[Preliminary linkage analysis on autosomal dominant microphthalmia with 12 microsatellite markers].
In this preliminary study a Chinese autosomal dominant microphthalmia family were investigated and the linkage analyses were performed with six previously reported loci (CHX10, MITF, RX, MCOP, NNO1, NNO2) and six microsatellite markers on chromosome 11 as well. The allelic polymorphisms of those microsatellite markers were identified by using polymerase chain reaction, polyacrylamide gel electrophoresis and silver-staining techniques. The LOD scores between microsatellite markers and the disease were obtained by using MLINK software. Our results showed that the linkage between the microphthalmia in this family with the 6 known loci could be excluded, indicating that the defect gene in this microphthalmia family was probably distinct from those of previously reported microphthalmia families.


Malignant lymphoma of the head and neck.
Malignant lymphomas represent approximately 5% of all malignant neoplasms of the head and neck area. They are classically divided into two subgroups, Hodgkin's lymphomas (HLs) and non-Hodgkin's lymphomas (NHLs). We describe the clinical characteristics of head and neck lymphomas and the methods to establish the diagnosis. The World Health Organization classification of lymphoid tissues describes more than 50 different histological types, and we analyse the most common staging system for lymphomas, the Ann Arbor staging system. Finally, the different therapeutic approaches are discussed.


ASSOCIATION OF POTENTIAL CELIAC DISEASE AND REFRACTORY IRON DEFICIENCY ANEMIA IN CHILDREN AND ADOLESCENTS.
Celiac disease is an enteropathy caused by dietary gluten. The combination of serologic, genetic and histologic data has led to description of other categories of this disease. There are a number of patients with iron deficiency anemia (IDA) that do not respond to iron treatment and may be repeated for many times, Therefore, we aimed to investigate celiac disease in this group. In this cross sectional transverse prospective study from August 2011 to February 2013, in a Pediatric care clinic affiliated to Shiraz University of Medical Sciences, 184 children including 92 IDA patients who responded to treatment using iron supplement, 45 non-responding iron deficient patients, and 47 healthy individuals, with the maximum age of 18 years, with written consent from their parents, participated in serologic screening (with Anti-TTG antibody and anti-Endomysial antibody) for celiac disease. Patients with at least one positive serology test underwent multiple mucosal biopsy from bulb and duodenum. Among 184 participants, 19 (10.3%) subjects had positive serologic test for celiac disease, including 13 (28.9%) patients in the group with refractory IDA, 5 (5.4%) patients in the group with treated IDA, and 1 patient in the healthy group. The frequency of positive serologic test in the group with IDA resistant to treatment was prominently higher than the other two groups (P<0.001). Among the patients with positive serologic celiac test who underwent endoscopy and biopsy, no histologic evidence of celiac disease was seen. They were diagnosed as potential celiac disease. Frequency of potential celiac disease in patients with refractory IDA was higher than control the subjects. Therefore, we recommend serologic screening for early detection and minimizing the complications of celiac disease and repeated iron therapy for this group.


Reversal of trends in global fine particulate matter air pollution.
Ambient fine particulate matter (PM2.5) is the world's leading environmental health risk factor. Quantification is needed of regional contributions to changes in global PM2.5 exposure. Here we interpret satellite-derived PM2.5 estimates over 1998-2019 and find a reversal of previous growth in global PM2.5 air pollution, which is quantitatively attributed to contributions from 13 regions. Global population-weighted (PW) PM2.5 exposure, related to both pollution levels and population size, increased from 1998 (28.3 μg/m3) to a peak in 2011 (38.9 μg/m3) and decreased steadily afterwards (34.7 μg/m3 in 2019). Post-2011 change was related to exposure reduction in China and slowed exposure growth in other regions (especially South Asia, the Middle East and Africa). The post-2011 exposure reduction contributes to stagnation of growth in global PM2.5-attributable mortality and increasing health benefits per µg/m3 marginal reduction in exposure, implying increasing urgency and benefits of PM2.5 mitigation with aging population and cleaner air.


Total syntheses of the squalene-derived halogenated polyethers ent-dioxepandehydrothyrsiferol and armatol A via bromonium- and Lewis acid-initiated epoxide-opening cascades.
Herein we describe in full our investigations leading to the first total syntheses of ent-dioxepandehydrothyrsiferol and armatol A. Discovery of a bromonium-initiated epoxide-opening cascade enabled novel tactics for constructing key fragments found in both natural products and have led us to revise the proposed biogeneses. Other common features found in the routes include convergent fragment coupling strategies to assemble the natural products' backbones and the use of epoxide-opening cascades for rapid constructions of the fused polyether subunits. Through de novo synthesis of armatol A, we elucidate the absolute and relative configuration of this natural product.


A highly effective photochemical system for complex treatment of heavily contaminated wastewaters.
Significant efforts have been committed to the research and development of many advanced oxidation processes, including photocatalytic oxidations with titanium dioxide or the hydrogen peroxide and ferrous/ferric ion (H2O2/Fe2+(Fe3+)/UV (photo-assisted Fenton) process. This study reports the development of a novel photochemical system for complex treatment of heavily contaminated wastewaters based on the use of UV-C light and H2O2. Special attention was focused on the technology employed, including the reactor design, process controls, and performance optimization. The effects of process parameters were studied using 4-chlorophenol (4CP) as model compound, and verification of this treatment technology was assessed using actual contaminated water. Among the most influential parameters were the 4CP concentration, reaction mixture volume, H2O2 concentration, and irradiation intensity. In contrast, for H2O2 dosing (proportional continuous or cumulative one-time), the flow rate did not significantly affect process efficacy.


Fish-oil fatty acid supplementation in active rheumatoid arthritis. A double-blinded, controlled, crossover study.
to determine the efficacy of fish-oil dietary supplements in active rheumatoid arthritis and their effect on neutrophil leukotriene levels. nonrandomized, double-blinded, placebo-controlled, crossover trial with 14-week treatment periods and 4-week washout periods. academic medical center, referral-based rheumatology clinic. forty volunteers with active, definite, or classical rheumatoid arthritis. Five patients dropped out, and two were removed for noncompliance. treatment with nonsteroidal anti-inflammatory drugs, slow-acting antirheumatic drugs, and prednisone was continued. Twenty-one patients began with a daily dosage of 2.7 g of eicosapaentanic acid and 1.8 g of docosahexenoic acid given in 15 MAX-EPA capsules (R.P. Scherer, Clearwater, Florida), and 19 began with identical-appearing placebos. The background diet was unchanged. the following results favored fish oil placebo after 14 weeks: mean time to onset of fatigue improved by 156 minutes (95% confidence interval, 1.2 to 311.0 minutes), and number of tender joints decreased by 3.5 (95% Cl, -6.0 to -1.0). Other clinical measures favored fish oil as well but did reach statistical significance. Neutrophil leukotriene B4 production was correlated with the decrease in number of tender joints (Spearman rank correlation r=0.53; p less than 0.05). There were no statistically significant differences in hemoglobin level, sedimentation rate, or presence of rheumatoid factor or in patient-reported adverse effects. An effect from the fish oil persisted beyond the 4-week washout period. fish-oil ingestion results in subjective alleviation of active rheumatoid arthritis and reduction in neutrophil leukotriene B4 production. Further studies are needed to elucidate mechanisms of action and optimal dose and duration of fish-oil supplementation.


Factors related to health-related quality of life (HRQoL) among children with ADHD in Europe at entry into treatment.
To describe the associations between a range of baseline factors (demographic, family and clinical) and parent-reported health-related quality of life (HRQoL) of children with ADHD taking part in the ADORE study. HRQoL was rated using the Parent Report Form of the Child Health and Illness Profile-Child Edition (CHIP-CE). Forward-stepwise linear regression models were used to investigate associations with 26 independent variables. Separate models were fitted for each of the five CHIP-CE domains (Satisfaction, Comfort, Resilience, Risk Avoidance and Achievement) and two subdomains of Achievement (Academic Performance and Peer Relations). CHIP-CE domain mean scores were lower than community norms, especially for Risk Avoidance and Achievement, indicating a low level of HRQoL. Clinical factors significantly associated with a poorer HRQoL included ADHD symptoms (inattention, hyperactivity-impulsivity), conduct problems, peer relationship problems, having asthma, multiple other somatic symptoms and co-ordination problems. Family factors, such as having a parent with a health or mental health problem possibly caused by the child's illness, child not living with both parents and maternal smoking during pregnancy were also associated with a worse HRQoL in some CHIP-CE domains/subdomains. Numerous factors independently impact on the HRQoL of children with ADHD.


