A t(6;9) was seen in bone marrow aspirates from two patients with sarcoidosis who developed acute myeloid leukemia. This is a new observation not previously reported.


Effect of visual environment on refractive error of cats.
33 eyes of 18 cats raised in cages or in small rooms under conditions of near vision were compared with 22 eyes of 11 street cats. Refraction of the caged cats showed that three quarters of them were myopic (average:-0.8 D) while 87.5 percent of the street cats were hypermetropic (average: +1.4 D). The antero-posterior diameter was practically equal in both groups (20.4 mm) and in both myopic and hypermetropic eyes. The site of the permanent refractive changes is suggested to be the lens.


Evidence for involvement of protein kinase in the activation by adenosine 3':5'-monophosphate of brain tyrosine 3-monooxygenase.
Addition of adenosine 3':5'-monophosphate (cAMP) to high speed supernatant preparations obtained from rat brain caused a 3- to 4-fold increase in tyrosine 3-monooxygenase (tyrosine hydroxylase) activity. The tyrosine 3-monooxygenase remained in an activated state upon removal of the cAMP by passing the enzyme through a Sephadex G-25 column. Substances which inhibit cAMP-dependent protein kinase, namely, EDTA, ADP, and adenosine, and protein kinase modulator, each antagonized the activation of tyrosine 3-monooxygenase produced by cAMP. Furthermore, addition of partially purified brain cAMP-dependent protein kinase caused a several-fold increase in tyrosin 3-monooxygenase activity. The activation of tyrosine 3-monooxygenase by added cAMP and protein kinase required the presence of ATP and Mg-2+. These data suggests that the cAMP activation of tyrosine 3-monooxygenase may be mediated by a cAMP-dependent protein kinase.


Molecular intrinsic subtypes, genomic, and immune landscapes of BRCA-proficient but HRD-high ER-positive/HER2-negative early breast cancers.
The vast majority of research studies that have described the links between DNA damage repair or homologous recombination deficiency (HRD) score, and tumor biology, have concerned either triple negative breast cancers or cancers with mutation of BRCA 1/2. We hypothesized that ER + /HER2- early breast tumors without BRCA 1/2 mutation could have high HRD score and aimed to describe their genomic, transcriptomic, and immune landscapes. In this study, we reported BRCA 1/2 mutational status, HRD score, and mutational signature 3 (S3) expression, in all early breast cancer (eBC) subtypes from the TCGA database, with a particular focus in ER + /HER2-. In this subtype, bioinformatics analyses of tumor transcriptomic, immune profile, and mutational landscape were performed, according to HRD status. Overall survival (OS), progression free-interval (PFI), and variables associated with outcome were also evaluated. Among the 928 tumor samples analyzed, 46 harbored BRCA 1/2 mutations, and 606 were ER + /HER2- (of which 24 were BRCA 1/2 mutated). We found a subset of BRCA-proficient ER + /HER2- eBC, with high HRD score. These tumors displayed significantly different immune, mutational, and tumor molecular signatures landscapes, compared to BRCA-mutated and BRCA-proficient HRD-low tumors. Outcome did not significantly differ between these 3 groups, but biological factors associated with survival are not the same across the 3 entities. This study highlights possible novel biological differences among ER + /HER2- breast cancer related to HRD status. Our results could have important implications for translational research and/or the design of future clinical trials, but require prospective clinical evaluation.


[Home-based devices for the treatment of female urinary incontinence: A literature review].
Literature review on the home-based options for the conservative management of stress urinary incontinence including biofeedback and weighted vaginal cones.. Research was conducted in the Cochrane Library and Pubmed to find articles, published until March 2020, dealing with the conservative management of incontinence. A total of 9 randomized controlled trials were included, 4 concerning biofeedback and 5 concerning vaginal cones. Most of them highlighted the superiority of these three methods compared to the absence of treatment but were not superior compared to the pelvic floor muscles training in the clinic setting. Home-based devices for female stress urinary incontinence is a safe and effective treatment for female urinary incontinence. It has not shown superiority to physiotherapist-guided pelvic floor muscle reinforcement and needs more evidence to gain its place as a first line therapeutic option.


The influence of scale structure and sex on parental reports of children's social (pragmatic) communication symptoms.
The addition of social (pragmatic) communication disorder [S(P)CD] to the DSM-5 taxonomy has left clinicians and researchers searching for appropriate diagnostic measures. Factor analysis procedures examined the extent to which S(P)CD symptoms presented within the Children's Communication Checklist-Second Edition (CCC-2) represented a unique construct and whether these factors were influenced by children's sex. Parents of 208 children (males = 125 and females = 83) from a community-based sample completed the CCC-2. Two pragmatic scores from the CCC-2 were analysed as follows: the social interaction difference index (SIDI) and a pragmatic composite from the original CCC (PC-5). Factor analysis failed to find a unique factor structure for either pragmatic composite. Analyses uncovered different factor structures for the CCC-2 SIDI and PC-5 composites and for boys and girls. S(P)CD represents a complex combination of symptoms that are poorly differentiated from other language and socioemotional behavioural difficulties.


Decision regret in men undergoing dose-escalated radiation therapy for prostate cancer.
Decision regret (DR) is a negative emotion associated with medical treatment decisions, and it is an important patient-centered outcome after therapy for localized prostate cancer. DR has been found to occur in up to 53% of patients treated for localized prostate cancer, and it may vary depending on treatment modality. DR after modern dose-escalated radiation therapy (DE-RT) has not been investigated previously, to our knowledge. Our primary aim was to evaluate DR in a cohort of patients treated with DE-RT. We surveyed 257 consecutive patients with localized prostate cancer who had previously received DE-RT, by means of a validated questionnaire. There were 220 responses (85.6% response rate). Image-guided intensity modulated radiation therapy was given in 85.0% of patients and 3-dimensional conformal radiation therapy in 15.0%. Doses received included 73.8 Gy (34.5% patients), 74 Gy (53.6%), and 76 Gy (10.9%). Neoadjuvant androgen deprivation (AD) was given in 51.8% of patients and both neoadjuvant and adjuvant AD in 34.5%. The median follow-up time was 23 months (range, 12-67 months). In all, 3.8% of patients expressed DR for their choice of treatment. When asked whether they would choose DE-RT or AD again, only 0.5% probably or definitely would not choose DE-RT again, compared with 8.4% for AD (P<.01). Few patients treated with modern DE-RT express DR, with regret appearing to be lower than in previously published reports of patients treated with radical prostatectomy or older radiation therapy techniques. Patients experienced more regret with the AD component of treatment than with the radiation therapy component, with implications for informed consent. Further research should investigate regret associated with individual components of modern therapy, including AD, radiation therapy and surgery.


