Survivorship analysis of hemiarthroplasties.
From 1976 until 1988, 679 hemiarthroplasties were inserted for displaced femoral neck fractures. Two hundred two were of the Austin Moore design (one-piece, noncemented), 209 of the Christiansen design (trunion bearing, cemented), and 268 of the Hastings design (bipolar, cemented). Five years after the hemiarthroplasty, the cumulative proportion of prostheses surviving was 90%, declining to 85% after ten years. A survivorship analysis indicated that the cemented bipolar Hastings prosthesis and old age (75 years or older) were two variables associated with significantly less failures. The survivorship analysis did not indicate that the group differences were influenced by improvements in surgical techniques over time. Gender and social setting had no influence on the survival of prostheses. Cemented bipolar hemiarthroplasty should be considered as an alternative in the internal fixation of displaced femoral neck fractures in the elderly.


Organizational and Human Factors Affecting Forensic Decision-Making: Workplace Stress and Feedback.
Although forensic examiners operate in a stressful environment, there is a lack of understanding about workplace stress and feedback. These organizational and human factors can potentially impact forensic science judgments. In this study, 150 practicing forensic examiners from one laboratory were surveyed about their experiences of workplace stress, and the explicit and implicit feedback they receive. Forensic examiners reported that their high stress levels originated more from workplace-related factors (management and/or supervision, backlogs, and the pressure to do many cases) than from personal related factors (family, medical, and/or financial). The findings showed that a few (8%) of the forensic examiners sometimes felt strong implicit feedback about what conclusions were expected from them and that some (14%) also strongly felt that they were more appreciated when they helped to solve a case (e.g., by reaching a "match" as opposed to an "inconclusive" conclusion). Differences were found when comparing workplace stress and feedback levels across three core forensic science fields (forensic biology, chemistry, and latent prints) and across career stages (early, mid, and late). Gaining insights into the stress factors within a workplace and explicit and implicit feedback has implications for developing policies to improve the well-being, motivation, and performance of forensic examiners.


Relapsing fever in asylum seekers from Somalia arriving in Belgium in August 2015.
Current population displacements favor the re-emerging of diseases, nowadays very rare in Europe. We report two cases of 'imported' relapsing fever in two Somali asylum seekers occurring shortly after their arrival in Belgium. A diagnosis of relapsing fever should be considered in all migrants coming from endemic regions or having traveled in low hygiene and crowded conditions, presenting with recurrent fever, especially if no malaria parasites are found.


Impact of Sacubitril/Valsartan on Right Heart Failure.
Sacubitril/valsartan improves mortality and morbidity in patients with heart failure with reduced ejection fraction. However, its impact on right heart failure remains unknown. We experienced a 70-year-old man who was started on sacubitril/valsartan to treat his right heart failure with moderate tricuspid regurgitation. Following the 3-month sacubitril/valsartan treatment, a functional and geological improvement was observed in the right heart as well as amelioration of his congestive symptoms. Sacubitril/valsartan might improve right heart failure in addition to conventionally-proven left heart failure. Further large-scale studies are warranted to validate our findings.


Bulk versus interfacial aqueous solvation of dicarboxylate dianions.
Solvation of dicarboxylate dianions of varying length of the aliphatic chain in water clusters and in extended aqueous slabs was investigated using photoelectron spectroscopy and molecular dynamics simulations. Photoelectron spectra of hydrated succinate, adipate, and tetradecandioic dianions with up to 20 water molecules were obtained. Even-odd effects were observed as a result of the alternate solvation mode of the two negative charges with increasing solvent numbers. The competition between hydrophilic interactions of the charged carboxylate groups and hydrophobic interactions of the aliphatic chain leads to conformation changes in large water clusters containing dicarboxylates bigger than adipate. It also leads to a transition from bulk aqueous solvation of small dicarboxylates to solvation at the water/vapor interface of the larger ones. Whereas oxalate and adipate solvate in the inner parts of the aqueous slab, suberate and longer dicarboxylate dianions have a strong propensity to the surface. This transition also has consequences for the folding of the flexible aliphatic chain and for the structure of aqueous solvation shells around the dianions.


Technical, angiographic and clinical outcomes of Neuroform 1, 2, 2 Treo and 3 devices in stent-assisted coiling of intracranial aneurysms.
Since 2002 the Neuroform stent has expanded endovascular treatment of wide-necked intracranial aneurysms. A study was undertaken to assess the technical success rates and angiographic and clinical outcomes in stent-assisted coiling with Neuroform 1, 2, 2 Treo and 3. Patients undergoing Neuroform stent-assisted coiling were enrolled in a prospective registry that included 156 stent deployment attempts in 113 consecutive patients (mean age 53, range 25-78). Deployment success and difficulty, stent movement, procedural complications, immediate/delayed aneurysm occlusion and in-stent stenosis on angiographic follow-up were compared among Neuroform 1, 2, 2 Treo and 3 stents using a log likelihood ratio χ2 test. Of 156 stent attempts, 123 (79%) were deployed (Neuroform 1: 8/9 (89%), Neuroform 2: 50/66 (76%), Neuroform 2 Treo: 9/11 (82%), Neuroform 3: 56/70 (80%)) with a symptomatic complication rate of 1.9% (3/156; 2 transient ischemic attacks, 1 stroke, no deaths). Non-target stent placement (1/8 (13%), 6/50 (12%), 2/9 (22%), 3/56 (5%)), difficult placement (2/8 (25%), 10/50 (20%), 5/9 (56%), 6/56 (11%)), stent movement (1/8 (13%), 4/50 (8%), 0/9 (0%), 4/56 (7%)), procedural complications (1/9 (11%), 7/66 (11%), 2/11 (18%), 2/70 (3%)) and immediate near complete aneurysm occlusion (6/6 (100%), 24/37 (65%), 5/7 (71%), 40/45 (89%)) trended towards improvement with each generation. Improvements in difficult stent placement and immediate aneurysm occlusion were significant (p=0.01 and 0.03, respectively). Neuroform stent-assisted coiling has evolved through four generations as a safe and effective means of treating wide-necked intracranial aneurysms.


Psychometric properties of the Drinking Motives Questionnaire-Revised among community-dwelling current drinkers in the Ningxia autonomous region of China.
The 20-item Drinking Motives Questionnaire-Revised (DMQ-R)-which assesses social, enhancement, coping and conformity-related motives for drinking-has not previously been used in China. The aim of this paper is to evaluate the psychometric properties of the DMQ-R in China. DMQ-R was administered to 612 current drinkers identified from a representative sample of 2425 non-institutionalised adults living in Ningxia Province, China; 44 of these current drinkers were re-administered the questionnaire an average of 2.5 days later. Confirmatory factor analysis compared the adequacy of fit of alternative conceptual models. Due to the collectivist culture in China, we considered the possibility that item 12 ('to fit in the group I like') is an indicator of a 'social' motive (in Western studies, it is an indicator of a 'conformity' motive). Social motives for drinking were more frequently endorsed than other motives. The intraclass correlation coefficients for the test-retest reliability of the four subscales varied from 0.63 to 0.80. The originally conceptualised four-factor model showed good fit to the data [root mean square error of approximation (RMSEA) = 0.043, comparative fit index = 0.949 and Tucker-Lewis index = 0.941]. Fit indices improved (RSMEA = 0.034, comparative fit index = 0.968 and Tucker-Lewis index = 0.963) when item 12 was included in the 'social' dimension rather than the 'conformity' dimension. The 12-item short form of DMQ-R showed similar psychometric properties, but the fit indices were suboptimal. DMQ-R is a valid and reliable tool to assess drinking motives among current drinkers in China. Future studies in China using the DMQ-R should consider item 12 a social motive. [Cheng HG, Phillips MR, Zhang Y, Wang Z. Psychometric properties of the Drinking Motives Questionnaire-Revised among community-dwelling current drinkers in the Ningxia autonomous region of China. Drug Alcohol Rev 2016;35:433-441].


Correlates and determinants of Early Infant Diagnosis outcomes in North-Central Nigeria.
A negative status following confirmatory Early Infant Diagnosis (EID) is the desired pediatric outcome of prevention of Mother to Child Transmission (PMTCT) programs. EID impacts epidemic control by confirming non-infected HIV-exposed infants (HEIs) and prompting timely initiation of ART in HIV-infected babies which improves treatment outcomes. We explored factors associated with EID outcomes among HEI in North-Central Nigeria. This is a cross-sectional study using EID data of PMTCT-enrollees matched with results of HEI's dried blood samples (DBS), processed for DNA-PCR from January 2015 through July 2017. Statistical analyses were done using SPSS version 20.0 to generate frequencies and examine associations, including binomial logistic regression with p < 0.05 being statistically significant. Of 14,448 HEI in this analysis, 51.8% were female and 95% (n = 12,801) were breastfed. The median age of the infants at sample collection was 8 weeks (IQR 6-20), compared to HEI tested after 20 weeks of age, those tested earlier had significantly greater odds of a negative HIV result (≤ 6 weeks: OR = 3.8; 6-8 weeks: OR = 2.1; 8-20 weeks: OR = 1.5) with evidence of a significant linear trend (p < 0.001). Similarly, HEI whose mothers received combination antiretroviral therapy (cART) before (OR = 11.8) or during the index pregnancy (OR = 8.4) had significantly higher odds as compared to those whose mothers did not receive cART. In addition, HEI not breastfed had greater odds of negative HIV result as compared to those breastfed (OR = 1.9). cART prior to and during pregnancy, earlier age of HEI at EID testing and alternative feeding other than breastfeeding were associated with an increased likelihood of being HIV-negative on EID. Therefore, strategies to scale-up PMTCT services are needed to mitigate the burden of HIV among children.


The case for DNA methylation based molecular profiling to improve diagnostic accuracy for central nervous system embryonal tumors (not otherwise specified) in adults.
Central nervous system primitive neuro-ectodermal tumors (CNS-PNETs), have recently been re-classified in the most recent 2016 WHO Classification into a standby catch all category, "CNS Embryonal Tumor, not otherwise specified" (CNS embryonal tumor, NOS) based on epigenetic, biologic and histopathologic criteria. CNS embryonal tumors (NOS) are a rare, histologically and molecularly heterogeneous group of tumors that predominantly affect children, and occasionally adults. Diagnosis of this entity continues to be challenging and the ramifications of misdiagnosis of this aggressive class of brain tumors are significant. We report the case of a 45-year-old woman who was diagnosed with a central nervous system embryonal tumor (NOS) based on immunohistochemical analysis of the patient's tumor at diagnosis. However, later genome-wide methylation profiling of the diagnostic tumor undertaken to guide treatment, revealed characteristics most consistent with IDH-mutant astrocytoma. DNA sequencing and immunohistochemistry confirmed the presence of IDH1 and ATRX mutations resulting in a revised diagnosis of high-grade small cell astrocytoma, and the implementation of a less aggressive treatment regime tailored more appropriately to the patient's tumor type. This case highlights the inadequacy of histology alone for the diagnosis of brain tumours and the utility of methylation profiling and integrated genomic analysis for the diagnostic verification of adults with suspected CNS embryonal tumor (NOS), and is consistent with the increasing realization in the field that a combined diagnostic approach based on clinical, histopathological and molecular data is required to more accurately distinguish brain tumor subtypes and inform more effective therapy.