Self-Assembled Hydroxyapatite-Graphene Scaffold for Photothermal Cancer Therapy and Bone Regeneration.
Repairing large tumor-related bone defects remains a difficult clinical problem because of the significant risk of locoregional relapse after surgical curettage. In this study, a composite scaffold of nano-hydroxyapatite (nHA) and reduced graphene oxide (rGO) sheets was fabricated by self-assembly, and a 20 wt% nHA-rGO sheet solution formed the most stable hydrogel. In vitro, nHA-rGO scaffolds killed all but 8% of osteosarcoma cells (MG-63) under 808 nm near-infrared laser irradiation for 20 min. SEM images and live/dead staining of MG-63 cells in nHA-rGO also confirmed the therapeutic efficacy of the scaffolds. Tumors implanted with nHA-rGO scaffolds reached 60 °C after 4 min. of irradiation; xenografted tumors stopped growth or even decreased in size after photothermal therapy. In vitro the scaffolds promoted adhesion, proliferation, and osteogenic mineralization of rat bone marrow stem cells (rBMSCs). Live cell staining and CCK-8 showed good proliferation for rBMSCs in nHA-rGO scaffolds. Alkaline phosphatase activity and qPCR demonstrated osteogenic mineralization of rBMSCs in nHA-rGO scaffolds. Micro-CT and histology verified that the scaffold promotes bone regeneration in rat cranial defects. At 8 weeks, 35% of the cranial defect area remained in the scaffold-implanted group, while 80% remained for the control. Bone mineral density of the scaffold-implanted group reached 284.58±20.78 mg/cm³, indicating new bone mineral deposition, versus only 96.04±2.67 mg/cm³ for the control. Histology showed scaffold stimulation of osteoblast mineralization and collagen deposition. Therefore, nHA-rGO scaffolds may be an effective treatment of large tumor-related bone defects due to their excellent photothermal and osteogenic effects.


Thyroid antibodies in Graves' disease. An immunofluorescence study.
The sera of fifty patients suffering from Graves' disease were analyzed by indirect immunofluorescence. Normal human thyroid tissue was used as antigen. Antibodies against four different thyroid antigens were detected i.e. follicular cell microsoma, thyroglobulin, follicular basement membrane and follicular cell nuclei. Two types of antibodies binding to the basement membrane were described. Antibodies against the first and second colloid antigens could also be detected. The results suggest that by indirect immunofluorescence four thyroid antibodies, more than known to the literature, are detectable.


Structure and dynamics of the protic ionic liquid monomethylammonium nitrate ([CH3NH3][NO3]) from ab initio molecular dynamics simulations.
The dynamics of the protic ionic liquid monomethylammonium nitrate is investigated by Car-Parrinello molecular dynamics simulations. On average, 1.8 of 3 possible hydrogen bond contacts are formed. Therefore, one hydrogen bond acceptor and one donor site in each ion pair of monomethylammonium nitrate remains free, which is similar to water. Furthermore, like water, monomethylammonium nitrate exhibits a fast fluctuating hydrogen bond network. The comparable hydrogen bond network and dynamics of both liquids might explain the similar impact on reactivity and selectivity found for chemical reactions. However, the hydrogen bond network of monomethylammonium nitrate and water show some structural differences. While the hydrogen bonds in water arrange in parallel fashion, the hydrogen bonds of monomethylammonium nitrate prefer angles of 0 degrees, 90 degrees, and 180 degrees. The ion dynamics of monomethylammonium nitrate indicate that at about 85% of the ion pairs are still connected after 14.5 ps. A closer inspection of the first solvation shell dynamics of one cation reveals that after 11 ps the current ion pair conformation is independent of the initial ion pair conformation because the ion pairs lose their information of the initial ion pair conformation much faster than the time needed to escape from their solvent cage. The ion dynamics of monomethylammonium nitrate can be described by the following model: There are ions rattling in long living cages which are formed by long living ion pairs.


The decade of exosomal long RNA species: an emerging cancer antagonist.
Exosomes have emerged as a novel approach for the treatment and diagnosis of cancer after RNA content was discovered in exosomes in 2007. As important meditators of intercellular communication, exosomes have become a strong focus of investigation for researchers in the past decade, as witnessed through the exponential increase of research on exosomes. The capability of exosomes to transfer functionally active cargo highlights their importance as promising biomarkers and diagnostic molecules, as well as prospective drug delivery systems. The accessibility of exosomes in nearly all biofluids additionally alludes to its unprecedented ability in various types of cancers due to its extensive impact on tumor formation and progression. This review analyzes the role of exosomal long RNA species, which is comprised of mRNA, lncRNA, and circRNA, in tumor formation and progression, with an emphasis on their potential as future diagnostic biomarkers and treatment vectors in cancer biology. Their alignment with the development of exosomal databases is further examined in this review, in view of the accumulation of studies published on exosomes in the past decade.


Modified genome comparison method: a new approach for identification of specific targets in molecular diagnostic tests using Mycobacterium tuberculosis complex as an example.
The first step of designing any genome-based molecular diagnostic test is to find a specific target sequence. The modified genome comparison method is one of the easiest and most comprehensive ways to achieve this goal. In this study, we aimed to explain this method with the example of Mycobacterium tuberculosis complex and investigate its efficacy in a diagnostic test. A specific target was identified using modified genome comparison method and an in-house PCR test was designed. To determine the analytical sensitivity and specificity, 10 standard specimens were used. Also, 230 specimens were used to determine the clinical sensitivity and specificity. The identity and query cover of our new diagnostic target (5KST) were ≥ 90% with M. tuberculosis complex. The 5KST-PCR sensitivity was 100% for smear-positive, culture-positive and 85.7% for smear-negative, culture-positive specimens. All of 100 smear-negative, culture-negative specimens were negative in 5KST-PCR (100% clinical specificity). Analytical sensitivity of 5KST-PCR was approximately 1 copy of genomic DNA per microliter. Modified genome comparison method is a confident way to find specific targets for use in diagnostic tests. Accordingly, the 5KST-PCR designed in this study has high sensitivity and specificity and can be replaced for conventional TB PCR tests.


Development of novel fluorescent histamine H1-receptor antagonists to study ligand-binding kinetics in living cells.
The histamine H1-receptor (H1R) is an important mediator of allergy and inflammation. H1R antagonists have particular clinical utility in allergic rhinitis and urticaria. Here we have developed six novel fluorescent probes for this receptor that are very effective for high resolution confocal imaging, alongside bioluminescence resonance energy transfer approaches to monitor H1R ligand binding kinetics in living cells. The latter technology exploits the opportunities provided by the recently described bright bioluminescent protein NanoLuc when it is fused to the N-terminus of a receptor. Two different pharmacophores (mepyramine or the fragment VUF13816) were used to generate fluorescent H1R antagonists conjugated via peptide linkers to the fluorophore BODIPY630/650. Kinetic properties of the probes showed wide variation, with the VUF13816 analogues having much longer H1R residence times relative to their mepyramine-based counterparts. The kinetics of these fluorescent ligands could also be monitored in membrane preparations providing new opportunities for future drug discovery applications.


Effect of Eccentric Calcification of an Aortic Valve on the Implant Depth of a Venus-A Prosthesis During Transcatheter Aortic Valve Replacement: A Retrospective Study.
Our goal was to assess the implant depth of a Venus-A prosthesis during transcatheter aortic valve replacement (TAVR) when the areas of eccentric calcification were distributed in different sections of the aortic valve. A total of 53 patients with eccentric calcification of the aortic valve who underwent TAVR with a Venus-A prosthesis from January 2018 to November 2019 were retrospectively analyzed. The patients were divided into three groups (A, B, and C) according to the location of the eccentric calcification, which was determined by preprocedural computerized tomography angiography (CTA) images. The prosthesis release process and position were evaluated by contrast aortography during TAVR, and the differences in valve implant depths were compared among the three groups. The effects of different aortic root structures and procedural strategies on prosthesis implant depth were analyzed. Eleven patients had eccentric calcification in region A; 19 patients, in region B; and 23 patients, in region C. The patients with eccentric calcification in region B had a higher risk of prosthesis migration (10.5% upward and 21.1% downward), and the position of the prosthesis after TAVR in group B was the deepest among the three groups. When eccentric calcification was located in region A or C, the prosthesis was released at the standard position with more stability, and the location of the prosthesis was less deep after TAVR (region A: 4.12 ± 3.4 mm; region B: 10.2 ± 5.3 mm; region C: 8.4 ± 4.0 mm; region A vs. region B, P = 0.0004; region C vs. region B; and P = 0.0360). In addition, the left ventricular outflow tract (LVOT) (P = 0.0213) and aortic root angulation (P = 0.0263) also had a significant effect on implant depth in the aortic root structure of the patients. The prosthesis size was 28.3 ± 2.4 in the deep implant group and 26.4 ± 2.0 in the appropriate implant group (P = 0.0068). The implant depth of the Venus-A prosthesis is closely related to the distribution of eccentric calcification in the aortic valve during TAVR. Surgeons should adjust the surgical strategy according to aortic root morphology to prevent prosthesis migration.