The thickness changes of retina in high myopia patients during the third trimester of pregnancy: a pilot study.
To observe and compare the difference in retinal thickness using optical coherence tomography (OCT) between patients with high myopia (HM) during the third trimester of pregnancy and age-matched HM non-pregnant women. A case-control study. A total of 39 eyes from 39 HM women in the third trimester (study group) and 50 eyes of 50 age-matched non-pregnant women with HM (control group) were included. All subjects underwent SD-OCT examination. The built-in software was used to measure the retinal thickness in macular region. The data from two groups were compared using independent-samples t test. Among the 89 subjects in this study, the mean gestational age of the study group was 35.09 ± 2.44 weeks, and the average age was 32.24 ± 3.75 years. The average age of the control group was 34.04 ± 7.19 years old. Compared with the control group, the average thickness of parafoveal area, and the average thickness of parafoveal superior, inferior, temporal quadrants of the superficial retina and the average thickness of the foveal and parafoveal of the superficial retina were significantly decreased in the study group (P < 0.05). Compared with the control group, the average thickness of all quadrants of the retina in the parafoveal area except the nasal quadrant were significantly decreased in the study group (P < 0.05). In this observational study, the retinal thickness of patients with high myopia during the third trimester of pregnancy was thinner than that of non-pregnant women with age-matched high myopia.


Knowledge about Hepatitis C Virus Infection and Acceptability of Testing in the 1945-1965 Birth Cohort (Baby Boomers) Presenting to a Large Urban Emergency Department: A Pilot Study.
Hepatitis C virus (HCV) is responsible for the most common chronic bloodborne infection in the United States. The Centers for Disease Control (CDC) recently recommended screening all patients born between 1945-1965 (baby boomers) at least once for HCV infection. New York State has since mandated screening of baby boomers for HCV in nearly all patient care settings and encouraged it in the emergency department (ED). This pilot study aimed to ascertain acceptability of an HCV screening test among the 1945-1965 birth cohort presenting to the ED in advance of a study investigating the prevalence of HCV infection in this birth cohort in the ED setting. We conducted a cross-sectional study of health knowledge about HCV and government recommendations regarding HCV testing using a convenience sample of baby boomers in an ED in a large public hospital in the New York metropolitan area. Surveys were administered via a series of semistructured interviews. There were 81 patient participants. Fifty-two percent of patients were born outside of the United States, 69% had a high school diploma level of education or lower, and 37% were unemployed. Patients demonstrated misconceptions about HCV transmission and curability and poor knowledge about the necessity of testing in their age cohort. Knowledge that "HCV can cause the liver to stop working" was significantly associated with acceptance of testing. Baby boomers showed limited knowledge about the necessity of HCV screening in their age group, but testing for HCV infection in the ED was acceptable for the majority.


Abdominothoracic gastric teratoma in a female newborn infant.
Gastric teratoma is a rare, benign tumor. The 47th case, reported here, is the first in which an abdominothoracic localization has been found.


Inactivation of jack bean urease by scutellarin: elucidation of inhibitory efficacy, kinetics and mechanism.
In the present study, the inactivation effect of scutellarin (SL) on jack bean urease was investigated to elucidate the inhibitory potency, kinetics and mechanism of inhibition. It was revealed that SL acted as a concentration- and time-dependent inactivator of urease characteristic of slow-binding inhibition with an IC50 of 1.35±0.15 mM. The rapid formation of the initial SL-urease complex with an inhibition constant of Ki=5.37×10(-2) mM was followed by a slow isomerization into the final complex with the overall inhibition constant of Ki*=3.49×10(-3) mM. High effectiveness of thiol protectors, such as L-cysteine (L-cys), 2-mercaptoethanol (2-ME) and dithiothreitol (DTT) significantly slowed down the rate of inactivation, indicating the strategic role of the active site sulfhydryl group in the blocking process. While the insignificant protection by boric acid and fluoride from the inactivation further confirmed that the active site cysteine should be obligatory for urease inhibition, which was also rationalized by the molecular docking study. The inhibition of SL on urease proved to be reversible since SL-blocked urease could be reactivated by DTT application and multidilution. The results obtained indicated that urease inactivation resulted from the reaction between SL and the sulfhydryl group.


Familial epilepsy in Algeria: Clinical features and inheritance profiles.
To document the clinical characteristics and inheritance pattern of epilepsy in multigeneration Algerian families. Affected members from extended families with familial epilepsy were assessed at the University Hospital of Oran in Algeria. Available medical records, neurological examination, electroencephalography and imaging data were reviewed. The epilepsy type was classified according to the criteria of the International League Against Epilepsy and modes of inheritance were deduced from pedigree analysis. The study population included 40 probands; 23 male (57.5%) and 17 female subjects (42.5%). The mean age of seizure onset was 9.5 ± 6.1 years. According to seizure onset, 16 patients (40%) had focal seizures and 20 (50%) had generalized seizures. Seizure control was achieved for two patients (5%) for 10 years, while 28 (70%) were seizure-free for 3 months. Eleven patients (27.5%) had prior febrile seizures, 12 were diagnosed with psychiatric disorders and four families had syndromic epilepsy. The consanguinity rate among parents of affected was 50% with phenotypic concordance observed in 25 families (62.5%). Pedigree analysis suggested autosomal dominant (AD) inheritance with or without reduced penetrance in 18 families (45%), probable autosomal recessive (AR) inheritance in 14 families (35%), and an X-linked recessive inheritance in one family. This study reveals large Algerian families with multigenerational inheritance of epilepsy. Molecular testing such as exome sequencing would clarify the genetic basis of epilepsy in some of our families.


Improving the sampling strategy of the Joint Danube Survey 3 (2013) by means of multivariate statistical techniques applied on selected physico-chemical and biological data.
The concept of basin-wide Joint Danube Survey (JDS) was launched by the International Commission for the Protection of the Danube River (ICPDR) as a tool for investigative monitoring under the Water Framework Directive (WFD), with a frequency of 6 years. The first JDS was carried out in 2001 and its success in providing key information for characterisation of the Danube River Basin District as required by WFD lead to the organisation of the second JDS in 2007, which was the world's biggest river research expedition in that year. The present paper presents an approach for improving the survey strategy for the next planned survey JDS3 (2013) by means of several multivariate statistical techniques. In order to design the optimum structure in terms of parameters and sampling sites, principal component analysis (PCA), factor analysis (FA) and cluster analysis were applied on JDS2 data for 13 selected physico-chemical and one biological element measured in 78 sampling sites located on the main course of the Danube. Results from PCA/FA showed that most of the dataset variance (above 75%) was explained by five varifactors loaded with 8 out of 14 variables: physical (transparency and total suspended solids), relevant nutrients (N-nitrates and P-orthophosphates), feedback effects of primary production (pH, alkalinity and dissolved oxygen) and algal biomass. Taking into account the representation of the factor scores given by FA versus sampling sites and the major groups generated by the clustering procedure, the spatial network of the next survey could be carefully tailored, leading to a decreasing of sampling sites by more than 30%. The approach of target oriented sampling strategy based on the selected multivariate statistics can provide a strong reduction in dimensionality of the original data and corresponding costs as well, without any loss of information.