Cost-effectiveness of magnetic resonance carotid plaque imaging for primary stroke prevention in Canada.
Magnetic resonance of the carotid arteries provides important insight into plaque composition and vulnerability in addition to the traditional measure of stenosis. The purpose of this study was to evaluate the cost-effectiveness of MR imaging as a first-line modality to assess carotid disease and guide management for high-risk patients with <50% stenosis. Using TreeAge Pro, a cost-effectiveness simulation was conducted comparing two strategies: (a) standard of care first-line carotid duplex ultrasound (DUS) with regular follow-up, vs (b) first-line MR assessment of stenosis and intraplaque haemorrhage (MRIPH) in which patients with IPH received annual DUS surveillance and immediate carotid endarterectomy in case of plaque progression. For patients aged 70 years old, using a first-line MRIPH strategy resulted in a 16.8% relative risk reduction in strokes compared to DUS (0.080 vs 0.097 strokes per patient per lifetime), and an increased quality-adjusted-life years (12.23 vs 12.20) at an increased cost of $897.33 over a patient's lifetime ($5784.53 vs $4887.20 average total cost per patient per lifetime). The incremental cost-effectiveness ratio was $29,744 per quality-adjusted-life years. MRIPH remained cost-effective below a willingness-to-pay threshold of $50,000 for 91.8% of sensitivity analyses. MRIPH was found to be a cost-effective first-line tool to identify asymptomatic patients at high risk for stroke requiring annual surveillance and prompt management. Advances in Knowledge: Using MR imaging as a fist-line method to detect the presence of IPH provides clinically useful and cost-effective information that allows for enhanced risk evaluation and primary stroke prevention.


Biochemical localization of hepatic surface-membrane Na+,K+-ATPase activity depends on membrane lipid fluidity.
Membrane proteins of transporting epithelia are often distributed between apical and basolateral surfaces to produce a functionally polarized cell. The distribution of Na+,K+-ATPase [ATP phosphohydrolase (Na+/K+-transporting), EC 22.214.171.124] between apical and basolateral membranes of hepatocytes has been controversial. Because Na+,K+-ATPase activity is fluidity dependent and the physiochemical properties of the apical membrane reduces its fluidity, we investigated whether altering membrane fluidity might uncover cryptic Na+,K+-ATPase in bile canalicular (apical) surface fractions free of detectable Na+,K+-ATPase and glucagon-stimulated adenylate cyclase activities. Apical fractions exhibited higher diphenylhexatriene-fluorescence polarization values when compared with sinusoidal (basolateral) membrane fractions. When 2-(2-methoxyethoxy)ethyl 8-(cis-2-n-octylcyclopropyl)octanoate (A2C) was added to each fraction, Na+,K+-ATPase, but not glucagon-stimulated adenylate cyclase activity, was activated in the apical fraction. In contrast, further activation of both enzymes was not seen in sinusoidal fractions. The A2C-induced increase in apical Na+,K+-ATPase approached 75% of the sinusoidal level. Parallel increases in apical Na+,K+-ATPase were produced by benzyl alcohol and Triton WR-1339. All three fluidizing agents decreased the order component of membrane fluidity. Na+,K+-ATPase activity in each subfraction was identically inhibited by the monoclonal antibody 9-A5, a specific inhibitor of this enzyme. These findings suggest that hepatic Na+,K+-ATPase is distributed in both surface membranes but functions more efficiently and, perhaps, specifically in the sinusoidal membranes because of their higher bulk lipid fluidity.


Broad based tissue uptake of polycationic near-infrared polymeric nanoparticles in living mice.
A near infrared (NIR) fluorescent polymeric nanoparticle, commercialized under the name X-Sight 761 (X761), was tested for compatibility with pre-clinical in vivo imaging applications. In one experiment, an optical clearance profile was obtained by performing whole animal fluorescence imaging over the course of 48 hours on mice injected intravenously with X761. In a second trial, a temporal biodistribution was assessed by conducting necropsy and ex vivo analysis of X761 tissue accumulation at selected time points over a 48 hours period after i.v. injection. Taken together, the data demonstrate a sustained distribution of X761 into all major tissues over the time course, with an extremely low net clearance from the animal. This unique behavior is attributed to cell uptake mediated by the polycationic surface of X761. These properties negate the use of X761 as a reporter within a classical targeted molecular probe construct, in which selective concentration at a target site and rapid clearance from background tissues are needed to develop contrast. Nevertheless, the brightness and stability of X761 is well suited for a range of other applications, ranging from broad based in vivo drug delivery to in vitro fluorescence assays.


MDCT Imaging of Non-Traumatic Thoracic Aortic Emergencies and Its Impact on Diagnosis and Management-A Reappraisal.
Non-traumatic thoracic aorta emergencies are associated with significant morbidity and mortality. Diseases of the intimomedial layers (aortic dissection and variants) have been grouped under the common term of acute aortic syndrome because they are life-threatening conditions clinically indistinguishable on presentation. Patients with aortic dissection may present with a wide variety of symptoms secondary to the pattern of dissection and end organ malperfusion. Other conditions may be seen in patients with acute symptoms, including ruptured and unstable thoracic aortic aneurysm, iatrogenic or infective pseudoaneurysms, aortic fistula, acute aortic thrombus/occlusive disease, and vasculitis. Imaging plays a pivotal role in the patient's management and care. In the emergency room, chest X-ray is the initial imaging test offering a screening evaluation for alternative common differential diagnoses and a preliminary assessment of the mediastinal dimensions. State-of-the-art multidetector computed tomography angiography (CTA) provides a widely available, rapid, replicable, noninvasive diagnostic imaging with sensitivity approaching 100%. It is an impressive tool in decision-making process with a deep impact on treatment including endovascular or open surgical or conservative treatment. Radiologists must be familiar with the spectrum of these entities to help triage patients appropriately and efficiently. Understanding the imaging findings and proper measurement techniques allow the radiologist to suggest the most appropriate next management step.


Computerized modeling techniques predict the 3D structure of H₄R: facts and fiction.
The functional characterization of proteins presents a daily challenge r biochemical, medical and computational sciences, especially when the structures are undetermined empirically, as in the case of the Histamine H4 Receptor (H₄R). H₄R is a member of the GPCR superfamily that plays a vital role in immune and inflammatory responses. To date, the concept of GPCRs modeling is highlighted in textbooks and pharmaceutical pamphlets, and this group of proteins has been the subject of almost 3500 publications in the scientific literature. The dynamic nature of determining the GPCRs structure was elucidated through elegant and creative modeling methodologies, implemented by many groups around the world. H₄R which belongs to the GPCR family was cloned in 2000; understandably, its biological activity was reported only 65 times in pubmed. Here we attempt to cover the fundamental concepts of H₄R structure modeling and its implementation in drug discovery, especially those that have been experimentally tested and to highlight some ideas that are currently being discussed on the dynamic nature of H₄R and GPCRs computerized techniques for 3D structure modeling.


[Factors influencing quality of mammograms].
Due to its outstanding role for screening and diagnosis of breast cancer, optimizing the quality of mammographies was in the main focus of interest within the past two decades. However, there exist additional, non-technical factors influencing diagnostic confidence of mammograms, which were usually not part of discussions concerning mammographic image quality. Nevertheless, these non-technical factors are of great interest into the female population. Information and instruction of the patient prior to mammography helps to increase the compliance of the patient during mammography, and thus not only cooperation during examination is optimized, but also cooperation in the screening program. Furthermore, timing the examination within the first part of the menstrual cycle and regarding specific patient-related factors can decrease pain and discomfort during mammography, which will increase image quality.


Thrombophilic risk factors for placental stillbirth.
To define the characteristics of placental stillbirth and the possible contribution of thrombophilic risk factors. A prospective cohort study was performed. Women diagnosed with antenatal stillbirth (>20 weeks) of singleton pregnancies between 2006 and 2008 were referred postpartum for evaluation. Maternal risk factors, fetal, placental and cord abnormalities, and a detailed thrombophilia screening, including inherited and acquired thrombophilia, were evaluated. Fetal autopsy and placental pathology were encouraged. Placental stillbirth was defined as death of a normally-formed fetus with evidence of intrauterine fetal growth restriction, oligohydramnios, placental abruption and/or histological evidence of placental contribution to fetal death. Pregnancy characteristics and thrombophilia profiles were compared between placental and non-placental stillbirth cases. Sixty-seven women with stillbirth comprised the study group. Placental stillbirth was evident in 33/67 (49.3%). Significantly more women with placental stillbirth were nulliparous, when compared with non-placental stillbirth women (21/33 vs. 9/34, p=0.002). Mean gestational age was lower for placental, compared with non-placental stillbirth (31.1 ± 6.1 weeks vs. 33.9 ± 4.8 weeks, p=0.04), as was birth weight. Thirty-six of the 67 women (53.7%) tested positive for at least one thrombophilia. The prevalence of maternal thrombophilia was higher for placental stillbirth women (63.6%), and even higher (69.6%) for women after preterm (<37 weeks) placental stillbirth. Factor V Leiden and/or prothrombin G20210A mutation were much more prevalent in placental versus non-placental stillbirth women (OR 3.06, 95% CI 1.07-8.7). Placental stillbirth comprises a unique subgroup with specific maternal characteristics. Maternal thrombophilia is highly prevalent, especially in preterm placental stillbirth. This may have implications for the management strategy in future pregnancies in this subgroup.