Senso-immunology: The Emerging Connection between Pain and Immunity.
The sensory and immune systems have been studied independently for a long time, whereas the interaction between the two has received little attention. We have carried out research to understand the interaction between the sensory and immune systems and have found that inflammation and bone destruction caused by fungal infection are suppressed by nociceptors. Furthermore, we have elucidated the molecular mechanism whereby fungal receptors are expressed on nociceptors and skin epithelium, how they cooperate to generate fungal pain, and how colitis and bone metabolism are regulated by mechanosensors expressed on the gut epithelium. Recently, we found that nociceptors prevent septic death by inhibiting microglia via nociceptor-derived hormones. This review summarizes our current state of knowledge on pain biology and outlines the mechanisms whereby pain and immunity interact. Our findings indicate that the sensory and immune systems share a variety of molecules and interact with each other to regulate our pathological and homeostatic conditions. This prompted us to advocate the interdisciplinary science named "senso-immunology," and this emerging field is expected to generate new ideas in both physiology and immunology, leading to the development of novel drugs to treat pain and inflammation.


Long-term Follow-up of Patients With Hernia Using the Hernia-Specific Quality-of-Life Mobile App: Feasibility Questionnaire Study.
Hernia repair is one of the most common surgical procedures; however, the long-term outcomes are seldom reported due to incomplete follow-up. The aim of this study was to examine the use of a mobile app for the long-term follow-up of hernia recurrence, complication, and quality-of-life perception. A cloud-based corroborative system drove a mobile app with the HERQL (Hernia-Specific Quality-of-Life) questionnaire built in. Patients who underwent hernia repair were identified from medical records, and an invitation to participate in this study was sent through the post. The response rate was 11.89% (311/2615) during the 1-year study period, whereas the recurrence rate was 1.0% (3/311). Causal relationships between symptomatic and functional domains of the HERQL questionnaire were indicated by satisfactory model fit indices and significant regression coefficients derived from structural equational modeling. Regarding patients' last hernia surgeries, 88.7% (276/311) of the patients reported them to be satisfactory or very satisfactory, 68.5% (213/311) of patients reported no discomfort, and 61.1% (190/311) of patients never experienced mesh foreign body sensation. Subgroup analysis for the most commonly used mesh repairs found that mesh plug repair inevitably resulted in worse symptoms and quality-of-life perception from the group with groin hernias. The mobile app has the potential to enhance the quality of care for patients with hernia and facilitate outcomes research with more complete follow-up.


Serum D-lactate, a novel serological biomarker, is promising for the diagnosis of periprosthetic joint infection.
Although many markers are used for diagnosis of periprosthetic joint infection (PJI), serological screening and diagnosis for PJI are still challenging. We evaluated the performance of serum D-lactate and compared it with ESR, coagulation-related biomarkers and synovial D-lactate for the diagnosis of PJI. Consecutive patients with preoperative blood and intraoperative joint aspiration of a prosthetic hip or knee joint before revision arthroplasty were prospectively included. The diagnosis of PJI was based on the criteria of the Musculoskeletal Infection Society, and the diagnostic values of markers were estimated based on receiver operating characteristic (ROC) curves by maximizing sensitivity and specificity using optimal cutoff values. Of 52 patients, 26 (50%) were diagnosed with PJI, and 26 (50%) were diagnosed with aseptic failure. ROC curves showed that serum D-lactate, fibrinogen (FIB) and ESR had equal areas under the curve (AUCs) of 0.80, followed by D-dimer and fibrin degradation product, which had AUCs of 0.67 and 0.69, respectively. Serum D-lactate had the highest sensitivity of 88.46% at the optimal threshold of 1.14 mmol/L, followed by FIB and ESR, with sensitivities of 80.77% and 73.08%, respectively, while there were no significant differences in specificity (73.08%, 73.08% and 76.92%, respectively). Serum D-lactate showed similar performance to FIB and ESR for diagnosis of PJI. The advantages of serum D-lactate are pathogen-specific, highly sensitive, minimally invasive and rapidly available making serum D-lactate useful as a point-of-care screening test for PJI.


Flavone induces cell death in human hepatoma HepG2 cells.
Flavones have received considerable attention because of their antiproliferative properties and selective effects on cancer cells, making them good candidates for use in cancer therapy. In contrast to other flavones, little is known about the effects of the flavone core structure (2-phenyl-4H-1-benzopyran-4one) on cancer cells. Here, we report that flavone induces cell death in human hepatoma HepG2 cells. Furthermore, annexin-V+/PI- and SubG1 populations of HepG2 cells increased after flavone treatment. Exposure of HepG2 to flavone did not result in either cytochrome c release into the cytosol or changes in the mitochondrial membrane potential. Treatment of HepG2 cells with flavone for 24 h reduced the accumulation of intracellular ROS, which correlated with upregulation of Gred, CuZnSOD and MnSOD mRNA levels. Taken together, our results provided useful insights into the mechanism of cell death caused by flavones, in order to evaluate their future application in hepatocarcinoma therapy.


Dietary patterns and obesity in preschool children in Australia: a cross-sectional study.
Dietary patterns have been linked to the risk of obesity in adults but little is known about such a link in young children. To examine the association between dietary patterns, nutrient intake and obesity in a representative population of preschool children in Australia. Dietary intake was assessed using a 3-day weighed food diary. Dietary patterns were identified by factor analysis. Children were classified as overweight or obesity if their BMI z-score was between the 85th-95th percentiles or was above the 95th percentile, respectively. Three dietary patterns were identified. The 'Traditional' pattern was characterised by grains, fruit, vegetables, and red meat. The 'Processed' pattern was characterised by processed meats, snack foods and confectionary. The 'Health conscious' pattern was characterised by eggs, fish, polyunsaturated margarines and low fat dairy products. The 'Traditional' pattern was positively associated with protein and zinc intake while the 'Processed' pattern was inversely associated. Both patterns were inversely associated with calcium intake. No associations were found between the 'Health conscious' pattern and macronutrients and key micronutrients intakes. The 'Traditional' pattern was positively associated with obesity but the association became non-significant after adjustment for energy and protein intake. No association was observed between the other two dietary patterns and weight status. In this cross-sectional study, dietary patterns were not associated with obesity. Longitudinal follow up will help to better understand the relationship between dietary patterns in early childhood and the risk of obesity later in life.


Inheritance of nocardiophage phi EC in matings of nocardial lysogens.
Lysogens of Nocardia erythropolis were mated with nonlysogenic strains to study the inheritance of the phi EC prophage. Crosses between lysogenic strains of the Mat-Ce mating type and nonlysogenic Mat-cE strains produced Mat-cE lysogens at a recovery rate of 17%, whereas recombination frequencies between chromosomal traits were about 2.3 x 10(-5). Crosses of lysogenic Mat-cE mating types with nonlysogenic Mat-Ce produced Mat-Ce lysogens at a recovery rate of 19%, whereas recombinants for chromosomal traits were recovered at only 1.8 x 10(-5). Crosses of homologous mating types, lysogenic Mat-Ce with nonlysogenic Mat-Ce or lysogenic Mat-cE with nonlysogenic Mat-cE, failed to transfer the prophage. It was concluded that the phi EC prophage exists as a plasmid and can be transferred at high frequencies with patterns of transfer controlled like typical nocardial fertility. Evidence that the prophage may also exist as an integrated element was observed from recombination analyses.


A double-inactivated whole virus candidate SARS coronavirus vaccine stimulates neutralising and protective antibody responses.
A double-inactivated, candidate whole virus vaccine against severe acute respiratory syndrome associated coronavirus (SARS-CoV) was developed and manufactured at large scale using fermenter cultures of serum protein free Vero cells. A two step inactivation procedure involving sequential formaldehyde and U.V. inactivation was utilised in order to ensure an extremely high safety margin with respect to residual infectivity. The immunogenicity of this double-inactivated vaccine was characterised in the mouse model. Mice that were immunised twice with the candidate SARS-CoV vaccine developed high antibody titres against the SARS-CoV spike protein and high levels of neutralising antibodies. The use of the adjuvant Al(OH)3 had only a minor effect on the immunogenicity of the vaccine. In addition, cell mediated immunity as measured by interferon-gamma and interleukin-4 stimulation, was elicited by vaccination. Moreover, the vaccine confers protective immunity as demonstrated by prevention of SARS-CoV replication in the respiratory tract of mice after intranasal challenge with SARS-CoV. Protection of mice was correlated to antibody titre against the SARS-CoV S protein and neutralising antibody titre.