Outcome Quality Beyond the Mean - An Analysis of 43,231 Pancreatic Surgical Procedures Related to Hospital Volume.
The aim of this study was to examine whether elevated in-hospital mortality rates in lower volume hospitals are only valid on average or also apply for individual hospitals. Various studies demonstrated a volume-outcome relationship in pancreatic surgery with increased mortality in low volume hospitals. However, almost all studies assessed quality indicators only for groups of hospitals by averaged measures, neglecting variability of hospital performance. The German nationwide hospital discharge data (diagnosis-related groups-statistics) was used to determine risk-adjusted in-hospital mortality for all distal pancreatectomies (DP), pancreatoduodenectomies (Whipple-proce-dure, PD), and pylorus-preserving pancreatoduodenectomies (PPD) performed between 2011 and 2015. Hospitals were stratified according to annual and 5-year total procedure volume and examined in relation to average in-hospital mortality of the highest volume quintile. Lowest adjusted mortality rates were observed in highest volume quintiles for each pancreatic resection procedure, with 6.2% for DP, 8.3% for PD, and 5.7% for PPD in the 5-year observation period. With these mortality rates as reference values the analysis revealed that a non-negligible proportion of hospitals performed equal or better (DP: 430/784, 54.5%; PD: 269/611, 44.0%; PPD: 255/565, 45.1%) than the hospitals of the highest volume quintile. High quality of care, with in-hospital mortality rates less or equal to high-volume hospitals, is also achieved in hospitals with lesser procedure volume. Therefore, mere volume seems not suitable as proximal measure for assessing individual hospital quality. instead, more sophisticated certification systems, that allow accurate quality assessment and better reflect clinical variability, should preferred to fixed minimum volume thresholds.


Post COVID-19 condition after delta infection and omicron reinfection in children and adolescents.
The burden of COVID-19 in children and adolescents has increased during the delta and omicron waves, necessitating studies of long-term symptoms such as fatigue, dyspnoea and cognitive problems. Furthermore, immune responses in relation to persisting symptoms in younger people have not been well characterised. In this cohort study, we investigated the role of antibodies, vaccination and omicron reinfection upon persisting and long-term symptoms up to 8 months post-delta infection. SARS-CoV-2 RT-PCR positive participants (n = 276, aged 10-20 years) were prospectively recruited in August 2021. We recorded the major symptoms of post COVID-19 condition and collected serum samples 3- and 8-months post delta infection. Binding antibodies were measured by spike IgG ELISA, and surrogate neutralising antibodies against Wuhan and delta variants by the hemagglutination test (HAT). After delta infection, persisting symptoms at 3 months were significantly associated with higher delta antibody titres (OR 2.97, 95% CI 1.57-6.04, p = 0.001). Asymptomatic acute infection compared to symptomatic infection lowered the risk of persisting (OR 0.13, 95% CI 0.02-0.55, p = 0.013) and long-term (OR 0.28 95% CI 0.11-0.66, p = 0.005) symptoms at 3 and 8 months, respectively. Adolescents (16-20 years) were more likely to have long-term symptoms compared to children (10-15 years) (OR 2.44, 95% CI 1.37-4.41, p = 0.003). This clinical and serological study compares long-term symptoms after delta infection between children and adolescents. The association between high antibody titres and persisting symptoms suggest the involvement of an immune mechanism. Similarly to adults, the dominant long-term symptoms in children are fatigue, dyspnoea and cognitive problems. This work was funded by the Ministry of Health and Care Services, Norway, the University of Bergen, Norway and Helse Vest, Norway (F-12621).


Developmental anomalies in Drosophila hybrids are apparently caused by loss of microchromosome.
Hybrids produced by crossing Drosophila virilis females to D. lummei males suffer from many developmental anomalies; the reciprocal hybridization yields normal offspring. Genetic analysis reveals that these anomalies involve a maternal effect: whether or not an individual will show an anomaly depends upon his mother's nuclear genotype. Several lines of evidence suggest that the proximal cause of the anomalies is the elimination of the D. lummei microchromosome (chromosome 6) from hybrids. Loss of the D. lummei microchromosome in this hybridization is known to involve a maternal effect (Evgen'ev, 1973), as mitosis in early development is under the control of maternally-acting genes.


Apochromatic X-ray focusing.
Achromatic doublets are combinations of two individual lenses designed to focus different wavelengths of light in the same position. Apochromatic optics are improved versions of the achromatic schemes which extend the wavelength range significantly. Both achromatic and apochromatic optics are well-established for visible light. However, X-ray achromatic lenses did not exist until very recently, and X-ray apochromatic lenses have never been experimentally demonstrated. Here, we create an X-ray apochromatic lens system using an appropriate combination of a Fresnel zone plate and a diverging compound refractive lens with a tuned separation distance. The energy-dependent performance of this apochromat was characterized at photon energies between 6.5 and 13.0 keV by ptychographic reconstruction of the focal spot and scanning transmission X-ray microscopy of a resolution test sample. The apochromat delivered a reconstructed focal spot size of 940 × 740 nm2. The apochromatic combination shows a four-fold improvement in the chromatic aberration correction range compared to an achromatic doublet configuration. Thus, apochromatic X-ray optics have the potential to increase the focal spot intensity for a wide variety of X-ray applications.


Age and Outcomes in Hip Arthroscopy for Femoroacetabular Impingement: A Comparison Across 3 Age Groups.
Limited evidence exists concerning the effect of age on hip arthroscopy outcomes for femoroacetabular impingement (FAI). The purpose was to investigate patient-reported outcomes (PROs) and clinical failure rates across various age groups in patients undergoing hip arthroscopy for FAI. We hypothesized that older patients would experience lower improvements in PROs and higher clinical failure rates. Cohort study; Level of evidence, 3. A total of 109 of 130 eligible consecutive patients underwent hip arthroscopy for FAI with a minimum 5-year follow-up. Patients were stratified into 3 groups for comparison (ages 15-34, 35-50, and 51-75 years). Clinical survival rates to revision surgery or total hip arthroplasty (THA) were determined by Kaplan-Meier analysis, and PROs were assessed using analysis of variance. Regression analysis was used to determine factors associated with clinical failure and ΔPROs from baseline to 5 years. The 5-year survival-to-revision rate was 71% (survival time, 69.2 months; 95% CI, 62.8 to 75.5 months). A significant difference in survival to THA was found between groups (P = .030). Being in the older group versus the young and middle-aged groups predicted increased risk of THA conversion (hazard ratio, 5.7; 95% CI, 1.1 to 28.6; P = .035). Overall modified Harris Hip Score (mHHS) and Nonarthritic Hip Score (NAHS) improved from baseline to 5 years (mHHS, P < .001; NAHS, P < .001). Body mass index (mHHS: beta, -1.2; 95% CI, -2.2 to -0.3; P = .013; NAHS: beta, -1.6; 95% CI, -2.6 to -0.5; P = .005) and baseline PROs (mHHS: beta, -0.8; 95% CI, -1.1 to -0.4; P < .001; NAHS: beta, -0.7; 95% CI, -1.1 to -0.4; P < .001) were predictive of 5-year ΔPROs. A decrease was seen in minimal clinically important difference rates in middle-aged (P = .011) and old (P = .030) groups from 6-month to 5-year outcomes. Although hip arthroscopy for FAI yielded improvements in PROs regardless of age, middle-aged and older patients experienced greater declines in clinical outcomes over time than younger patients. Older patients remain good candidates for arthroscopy despite a greater risk for conversion to THA.