Nonsteroidal anti-inflammatory drugs in clinical and experimental epilepsy.
Current antiepileptic drugs have limited efficacy and provide little or no benefits in 30% of the patients. Given that a role for brain inflammation in epilepsy has been repeatedly reported in recent years, the potential of anti-inflammatory drugs should be explored in depth, as they may provide new therapeutical approaches in preventing or reducing epileptogenesis. Here, we review preclinical (both in vivo and in vitro) and clinical epilepsy studies in which nonsteroidal antiinflammatory drugs (NSAIDs), i.e. cyclooxygenase-2 (COX-2) selective inhibitors (COXIBs) and nonselective NSAIDs, were used for seizure control. The effects of NSAIDs are reviewed in animal models of both chemical (pilocarpine, kainic acid, pentylenetetrazol, or carbachol administration) and electrical (tetanic hippocampal stimulation, electroshock) seizure induction. In the pilocarpine model, NSAIDs are neuroprotective, reduce mossy fiber sprouting or diminish P-glycoprotein upregulation, but only rarely protect against seizures. While neuroprotective effects have also been observed in the kainic acid model, NSAIDs tend in general to worsen seizure activity. Effects of COXIB administration in the pentylenetetrazol-induced seizures model are variable, alternating from protection against seizures to null effects or even increased incidence of convulsions. Moreover, NSAIDs tested in the tetanic hippocampal stimulation model diminished the seizure-associated P-glycoprotein upregulation, but were not very effective in seizure control. NSAIDs efficacy in experimental in vivo epilepsy studies may be influenced by multiple factors, including the timing of administration (before or after status epilepticus induction), the animal model of epilepsy or some of the signaling pathways involved in cyclooxygenase induction (e.g. prostaglandins and their receptors). On the other hand, the few clinical studies on the use of NSAIDs in neurological pathologies accompanied/characterized by seizures indicate that nonselective NSAIDs (e.g. aspirin) in prolonged, low-dose treatments may offer protection against seizures and stroke-like events. No clinical trials in epileptic patients using COXIBs have been conducted so far, as several international drug-control authorities have withdrawn these drugs from the market; future studies should focus on improved COXIB formulations. We argue that, while the available evidence is still inconclusive, the potential therapeutic benefits of controlling and diminishing brain inflammation in the treatment of epilepsy should be actively explored.


Effects of melatonin administration on testicular hemodynamics, echotexture, steroids production, and semen parameters during the non-breeding season in Ossimi rams.
This study was conducted to determine the influence of a single subcutaneous (SC) injection of melatonin (18 and 36 mg) on testicular hemodynamics, echotexture, plasma testosterone concentration, and sperm quality characteristics during the non-breeding season in Ossimi rams. Eighteen sexually mature, Ossimi rams were randomly allocated into two treated groups that received either 18 mg (Mel 18 group; n = 6) or 36 mg (Mel 36 group; n = 6) of melatonin powder dissolved in 1 ml corn oil (SC) and a control group (n = 6) that received 1 ml corn oil only. Blood collection and ultrasonographic assessment of the testes and supratesticular arteries were conducted immediately before treatment (W0) and once weekly for 8 successive weeks after melatonin injection (W1-W8). Resistive index (RI) and pulsatility index (PI) values were markedly decreased (P ˂ 0.05) within Mel 36 (at W4-W8) and e Mel 18 (at W8) groups, which was not observed within the control group (P ˃ 0.05). Testicular echogenicity was severely reduced (P ˂ 0.05) in Mel 36 (at W4-W5) and Mel 18 (at W8) groups, which was not occurred in the control one (P ˃ 0.05). The concentration of plasma testosterone was increased (P ˂ 0.05) in Mel 36 (at W3-W8) and Mel 18 (at W8) groups, which was not clear for the control rams (P ˃ 0.05). The percentage of progressively motile sperm cells was higher (P ˂ 0.05) in Mel 36 group (at W5-W8), which was not recorded within the Mel 18 or control groups (P ˃ 0.05).The percentages of sperm cells viability and normal morphology were higher (P ˂ 0.05) within Mel 36 (at W6-W8) and Mel 18 (at W7-W8) groups, which was not detected within the control group (P ˃ 0.05).In conclusion, the administration of melatonin ameliorates the testicular function via enhancing the testicular vascular irrigation, testosterone production, and sperm cells' quality parameters in Ossimi rams. So, we recommend administration of a single SC dose of melatonin (36 mg) at least one month before using rams for breeding especially out of the reproductive season.


The essential role of guinea pig cytomegalovirus (GPCMV) IE1 and IE2 homologs in viral replication and IE1-mediated ND10 targeting.
Guinea pig cytomegalovirus (GPCMV) immediate early proteins, IE1 and IE2, demonstrated structural and functional homologies with human cytomegalovirus (HCMV). GPCMV IE1 and IE2 co-localized in the nucleus with each other, the viral polymerase and guinea pig ND10 components (gpPML, gpDaxx, gpSp100, gpATRX). IE1 showed direct interaction with ND10 components by immunoprecipitation unlike IE2. Additionally, IE1 protein disrupted ND10 bodies. IE1 mutagenesis mapped the nuclear localization signal to the C-terminus and identified the core domain for gpPML interaction. Individual knockout of GPCMV GP122 or GP123 (IE2 and IE1 unique exons respectively) was lethal to the virus. However, an IE1 mutant (codons 234-474 deleted), was viable with attenuated viral growth kinetics and increased susceptibility to type I interferon (IFN-I). In HCMV, the IE proteins are important T cell target antigens. Consequently, characterization of the homologs in GPCMV provides a basis for their evaluation in candidate vaccines against congenital infection.


Co-visualization of DNA damage and ion traversals in live mammalian cells using a fluorescent nuclear track detector.
The geometric locations of ion traversals in mammalian cells constitute important information in the study of heavy ion-induced biological effect. Single ion traversal through a cellular nucleus produces complex and massive DNA damage at a nanometer level, leading to cell inactivation, mutations and transformation. We present a novel approach that uses a fluorescent nuclear track detector (FNTD) for the simultaneous detection of the geometrical images of ion traversals and DNA damage in single cells using confocal microscopy. HT1080 or HT1080-53BP1-GFP cells were cultured on the surface of a FNTD and exposed to 5.1-MeV/n neon ions. The positions of the ion traversals were obtained as fluorescent images of a FNTD. Localized DNA damage in cells was identified as fluorescent spots of γ-H2AX or 53BP1-GFP. These track images and images of damaged DNA were obtained in a short time using a confocal laser scanning microscope. The geometrical distribution of DNA damage indicated by fluorescent γ-H2AX spots in fixed cells or fluorescent 53BP1-GFP spots in living cells was found to correlate well with the distribution of the ion traversals. This method will be useful for evaluating the number of ion hits on individual cells, not only for micro-beam but also for random-beam experiments.


Simultaneous determination of Rubisco carboxylase and oxygenase kinetic parameters in Triticum aestivum and Zea mays using membrane inlet mass spectrometry.
The lack of complete Rubisco kinetic data for numerous species is partly because of the time consuming nature of the multiple methods needed to assay all of the Rubisco parameters. We have developed a membrane inlet mass spectrometer method that simultaneously determines the rate of Rubisco carboxylation (v(c)) and oxygenation (v(o)), and the CO(2) and O(2) concentrations. Using the collected data, the Michaels-Menten equations for v(c) and v(o) in response to changing CO(2) and O(2) concentrations were simultaneously solved for the CO(2) (K(c)) and O(2) (K(o)) constants, the maximum turnover rates of the enzyme for CO(2) (kcat(CO2)) and O(2) (kcat(O2)) and the specificity for CO(2) relative to O(2) (S(c/o)). In the C(4) species Zea mays K(c) was higher but K(o) was lower compared with the C(3) species Triticum aestivum. The kcat(CO2) was higher and the kcat(O2) lower in Z. mays compared with T. aestivum and S(c/o) was similar in the two species. The V(omax)/V(cmax) was lower in Z. mays and thus did not correlate with changes in S(c/o). In conclusion, this mass spectrometer system provides a means of simultaneously determining the important Rubisco kinetic parameters, K(c), K(o), kcat(CO2,)kcat(O2) and S(c/o) from the same set of assays.


Cartilage destruction in septic arthritis--electron microscopy and historical considerations.
Light and electron microscopic investigations of joint cartilage in 13 cases of septic arthritis revealed sites of cartilaginous matrix infiltrated with polymorphonuclear granulocytes. This finding confirms rather unknown morphological works done by investigators on this diseases in the late 19th and beginning of the 20th century. Around neutrophils ultrastructural signs of direct chondrolytic activity were observed. In three cases bacteria were discovered inside the cartilaginous matrix. It is assumed that the invasion of polymorphonuclear granulocytes into the cartilaginous matrix is an important process in septic arthritis leading to cartilage destruction.


Chest physicians' knowledge of appropriate thromboprophylaxis: insights from the PROMOTE study.
Venous thromboembolism (VTE) is a major cause of in-hospital mortality. Several international guidelines provide thromboprophylaxis recommendations; however, guidelines adherence is missing worldwide. We evaluated the chest physicians' knowledge regarding VTE prophylaxis, using a systematically developed questionnaire. The Prophylaxis-foR-venOus-throMbOembolism-assessmenT-questionnairE (PROMOTE) questionnaire was developed using an algorithm encompassing the most important VTE prophylaxis topics and included 13 clinical scenarios. Responses were evaluated with reference to the eighth edition of American College of Chest Physicians guidelines for VTE prevention to assess thromboprophylaxis appropriateness. The questionnaires were distributed during the fourth International Congress on Pulmonary Disease, Intensive Care and Tuberculosis. From the 88 received questionnaires (response rate: 39.8%), 82 were acceptable (62 men, 20 women). The most commonly cited VTE risk factors were immobility (79.2%), surgery (68.2%), and cancer (60.9%). The mean correct response ratio to the questions was 67% [95% confidence interval (CI) 64-70%] with highest appropriateness ratios amongst cardiologists (77.1 ± 5.8%) and lowest ratios among thoracic surgeons (59.2 ± 5%). Physicians' specialty had a significant effect on the overall appropriateness (P = 0.04) and most of appropriateness subcategories. Thoracic surgeons had the lowest rate of over-prophylaxis (P = 0.02). Years passed from graduation were inversely associated with overall appropriateness (P = 0.006). Physicians with academic engagements had a higher overall appropriateness (P = 0.04). We found a wide gap between the guideline recommendations and the responses. PROMOTE is the first systematically developed questionnaire that addresses chest physicians' thromboprophylaxis knowledge and could be useful to strategies to improve VTE prophylaxis. Because of the dissimilar prophylaxis pitfalls of different specialists, distinct educational programs seem necessary to improve their knowledge of proper VTE prophylaxis.