Directly observed pegylated interferon plus self-administered ribavirin for the treatment of hepatitis C virus infection in people actively using drugs: a randomized controlled trial.
This study investigated the efficacy and safety of directly observed pegylated interferon (peg-IFN) alfa-2a plus self-administered ribavirin (RBV) for the treatment of hepatitis C virus (HCV) among people with active drug use. A randomized, open-label, parallel group trial of immediate vs delayed treatment with peg-IFN alfa-2a plus RBV in participants with recent injection drug and/or crack cocaine use (prior 3 months). The primary end point was sustained virologic response (SVR). Sixty-six participants were randomized (immediate treatment, n = 48; delayed treatment, n = 18). Loss to follow-up was comparable among those randomized to immediate and delayed treatment (23% vs 33%, P = .389). In a post hoc intent-to-treat analysis of all randomized individuals, the SVR was 65% (95% confidence interval [CI], 49%-78%; 31/48) in those randomized to immediate treatment as compared to 39% (95% CI, 17%-64%; 7/18) in those randomized to delayed treatment (P = .060). Among those who received delayed treatment (12/18), SVR was 58% (7/12). Among 60 participants who received at least 1 dose of study medication, SVR was 63% (95% CI, 50%-75%, n = 38). Recent drug use at baseline (past month) did not impact completion or SVR. Discontinuation due to adverse events occurred in 7%. The HCV reinfection rate was 2.8 per 100 person-years (95% CI, 0.0-14.5 person-years) with 1 reinfection observed among 23 remaining in follow-up post-SVR (median, 1.8 years; range, 0.5-1.8 years). Among people actively using drugs treated with directly observed peg-IFN alfa-2a plus self-administered RBV, SVR is comparable to that seen in clinical trials of non-drug users, and the rate of HCV reinfection is low.


Bothrops snakebites in the Amazon: recovery from hemostatic disorders after Brazilian antivenom therapy.
Introduction:Bothrops atrox snakebites are a major public health problem in the Amazon region and also cause hemostatic disorders. In this study, we assessed the recovery from hemostatic disorders in Bothrops snakebite patients after being given antivenom therapy.Methods: This is a prospective study of Bothrops snakebite patients (n = 100) treated at the Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, Brazilian Amazon, between January 2016 and December 2017. Blood samples were taken for the measurement of venom concentrations, platelets, clotting time and factors of patients on admission, 12, 24 and 48 h after antivenom therapy, and taken again on discharge. The presence of systemic bleeding was recorded during the follow-up.Results: On admission, systemic bleeding was observed in 14% of the patients. Thrombocytopenia was noted in 10% of the patients. A total of 54% of the patients presented unclottable blood with low levels of fibrinogen and alpha 2-antiplasmin, and high levels of fibrin/fibrinogen degradation product (FDP) and D-dimers. Unclottable blood and systemic bleeding were overcome in most patients 12 h after the antivenom therapy. Three patients developed systemic bleeding 48 h after antivenom therapy. Levels of fibrinogen and alpha 2-antiplasmin, FDP and D-dimer returned to normal around 48 h after the treatment or on discharge. The frequency of thrombocytopenia with high mean platelet volume increased in the first 24 h after antivenom therapy, and decreased on discharge. Bothrops venom levels in patients decreased 12 h after antivenom therapy and were not correlated with coagulation and fibrinolytic parameters. There were no deaths.Conclusion: Laboratorial parameters of coagulopathy returned to normal values within 48 h after the antivenom therapy until discharge. A few patients still presented bleeding signs within 48 h after beginning antivenom therapy. However, the Brazilian antivenom was able to overcome the hemostatic disorders in these cases of envenomation.


Synthesis of Pt3Y and Other Early-Late Intermetallic Nanoparticles by Way of a Molten Reducing Agent.
Early-late intermetallic phases have garnered increased attention recently for their catalytic properties. To achieve the high surface areas needed for industrially relevant applications, these phases must be synthesized as nanoparticles in a scalable fashion. Herein, Pt3Y-targeted as a prototypical example of an early-late intermetallic-has been synthesized as nanoparticles approximately 5-20 nm in diameter via a solution process and characterized by XRD, TEM, EDS, and XPS. The key development is the use of a molten borohydride (MEt3BH, M = Na, K) as both the reducing agent and reaction medium. Readily available halide precursors of the two metals are used. Accordingly, no organic ligands are necessary, as the resulting halide salt byproduct prevents sintering, which further permits dispersion of the nanoscale intermetallic onto a support. The versatility of this approach was validated by the synthesis of other intermetallic phases such as Pt3Sc, Pt3Lu, Pt2Na, and Au2Y.


Studies on the relationship between changes in dietary patterns and health status.
In order to study the relationship between dietary composition and health and disease, we investigated retrospectively the changes in diet composition, health status and disease specific mortality of the Shanghai population from 1950 to 1985. The results showed that remarkable changes occurred in dietary composition, health status and disease mortality. The energy from grain products decreased from 80-83% in the 1950s to 68-72% in the 1980s, and the energy from animal foods increased from 6.5-8.5% in the 1950s to 17.5-18.0% in the 1980s. With the changes in dietary composition, notable changes also occurred in the nutritional composition of the diet. From the 1950s to the 1980s, energy from fat was increased from 16.3-20.1% to 24.0-28.0%, and the energy from carbohydrates decreased from 72.0-73.5% to 62.2-65.8%. Almost certainly as a result of the changes in diet, health status and disease mortality also changed. For example, the average height in males of 18-20 years old increased from 164.89 cm in 1955 to 167.33 cm in 1974, and the average life span of males and females increased from 42.0 years and 45.6 years in 1950 to 72.1 years and 76.4 years in 1985, respectively. At the same time, the rank order of mortality causes also changed. Before 1950, the first three causes of death were measles, tuberculosis and senility, but in 1985 they were malignant tumours, cerebrovascular disease, and ischaemic heart disease. In particular, the mortality from ischaemic heart disease is now higher than in Japan. The causes of these changes may be the changes of dietary composition and nutritional composition of diet, although there are other factors. Therefore, changes in dietary composition which maintain or improve life expectancy, yet decrease the burden of chronic non-communicable disease is required.


Multistate approaches in computational protein design.
Computational protein design (CPD) is a useful tool for protein engineers. It has been successfully applied towards the creation of proteins with increased thermostability, improved binding affinity, novel enzymatic activity, and altered ligand specificity. Traditionally, CPD calculations search and rank sequences using a single fixed protein backbone template in an approach referred to as single-state design (SSD). While SSD has enjoyed considerable success, certain design objectives require the explicit consideration of multiple conformational and/or chemical states. Cases where a "multistate" approach may be advantageous over the SSD approach include designing conformational changes into proteins, using native ensembles to mimic backbone flexibility, and designing ligand or oligomeric association specificities. These design objectives can be efficiently tackled using multistate design (MSD), an emerging methodology in CPD that considers any number of protein conformational or chemical states as inputs instead of a single protein backbone template, as in SSD. In this review article, recent examples of the successful design of a desired property into proteins using MSD are described. These studies employing MSD are divided into two categories--those that utilized multiple conformational states, and those that utilized multiple chemical states. In addition, the scoring of competing states during negative design is discussed as a current challenge for MSD.


Evidence of the existence of alpha 1B-adrenoceptors on hepatocytes of domestic fowl (Gallus domesticus).
In liver cell membranes of laying hens alpha 1-adrenergic receptors were characterized using 3H-prazosin. Specific binding was saturable and indicative of a single class of high-affinity binding sites with a KD of 0.40 +/- 16 nM and a Bmax of 390 +/- 38 fmol/mg membrane protein. Preincubation of membranes with chlorethylclonidine significantly diminished the binding of 3H-prazosin (Bmax = 99 +/- 14 fmol/mg membrane protein). Furthermore, competition experiments revealed a rank order of prazosin >> phentolamine = oxymetazoline >> WB 4101, with Ki values of 0.71 +/- 0.62, 20 +/- 6, 32 +/- 13, and 119 +/- 48 nM, respectively. These results suggest the existence of alpha 1B-adrenergic receptors in hen liver cell membranes.


Weighing polyelectrolytes packaged in viruslike particles.
This Letter reports on the remarkable selectivity of capsid proteins for packaging synthetic polyelectrolytes in viruslike particles. By applying the contrast variation method in small-angle neutron scattering, we accurately estimated the mean mass of packaged polyelectrolytes ⟨Mp⟩ and that of the surrounding capsid ⟨Mcap⟩. Remarkably, the mass ratio ⟨Mp⟩/⟨Mcap⟩ was invariant for polyelectrolyte molecular weights spanning more than 2 orders of magnitude. To do so, capsids either packaged several chains simultaneously or selectively retained the shortest chains that could fit the capsid interior. Our data are in qualitative agreement with theoretical predictions based on free energy minimization and emphasize the importance of protein self-energy. These findings may give new insights into the nonspecific origin of genome selectivity for a number of viral systems.


[In vivo study of the sensitivity of Treponema pallidum to ofloxacin].
Treponema pallidum has not been yet cultivated. Hence any in vitro investigation is excluded, and it is owing to the experimental animal model, the rabbit, that we have studied the susceptibility of that germ to ofloxacin. This quinolone, owing to its pharmacokinetic and therapeutic properties, can specially be indicated in the treatment of Sexually Transmitted Diseases. Thus, its appeared to be of the utmost importance to know if the suggested schedule of treatment for STD, might not be susceptible to modify the course of a co-existing incubating syphilis by either delaying or inhibiting the apparition of the clinical features of primary syphilis. This study was undertaken at the incubation period, in syphilitic rabbits, using kinetic data obtained in man, after a given dosage of ofloxacin. Results were appraised upon converging data: lesions, bacteriology, and serology of the tested lot compared with two control batches of infected rabbits, the first one being untreated, the other having received the reference antibiotic treatment. From the data obtained and in the experimental settled conditions where this study was done, it results that ofloxacin has no effect on the course of the experimental syphilitic infection.