Solvent-dependent aggregation behavior of a new Ru(II)-polypyridyl based metallosurfactant.
Variation of the solvent polarity leads to the formation of vesicles and reverse vesicles of a newly synthesized amphiphilic Ru(II)-polypyridyl complex.


Effect of Three Different Grip Angles on Physiological Parameters During Laboratory Handcycling Test in Able-Bodied Participants.
Handcycling is a relatively new wheelchair sport that has gained increased popularity for people with lower limb disabilities. The aim of this study was to examine the effect of three different grip positions on physical parameters during handcycling in a laboratory setting. Twenty one able-bodied participants performed three maximum incremental handcycling tests until exhaustion, each with a different grip angle. The angle between the grip and the crank was randomly set at 90° (horizontal), 0° (vertical), or 10° (diagonal). The initial load was 20 W and increased by 20 W each 5 min. In addition, participants performed a 20 s maximum effort. The relative peak functional performance (W/kg), peak heart rate (bpm), associated lactate concentrations (mmol/l) and peak oxygen uptake per kilogram body weight (ml.min(-1).kg(-1)) for the different grip positions during the stage test were: (a) Horizontal: 1.43 ± 0.21 W/kg, 170.14 ± 12.81 bpm, 9.54 ± 1.93 mmol/l, 30.86 ± 4.57 ml/kg; (b) Vertical: 1.38 ± 0.20 W/kg, 171.81 ± 13.87 bpm, 9.91 ± 2.29 mmol/l, 29.75 ± 5.13 ml/kg; (c) Diagonal: 1.40 ± 0.22 W/kg, 169.19 ± 13.31 bpm, 9.34 ± 2.36 mmol/l, 29.39 ± 4.70 ml/kg. Statistically significant (p < 0.05) differences could only be found for lactate concentration between the vertical grip position and the other grips during submaximal handcycling. The orientation of three different grip angles made no difference to the peak load achieved during an incremental handcycling test and a 20 s maximum effort. At submaximal load, higher lactate concentrations were found when the vertical grip position was used, suggesting that this position may be less efficient than the alternative diagonal or horizontal grip positions.


Colonization with multiresistant bacteria in acute hospital care: the association of prior antibiotic consumption as a risk factor.
Antibiotic resistance poses a worldwide threat and knowledge concerning risk factors for colonization with multiresistant bacteria (MRB) is limited. To examine the impact of prior antibiotic consumption on MRB colonization, with focus on type of antibiotic and timeline between antibiotic prescription and MRB colonization. A nationwide case-control study was conducted and adults visiting emergency departments were invited to participate. All patients were swabbed in the throat, nose and rectum, and analysed for colonization with ESBL-producing Enterobacteriaceae (ESBL-E), MRSA, carbapenemase-producing enterobacteria and VRE. Antibiotic history 2 years prior to enrolment was collected at an individual level through a national register. Multivariate analyses were performed to examine the association between antibiotic consumption and MRB status. A subgroup analysis of ESBL-E-colonized cases was made. We included 256 patients colonized with MRB and 4763 controls. In the 2 years prior to study inclusion, 77% of cases and 68% of controls had at least one antibiotic prescription (P = 0.002). We found a significant increase in risk of colonization with ESBL-E if penicillins (OR = 1.58-1.65) or fluoroquinolones (OR = 2.25-6.15) were prescribed. The analysis of all MRB-colonized patients showed similar results. An assessment of the timeline showed a significant increase in risk of colonization up to 2 years after exposure to penicillins, fluoroquinolones and macrolides. The prevalence of ESBL-E colonization was related to fluoroquinolone, macrolide and penicillin consumption for at least 2 years after antibiotic treatment.


Phosphorylation of myosin light chain kinase by the multifunctional calmodulin-dependent protein kinase II in smooth muscle cells.
Stimulation of tracheal smooth muscle cells in culture with ionomycin resulted in a rapid increase in cytosolic free Ca2+ concentration ([Ca2+]i) and an increase in both myosin light chain kinase and myosin light chain phosphorylation. These responses were markedly inhibited in the absence of extracellular Ca2+. Pretreatment of cells with 1-[N-O-bis(5-isoquinolinesulfonyl)-N- methyl-L-tyrosyl]-4-phenylpiperazine (KN-62), a specific inhibitor of the multifunctional calmodulin-dependent protein kinase II (CaM kinase II), did not affect the increase in [Ca2+]i but inhibited ionomycin-induced phosphorylation of myosin light chain kinase at the regulatory site near the calmodulin-binding domain. KN-62 inhibited CaM kinase II activity toward purified myosin light chain kinase. Phosphorylation of myosin light chain kinase decreased its sensitivity to activation by Ca2+ in cell lysates. Pretreatment of cells with KN-62 prevented this desensitization to Ca2+ and potentiated myosin light chain phosphorylation. We propose that the Ca(2+)-dependent phosphorylation of myosin light chain kinase by CaM kinase II decreases the Ca2+ sensitivity of myosin light chain phosphorylation in smooth muscle.


Could LUTS be early symptoms of COVID-19.
To show if lower urinary tract symptoms (LUTS) could be symptoms of COVID-19 with validated questionnaires. The 96 COVID-19 patients who were hospitalised at a tertiary centre were collected retrospectively. After the exclusion criteria, 46 patients consisted the study population. All patients then fill formed the International Prostate Symptom Score and Urinary Symptom Profile respectively. All patients responded to these questions for the three period. Twenty-seven female (58.6%) and 19 male (41.4%) COVID-19 patients answered the questions. In the male patients, while there were no statistically significant differences in the total IPSS, the voiding IPSS score, and quality of life between the three periods (P = .148; P = .933, P = .079, respectively), the storage IPSS scores had a significant difference between the three periods (P = .05). In female patients, low stream scores were similar between the three periods (P = .368). The scores of stress incontinence and an overactive bladder had a significant difference between the three periods (P = .05 and P = .05). LUTS, especially storage symptoms, might be one of the initial symptoms of COVID-19 and the clinicians should evaluate LUTS with other known symptoms of the virus when a patient is suspected of having COVID-19.


Dense genomewide linkage scan for alcohol dependence in African Americans: significant linkage on chromosome 10.
Alcohol dependence (AD) is costly to societies worldwide, moderately heritable, and genetically complex. Risk loci in several populations have been identified with genetic linkage analysis. To date, there has been no published linkage study of AD focused on African Americans (AAs). We completed a genomewide linkage scan with approximately 6000 single nucleotide polymorphism markers to map loci increasing risk for DSM-IV AD in a set of 238 small nuclear families ascertained on the basis of multiple individuals affected with cocaine or opioid dependence. Model free linkage analysis was completed with Merlin software. A modified marker set was used to avoid bias due to markers in strong linkage disequilibrium. We identified a genomewide-significant linkage to markers near 117.2 centiMorgans on chromosome 10q23.3-24.1 (logarithm of odds score 3.32; p = 5.0E-05; empirical genomewide p = .033). These data add to the growing evidence for locations for AD risk loci and provide the first linkage evidence for such a locus in the AA population.