Emotional reactivity and the association between psychopathy-linked narcissism and aggression in detained adolescent boys.
Different patterns of emotional reactivity characterize proactive and reactive functions of aggressive behavior, and theory also suggests a link of both types with narcissism. How people with narcissistic traits respond emotionally to competitive scenarios could influence their aggressiveness. Participants were 85 adolescent boys from a detention center. Several indices of emotional functioning were assessed, including attentional bias to negative emotional stimuli and psychophysiological responding. In addition, we included self-report and laboratory measures of aggression and measures of psychopathy-linked narcissism, callous-unemotional traits, and impulsivity. Psychopathy-linked narcissism was uniquely related to unprovoked aggression (i.e., proactive aggression) and to heightened attention to pictures depicting others' distress. Compared with those scoring low on narcissism, those high on narcissism, who were the least physiologically reactive group, evinced greater proactive aggression, whereas those showing a pattern of coactivation (i.e., sympathetic and parasympathetic autonomic reactivity) evinced greater reactive aggression. Results are consistent with descriptions of narcissistic individuals as being hypervigilant to negative cues and exhibiting poor emotion regulation. These characteristics may lead to aggressive and violent behavior aimed at maintaining dominance over others.


Cloning and analysis of the gene (rpoDA) for the principal sigma factor of Pseudomonas aeruginosa.
A gene (rpoDA) of Pseudomonas aeruginosa whose gene product has a homologous function and structure with the principal sigma factor of Escherichia coli was cloned and sequenced. The DNA region corresponding to one of the two hybridization signals found in P. aeruginosa DNA with a synthetic oligonucleotide probe (rpoD probe) was shown to be able to complement a temperature sensitive mutation of Escherichia coli rpoD gene. The amino acid sequence deduced from the nucleotide sequence of rpoDA showed an extensive homology with that of the principal sigma factor of E. coli throughout the entire region, which indicates that the two gene products have an essentially identical domain structure. A common basic structure observed among principal sigma factors of different eubacterial strains was proposed. RpoDA protein was identified in the extract of the cell carrying a plasmid clone with the rpoDA gene insert by Western blot analysis.


Symptoms of traumatic stress after coronary artery bypass grafting.
Traumatic stress symptoms have only recently been studied in association with medical treatment procedures. The study examined associations of physical and psychological functioning during hospitalization to symptoms of traumatic stress after cardiac surgery. One hundred thirteen patients admitted for coronary artery bypass grafting participated in the study. Symptoms of traumatic stress were assessed one and six months after surgery, with the Impact of Event Scale. Preoperative stress and ruminative thinking, length of preoperative waiting, duration of surgery, and postoperative recovery indices (length of stay in the intensive care unit, cognitive functioning during intensive care, length of stay in the hospital) were examined. Ten percent of the patients reported severe (> 19) symptoms of avoidance, and five percent reported severe symptoms of intrusion in both follow-ups. Hierarchical regression analyses showed that preoperative stress was positively associated to avoidance symptoms in both follow-ups (p < .01). Preoperative stress and ruminative thinking was positively associated to intrusion symptoms one month after surgery (p < .01). Disease related factors were not related to symptoms of traumatic stress during the postoperative period. This study highlights the role of preoperative surgery-related stress as a risk factor for traumatic stress in the postoperative period.


CD4+ T regulatory cell induction and function in transplant recipients after CD154 blockade is TLR4 independent.
Although the role of CD4(+) T regulatory cells (Treg) in transplantation tolerance has been established, putative mechanisms of Treg induction and function in vivo remain unclear. TLR4 signaling has been implicated in the regulation of CD4(+)CD25(+) Treg functions recently. In this study, we first examined the role of recipient TLR4 in the acquisition of operational CD4(+) Treg following CD154 blockade in a murine cardiac transplant model. Then, we determined whether TLR4 activation in allograft tolerant recipients would reverse alloimmune suppression mediated by CD4(+) Treg. We document that donor-specific immune tolerance was readily induced in TLR4-deficient recipients by a single dose of anti-CD154 mAb, similar to wild-type counterparts. The function and phenotype of CD4(+) Treg in both wild-type and TLR4 knockout long-term hosts was demonstrated by a series of depletion experiments examining their ability to suppress the rejection of secondary donor-type test skin grafts and to inhibit alloreactive CD8(+) T cell activation in vivo. Furthermore, TLR4 activation in tolerant recipients following exogenous LPS infusion in conjunction with donor-type skin graft challenge, failed to break Treg-mediated immune suppression. In conclusion, our data reveals a distinctive property of CD4(+) Treg in tolerant allograft recipients, whose induction and function are independent of TLR4 signaling.


A one-year follow-up study of ocular and systemic complications of intravitreal injection of bevacizumab (Avastin).
To report systemic and ocular complications within a year of intravitreal injection of bevacizumab (Avastin) in ocular neovascularisation. The quasi-experimental (randomized without control) study was carried out at the Eye Department of Abbasi Shaheed Hospital, Karachi, from July 2008 to June 2010. It comprised 150 patients selected from the outpatient department with ocular neovascularisation through non-probability purposive sampling. After detailed history and examination, the patients were counseled for intravitreal injection Avastin (bevacjzumab) which was injected into the vitreous cavity in sterile environment in the operation theatre using fully aseptic technique. The injection site was compressed for several seconds to avoid reflux when the needle was removed. Paracentesis was done following the injection as soon as possible. Patients were discharged on moxifloxcin eye drops and steroid antibiotic combination ointment at night time. They were followed up the very next day, after 2 weeks, 6 weeks, 3 months, 6 months and 1 year. Injection was repeated after 6 weeks if required and further repetition was done again after 6 weeks according to the need of the patient. Of the 150 patients, 93 (62%) were males and 57 (38%) were females. Most commonly presenting age group was between 50-60 years (n=51; 34%) followed by 41-50 years (n=41; 27.4%). Most common indication for intravitreal injection Avastin (bevacizumab) was proliferative diabetic retinopathy in 134 (89.33%) patients, followed by age-related macular degeneration (wet type) in 5 (3.3%) patients. Most frequently presenting ocular complication was subconjunctival haemorrhage seen in 35 (23%) patients, followed by regurgitation of drug from the site of injection in 8 (5.3%) patients, transient rise of intraocular pressure in 7 (4.7%) patients, mild uveitiS in 4 (2.7%) patients, lens injury in 3 (2%) patients, conjunctival chemosis and iatrogenic vitreous haemorrhage in 1 (0.7%) patients. Among the systemic complications were acute rise of blood pressure in 4 (2.7%) patients, and mild irritation and allergic reaction on skin in 1 (0.7%) patient. Avastin is generally a safe drug for treatment of ocular neovascularization. The complications reported were more associated with the technique of the procedure and not the drug itself and were easily manageable. Drug-related complications were limited, transient and easily managed with treatment.


The adiposity indicators in relation to diabetes among adults in China: a cross-sectional study from China Health and Nutrition Survey.
Diabetes is a metabolic disease which has been confirmed to be involved with abnormal or excessive body fat accumulation. There is still a lack of nationwide research in China to discuss the relationship between adiposity indicators included body mass index (BMI), waist circumference (WC), visceral adiposity index, waist-height ratio, waist-to-hip ratio (WHR) and diabetes. The question of which one is the best indicator of obesity to predict diabetes in China remains to be unclear. Data were collected from the China Health and Nutrition Survey (CHNS) in 2009, including 7,930 participants aged over 18 years old for cross-sectional analysis. Information about height, weight, WC, hip circumference, smoking status, alcohol consumption, physical activity, energy intake and blood samples were analyzed. Binary logistic regression models were used to explore the association of WC, BMI, WHR, waist-to-height ration (WHtR) and visceral adipose index (VAI) with the prevalence of diabetes in the 2009 CHNS respectively. Predictive potential of five adiposity indicators was validated by the area under the receiver operator characteristic curve (AUROC). The optimal cut-off points were determined by Youden's index, which was used to estimate the performance of adiposity indicators. The study shows patients in the highest quartile were more likely to have diabetes than those in the lowest quartile of WC (OR: 4.237, 95% CI: 3.265-5.499), BMI (OR: 3.312, 95% CI: 2.601-4.218), WHR (OR: 3.199, 95% CI: 2.493-4.104), WHtR (OR: 3.760, 95% CI: 2.891-4.890), VAI (OR: 4.347, 95% CI: 3.411-5.541). The area under the receiver operator characteristic curve of WC, BMI, WHR, WHtR and VAI for diabetes was 0.700, 0.663, 0.668, and 0.697 and 0.694, respectively. The optimal cut-offs regarding diabetes in Chinese are WHtR ≥0.520 for men and VAI ≥1.878 for women. Our findings indicate that WC, WHtR, BMI, WHR and VAI are all independent risk factors for diabetes among Chinese adults. WHtR is the most accurate indicator for diabetes in men, while VAI for women.


The dying child: should we tell the truth?
Children and young people who are dying after having lived with a life-limiting or life-threatening condition will often be aware of their impending death. Whether that awareness is acknowledged and talked about will depend on the child, the parents and the professionals involved. A review of these three perspectives on truth telling reveals some of the many factors that influence openness, communication and truthfulness. Creation of a truthful care environment requires development of appropriate skills and attitudes in professionals, use of research evidence, ongoing assessment of the child and family's communication needs and support for members of the multidisciplinary care team.


Adherence to Dietary Recommendations of 7-Year-Old Children from a Birth Cohort in Friuli Venezia Giulia, Italy.
Few Italian and European studies have assessed adherence to dietary recommendations in primary school children using dietary records. No Italian studies have provided an index-based nutritional adequacy assessment. We provided a comprehensive overview of dietary intake in 381 7-year-old children from NAC-II cohort study, Friuli Venezia Giulia (Italy). Energy, macro-, and micronutrient intakes were derived from 3-day dietary records. Standard (median and percentage) and index-based (Nutrient Adequacy Ratio (NAR) and Mean Adequacy Ratio (MAR)) approaches were used to evaluate adequacy to Italian dietary reference values at nutrient- and overall-diet-level. Percentage contribution of macronutrients to energy intake (%En) was unbalanced towards total fats and protein. In 25% of children, total fats intake exceeded the reference intake upper limit. In ~63% of children, protein intake was at least doubled in their child-specific population reference intake. Median intakes of sodium (1.7 g/day), saturated fatty acids (12.2 %En), and soluble carbohydrates (19.4 %En) exceeded the suggested dietary target in most (65-84%) children. Inadequacy was also observed for micronutrients, with median NARs ranging from 0.11 (vitamin D) to 0.90 (zinc). The median MAR was 0.75 (0.69-0.79), with 1 indicating optimal overall dietary intake. In conclusion, the enrolled children showed suboptimal intakes of several macro- and micronutrients, in line with Italian and European studies on primary school children. Based on the current findings, public health interventions may be targeted to specific nutrients or subpopulations.