Panmictic structure of Helicobacter pylori demonstrated by the comparative study of six genetic markers.
We compared the classifications of strains obtained by analysis of several genetic markers to demonstrate the panmictic structure of Helicobacter pylori, previously suggested by the study of multilocus enzyme electrophoresis. A series of 39 strains, including 37 clinical isolates from patients with gastritis or ulcers from two regions of France, reference strain CIP 101260 and the Sydney strain (strain SSI), were used. They were studied by restriction fragment length polymorphism analysis of ribosomal DNA (ribotyping) using HindIII and HaeIII, by polymorphism analysis of the ureA-ureB and flaA genes by PCR-RFLP using HaeIII and MboI, by vacA genotyping and by the presence or absence of the cagA gene and of the insertion sequence IS605 detected by PCR. There was a high level of genetic polymorphism over the studied strains, with 38 ribotypes, 38 restriction profiles for the ureA-ureB gene, 19 restriction profiles for the flaA gene and five combinations of the signal and mid-region sequences of the vacA gene. Factorial analysis of correspondence and hierarchical clustering performed using each marker revealed that the different classifications of the strains were not correlated. This suggests there is much genetic recombination between strains and supports the hypothesis of a panmictic structure for the H. pylori species.


Dual-angle, self-calibrating Thomson scattering measurements in RFX-MOD.
In the multipoint Thomson scattering (TS) system of the RFX-MOD experiment the signals from a few spatial positions can be observed simultaneously under two different scattering angles. In addition the detection system uses optical multiplexing by signal delays in fiber optic cables of different length so that the two sets of TS signals can be observed by the same polychromator. Owing to the dependence of the TS spectrum on the scattering angle, it was then possible to implement self-calibrating TS measurements in which the electron temperature Te, the electron density ne and the relative calibration coefficients of spectral channels sensitivity Ci were simultaneously determined by a suitable analysis of the two sets of TS data collected at the two angles. The analysis has shown that, in spite of the small difference in the spectra obtained at the two angles, reliable values of the relative calibration coefficients can be determined by the analysis of good S/N dual‑angle spectra recorded in a few tens of plasma shots. This analysis suggests that in RFX-MOD the calibration of the entire set of TS polychromators by means of the similar, dual-laser (Nd:YAG/Nd:YLF) TS technique, should be feasible.


[Septic arthritis and spondylitis].
Septic arthritis and spondylitis in elderly adult are uncommon disease. But symptoms and signs of septic arthritis and spondylitis are an important medical emergency, with high mortality and morbidity. Delayed or inadequate treatment can result in irreversible joint destruction and neurological condition. Early diagnoses as well as prompt and effective treatment are essential for avoiding severe outcomes. In spite of advances in diagnostic imaging techniques, the incidence of septic arthritis and spondylitis appears to have been increased. The aging of the population, the widespread use of immunosuppressant therapies, including systemic corticosteroids, cytokines and anticytokines, and growing resistance to conventional antibiotics seem to be the major cause.


Stable alteration of pre-mRNA splicing patterns by modified U7 small nuclear RNAs.
In several forms of beta-thalassemia, mutations in the second intron of the beta-globin gene create aberrant 5' splice sites and activate a common cryptic 3' splice site upstream. As a result, the thalassemic beta-globin pre-mRNAs are spliced almost exclusively via the aberrant splice sites leading to a deficiency of correctly spliced beta-globin mRNA and, consequently, beta-globin. We have designed a series of vectors that express modified U7 snRNAs containing sequences antisense to either the aberrant 5' or 3' splice sites in the IVS2-705 thalassemic pre-mRNA. Transient expression of modified U7 snRNAs in a HeLa cell line stably expressing the IVS2-705 beta-globin gene restored up to 65% of correct splicing in a sequence-specific and dose-dependent manner. Cell lines that stably coexpressed IVS2-705 pre-mRNA and appropriately modified U7 snRNA exhibited up to 55% of permanent restoration of correct splicing and expression of full-length beta-globin protein. This novel approach provides a potential alternative to gene replacement therapies.


Novel anticonvulsant drugs targeting voltage-dependent ion channels.
Epilepsy is one of the most common neurological disorders with a prevalence of 0.5-1%. About two-thirds of epilepsy patients respond well to anticonvulsant pharmacotherapy and become seizure free. There is a third who remain pharmacoresistant, demonstrating the pressing need for novel treatment options that could be drugs with a different mechanism of action compared with those that are currently in clinical use. During the past, many new substances have been screened for blocking or activating effects on specific ion channels, particularly those that are not targets for currently used antiepileptic drugs. This review provides an overview of new anticonvulsant compounds targeting voltage-dependent ion channels.


Genetic fingerprinting of Flavobacterium columnare isolates from cultured fish.
To evaluate the intraspecific diversity of the fish pathogen Flavobacterium columnare. Genetic variability among Fl. columnare isolates was characterized using restriction fragment length polymorphism analysis of the 16S rDNA gene, intergenic spacer region (ISR) sequencing, and amplified fragment length polymorphism (AFLP) fingerprinting. Thirty Fl. columnare cultures isolated from different fish species and geographical origins as well as reference strains were included in the study. Fifteen isolates belonged to genomovar I while eleven were ascribed to genomovar II. Analysis of the ISR sequence confirmed the genetic differences between both genomovars but revealed a higher diversity among genomovar I isolates. The maximum resolution was provided by AFLP fingerprinting, as up to 22 AFLP profiles could be defined within the species. We confirmed the division of Fl. columnare isolates from cultured fish into different genogroups. We showed that both genomovars I and II are present in channel catfish from the US. We described a unique genetic group represented by four Fl. columnare isolates from tilapia in Brazil which appears to be related to both genomovars. We were able to further subdivide the species by analysing the ISR. Finally, the use of AFLP allowed us to fingerprint the species at clone level without losing the higher genetic hierarchy of genomovar division. This paper reports on an extensive assessment of the use of molecular tools for the study of the epidemiology of the fish pathogen Fl. columnare.


[Neurogenic etiology in patients with erectile dysfunction].
Erectile dysfunction (ED) is a disorder with a high prevalence that increases with age. It is estimated that 18.9% of men's between 25 and 70 years suffer it in Spain. Most cases have a multifactorial origin and it is admitted the influence on its pathogenesis of systemic diseases, different kind of drugs, psychogenic factors, cardiovascular, endocrinological and neurological diseases. Neurologic cause erectile dysfunction may have its origin in the central or peripheral nervous system. Among possible process of neurogenic erectile dysfunction of central origin would be tumors, cerebral vascular accidents, encephalitis, Parkinson disease, multiple sclerosis and other demyelinization diseases, dementias, olivopontocerebellar degeneration and epilepsy. Myelopathies of any etiology may be, depending on their localization and extension, cause of erectile dysfunction. At the peripheral level, disorders of the sensitive tracts constituting the afferent limb of the erection spinal reflex, and the efferent vegetative or somatic tracts mediating arterial vasodilatation, cavernous smooth muscle relaxation or pelvic floor striated muscle contraction. The aim of this work is to review in detail the most relevant causes of neurogenic erectile dysfunction, their etiopathogenic mechanisms and therapeutic approaches currently considered more adequate for each particular case. The correct diagnostic approach to patients with erectile dysfunction passes through identification, if possible, of the etiopathogenic factors implied. Regarding this, detection and identification of a possible neurogenic risk factor will contribute to a better understanding of the physiopathologic mechanisms, and more adequate diagnostic, prognostic and therapeutic approaches, mainly in those patients refractory to first line therapy.


12-year experience of spontaneous hemopneumothorax.
Spontaneous hemopneumothorax is a rare clinical disorder that results from a torn small vessel located in adhesions between the visceral and parietal pleurae resulting from the progress of lung collapse. A large spontaneous hemopneumothorax is often life threatening, so the late recognition and delayed intervention can increase mortality rate. From March 1994 to February 2006, a total of 983 patients were treated with spontaneous pneumothorax. Seventeen (1.7%) developed spontaneous hemopneumothorax. We analyzed many factors such as sex and age distribution, affected site, clinical symptoms, bleeding volume, causes, treatments, complications, and others. All 17 patients were males between the ages of 16 and 33 with the average being 19.5 years, except for 1 patient who was 60 years old. In all patients, it was the first occurrence of pneumothorax. Thirteen patients had a history of smoking (76.5%, average 8.6 pack-years). The amount of bleeding ranged from 450 to 2,900 mL (average 1,308.8 mL). Eight patients were given a homologous blood transfusion. In all patients, the cause of hemopneumothorax was a torn pleural adhesion band. All patients were treated with the closed thoracostomy; five were treated with only the closed thoracostomy, and the other 12 were treated by the thoracostomy combined with video-assisted thoracic surgery (VATS) or thoracotomy. One patient, who had had a thoracotomy, needed an exploratory thoracotomy because of a trapped lung after 1 week. We are reporting 17 patients with spontaneous hemopneumothorax to emphasize the following: (i) the mechanism of spontaneous hemopneumothorax, which was caused by a torn pleural adhesion band resulting from the lung collapse. The collapse was developed mainly by an air leak from ruptured bullae, and rarely by additional pressure from the outside during a drainage procedure. (ii) The importance of early recognition and prompt surgical intervention by VATS or thoracotomy. We preferred VATS to thoracotomy because it is easier to access the bleeding point near the Sibson's fascia by VATS, and it can reduce the loss of blood by relatively shorter operating time.