Structure of a randomly grown 2-d network.
We introduce a growing random network on a plane as a model of a growing neuronal network. The properties of the structure of the induced graph are derived. We compare our results with available data. In particular, it is shown that depending on the parameters of the model the system undergoes in time different phases of the structure. We conclude with a possible explanation of some empirical data on the connections between neurons.


Factors influencing release of granulocyte-macrophage colony-stimulating activity from human mononuclear phagocytes.
Mononuclear phagocytes play an important role in the regulation of hematopoiesis, not only by producing regulatory monokines such as prostaglandins, tumor necrosis factor and interleukin-1 (IL-1), but also by the production of colony-stimulating activity (CSA). Previously, we have demonstrated that granulocyte-macrophage CSA (GM-CSA) production by mononuclear phagocytes can be induced by IL-1. In the present study, the influence of culture conditions on the production of GM-CSA was studied. It was found that both human sera and fetal bovine sera contain constituents - at present undefined - that induce GM-CSA production. These factors are distinct from IL-1 and lipopolysaccharide. In selected experiments, no GM-CSA-inducing effect of serum was found, suggesting that the effect may be donor-related. GM-CSA release in the presence of serum could be reduced by 40% after incubation of mononuclear phagocytes at low cell concentrations in methylcellulose, indicating that intimate cell-cell contact is an additional factor that enhances GM-CSA release.


Japanese Encephalitis Virus as Cause of Acute Encephalitis, Bhutan.
In 2011, Bhutan's Royal Centre for Disease Control began Japanese encephalitis (JE) surveillance at 5 sentinel hospitals throughout Bhutan. During 2011-2018, a total of 20 JE cases were detected, indicating JE virus causes encephalitis in Bhutan. Maintaining JE surveillance will help improve understanding of JE epidemiology in this country.


Chronic treatment with the α2-adrenoceptor antagonist fluparoxan prevents age-related deficits in spatial working memory in APP×PS1 transgenic mice without altering β-amyloid plaque load or astrocytosis.
Locus coeruleus degeneration and reduced central noradrenaline content is an early feature of Alzheimer's disease. In transgenic mouse models of Alzheimer's disease-like pathology, lesioning the locus coeruleus exacerbates β-amyloid (Aβ) pathology, neuroinflammation and memory deficits. Here we aimed to determine whether chronic treatment with the α(2)-adrenoceptor antagonist fluparoxan, that enhances noradrenaline release, can prevent the onset of Alzheimer's-like pathology and memory deficits in APP/PS1 transgenic mice (TASTPM). Fluparoxan (1mg/kg/day) was administered to TASTPM and wild type mice from 4 to 8 months of age. Memory was assessed at 4 and 8 months of age using the Morris water maze and contextual fear conditioning and at monthly intervals during the duration of treatment using the object recognition and spontaneous alternation task. Aβ plaque load and astrocytosis were measured at 4 and 8 months of age by immunohistochemistry. Fluparoxan treatment prevented age-related spatial working memory deficits in the spontaneous alternation task but not spatial reference memory deficits in the Morris water maze. Aβ plaque load and astrocytosis were unaltered by fluparoxan treatment in TASTPM mice. The findings suggest that fluparoxan treatment selectively prevent the decline of forms of memory where noradrenaline plays an integral role and that this beneficial effect is not due to altered Aβ plaque pathology or astrocytosis.


Prevalence of opportunistic invasive aspergillosis in COVID-19 patients with severe pneumonia.
As the global coronavirus pandemic (COVID-19) spreads across the world, new clinical challenges emerge in the hospital landscape. Among these challenges, the increased risk of coinfections is a major threat to the patients. Although still in a low number, due to the short time of the pandemic, studies that identified a significant number of hospitalised patients with COVID-19 who developed secondary fungal infections that led to serious complications and even death have been published. In this scenario, we aim to determine the prevalence of invasive fungal infections (IFIs) and describe possible associated risk factors in patients admitted due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We designed an open prospective observational study at the Rey Juan Carlos University Hospital (Mostoles, Spain), during the period from February 1 to April 30, 2020. In this article, we reported seven patients with COVID-19-associated pulmonary aspergillosis (CAPA) who had a poor prognosis. Severely ill patients represent a high-risk group; therefore, we must actively investigate the possibility of aspergillosis in all of these patients. Larger cohort studies are needed to unravel the role of COVID-19 immunosuppressive therapy as a risk factor for aspergillosis. As the pandemic continues to spread across the world, further reports are needed to assess the frequency of emergent and highly resistant reemergent fungal infections during severe COVID-19. These coinfections are leading a significant number of patients with COVID-19 to death due to complications following the primary viral disease.


Urine erythrocyte morphology in patients with microscopic haematuria caused by a glomerulopathy.
The evaluation of urinary erythrocyte morphology (UEM) has been proposed for patients with isolated microscopic haematuria (IMH) to early orientate the diagnosis towards a glomerular or a nonglomerular disease. However, to date, the role of this test in patients with IMH has very rarely been investigated. Sixteen patients (ten children, six adults) with persistent IMH classified as glomerular on the basis of repeated UEM evaluations (55 urine samples, two to eight per patient) were submitted to renal biopsy. This showed a glomerular disease in 14/16 patients (87.5%) (nine thin basement membrane disease; three Alport syndrome; two other), whereas in two patients, no abnormalities were found. Of four microscopic criteria investigated to define a IMH as glomerular, >80% dysmorphic erythrocytes were not found in any sample, >or=40% dysmorphic erythrocytes alone were seen in seven samples (12.7%), >or=5% acanthocytes alone in 15 samples (27.3%) and erythrocytic casts in six samples (10.9%). There was >or=40% dysmorphic erythrocytes associated with >or=5% acanthocytes in 25 samples (45.5%). Sensitivity and positive predictive values in diagnosing a glomerular haematuria were 59.2% and 90.6%, respectively, for >or=40% dysmorphic erythrocytes, 69.4% and 85% for >or=5% acanthocytes/G1 cells and 12.2% and 100% for erythrocytic casts. Our findings demonstrate that the evaluation of UEM is useful to identify patients with an IMH of glomerular origin.


Characterization of a novel steviol-producing β-glucosidase from Penicillium decumbens and optimal production of the steviol.
This study aimed to develop an economically viable enzyme for the optimal production of steviol (S) from stevioside (ST). Of 9 commercially available glycosidases tested, S-producing β-glucosidase (SPGase) was selected and purified 74-fold from Penicillium decumbens naringinase by a three-step column chromatography procedure. The 121-kDa protein was stable at pH 2.3-6.0 and at 40-60 °C. Hydrolysis of ST by SPGase produced rubusoside (R), steviolbioside (SteB), steviol mono-glucoside (SMG), and S, as determined by HPLC, HPLC-MS, and (1)H- and (13)C-nuclear magnetic resonance. SPGase showed higher activity toward steviol mono-glucosyl ester, ST, R, and SMG than other β-linked glucobioses. The optimal conditions for S production (30 mM, 64 % yield) were 47 mM ST and 43 μl of SPGase at pH 4.0 and 55 °C. This is the first report detailing the production of S from ST hydrolysis by a novel β-glucosidase, which may be useful for the pharmaceutical and agricultural areas.