Variants of interleukin-16 associated with gastric cancer risk.
We conducted a case-control matched study to investigate the role of IL-16 gene polymorphisms, rs4072111, rs1131445, rs4778889 and rs11556218, in the risk of gastric cancer in a Chinese population, also performing subgroup analysis by subsites. To test the hypothesis of involvement, we analyzed the four SNPs of IL16 in 347 cancer patients and 368 controls. Demographic data and other information were collected using a newly designed questionnaire. Genotyping of IL16 (rs4072111, rs1131445, rs4778889 and rs11556218) was performed in a 384-well plate format on the MassARRAY® platform. In our study, we found the gastric cancer patients were more likely to be male and have a family history of cancer (P < 0.05). We found the rs4778889 CC and rs11556218 GG genotype was significantly associated with 1.97 and 1.84-fold increased risk of non-cardia gastric cancer, while we did not find significant association between the four IL-16 SNPs and cardia gastric cancer. In conclusion, our study indicated that IL-16 rs4778889 CC and rs11556218 GG genotypes are associated with an increased risk of non-cardia gastric cancer in a Chinese population. Our results offer insights into the influence of IL-16 on development of gastric cancer.


Acute appendicitis: does removal of a normal appendix matter, what is the value of diagnostic accuracy and is surgical delay important?
A prospective study with long-term follow-up was undertaken of 248 patients (137 males, median age 18 years (range 6-81 years), undergoing emergency appendicectomy during a 12-month period. Acute inflammation was present in 182 patients (73.4%) (males 86.1%, females 57.8%; P < 0.001). Before surgery, the positive predictive value of diagnostic accuracy was 82.0% (males 91.2%, females 67.7%). Delaying surgery did not significantly increase the proportion of perforated appendices (22.0%), hospital stay, or frequency of postoperative complications (overall 49.6%). Hospital complications were significantly more common among patients with a perforated appendix. There was no significant difference in the complication rate between patients with or without appendicitis while in hospital, during the first 18 months after operation or 8 years after operation. At 18 months, 17 of 238 patients (7.1%) continued to experience their original pain. After 8 years the original pain was still present in 10 of 155 patients (6.5%). Continued pain was more likely in patients having undergone removal of a normal appendix (P < 0.001)


Self-diffusion of ions in Nafion-117 membrane having mixed ionic composition.
The self-diffusion coefficients (SDCs) of Na(+), Cs(+), and Ba(2+) have been determined in Nafion-117 membrane having mixed cationic compositions. Membranes with different proportions of Na(+)-Cs(+), Cs(+)-Ba(2+), Na(+)-Ba(2+), and Ag(+)-Ba(2+) cations have been prepared by equilibrating with solutions containing different ratios of these cations. The SDCs of the cations (D(Na), D(Cs), D(Ba)) and the ionic compositions of the membrane have been determined using a radiotracer method. For the Na-Cs and Cs-Ba systems, the SDCs of the cations have been found to be independent of the ionic compositions of the membrane. In the case of the Na-Ba system, D(Na) does not change with ionic composition, while D(Ba) has been found to be strongly dependent on the ionic composition of the membrane and decreases continuously with increasing Na(+) content in the membrane. Similar results have also been obtained for D(Ba) in the case of the Ag-Ba system. The specific conductivities (κ(imp)) of the membrane in mixed cationic forms have also been obtained from ac impedance measurement and compared with that (κ(cal)) calculated from the SDC data. For the Na-Ba system, the increment of κ(imp) with increase in the Na(+) content of the membrane has been found to be parabolic, whereas for the Na-Cs system the increment is linear. The reason behind the different behaviors for different types of ionic systems has been qualitatively explained based on different transport pathways of the cations in the membrane.


Salicylic Acid and Phytoalexin Induction by a Bacterium that Causes Halo Blight in Beans.
Pseudomonas savastanoi pv. phaseolicola is a bacterium that causes halo blight in beans. Different varieties of beans have hypersensitive resistance to specific races of P. savastanoi pv. phaseolicola. During hypersensitive resistance, also known as effector-triggered immunity (ETI), beans produce hormones that signal molecular processes to produce phytoalexins that are presumed to be antibiotic to bacteria. To shed light on hormone and phytoalexin production during immunity, we inoculated beans with virulent and avirulent races of P. savastanoi pv. phaseolicola. We then used mass spectrometry to measure the accumulation of salicylic acid (SA), the primary hormone that controls immunity in plants, and other hormones including jasmonate, methyljasmonate, indole-3-acetic acid, abscisic acid, cytokinin, gibberellic acid, and 1-aminocyclopropane-1-carboxylic acid. SA, but no other examined hormone, consistently increased at sites of infection to greater levels in resistant beans compared with susceptible beans at 4 days after inoculation. We then monitored 10 candidate bean phytoalexins. Daidzein, genistein, kievitone, phaseollin, phaseollidin, coumestrol, and resveratrol substantially increased alongside SA in resistant beans but not in susceptible beans. In vitro culture assays revealed that SA, daidzein, genistein, coumestrol, and resveratrol inhibited P. savastanoi pv. phaseolicola race 5 culture growth. These results demonstrate that these phytoalexins may be regulated by SA and work with SA during ETI to restrict bacterial replication. This is the first report of antibiotic activity for daidzein, genistein, and resveratrol to P. savastanoi pv. phaseolicola. These results improve our understanding of the mechanistic output of ETI toward this bacterial pathogen of beans.


[Spontaneous tumors in the Mongolian gerbil (Meriones unguiculatus)].
The post mortem examination of 158 Mongolian gerbils (80 males and 78 females) revealed that 61 cases (38.6%) of them carried spontaneous neoplasms [22/80 (27.5%) of males and 39/78 (50%) of females]. In the male, sebaceous gland carcinoma at the abdominal skin was observed in 18/22 (81.8%) of tumor cases. In the female, granulosa cell tumor was seen in 31/39 (79.4%) of tumor cases. These two tumor types were markedly predominant in gerbils older than 3 years. The each incidence of other types of tumor was less than 5% in male and female animals.


The longitudinal development of a rehabilitation agency: an integrated rehabilitation service delivery model.
Health care services in the late 1980's are undergoing drastic changes. Similarly the laws, insurance regulations, etc. are changing so rapidly that the health care system appears to be having a difficult time keeping up with the ever changing needs of the consumers (that is, the patients). Diagnosis Related Groups (DRGs) have resulted in decreased hospital stays for patients with subacute and chronic conditions, and therefore patients are being care for in outpatient rehabilitation agencies, and/or outpatient clinics associated with hospitals. In short, a patient cannot stay in the hospital unless he or she is acutely ill or in need of surgery. Outpatient care is gradually becoming more important since patients who would have still been in the hospital several years ago, are now released to go home, with an order to receive outpatient therapy at the local rehabilitation agency. Currently there is no model available for starting an outpatient rehabilitation agency, and as a result health care professionals interested in starting such a facility have no guidelines or methodology for establishing a private rehabilitation practice.


Hyperinsulinemia and dyslipidemia in non-obese, normotensive offspring of hypertensive parents in northern India.
Insulin resistance contributes to initiation and acceleration of hypertension and atherosclerosis. This study attempted to detect occurrence of pre-hypertensive metabolic abnormalities, including hyperinsulinemia, in the offspring of hypertensive patients. Thirty-eight healthy offspring of hypertensive parents (group I, mean age 23.6+/-3.7 years) and 18 control offspring of normotensive parents (group II, mean age 24.2+/-2.8 years) were clinically examined, subjected to oral glucose tolerance test (OGTT), and the samples were analysed for blood glucose, insulin and lipid profile. Subjects in group I with fasting serum insulin <90 nmol/L constituted group Ia (n = 23, 62%) and those with >90 nmol/L constituted group Ib (n = 15, 38%). Both groups consisted of non-obese and normotensive subjects matched for body mass index and waist-hip ratio. There were no statistically significant differences in blood glucose levels between groups Ia, Ib and II during OGTT. Serum insulin levels during OGTT in group I were significantly higher than in group II (p<0.05), except at 30 min. Fasting insulin and 2 h post-OGTT insulin in group Ib were significantly higher than the other groups. Serum triglyceride levels, though within normal range, were higher in group I than group II (p<0.01). Similarly, high-density lipoprotein cholesterol levels in groups Ia and Ib were lower than those observed in group II (p<0.01). In conclusion, non-obese, normotensive offspring of hypertensive parents were observed to be hyperinsulinemic and dyslipidemic at an early age. These metabolic abnormalities may be associated with hypertension, glucose intolerance and accelerated atherosclerosis in adulthood.


Atypical beta(s) haplotypes are generated by diverse genetic mechanisms.
The majority of the chromosomes with the beta(S) gene have one of the five common haplotypes, designated as Benin, Bantu, Senegal, Cameroon, and Arab-Indian haplotypes. However, in every large series of sickle cell patients, 5-10% of the chromosomes have less common haplotypes, usually referred to as "atypical" haplotypes. In order to explore the genetic mechanisms that could generate these atypical haplotypes, we extended our analysis to other rarely studied polymorphic markers of the beta(S)-gene cluster, in a total of 40 chromosomes with uncommon haplotypes from Brazil and Cameroon. The following polymorphisms were examined: seven restriction site polymorphisms of the epsilongammadeltabeta-cluster, the pre-(G)gamma framework sequence including the 6-bp deletion/insertion pattern, HS-2 LCR (AT)xR(AT)y and pre-beta (AT)xTy repeat motifs, the GC/TT polymorphism at -1105-1106 of (G)gamma-globin gene, the C/T polymorphism at -551 of the beta-globin gene, and the intragenic beta-globin gene framework. Among the Brazilian subjects, the most common atypical structure (7/16) was a Bantu 3'-subhaplotype associated with different 5'-sequences, while in two chromosomes a Benin 3'-subhaplotype was associated with two different 5'-subhaplotypes. A hybrid Benin/Bantu configuration was also observed. In three chromosomes, the atypical haplotype differed from the typical one by the change of a single restriction site. In 2/134 chromosomes identified as having a typical Bantu RFLP-haplotype, a discrepant LCR repeat sequence was observed, probably owing to a crossover 5' to the epsilon-gene. Among 80 beta(S) chromosomes from Cameroon, 22 were associated with an atypical haplotype. The most common structure was represented by a Benin haplotype (from the LCR to the beta-gene) with a non-Benin segment 3' to the beta-globin gene. In two cases a Bantu LCR was associated with a Benin haplotype and a non-Benin segment 3' to the beta-globin gene. In three other cases, a more complex structure was observed that can be considered as a hybrid of Benin, Bantu, Senegal, or other chromosomes was observed. These data suggest that the atypical beta(S) haplotypes are not uncommon in America and in Africa. These haplotypes are probably generated by a variety of genetic mechanisms including (a) isolated nucleotide changes in one of the polymorphic restriction sites, (b) simple and double crossovers between two typical beta(S) haplotypes or much more frequently between a typical beta(S) haplotype and a different beta(A)-associated haplotype that was present in the population, and (c) gene conversions.