Cefepime pharmacokinetics in critically ill children and young adults undergoing continuous kidney replacement therapy.
Cefepime is an antibiotic commonly used to treat sepsis and is cleared by renal excretion. Cefepime dosing requires adjustment in patients with decreased kidney function and in those receiving continuous kidney replacement therapy (CKRT). We aimed to characterize cefepime PK in a diverse cohort of critically ill paediatric patients on CKRT. Patients were identified from an ongoing pharmacokinetic/pharmacodynamic (PK/PD) study of beta-lactam antibiotics, and were included if they had received at least two cefepime doses in the ICU and were on CKRT for at least 24 h. PK parameters were estimated using MwPharm++ with Bayesian estimation and a paediatric population PK model. Target attainment was assessed as time of free cefepime concentrations above minimum inhibitory concentration (fT > 1× or 4 × MIC). Seven patients were included in the study (ages 2 to 20 years). CKRT indications included liver failure (n = 1), renal failure (n = 4) and fluid overload (n = 2). Total effluent flow rates ranged from 1833 to 3115 (mean 2603) mL/1.73 m2/h, while clearance was 2.11-3.70 (mean 3.0) L/h/70 kg. Effluent flows were lower, but clearance and fT > MIC were similar to paediatric data published previously. Using Pseudomonas aeruginosa MIC breakpoints, all patients had 100% of dosing interval above MIC, but only one had 100% of dosing interval above 4× MIC. Since most patients failed to attain stringent targets of 100% fT > 4× MIC, model-informed precision dosing may benefit such patients.


Exact moment scaling from multiplicative noise.
For a general class of diffusion processes with multiplicative noise, describing a variety of physical as well as financial phenomena, mostly typical of complex systems, we obtain the analytical solution for the moments at all times. We allow for a nontrivial time dependence of the microscopic dynamics and we analytically characterize the process evolution, possibly toward a stationary state, and the direct relationship existing between the drift and diffusion coefficients and the time scaling of the moments.


[Pharmacokinetics of 5-fluorouracil and its permeation in pleural effusions in the therapy of metastatic breast cancer].
The pharmacokinetic of 5-Fluorouracil and its permeation into malignant pleural effusion was investigated in 9 patients with breast carcinoma who received 600 mg/m2 5-Fluorouracil i.v. within the CMF protocol. Despite the short plasma halflife of 5-Fluorouracil (16,8 min) distinct concentrations with peak levels up to 115 nmol/ml after 30 min were observed in the effusions. In consequence of the rapid elimination of 5-Fluorouracil from the plasma and the comparatively slow retrograde diffusion (t 1/2 55 min) from the pleural space, the drug levels persisted longer in the effusions, than in the blood. Thus the area under the curve of the pleural level (AUC) reached 50% (27-85%) of the corresponding plasma AUC (10,9 +/- 2,3 mumol x min x ml-1). From a pharmacokinetic point of view, no additional local instillations of 5-Fluorouracil are necessary during a systemic therapy of breast cancer with pleural effusions.


Evaluation of advanced treatment technologies for the elimination of pharmaceutical compounds.
Pharmaceuticals and their metabolites have developed as ecotoxicologically relevant micropollutants in the aquatic environment. During conventional biological wastewater treatment they are eliminated insufficiently and therefore reach surface waters via discharges. They are either partially or completely non-biodegradable and/or hardly eliminable by activated sludge adsorption because they often have polar structures. Membrane bioreactor treatment (MBR) was applied to pre-treat wastewater containing pharmaceutical compounds, e.g., antibiotics like floxacins and their synthetic precursor compounds. Our objectives were to eliminate these persistent target compounds from wastewater prior to discharge into receiving waters. Therefore an advanced treatment applying MBR combined with different chemical and physicochemical processes was performed. The addition of powdered activated carbon (PAC), nano filtration (NF), reverse osmosis (UO) or ozone (O3) and O3/UV were applied to MBR permeate spiked with the selected target compounds. Treatment efficiency was assessed using conventional inorganic and organic chemical analyses besides advanced physicochemical methods like liquid chromatography coupled with mass and tandem mass spectrometry (LC-MS and -MS-MS).


Cryopreservation of intact human ovary with its vascular pedicle.
The aim of this study was to assess the immediate post-thawing injury to the human ovary that was cryopreserved either as a whole with its vascular pedicle or as ovarian cortical strips. Bilateral oophorectomy was performed in two women (46 and 44 years old) undergoing vaginal hysterectomy and laparoscopic hysterectomy, respectively. Both women agreed to donate their ovaries for experimental research. In both patients, one of the harvested ovaries was sectioned and cryopreserved (by slow freezing) as ovarian cortical strips of 1.0 x 1.0 x 5.0 mm(3) each. The other ovary was cryopreserved intact with its vascular pedicle. After thawing 7 days later, follicular viability, histology, terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-digoxigenin nick-end labelling (TUNEL) assay (to detect apoptosis) and immunoperoxidase staining (to define Bcl-2 and p53 protein expression profiles) of the ovarian tissue were performed. Tissues from non-cryopreserved ovaries served as control specimens (two cases). The overall viability of the primordial follicles was 75 and 78% in intact cryopreserved-thawed (C-T) ovaries and 81 and 83% in ovarian cortical strips in the 46- and 44-year-old patients, respectively. Comparable primordial follicle counts, absence of features of necrosis, mean values of apoptosis and weak Bcl-2 and p53 protein expressions were observed both in the intact C-T ovary and in the C-T ovarian cortical strips. Cryoperfusion and cryopreservation of entire human ovary can be achieved with the maintenance of excellent viability of the superficial and the deeper tissues using a slow-freezing protocol. Cryopreservation injury is associated neither with significant alteration in the expression pattern of Bcl-2 and p53 proteins in the ovarian tissues nor with significant follicular damage.


Multiple repressive mechanisms in the hippocampus during memory formation.
Memory stabilization after learning requires translational and transcriptional regulations in the brain, yet the temporal molecular changes that occur after learning have not been explored at the genomic scale. We used ribosome profiling and RNA sequencing to quantify the translational status and transcript levels in the mouse hippocampus after contextual fear conditioning. We revealed three types of repressive regulations: translational suppression of ribosomal protein-coding genes in the hippocampus, learning-induced early translational repression of specific genes, and late persistent suppression of a subset of genes via inhibition of estrogen receptor 1 (ESR1/ERα) signaling. In behavioral analyses, overexpressing Nrsn1, one of the newly identified genes undergoing rapid translational repression, or activating ESR1 in the hippocampus impaired memory formation. Collectively, this study unveils the yet-unappreciated importance of gene repression mechanisms for memory formation.


Discovery and Biochemical Characterization of UDP-Glucose Dehydrogenase from Akkermansia muciniphila.
The biocatalytic oxidation of UDP-glucose in the presence of NAD+ is catalyzed by UDP-glucose dehydrogenases. The main objective of this study was the characterization of a UDP-glucose dehydrogenase (AmUGD) from Akkermansia muciniphila, a bacterium originally isolated from human faeces in an anaerobic medium containing gastric mucin as the sole carbon source. The biochemical analysis of AmUGD was performed using a plate reader-based assay measuring the reaction by-product NADH. Furthermore, HPLC- and MALDI-ToF-MS- based methods were used for the enzyme characterization. The recombinant form of the protein was expressed in E. coli and the purified enzyme exhibited optimum levels of activity at 37°C and pH 9.0. While the enzyme is active in the absence of metal ions, the presence of Zn2+ ions results in markedly enhanced levels of catalysis. This study describes the first characterization of a nucleotide-processing enzyme from A. muciniphila. The ease of expression and purification of this enzyme make it ideal for biotechnological applications such as the enzymatic synthesis of nucleotide sugars, which may in turn be used for the synthesis of complex carbohydrates or glycoconjugates.