Characterization of unknown iodinated disinfection byproducts during chlorination/chloramination using ultrahigh resolution mass spectrometry.
Iodinated disinfection byproducts (I-DBPs), formed from the reaction of disinfectant(s) with organic matter in the presence of iodide in raw water, have recently been focused because of their more cytotoxic and genotoxic properties than their chlorinated or brominated analogues. To date, only a few I-DBPs in drinking water have been identified. In this study, C18 solid phase extraction coupled with electrospray ionization ultrahigh resolution Fourier transform ion cyclotron resonance mass spectrometry (ESI FT-ICR MS) was used to characterize unknown I-DBPs in chloraminated/chlorinated water spiked with iodide and humic substances. In total, 178 formulas for one-iodine-containing products, 13 formulas for two-iodine-containing products, and 15 formulas for one-chlorine and one-iodine-containing products were detected in the chloraminated water sample, while only 9 formulas for one-iodine-containing products and 6 formulas for one-chlorine and one-iodine-containing products were found in the chlorinated water sample. Most I-DBPs have corresponding chlorine-containing analogues with identical CHO compositions. As indicated by the modified aromaticity index (AImod), in the C18 extracts, more than 68% of the I-DBPs have aromatic structures or polycyclic aromatic structures. This result demonstrates that the use of chloramination as an alternative disinfection method may lead to the formation of abundant species of I-DBPs in the presence of iodide. Thus, the suitability of adopting chloramination as an alternative disinfection method should be reevaluated, particularly when iodide is present in raw water.


Double-bundle PCL reconstruction using autogenous quadriceps tendon and semitendinous graft: surgical technique with 2-year follow-up clinical results.
The objective of this study was to evaluate the results obtained from posterior cruciate ligament (PCL) reconstruction with the double femoral tunnel technique, using quadriceps tendon and semitendinous autograft, in patients with isolated PCL tears or PCL tears associated with other ligament lesions, 2 years after surgery. The study included 14 patients with isolated PCL lesions and 20 with combined ligament lesions, who underwent PCL reconstruction using the double femoral tunnel technique and were evaluated 24 months after surgery using the International Knee Documentation Committee (IKDC) and Lysholm scores, a KT-1000 arthrometer, and the graduation of the posterior drawer test. Knees were considered normal ("A") or nearly normal ("B") in 92.9% of patients with isolated lesions and in 95.0% of patients with combined tears, according to the IKDC score. Good or excellent results were obtained in 100% of patients in both groups according to the Lysholm score. Absence or outstanding reduction of posterior tibial translation was seen in 92.9% of patients with isolated lesions and in 100% of patients with combined ligament tears, in the posterior drawer evaluation. The PCL double femoral tunnel reconstruction technique using autografts was effective in restoring posterior knee stability, in isolated and/or combined PCL tears, showing remarkable clinical improvement in all patients. 2C.


COVID-19 adenovirus vector vaccine induces higher interferon and pro-inflammatory responses than mRNA vaccines in human PBMCs, macrophages and moDCs.
During the COVID-19 pandemic multiple vaccines were rapidly developed and widely used throughout the world. At present there is very little information on COVID-19 vaccine interactions with primary human immune cells such as peripheral blood mononuclear cells (PBMCs), monocyte-derived macrophages and dendritic cells (moDCs). Human PBMCs, macrophages and moDCs were stimulated with different COVID-19 vaccines, and the expression of interferon (IFN-λ1, IFN-α1), pro-inflammatory (IL-1β, IL-6, IL-8, IL-18, CXCL-4, CXCL-10, TNF-α) and Th1-type cytokine mRNAs (IL-2, IFN-γ) were analyzed by qPCR. In addition, the expression of vaccine induced spike (S) protein and antiviral molecules were studied in primary immune cells and in A549 lung epithelial cells. Adenovirus vector (Ad-vector) vaccine AZD1222 induced high levels of IFN-λ1, IFN-α1, CXCL-10, IL-6, and TNF-α mRNAs in PBMCs at early time points of stimulation while the expression of IFN-γ and IL-2 mRNA took place at later times. AZD1222 also induced IFN-λ1, CXCL-10 and IL-6 mRNA expression in monocyte-derived macrophages and DCs in a dose-dependent fashion. AZD1222 also activated the phosphorylation of IRF3 and induced MxA expression. BNT162b2 and mRNA-1273 mRNA vaccines failed to induce or induced very weak cytokine gene expression in all cell models. None of the vaccines enhanced the expression of CXCL-4. AZD1222 and mRNA-1273 vaccines induced high expression of S protein in all studied cells. Ad-vector vaccine induces higher IFN and pro-inflammatory responses than the mRNA vaccines in human immune cells. This data shows that AZD1222 readily activates IFN and pro-inflammatory cytokine gene expression in PBMCs, macrophages and DCs, but fails to further enhance CXCL-4 mRNA expression.


The Sky's the LEMit: New insights into nuclear structure regulation of transcription factor activity.
The nucleoskeleton has been associated with partitioning the genome into active and inactive compartments that dictate local transcription factor (TF) activity. However, recent data indicate that the nucleoskeleton and TFs reciprocally influence each other in dynamic TF trafficking pathways through the functions of LEM proteins. While the conserved peripheral recruitment of TFs by LEM proteins has been viewed as a mechanism of repressing transcription, a diversity of release mechanisms from the lamina suggest this compartment serves as a refuge for nuclear TF accumulation for rapid mobilization and signal stability. Detailed mechanisms suggest that TFs toggle between nuclear lamina refuge and nuclear matrix lamin-LEM protein complexes at sites of active transcription. In this review we will highlight emerging LEM functions acting at the interface of chromatin and nucleoskeleton to create TF trafficking networks.


Passive oral drug absorption can be predicted more reliably by experimental than computational models--fact or myth.
This study assessed the prediction power of experimental and computational models that are widely used to predict human passive intestinal absorption. The models evaluated included two cell lines, three artificial membrane models, in vivo rat experiments, and seven previously described computational quantitative structure property relationship models based on human absorption values. The data sets used in the assessment of the models were carefully chosen from the literature, and different models were compared using the same compounds to ensure objective results. Three of the computational models were found to be significantly more reliable in predicting human passive intestinal absorption than the artificial membrane models that have been developed for the prediction of passive intestinal absorption. Two of these computational models were found to be as reliable as the Caco-2 and the 2/4/A1 cell lines and, furthermore, one of the models was able to predict the absorption of a set of 65 drugs nearly as well as absorption studies in rats. The unexpectedly good prediction power of the simple computational models with high throughput makes them ideal tools in the early screening of drug candidates, whereas laborious cell culture models and animal studies can be useful in the later phases when detailed information about the transport mechanisms is needed.