[Preclinical studies for the use of the platelet function analyser PFA-100 with the collagen/ADP cartridge in dogs].
In this study, the following three aspects of platelet function analyser were investigated in dogs, using a collagen/ADP cartridge: precision, influence of the cartridge batch and of the sample storage time. Closure time and total volume of blood flow until closure of the capillary were measured. Based on several series of 5 repeated measurements mean coefficients of variation were 5% (3-6%; closure time) or 3% (1-5%; total volume). Neither closure time, nor total volume showed significant differences (p > 0.05) when comparing the results of 6 different batches of the collagen/ADP cartridge. Closure time (p = 0.0211, analysis of variance) and total volume (p = 0.0310) were significantly influenced by storage time, based on the sample material of 6 healthy dogs which was stored for 24 hours. Shortening of the closure time and decrease of the total volume observed in the time interval 1-2 hours after blood collection was followed by a significant prolongation of closure time and increase of the total volume (p < 0.05) starting 8 hours after blood collection. This study shows sufficient reproducibility which is not affected by reagent batch number. The results of the studies on storage indicated nearly identical recommendations for storage time before measurement of canine (0.5-2 hours) and human (0.5-3 hours) sample material.


Reliability and Validity of an MRI-Based Knee Sagittal Alignment Measure in a Pediatric Cohort.
Magnetic resonance imaging (MRI) sagittal alignment is a measure that has been described and validated in the adult population as a means of distinguishing normal knees from those with anterior cruciate ligament (ACL) injury, but this measure has not been formally assessed among pediatric patients. The purpose of this study was to (1) assess the reliability of this MRI-based measure in a pediatric cohort, and (2) validate its ability to distinguish between ACL and non-ACL-injured knees in this population. A consecutive series of knee MRI examinations performed at our center were reviewed to identify studies of pediatric patients (1) with ACL injury, and (2) without significant pathology. Patient age, sex, physeal status (open, closing, or closed), knee laterality, and magnet strength (1.5 or 3-Tesla) were collected. The sagittal alignment was measured in both medial and lateral tibiofemoral compartments using a previously described method. Mean anterior tibial translation was then calculated for each study. Inter-rater and intrarater reliability testing was performed on a subset of randomly-selected patients from each cohort by three raters by calculating intraclass correlation coefficients. Sagittal alignment measurements of all patients were then completed by a single author after reliability was confirmed. The medial and lateral compartment translation and mean anterior tibial translation measurements of normal and ACL-injured knees were compared. Inclusion criteria were met by 131 studies: 86 from uninjured knees (normal cohort) and 45 knees with ACL injury (ACL cohort). Studies were performed at a mean age of 13.4 with a near equivalent sex distribution. Inter-rater and intrarater reliability were good to excellent for all measures for patients in both normal and ACL cohorts. Normal and ACL-injured knees demonstrated a significant difference in anterior tibial translation in all measured regions. The mean anterior tibia translation for ACL-injured knees was 2.01 mm (95% confidence interval: 1.03-2.98) versus -0.44 mm (95% confidence interval: -0.89-0.014). This study identified good to excellent inter-rater and intrarater reliability of knee sagittal alignment measurements among pediatric patients. It also demonstrated a significant difference in medial compartment, lateral compartment, and mean tibial translation in patients with and without ACL injury, validating previous findings demonstrated in adult cohorts. These findings may be useful in assisting providers in the confirmation of suspected ACL injury and insufficiency and guide operative management in cases of clinical uncertainty. Level III-retrospective comparative study.


Optical coherence tomography in late solar retinopathy.
Solar retinopathy refers to retinal injury induced by direct or indirect solar viewing. We presented a patient who had observed partial solar eclipse 51 year before. He had bilaterally decreased vision and scar of the macular region at the time of presentation. The basic diagnostic tool applied in the presented patient, optical coherence tomography, showed hyporeflexivity of the outer retina in the segment of retinal pigment epithelial-photoreceptors complex with atrophy and thinning of the foveolar region. Optical coherence tomography is a powerful, non-invasive diagnostic tool which can ease the diagnosis and estimate the level and nature of the macular region damage.


Changes over 6 years in secondary health conditions and activity limitations in older adults aging with long-term spinal cord injury.
The number of individuals aging with long-term spinal cord injury (SCI) is increasing. Still, there is limited knowledge about changes in secondary health conditions (SHCs) and activity limitations over time. To determine changes in SHCs and activity limitations in older adults aging with long-term SCI over 6 years, and to investigate how changes in SHCs and activity limitations are associated with gender, age, and injury characteristics. Longitudinal cohort study from the Swedish Aging with Spinal Cord Injury Study (SASCIS). Community settings, Sweden. From the initial 123 participants in the SASCIS: 78 individuals (32% women); mean age 68 years; mean time since injury 31 years; injury levels C1-L3, AIS A-D. Not applicable MAIN OUTCOME MEASURE: Bowel and bladder function and problems, pain, spasticity, and the Spinal Cord Independence Measure (SCIM III). Over 6 years, bowel-related problems increased (31% to 47%, p = .015) and the occurrence of constipation doubled to 24% (p = .013). There were increases in frequent urinary tract infections (10% to 26%, p = .004), use of indwelling urinary catheters (15% to 23%, p = .031), and other bladder-related problems (4% to 22%, p < .001). The occurrence of pain was high (85%), with no significant change. Spasticity increased from 41% to 62% (p < .001). Activity limitations increased (SCIM III total score mean 67 to 61, p < .001, with significant decreases in all subscales). The increase in bowel-related problems was greater in males, and the deterioration in self-care was greater in participants with longer time since injury and with traumatic injuries. These findings support the notion that SHCs and activity limitations increase over time in older adults aging with long-term SCI. The results can inform clinicians and call for a proactive, holistic approach in the long-term follow-up to support healthy and active aging.


Clinical and radiological cervical spine evaluation in retired professional rugby players.
OBJECT Acute cervical spine injuries have been extensively studied in high-level contact sports. However, the relation between the appearance of degenerative cervical spine disease and the exposure to repeated trauma in such sports as rugby is still unclear. Using clinical and MRI evaluation, we aimed to determine if former professional rugby players had more serious degenerative cervical spine symptoms than the general population. METHODS Two groups, one composed of 101 former rugby players (all men, mean age 40.3 years, range 35-47 years, SD 2.3 years) and the other of 85 male volunteers serving as a control group (mean age 41.6 years, range 35-49 years, SD 4.5 years) were studied. The former rugby players were evaluated on average 5.8 years after retirement (range 1-16 years, SD 3.5 years). The groups were matched in terms of sex, age, job, current sports training, and smoking habits. Each participant received a complete neurological evaluation. Clinical symptoms were evaluated using the Japanese Orthopaedic Association (JOA) questionnaire, and chronic neck pain was specifically evaluated using a visual analog scale (VAS) and the Neck Disability Index (NDI). Overall, 25 MRI studies were performed in each group. MRI studies, including dynamic sequences, focused on degenerative lesions (Matsumoto score and canal diameter) and on muscular and medullary morphological analysis. RESULTS Significantly more former rugby players than controls complained of chronic neck pain (51 [50.50%] of 101 vs 27 [31.76%] of 85, p = 0.01). Rugby players also had significant reductions of neck mobility. Nevertheless, in those complaining of pain, there was no statistically significant difference between groups with respect to VAS and NDI scores (p = 0.57). On MRI, former rugby players had a narrower vertebral canal (on average 0.88 ± 0.167 cm vs 0.99 ± 0.130 cm, p = 0.007) and more foraminal stenosis (p = 0.01). No significant difference in the Matsumoto score was found between the 2 groups with respect to other degenerative lesions. Former rugby players had more often undergone surgery for a degenerative condition than had members of the control group (10 cases vs 0 in the control group, p = 0.0021). CONCLUSIONS A few years after retirement, former professional rugby players seem to have more frequent cervical spine pain and MRI degenerative lesions, such as foraminal stenosis and narrowing of the spinal canal, compared with controls who had not been professional rugby players. A longer evaluation is necessary to determine if these findings persist over time.


Expression of Metallothionein after Administration of Aspirin, Vitamin C or Zinc Supplement in the DMH Induced Colon Carcinoma in Rat
Background: Chemoprevention refers to the use of specificnatural or synthetic chemical agents to suppress the development and progression to carcinoma. The purpose of this study was to assess the effect of aspirin, vitamin C or zinc on the metallothionein (MT) mRNA gene expression as well as MT protein content byimmunohistochemistry andradioimmunoassay (RIA) in 1, 2-dimethyl hydrazine (DMH) induced cancerous colonic tissuein rats. Methods: Rats were randomly divided into three groups, group 1 (aspirin), group 2 (vitamin C) group 3 (zinc), each of which was further sub divided into two groups and given subcutaneous injections of DMH (30 mg/kg body weight) twice a week for 3 months and sacrificed at either 4 months (A-precancer model) or at 6 months (B-cancer model).The control groups were administered 0.5 ml saline subcutaneously. All the 3 groups were simultaneouslyadministered aspirin, vitamin Cor zinc supplement respectively from the beginning till the end of the study. Results: It was observed that rats co-treated with aspirin, vitamin C or zinc resulted in a significant increase in the colonic MT mRNA expression in the precancer and cancer model as compared to the saline only controls. MT protein expression showed a 60%, 64% and 78% immunopositivity in the co-treated groups respectively.The mean MT content in the precancer and the cancer model was restored to near normal levels in all the three co-treated groups. Conclusion: These results suggest that co-administration of aspirin, vitamin C or zinc resulted in a significant increase in MT mRNA gene expression, MT protein expression and MT protein content which could possibly be one of the reasons for a chemo protective effect against progression to colonic cancer in a chemically induced DMH model in rat.Zinc supplement had a greater effect on metallothionein expression than aspirin or vitamin C.


Regulation by blue light of the fluffy gene encoding a major regulator of conidiation in Neurospora crassa.
The development of asexual spores, that is, the process of conidiation, in the fungus Neurospora crassa is increased by light. The fluffy (fl) gene, encoding a major regulator of conidiation, is activated by light. We describe here a detailed characterization of the regulation by blue light of fl in vegetative hyphae. This induction requires the white collar complex (WCC) while the FLD protein acts as a dark repressor of fl transcription. We show that the WCC directly regulates fl transcription in response to blue light after transiently binding the promoter. We propose that fl is repressed by FLD in vegetative mycelia and that the repression is lost after light exposure and WCC activation. The increase in fl mRNA in vegetative mycelia after light exposure, and the corresponding increase in the amount of the regulatory FL protein, should promote the activation of the conidiation pathway. The activation by light of fl provides a simple mechanism for the activation of conidiation by blue light in Neurospora that may be at work in other fungi.