Unusual occurrence of a ZZ/ZW sex-chromosome system and supernumerary chromosomes in Characidium cf. fasciatum (Pisces, Characiformes, Characidiinae).
Individuals of two populations of the fish Characidium cf. fasciatum were cytogenetically studied and showed a basic diploid number of 50 chromosomes. Some fishes were found to have 51 to 54 chromosomes due to the presence of one to four small subtelocentric/acrocentric supernumerary chromosomes. When analyzed by conventional Giemsa staining, male and female specimens of C. cf. fasciatum from the Quinta stream and Pardo River presented the same basic karyotypic macro- and microstructure, consisting of 32 metacentric and 18 submetacentric chromosomes. Ag-NORs were terminally located on the long arms of two submetacentric chromosome pairs. Constitutive heterochromatin was identified by C-banding as small pericentromeric blocks in the majority of the chromosomes, and B-chromosomes were found to be heterochromatic. The occurrence of one totally heterochromatic submetacentric chromosome restricted to females and considered as an unusual feature in fish karyotypes led to the identification of a ZZ/ZW sex-chromosome system. The implications of chromosomic differentiation observed in the genus Characidium are discussed.


The vascular function of the long-term coronary artery after Kawasaki disease--evaluation by intracoronary injection of acetylcholine.
The vascular function of the coronary arteries in children after Kawasaki disease (KD) as yet remains uncertain. Here we report our findings of the vascular response of the coronary arteries after intracoronary injection of acetylcholine in patients after KD. A total of 29 patients, 19 after KD and 10 as control, were examined using coronary angiography (CAG). These were divided into 4 groups according to the type of the coronary artery lesions: Group 1 consisted of those with regressed aneurysms and involved 29 sites. These aneurysms had developed in the acute stage and had subsequently regressed and demonstrated normal findings in follow-up CAG. Group 2 consisted of those with persistent aneurysms involved 30 sites. Group 3 involved 52 angiographically normal sites in patients after KD. And Group 4 consisted of control patients and involved 70 sites. These patients had congenital heart disease with normal coronary arteries. During CAG we infused 15 micrograms acetylcholine chloride into the right or left coronary artery. The luminal diameters were measured using a cine-videodensitometric analyser to study the distensibility of the coronary artery wall. The change in the diameter was an increase of 13.71% +/- 15.09% (mean +/- SD) in the normal KD Group 3, and 12.21% +/- 13.83% in the control Group 4, demonstrating marked vasodilatation. In contrast, the change in the regressed aneurysms Group 1, and in the persistent aneurysms Group 2, was -2.65% +/- 16.65%, and -0.08% +/- 6.51%, respectively, demonstrating no change or mild vasoconstriction. The change in Group 1, and in Group 2, was less than in normal Group 3 or control Group 4. The normal Group 3 showed no significant difference from control Group 4. These findings suggested that the coronary artery with regressed aneurysms, or with persistent aneurysms after KD has impaired vascular function and is therefore at risk for developing to atherosclerosis in the long-term.


Influence of hyperoxia on skin vasomotor control in normothermic and heat-stressed humans.
Hyperoxia induces skin vasoconstriction in humans, but the mechanism is still unclear. In the present study we examined whether the vasoconstrictor response to hyperoxia is through activated adrenergic function (protocol 1) or through inhibitory effects on nitric oxide synthase (NOS) and/or cyclooxygenase (COX) (protocol 2). We also tested whether any such vasoconstrictor effect is altered by body heating. In protocol 1 (n = 11 male subjects), release of norepinephrine from adrenergic terminals in the forearm skin was blocked locally by iontophoresis of bretylium (BT). In protocol 2, the NOS inhibitor N(G)-nitro-l-arginine methyl ester (l-NAME) and the nonselective COX antagonist ketorolac (Keto) were separately administered by intradermal microdialysis in 11 male subjects. In the two protocols, subjects breathed 21% (room air) or 100% O(2) in both normothermia and hyperthermia. Skin blood flow (SkBF) was monitored by laser-Doppler flowmetry. Cutaneous vascular conductance (CVC) was calculated as the ratio of SkBF to blood pressure measured by Finapres. In protocol 1, breathing 100% O(2) decreased (P < 0.05) CVC at the BT-treated and at untreated sites from the levels of CVC during 21% O(2) breathing both in normothermia and hyperthermia. In protocol 2, the administration of l-NAME inhibited (P < 0.05) the reduction of CVC during 100% O(2) breathing in both thermal conditions. The administration of Keto inhibited (P < 0.05) the reduction of CVC during 100% O(2) breathing in hyperthermia but not in normothermia. These results suggest that skin vasoconstriction with hyperoxia is partly due to the decreased activity of functional NOS in normothermia and hyperthermia. We found no significant role for adrenergic mechanisms in hyperoxic vasoconstriction. Decreased production of vasodilator prostaglandins may play a role in hyperoxia-induced cutaneous vasoconstriction in heat-stressed humans.


Long-term effects of silver nanoparticles in caco-2 cells.
The high success of silver nanoparticles (AgNPs), mainly associated with their proved antimicrobial properties, has led to an increasing spread in our close environment. Although many studies have been carried out to detect potential toxicity of AgNPs, most of them have been developed under unrealistic exposure conditions. In terms of human risk, the evaluation of long-term exposures to subtoxic doses of NPs remains a challenge. Here, we have determined different transformation-related end points under a scenario of 6 weeks long-term exposure to low noncytotoxic AgNPs concentrations (0.5 and 1 μg/mL) in Caco-2 cells. A significant uptake of AgNPs was demonstrated by using confocal microscopy showing a high presence of AgNPs in both the cytoplasm and the nucleus. As for the assayed parameters of cell transformation such as ability to growth without requiring adherence to a surface (soft-agar assay), the secretion of extracellular matrix metalloproteinase to the medium (zymography), migration capacity and ability of the secretome of exposed cells to promote tumor growth, significant effects were detected in all cases, with the exception of the extracellular matrix metalloproteinases (MMP2 and MMP9) secretion. Our results point out the potential carcinogenic risk associated with AgNPs exposure under long-term exposure conditions, as well as the importance of using realistic exposure scenarios to test nanomaterials.


The Water Content Drives the Susceptibility of the Lichen Evernia prunastri and the Moss Brachythecium sp. to High Ozone Concentrations.
The aim of this study was to evaluate the tolerance of lichens (Evernia prunastri) and mosses (Brachythecium sp.) to short-term (1 h), acute (1 ppm) O3 fumigation under different hydration states (dry, <10% water content, metabolism almost inactive; wet, >200% water content, metabolism fully active). We hypothesized that stronger damage would occur following exposure under wet conditions. In addition, we checked for the effect of recovery (1 week) after the exposure. Ozone fumigation negatively affected the content of chlorophyll only in wet samples, but in the moss, such a difference was no longer evident after one week of recovery. Photosynthetic efficiency was always impaired by O3 exposure, irrespective of the dry or wet state, and also after one week of recovery, but the effect was much stronger in wet samples. The antioxidant power was increased in wet moss and in dry lichen, while a decrease was found for wet lichens after 1 week. Our results confirm that the tolerance to O3 of lichens and mosses may be determined by their low water content, which is the case during the peaks of O3 occurring during the Mediterranean summer. The role of antioxidant power as a mechanism of resistance to high O3 concentrations needs to be further investigated.


Comparison of transient otoacoustic emission responses from neonatal and adult ears.
Transient otoacoustic emission (TEOAE) responses from neonatal (age: 48 h) and adult subjects (age: 26.6 +/- 10.0 yr) were analyzed by the combined use of recurrence quantification analysis and singular value decomposition. The data from the two age groups showed significant differences and similarities. The neonatal responses presented less deterministic structures than those of the adults in terms of recurrent dynamic features. In both data sets, the same high level of individual specific dynamic features was observed. The results from the singular value decomposition analysis suggest that a large percentage of variability in all of the analyzed responses can be explained by four to five essential modes. This number is lower than that observed in simulated TEOAE responses generated by a five-component gammatone model. A possible explanation is presented, based on simple instrumental and morphoanatomic considerations.


Abdominal compartment syndrome: case reports and implications for management in critically ill patients.
Five cases are reviewed in which intra-abdominal pressures were used to decide whether critically ill patients would undergo exploratory laparotomy. This is a retrospective case series of a convenience sample of five critically ill, postoperative patients with a variety of underlying illnesses admitted to a surgical intensive care unit in a university hospital. Intra-abdominal compartment pressures were measured using the indirect method of urinary bladder pressure. In patients with signs of abdominal compartment syndrome, intra-abdominal pressures were measured. The pressures were measured every 6 hours until the signs had resolved or the patient was taken for exploratory laparotomy. All patients had Foley catheters. The drainage tubing to the catheters was clamped after the infusion of 200 cc of sterile water. An 18-gauge needle was inserted into the sampling port of the drainage tubing proximal to the clamp, and the needle was connected to a pressure transducer. An elevated abdominal compartment pressure was considered at greater than 25 mm Hg. The case series were reviewed to determine in critically ill patients whether intra-abdominal pressures could assist in deciding which patients required emergent exploratory laparotomy. The patients underwent frequent venous and arterial blood gas and hemodynamic measurements. If the clinical course of the patients worsened as indicated by requiring additional pressors, ventilator support and/or oliguria intra-abdominal pressures were measured every 6 hours. The five patients whose intra-abdominal pressures were elevated were taken for exploratory laparotomy. Four patients were found to have urgent surgical conditions. Intra-abdominal pressures can be used to help decide which patients can be aggressively supported and observed and which patients need re-exploration. At exploration the patient may be found to have necrotic large or small intestines instead of the classical abdominal compartment syndrome findings of ascites, hematoma, and bowel wall edema. In symptomatic patients with abdominal compartment pressures greater than 30 mm Hg, the patient should be taken for exploration. It is not necessary to perform any further diagnostic tests before exploring the patient.