Peripubic urethropexy for urinary stress incontinence in women.
A technique for urinary stress incontinence is described that suspends the bladder neck and urethra by placing two vertical sutures along each posterior-lateral side of the entire urethra and tying them completely around the public bones. Six cases are reported and results given.


Effect of gestational age at birth on neonatal outcomes in gastroschisis.
Induced birth of fetuses with gastroschisis from 34weeks gestational age (GA) has been proposed to reduce bowel damage. We aimed to determine the effect of birth timing on time to full enteral feeds (ENT), length of hospital stay (LOS), and sepsis. A retrospective analysis (2000-2014) of gastroschisis born at ≥34weeks GA was performed. Associations between birth timing and outcomes were analyzed by Mann-Whitney test, Cox regression, and Fisher's exact test. 217 patients were analyzed. Although there was no difference in ENT between those born at 34-36+6weeks GA (median 28 range [6-639] days) compared with ≥37weeks GA (27 [8-349] days) when analyzed by Mann-Whitney test (p=0.5), Cox regression analysis revealed that lower birth GA significantly prolonged ENT (p=0.001). LOS was significantly longer in those born at 34-36+6weeks GA (42 [8-346] days) compared with ≥37weeks GA 34 [11-349] days by both Mann-Whitney (p=0.02) and Cox regression analysis (p<0.0005). Incidence of sepsis was higher in infants born at 34-36+6weeks (32%) vs. infants born at ≥37weeks (17%; p=0.02). Early birth of fetuses with gastroschisis was associated with delay in reaching full enteral feeds, prolonged hospitalization, and a higher incidence of sepsis.


Increased frequency of activated regulatory T cells in patients with lupus nephritis.
Lupus nephritis (LN) is one of the common manifestations of systemic lupus erythematosus (SLE), affecting the quality of life of patients. Abnormality in the adaptive immune response, such as T cell response, plays the main role in the pathogenesis of SLE and LN. In this study, we aimed to evaluate the role of different subpopulations of regulatory T cells (Tregs) and effector T cells (Teff) in LN patients and compare them with SLE patients. A total of 48 participants were enrolled in this study and divided into 3 groups: (i) patients with SLE; (ii) patients with LN; and (iii) healthy controls (HCs). The frequencies of CD4+ CD25++ CD45RA- Foxp3hi activated Tregs (aTregs), CD4+ CD25+ CD45RA+ Foxp3lo resting Tregs (rTregs), CD4+ CD25+ CD45RA- Foxp3lo non-Tregs, CD4+ CD25+ Foxp3- Teff, and Tregs were analyzed in all subjects using a flow cytometer. LN patients had a significantly increased frequency of aTregs and Tregs compared with SLE patients (standardized mean difference [SMD] = 0.50; 95% CI [-0.26, 1.25]; p > 0.05 and SMD = 0.60; 95% CI [-0.16, 1.36]; p > 0.05, respectively). Patients with LN had a significantly increased frequency of Teff compared with SLE patients (SMD = 0.49; 95% CI [-0.26, 1.24]; p > 0.05). However, an increased ratio of Tregs/Teff was observed in LN patients compared with SLE patients (SMD = -0.25; 95% CI [-0.97, 0.48]; p > 0.05). Patients with LN showed immunoregulatory properties, in which both aTregs and Tregs had increased frequencies.


Analysis of Gut Microbiome Reveals Significant Differences between Men with Chronic Prostatitis/Chronic Pelvic Pain Syndrome and Controls.
Chronic prostatitis/chronic pelvic pain syndrome is a common disorder with heterogeneous etiologies and clinical features. The gut microbiome is a metabolically active ecosystem linked to systemic conditions (gut-brain axis). We hypothesize that the gut microbiome will show alterations between patients with chronic pelvic pain syndrome and controls. We identified patients with chronic pelvic pain syndrome and controls who were asymptomatic or only had urinary tract symptoms. After rectal examination the soiled glove tip was immersed in sterile saline and stored on ice. Symptom severity was measured with the NIH-Chronic Prostatitis Symptom Index and clinical phenotype with UPOINT. Total DNA was extracted from the pellet of samples. MiSeq sequencing of bacterial specific 16S rRNA capture was performed. Taxonomic and bioinformatic analyses were performed using principal coordinate analysis, QIIME and LEfSe algorithms. There were 25 patients and 25 controls with complete data. Mean age was similar (chronic pelvic pain syndrome 52.3 vs control 57.0 years, p=0.27). For patients with chronic pelvic pain syndrome median symptom duration was 48 months, mean Chronic Prostatitis Symptom Index was 26.0 and mean UPOINT domain was 3.6. Three-dimensional UniFrac principal coordinate analysis revealed tighter clustering of controls in a space distinct from the wider clustering of cases (p=0.001) with cases having decreased alpha diversity (p=0.001). Compared to controls, 3 taxa were overrepresented in cases and 12 were underrepresented, eg Prevotella. Patients with chronic pelvic pain syndrome have significantly less gut microbiome diversity which clusters differently from controls, and robustly lower counts of Prevotella, with separation sufficient to serve as a potential biomarker. The gut microbiome may serve as disease biomarker and potential therapeutic target in chronic pelvic pain syndrome.


The efficacy of a brief intervention to reduce alcohol misuse in patients with HIV in South Africa: study protocol for a randomized controlled trial.
Alcohol abuse comes with risks for increased morbidity and mortality among patients with HIV. This study aims to determine the prevalence of alcohol use and other risk factors in a sample of primary care patients with HIV in South Africa and to assess a brief intervention to reduce the use of alcohol in this group. A single-blinded randomized controlled trial is designed to determine the efficacy of a brief intervention to reduce hazardous alcohol use in patients with HIV. The study will be carried out on out-patients with HIV in two primary healthcare HIV clinics near Pretoria, South Africa. Alcohol use will be assessed with the Alcohol Use Disorder Identification Test questionnaire. Other data that will be collected relate to health-related quality of life, depression, sexual behavior, internalized AIDS stigma, HIV-related information and adherence to antiretroviral therapy (self-reported 7-day recall of missed doses, Visual Analog Scale and pill count). The intervention consists of a brief counseling session to reduce alcohol risk; the control group receives a health education leaflet. The findings will be important in the public health setting. If the intervention proves to be efficient, it could potentially be incorporated into the HIV care policy of the Ministry of Health. Pan African Clinical trial Registry: PACTR201202000355384.


Accumulation of selenium in aquatic systems downstream of a uranium mining operation in northern Saskatchewan, Canada.
The objective of this study was to investigate the accumulation of selenium in lakes downstream of a uranium mine operation in northern Saskatchewan, Canada. Selenium concentrations in sediment and biota were elevated in exposure areas even though water concentrations were low (<5 microg/L). The pattern (from smallest to largest) of selenium accumulation was: periphyton<plankton and filterer invertebrates<detritivore and predator invertebrates<small bodied (forage) fish and predatory fish. Biomagnification of selenium resulted in an approximately 1.5-6 fold increase in the selenium content between plankton, invertebrates and forage fish. However, no biomagnification was observed between forage fish and predatory fish. Selenium content in organisms from exposure areas exceeded the proposed 3-11 microg/g (dry weight) dietary toxicity threshold for fish, suggesting that the selenium released into these aquatic systems has the potential to bioaccumulate and reach levels that could impair fish reproduction.