Women's healthcare decision-making capacity and HIV testing in sub-Saharan Africa: a multi-country analysis of demographic and health surveys.
Global commitment to stop Human Immunodeficiency Virus (HIV) and ensure access to HIV treatment calls for women empowerment, as these efforts play major roles in mother-to-child transmission. We examined the association between women's healthcare decision-making capacity and uptake of HIV testing in sub-Saharan Africa. We used data from the current Demographic and Health Surveys (DHS) of 28 countries in sub-Saharan Africa, conducted between January 1, 2010 and December 31, 2018. At the descriptive level, we calculated the prevalence of HIV testing in each of the countries. This was followed by the distribution of HIV testing across the socio-demographic characteristics of women. Finally, we used binary logistic regression assess the likelihood of HIV testing uptake by women's health care decision-making capacity and socio-demographic characteristics. The results were presented as Crude Odds Ratios (COR) and Adjusted Odds Ratios (AOR) with their corresponding 95% confidence intervals signifying precision. Statistical significance was set at p-value < 0.05. We found that prevalence of HIV testing uptake in the 28 sub-Saharan African countries was 64.4%, with Congo DR having the least (20.2%) and the highest occurred in Rwanda (97.4%). Women who took healthcare decisions alone [COR = 3.183, CI = 2.880-3.519] or with their partners [COR = 2.577, CI = 2.335-2.844] were more likely to test for HIV, compared to those whose healthcare decisions were taken by others, and this persisted after controlling for significant covariates: [AOR = 1.507, CI = 1.321-1.720] and [AOR = 1.518, CI = 1.334-1.728] respectively. Sub-Saharan African countries intending to improve HIV testing need to incorporate women's healthcare decision-making capacity strategies. These strategies can include education and counselling. This is essential because our study indicates that the capacity of women to make healthcare decisions has an association with decision to test for their HIV status.


Dioscin attenuates high‑fat diet‑induced insulin resistance of adipose tissue through the IRS‑1/PI3K/Akt signaling pathway.
Insulin resistance, as a common metabolic disorder, may be caused by diet‑induced obesity. The aim of the present study is to investigate the effects of dioscin on regulating insulin resistance of adipose tissue induced by a high‑fat diet (HFD). An animal model was established successfully using C57BL/6J mice with high‑fat feeding, followed by treatment with 5, 10 and 20 mg/kg dioscin through gavage for 18 weeks, and randomly divided into a control group, a HFD model group and a dioscin group treated with 5, 10 and 20 mg/kg/day dioscin for 12 weeks. Histopathological changes in adipose tissues were examined using hematoxylin and eosin staining. Biochemical parameters of the serum were also monitored, including glucose, insulin, total triglyceride, homeostasis model assessment of insulin resistance (HOMA‑IR) and adipose insulin resistance (Adipo‑IR) levels. Expression of the mRNA and associated proteins of the insulin receptor substrate 1 (IRS‑1)/phosphoinositide 3‑kinase (PI3K)/protein kinase B (Akt) pathways were determined using reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and western blot analysis, respectively. HOMA‑IR and Adipo‑IR values of mice fed with a HFD were significantly higher compared with those in the control group (P<0.01). However, dioscin administration significantly decreased HOMA‑IR and Adipo‑IR values in a dose‑dependent manner (P<0.05), suggesting the effects of dioscin on attenuating insulin resistance. RT‑qPCR results indicated that the associated genes of the IRS‑1/PI3K/Akt pathway were significantly downregulated by HFD compared with the control group (P<0.05), while dioscin significantly increased the expression of those genes compared with the control group (P<0.05). Similarly, the significant increase in phosphorylated (p‑)IRS‑1/IRS‑1 (P<0.05) and p‑Akt/Akt (P<0.05) values were substantially reversed by dioscin treatment. Dioscin pronouncedly mitigated insulin resistance in adipose tissues through the IRS‑1/PI3K/Akt pathway and has potential to be used as a novel therapeutic agent for the therapy of HFD‑induced insulin resistance in adipose tissue.


A model for constitutive lutropin receptor activation based on molecular simulation and engineered mutations in transmembrane helices 6 and 7.
Many naturally occurring and engineered mutations lead to constitutive activation of the G protein-coupled lutropin receptor (LHR), some of which also result in reduced ligand responsiveness. To elucidate the nature of interhelical interactions in this heptahelical receptor and changes thereof accompanying activation, we have utilized site-directed mutagenesis on transmembrane helices 6 and 7 of rat LHR to prepare and characterize a number of single, double, and triple mutants. The potent constitutively activating mutants, D556(6.44)H and D556(6.44)Q, were combined with weaker activating mutants, N593(7.45)R and N597(7.49)Q, and the loss-of-responsiveness mutant, N593(7.45)A. The engineered mutants have also been simulated using a new receptor model based on the crystal structure of rhodopsin. The results suggest that constitutive LHR activation by mutations at Asp-556(6.44) is triggered by the breakage or weakening of the interaction found in the wild type receptor between Asp-556(6.44) and Asn-593(7.45). Whereas this perturbation is unique to the activating mutations at Asp-556(6.44), common features to all of the most active LHR mutants are the breakage of the charge-reinforced H-bonding interaction between Arg-442(3.50) and Asp-542(6.30) and the increase in solvent accessibility of the cytosolic extensions of helices 3 and 6, which probably participate in the receptor-G protein interface. Asn-593(7.45) and Asn-597(7.49) also seem to be necessary for the high constitutive activities of D556(6.44)H and D556(6.44)Q and for full ligand responsiveness. The new theoretical model provides a foundation for further experimental work on the molecular mechanism(s) of receptor activation.


Membrane topology and mutational analysis of Mycobacterium tuberculosis VKOR, a protein involved in disulfide bond formation and a homologue of human vitamin K epoxide reductase.
We have presented evidence that a homologue of vertebrate membrane protein vitamin K epoxide reductase (VKOR) is an important component of the protein disulfide bond-forming pathway in many bacteria. Bacterial VKOR appears to take the place of the nonhomologous DsbB found in Escherichia coli. We also determined the structure of a VKOR from a Cyanobacterium and showed that two or four conserved cysteines are required, according to different reductants for activity in an in vitro assay. Here we present evidence for the topologic arrangement in the cytoplasmic membrane of the VKOR from Mycobacterium tuberculosis (Mtb). The results show that Mtb VKOR is a membrane protein that spans the membrane 5 times with its N-terminus in the cytoplasm, C-terminus in the periplasm, and all four cysteines facing the periplasm. The essentiality of the four conserved cysteine residues has also been demonstrated in promoting disulfide bond formation in vivo and a mixed disulfide between a cysteine of DsbA of E. coli, and one of the cysteines (Cys(57)) of the VKOR homologue has been identified to be a likely intermediate in the disulfide bond-forming pathway. These studies may inform future resolution of issues surrounding the functioning of human VKOR.


[Application of niche theory in evaluation of main tourism scenic areas in Zhangjiajie City].
Five tourism scenic areas in Zhangjiajie City were selected as research objects, and fifty kinds of resource conditions affecting the development of tourism scenic area were taken as evaluation indices. Through disposing and consolidating the indices level by level, an analysis was made on the niche breadth and niche overlap of the five tourism scenic areas at three levels (I, II, and III). In the five scenic areas, index level had significant effects on the niche breadth (F = 10.278, P = 0.006), but less effects on the relative niche breadth, suggesting that in the evaluation of the development potential of tourism scenic area, relative niche breadth was more reasonable than absolute niche breadth. From level III to level I, the niche overlap of the five scenic areas was increasing, indicating that level choice would affect the evaluation of the actual niche overlap of the scenic areas. With the progressive refinement of the indices to certain level, and when the difference between observed and Monte Carlo-simulated Pianka indices achieved to significant level, this index level could be used as the minimum standard of the refinement, and the simulated niche overlap could be taken as an important reference in the competition evaluation of tourism scenic area.


The proton injector for the accelerator facility of antiproton and ion research (FAIR).
The new international accelerator facility for antiproton and ion research (FAIR) at GSI in Darmstadt, Germany, is one of the largest research projects worldwide and will provide an antiproton production rate of 7 × 10(10) cooled pbars per hour. This is equivalent to a primary proton beam current of 2 × 10(16) protons per hour. For this request a high intensity proton linac (p-linac) will be built with an operating rf-frequency of 325 MHz to accelerate a 35 mA proton beam at 70 MeV, using conducting crossed-bar H-cavities. The repetition rate is 4 Hz with beam pulse length of 36 μs. The microwave ion source and low energy beam transport developed within a joint French-German collaboration GSI/CEA-SACLAY will serve as an injector of the compact proton linac. The 2.45 GHz ion source allows high brightness ion beams at an energy of 95 keV and will deliver a proton beam current of 100 mA at the entrance of the radio frequency quadrupole (RFQ) within an acceptance of 0.3π mm mrad (norm., rms).


Immunocytolocalization of Plasma Membrane H-ATPase.
The localization of plasma membrane H(+)-ATPase has been studied at the optical microscope level utilizing frozen and paraffin sections of Avena sativa and Pisum sativum, specific anti-ATPase polyclonal antibody, and second antibody coupled to alkaline phosphatase. In leaves and stems the ATPase is concentrated at the phloem, supporting the notion that it generates the driving force for phloem loading. In roots the ATPase is concentrated at both the periphery (rootcap and epidermis) and at the central cylinder, including endodermis and vascular cells. This supports a ;two-pump' mechanism for ion absorption, involving active uptake at the epidermis, symplast transport across the cortex, and active efflux at the xylem. The low ATPase content of root meristem and elongation zone may explain the observed transorgan H(+) currents, which leave nongrowing parts and enter growing tips.


Flexible Ab initio boundary conditions: simulating isolated dislocations in bcc Mo and Ta.
We report the first ab initio density-functional study of the strain field and Peierls stress of isolated <111> screw dislocations in bcc Mo and Ta. The local dislocation strain field is self-consistently coupled to the long-range elastic field using a flexible boundary condition method. This reduces the mesoscopic atomistic calculation to one involving only degrees of freedom near the dislocation core. The predicted equilibrium core for Mo is significantly different from previous atomistic results and the Peierls stress shows significant non-Schmid behavior as expected for the bcc metals.


Current and future trends in ambulatory surgery and their impact on nursing practice.
The rapidly changing ambulatory surgery arena requires the professional nurse practicing in that area to be constantly aware of practices and policies to meet the demands of providing high-quality care at a low cost. Programs to effectively streamline the ambulatory surgery process as well as enhance the patient's experience will facilitate the success of ambulatory surgery units. This article discusses specific trends in ambulatory surgery and mechanisms to facilitate smooth functioning of the ambulatory surgery unit.