A general diffusion model for analyzing the efficacy of synaptic input to threshold neurons.
We describe a general diffusion model for analyzing the efficacy of individual synaptic inputs to threshold neurons. A formal expression is obtained for the system propagator which, when given an arbitrary initial state for the cell, yields the conditional probability distribution for the state at all later times. The propagator for a cell with a finite threshold is written as a series expansion, such that each term in the series depends only on the infinite threshold propagator, which in the diffusion limit reduces to a Gaussian form. This procedure admits a graphical representation in terms of an infinite sequence of diagrams. To connect the theory to experiment, we construct an analytical expression for the primary correlation kernel (PCK) which profiles the change in the instantaneous firing rate produced by a single postsynaptic potential (PSP). Explicit solutions are obtained in the diffusion limit to first order in perturbation theory. Our approximate expression resembles the PCK obtained by computer simulation, with the accuracy depending strongly on the mode of firing. The theory is most accurate when the synaptic input drives the membrane potential to a mean level more than one standard deviation below the firing threshold, making such cells highly sensitive to synchronous synaptic input.


Cervical aortic arch with retroesophageal aortic obstruction: report of a case with successful surgical intervention.
The clinical, roentgenographic, hemodynamic, and angiographic features of a patient with a right cervical aortic arch and retroesophageal aortic obstruction associated with a ventricular septal defect are presented. Surgical relief of the aortic obstruction was successfully achieved by placement of a bypass graft between the left common carotid artery and the descending thoracic aorta.


Dose-dense paclitaxel and carboplatin vs. conventional paclitaxel and carboplatin as neoadjuvant chemotherapy for advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer: a retrospective study.
The purpose of this study was to determine the optimal regimen of neoadjuvant chemotherapy (NAC) for advanced epithelial ovarian, fallopian tube, and peritoneal cancers. A clinical information survey involving 171 patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer was conducted. These patients underwent NAC followed by interval debulking surgery at the Hyogo Cancer Center (Hyogo, Japan) between January 2006 and December 2015. The median observation period was 41 (range 4-138) months. Dose-dense paclitaxel and carboplatin (TC) was administered in 101 patients (59%); tri-weekly TC was administered 70 patients (41%). Median progression-free survival was 21 [95% confidence interval (CI) 18-23] months and 15 (95% CI 13-17) months in the dose-dense TC and conventional-TC group [hazard ratio (HR) = 0.69, 95% CI 0.46-0.96; p = 0.02], respectively. The median overall survival was 59 (95% CI 46-72) and 40 (95% CI 32-57) months in the dose-dense TC group and conventional-TC group (HR = 0.72, 95% CI 0.48-1.06; p = 0.09). Multivariate analysis for progression-free survival demonstrated that dose-dense TC represented an independent prognostic factor (HR = 0.70, 95% CI 0.50-0.99; p = 0.04). Dose-dense TC is a promising regimen of NAC for advanced epithelial ovarian cancer.


Staging of carcinoma of the uterine cervix: MRI-surgical correlation.
Forty-six patients with carcinoma of the uterine cervix were examined with spin-echo magnetic resonance imaging (MRI) using a superconducting magnet operating at a field strength of 0.5 T. All subjects later underwent lymphadenectomy and, when appropriate, radical hysterectomy. Surgical-pathologic correlation was carried out in order to assess the accuracy of the imaging modality in the staging of the disease. In the detection of nodal involvement, the accuracy of MR was 76%. The accuracy in determination of tumour size approached 100%. In the assessment of parametrial and vaginal involvement, the accuracy was 85% and 100% respectively.


Identification and characterization of novel bacterial polyaromatic hydrocarbon-degrading enzymes as potential tools for cleaning up hydrocarbon pollutants from different environmental sources.
Polycyclic aromatic hydrocarbons (PAHs) are recalcitrant hazardous environmental contaminants. Various strategies, including chemical and physical like oxidation, fixation, leaching, and electrokinetic or biological-based techniques are used for remediation of polluted sites. Bioremediation of PAHs, via PAH-degrading endophytic and rhizospheric microbes, represent a time-/cost-effective way for ecorestoration. Four bacterial strains were isolated from contaminated soil on MSM supplemented with anthracene, alpha-naphthalene or catechol as sole carbon sources. These isolates were identified with 16S rRNA as Bacillus anthracis, B. cereus, B. mojavensis and B. subtilis. The degradation efficiency on the selected aromatic compounds was tested by HPLC analysis. B. subtilis showed the highest degradation efficiency of anthracene (99%) after five days of incubation. B. subtilis showed the highest catechol 1, 2 dioxygenase activity in MSM supplemented with anthracene. The enzyme was purified by gel filtration chromatography and characterized (70 kD, Km 2.7 μg and Vmax 178U/mg protein). The catechol 1,2 dioxygenase gene from the identified four bacterial strains were isolated and submitted to GenBank (accession numbers MG255165-MG255168). The gene expression level of catechol 1,2 dioxygenase was upregulated 23.2-fold during the 72 h of incubation period. Furthermore, B. subtilis is a promising strain to be used in bioremediation of aromatic compounds-contaminated environments.


Diffuse epidermal and periadnexal squamous cell carcinoma in situ: a report of 13 patients.
Diffuse epidermal and periadnexal squamous cell carcinoma in situ (DEPS) is a condition in which large areas of skin are affected by atypical keratinocytes that grow beneath the epidermis and encase adnexal epithelia. Normal differentiation of the overlying epidermis and adnexal epithelium is seen. Our aim was to describe the clinical features of DEPS. We undertook a retrospective case series of 13 patients with DEPS. All 13 patients were fair-skinned men older than 50 years with a history of significant sun exposure. The lesions were present on the scalp, face, and neck. Histologic examination showed a growth of atypical keratinocytes in the lower epidermis with encasement of adnexal structures by atypical neoplastic keratinocytes. In the 52 cumulative patient-years of follow-up, we treated 80 invasive squamous cell and 48 basal cell carcinomas in these patients. Despite improvement of DEPS with aggressive topical and destructive therapy, multifocal recurrence would typically develop within a few months. DEPS is characterized by diffuse involvement of chronically sun-exposed skin with atypical keratinocytes that grow along the inferior portion of the basal layer of the epidermis and around adnexal structures. The treatment of DEPS is challenging because of its widespread nature and deeper periadnexal involvement. DEPS is also associated with the development of invasive squamous cell and basal cell carcinomas.


[Accumulation of heavy metals in biocrystals in the shell of Mytilus galloprovincialis from different zones of the Gulf of Naples].
The amounts of Fe, Zn, Cu, Mg were determined in the inner and outer layers of shells of Mytilus g.. Different values significatively between the layers were found only for Mg. The ratio [Me]Calcite/ [Me]Aragonite was calculated and it is not more than one, for all the colonies of different sampling zones. The Authors conclude that perhaps the reason of this behaviour is the different pollution of their habitat.