Nutritional Modulation of Gut Microbiota Alleviates Severe Gastrointestinal Symptoms in a Patient with Post-Acute COVID-19 Syndrome.
With the increase in total coronavirus disease 2019 (COVID-19) infection cases, post-acute COVID-19 syndrome, defined as experiencing ongoing health problems 4 or more weeks after the first severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, has become a new arising public health concern. As part of post-acute COVID-19 syndrome, gastrointestinal symptoms might be associated with dysbiosis of the gut microbiota, which has the potential to become a target for intervention. In this study, a patient with post-acute COVID-19 syndrome with long-lasting severe gastrointestinal symptoms was provided 2-month expanded access to a high-fiber formula with investigational new drug (IND) status developed to alleviate COVID-19-related symptoms by modulating the gut microbiota. Symptoms including severe "loss of appetite," palpitation, and anxiety were significantly alleviated by the end of the intervention. The medication dosage for controlling nausea decreased during the intervention. The serum lipid profile, insulin level, and leptin level were improved compared to the baseline values. Significant structural changes of the patient's gut microbiota and reduced microbial fermentation activity in the small intestine were found during the intervention. Eighteen amplicon sequence variants (ASVs) of the V4 region of the 16S rRNA gene significantly responded to this nutritional intervention. Six out of the 18 ASVs were also found to be negatively correlated with symptom severity/medication dosage. Five of the six ASVs (ASV0AKS_Oscillibacter, ASV009F_Anaerofustis, ASV02YT_Blautia, ASV07LA_Blautia, and ASV0AM6_Eubacterium hallii) were potential short-chain fatty acid (SCFA)-producing bacteria, which might be associated with the alleviation of symptoms. Our study indicates the feasibility of alleviating gastrointestinal symptoms in patients with post-acute COVID-19 syndrome by way of nutritional modulation of their gut microbiota. IMPORTANCE It has become evident that the care of patients with COVID-19 does not end at the time of negative SARS-CoV-2 detection, as the number of patients with post-acute COVID-19 syndrome increases with an ever-increasing total infected patient population. This case report shows the possibility of alleviating the gastrointestinal symptoms of post-acute COVID-19 syndrome via microbiota-targeted nutritional intervention. As a promising strategy, it might not only improve the quality of life of patients but also reduce the burden to the public health system when the end of the COVID-19 pandemic is not in sight.


A placebo-controlled phase I/II study of adefovir dipivoxil in patients with chronic hepatitis B virus infection.
Adefovir dipivoxil (bis-POM PMEA) is an adenine nucleotide analogue with activity against retroviruses and herpesviruses, and in vitro activity against hepatitis B virus (HBV). This study was conducted to evaluate its safety and antiviral activity in patients with chronic HBV infection. Twenty patients (13 co-infected with human immunodeficiency virus, HIV) were randomized in a phase I/II, double-blind, placebo-controlled study. Patients who had been hepatitis B surface antigen (HBsAg)/hepatitis B e antigen (HBeAg) positive for > or = 6 months, with elevated hepatic transaminases and serum HBV DNA > or = 50 pg ml-1, were randomized to adefovir dipivoxil 125 mg (n = 15) or placebo (n = 5) as a single, daily, oral dose for 28 days. Antiviral activity was assessed by changes in serum HBV DNA (using the Digene Hybrid Capture assay) and HBeAg/hepatitis B e antibody (HBeAb) status. HBV DNA levels fell rapidly by > 1 log10 in all active drug recipients (median fall 1.8 log10 pg ml-1) but increased by 0.01 log10 pg ml-1 in controls (P = 0.002). Reductions were sustained during treatment. HBV DNA returned to baseline over 1-6 weeks following discontinuation of active drug. HBeAg became transiently undetectable in one patient on treatment and, in another, sustained seroconversion to HBeAb occurred 12 weeks after treatment ended. Liver transaminase elevations > 300 U l-1 were observed in three patients during therapy (leading to protocol-specified treatment discontinuation or dose reduction) and in four patients during follow-up. On-treatment transaminase elevations were associated with HIV status, occurring in three of six HIV-uninfected patients compared with none of nine who were HIV infected. In addition, a slower return to baseline of serum HBV DNA levels was observed in the non-HIV-infected patients. Treatment for chronic hepatitis B as a once-daily oral dose was well tolerated and associated with significant and sustained reductions in serum HBV DNA levels during treatment. Transaminase elevations, which may be related to the therapeutic effect, were observed during and after treatment. Further studies are warranted to investigate the safety, and optimum dose and duration, of adefovir dipivoxil treatment for chronic hepatitis B.


Metatarsal epiphyseal bracket: treatment by central physiolysis.
Longitudinal epiphyseal bracket (LEB) is a rare ossification anomaly in which an epiphysis brackets the diaphysis of a phalanx, metacarpal, or metatarsal. This abnormal epiphysis tethers longitudinal growth, resulting in a shortened and oval-shaped bone. Four patients with five LEBs were treated by central physiolysis and followed for a mean of 6 years. The patients had significant hallux varus deformity. Three patients had duplicated great toes, and two had tibia hemimelia significant enough to require epiphysiodesis as they neared adolescence. Resection of the LEB allowed the proximal and distal epiphysis to resume untethered growth. Silastic or methyl methacrylate was placed over the resected physis to prevent bony rebridging. The associated hallux varus deformity was corrected by capsulorrhaphy and K-wire fixation. In all patients, the metatarsal resumed longitudinal growth and correction of the hallux varus was maintained.


Novel protective agent GF-6 for skin wounds.
The aim of present investigation was the determination of specific pharmacological (wound healing) properties and the evaluation of possible irritative, allergenic and toxic effects of GF-6 - novel protective agent for skin mechanical and burn wounds. In mouse excisional wound model GF-6 (topically 0.1 ml per wound) exhibited the ability to accelerate scab rejection and full reepithelization in test wounds with no signs of bacterial contamination. GF-6 caused no irritation responses such as erythema, oedema, dotted hemorrhage, hyperkeratosis, hyperplasia, alopecia and scaling in 14-day acute dermal irritation test. As well no signs of skin hypersensitivity (itch, erythema, oedema), and histological alteration (ulceration, dotted hemorrhage, changed capillary lumen, damaged hair follicle) were observed in skin application test at all time points during the 14-day observation period, evidencing that GF-6 is non-allergenic. In subchronic dermal toxicity 90-day study of five-fold concentrated GF-6 no statistically significant changes in respiratory, circulatory, autonomic and central nervous system, somatomotor activity and behavior patterns were detected. The results of hematological study testified to no influence of the GF-6 90-day application on blood formed elements. Thus, GF-6 should be considered non-toxic, non-irritant, non-allergenic wound healing and wound protecting agent.


[A case of alpha-fetoprotein-producing fetal gut-like small intestinal cancer].
A 72-year-old Japanese woman was admitted because of vomiting and abdominal pain. An enhanced computed tomography scan showed a small intestinal obstruction due to ileal wall thickening and multiple liver metastases. Her serum alpha-fetoprotein (AFP) level was high at 1671.9ng/ml. An ileocecal resection was performed. The histological diagnosis was AFP-producing small intestinal cancer resembling the primitive gut epithelium of a fetus. The present case suggested that even intestinal cancer could produce AFP.


Antinociceptive activity of steroid alkaloids isolated from Solanum trilobatum Linn.
Solasodine (1) was isolated for the first time from the roots of Solanum trilobatum Linn., a member of the Solanaceae, and assessed for its presumed antinociceptive activity using several experimental murine models, viz. the writhing, formalin, and hot plate tests. When used at doses of 2, 4, and 8 mg/kg, this steroidal alkaloid caused a significant and dose-dependent decrease in the nociception induced by an intraperitoneal injection of acetic acid (p < 0.001). It also led to a significant reduction of the painful sensation caused by formalin in both phases of the formalin test (p < 0.001). Furthermore, the alkaloid produced a significant increase in the reaction time in the hot plate test (p < 0.001). These results suggest that solasodine elicited antinociceptive activity through both central and peripheral mechanisms.


[Relationship between the vertical loop structure and the mechanical properties.].
The relationship between vertical loop structure and its mechanical properties was investigated in order to provide reference data for more proper use of vertical loop. According to the acting manner in use, finite elements model of vertical loop was established and the finite elements software ANSYS was used to simulate the mechanical characteristics of the loops. The simulated data were summarized at the end. The force and moment decreased with the increase of arm length, height and arc radius of the loop. The ratios of force to moment (M/F) decreased with the increase of arm length, but increased with the increase of height and arm radius. When the interval between the vertical arms enlarged, the force and moment rose and the M/F did not vary significantly. To satisfy the requirement of individual patient, the structure of loop can be adjusted properly to output mediate force, moment and M/F value.


Experimental demonstration of continuous variable polarization entanglement.
We report the experimental transformation of quadrature entanglement between two optical beams into continuous variable polarization entanglement. We extend the inseparability criterion proposed by Duan et al. [Phys. Rev. Lett. 84, 2722 (2000)]] to polarization states and use it to quantify the entanglement. We propose an elaboration utilizing two quadrature entangled pairs for which all three Stokes operators between a pair of beams are entangled.


Legionella species as hospital-acquired respiratory pathogens.
Nosocomial pneumonia caused by legionella is an increasingly recognized entity. Legionella sp responsible for documented nosocomial disease include Legionella pneumophila, Tatlockia micdadei, Legionella bozemanii, Legionella dumoffi and Legionella oakridgensis. The clinical presentation is nonspecific although diarrhea occurs frequently. Hyponatremia occurs significantly more frequently in legionnaires' disease than pneumonias caused by other agents. Chest roentgenographic findings are nonspecific, although cavitation can be seen in immunosuppressed patients. Laboratory methods require the use of direct fluorescent antibody (DFA) stains, culture using selective media, serologic testing, and detection of antigen in urine. The DFA test is not sensitive; however, it does correlate with the severity of disease. Culture from sputa is now feasible. Bronchoalveolar lavage is a promising technique for obtaining specimens. The ideal specimen for culture is that obtained by transtracheal aspiration, which bypasses oropharyngeal contamination. Combination therapy of erythromycin and rifampin is recommended for selected patients. Because the source of the organism is the hospital water distribution system, we recommend routine environmental surveillance, especially in hospitals in which organ transplants are performed. The role of cooling towers as a vector for dissemination of the organism is disputed. Disinfection of the water supply can be accomplished by using heat eradication. Chlorination has generally proven unsatisfactory because of organism persistence as well as corrosive damage to the plumbing system from the chlorine. Both physician awareness and availability of specialized laboratory testing are necessary for the detection of cases.