Effects of hyperthyroidism and diabetes mellitus on spermatogenesis in peri- and post-pubertal mice.
Diabetes and thyroid dysfunction often co-exist. One autoimmune disorder always invites another and it has been reported that such co-morbid ailments always become detrimental to the health of the patients. In our previous work, we elucidated the interactions of diabetes and hypothyroidism on testicular development and spermatogenesis. However, the present study illuminates the interface between diabetes and hyperthyroidism, where 16 ICR pregnant primiparous mice were used and subsequently 48 male pups were randomly selected (n=12/group) and separated into 4 groups: control (C), diabetic (D), diabetic + hyperthyroidism (DH) and hyperthyroidism (H). Computerized sperm analyses showed significant reductions in count by 20% and increases of 15% in D and H animals, respectively, vs. controls. However, rapid progressive sperm motility was significantly lower only in D (30%) compared with C mice. Our histomorphometric investigation depicted damaging effects on testicular and epididymal tissues; the stroma adjacent to the seminiferous tubules of the D mice revealed edematous fluid and unstructured material. However, in the epididymis, germ cell diminution contraction of tubules, compacted principal and clear cells, lipid vacuolization, atypical cellular connections, exfoliated epithelial cells, and round spermatids were conspicuous in DH mice. Collectively, our experiment was undertaken to ultimately better recognize male reproductive disorders in diabetic-hyperthyroid patients.


Population structure of an island malaria vector.
The impact of islands on the population structure of Anopheles flavirostris (Ludlow) (Diptera: Culicidae), the primary malaria vector in the Philippines, was assessed. A phylogenetic analysis of 16 cytochrome oxidase subunit 1 (CO1) haplotypes revealed three clades: one basal clade containing genetically disparate haplotypes from Mindanao, and two derived clades, one of which was largely confined to the largest island, Luzon, and one that was widespread except for Luzon. For the Luzon clade, nested clade analysis revealed an isolation-by-distance effect, and a mismatch distribution analysis diagnosed a recent demographic expansion (sum of squared deviation, SDD = 0.0093, P= 0.075), which mirrors demographic attributes found in mainland primary malaria vectors and could inflate estimates of gene flow from F(ST). For the widespread clade, evidence of range expansion and past fragmentation and/or long distance colonization from the Visayas or Mindanao to Palawan is suggested. A south-to-north range expansion of An. flavirostris is suggested; estimates of coalescence for the Luzon clade was 214 000 years ago (ya) (95% confidence interval 35 600-298 000 ya), i.e. late Pleistocene. Present day rather than Pleistocene island association and some, but not all, sea barriers appeared to be important for An. flavirostris population structure. Our results suggest that endemic island malaria vector species need to be considered before any generalizations are made about the population structure of primary and secondary vectors.


Regulatory effect of lncRNA NKILA on autophagy induced by sepsis kidney injury.
The article "Regulatory effect of lncRNA NKILA on autophagy induced by sepsis kidney injury, by Y.-M. Yang, Y.-H. Li, L.-L. Ding, Y. Fu, N. Li, published in Eur Rev Med Pharmacol Sci 2019; 23(18):8011-8017. DOI: 10.26355/eurrev_201909_19017. PMID: 31599426" has been withdrawn from the authors. The Publisher apologizes for any inconvenience this may cause.


Conditional centiles for the quantification of fetal growth.
A total of 274 low-risk pregnancies underwent predetermined, scheduled, serial ultrasound examinations and measurement of the biparietal diameter, fetal abdominal area, femur length and estimated fetal weight. The longitudinal nature of this dataset permits the construction of conditional centiles for these measurements, whereby the dimensions of an individual fetus at a given gestational age can be extrapolated to give a range of expected values (expressed as centiles) at a later gestational age. Examples of conditional centiles based upon 4-week measurement separations are presented. These conditional centiles permit the appropriate quantification and subsequent evaluation of time-dependent changes in fetal dimensions to be made.


Dietary lipid droplet structure in postnatal life improves hepatic energy and lipid metabolism in a mouse model for postnatal programming.
Early-life diets may have a long-lasting impact on metabolic health. This study tested the hypothesis that an early-life diet with large, phospholipid-coated lipid droplets (Concept) induces sustained improvements of hepatic mitochondrial function and metabolism. Young C57BL/6j mice were fed Concept or control (CTRL) diet from postnatal day 15 (PN15) to PN42, followed by western style (WSD) or standard rodent diet (AIN) until PN98. Measurements comprised body composition, insulin resistance (HOMA-IR), tricarboxylic acid (TCA) cycle- and β-oxidation-related hepatic oxidative capacity using high-resolution respirometry, mitochondrial dynamics, mediators of insulin resistance (diacylglycerols, DAG) or ceramides) in subcellular compartments as well as systemic oxidative stress. Concept feeding increased TCA cycle-related respiration by 33% and mitochondrial fusion protein-1 by 65% at PN42 (both p 0.05). At PN98, CTRL, but not Concept, mice developed hyperinsulinemia (CTRL/AIN 0.22 ± 0.44 vs. CTRL/WSD 1.49 ± 0.53 nmol/l, p 0.05 and Concept/AIN 0.20 ± 0.38 vs. Concept/WSD 1.00 ± 0.29 nmol/l, n.s.) and insulin resistance after WSD (CTRL/AIN 107 ± 23 vs. CTRL/WSD 738 ± 284, p 0.05 and Concept/AIN 109 ± 24 vs. Concept/WSD 524 ± 157, n.s.). WSD-induced liver weight was 18% lower in adult Concept-fed mice and β-oxidation-related respiration was 69% higher (p 0.05; Concept/WSD vs. Concept/AIN) along with lower plasma lipid peroxides (CTRL/AIN 4.85 ± 0.28 vs. CTRL/WSD 5.73 ± 0.47 µmol/l, p 0.05 and Concept/AIN 4.49 ± 0.31 vs. Concept/WSD 4.42 ± 0.33 µmol/l, n.s.) and were in part protected from WSD-induced increase in hepatic cytosolic DAG C16:0/C18:1. Early-life feeding of Concept partly protected from WSD-induced insulin resistance and systemic oxidative stress, potentially via changes in specific DAG and mitochondrial function, highlighting the role of early life diets on metabolic health later in life.


One Size Does Not Fit All: Contextualising Family Physical Activity Using a Write, Draw, Show and Tell Approach.
Understanding family physical activity (PA) behaviour is essential for designing effective family-based PA interventions. However, effective approaches to capture the perceptions and "lived experiences" of families are not yet well established. The aims of the study were to: (1) demonstrate how a "write, draw, show and tell" (WDST) methodological approach can be appropriate to family-based PA research, and (2) present two distinct family case studies to provide insights into the habitual PA behaviour and experiences of a nuclear and single-parent family. Six participants (including two "target" children aged 9-11 years, two mothers and two siblings aged 6-8 years) from two families were purposefully selected to take part in the study, based on their family structure. Participants completed a paper-based PA diary and wore an ActiGraph GT9X accelerometer on their left wrist for up to 10 weekdays and 16 weekend days. A range of WDST tasks were then undertaken by each family to offer contextual insight into their family-based PA. The selected families participated in different levels and modes of PA, and reported contrasting leisure opportunities and experiences. These novel findings encourage researchers to tailor family-based PA intervention programmes to the characteristics of the family.


Genetic variant in vitamin D-binding protein is associated with metabolic syndrome and lower 25-hydroxyvitamin D levels in polycystic ovary syndrome: A cross-sectional study.
Vitamin D deficiency has been related to metabolic syndrome (MetS) in polycystic ovary syndrome (PCOS). The vitamin D-binding protein (DBP) is the main protein involved in vitamin D transport. Two single-nucleotide polymorphisms (SNPs) of the DBP gene, rs4588 and rs7041, have been associated with low circulating levels of 25-hydroxyvitamin D [25(OH)D] in various populations, but not in women with PCOS. Therefore, we determined the genotype and haplotype distribution of DBP gene polymorphisms and investigated the associations between these genetic variants and their haplotypes with PCOS, MetS, and 25(OH)D levels in women with PCOS and controls from the South of Brazil. The sample included 291 women (191 with PCOS and 100 controls). All participants were genotyped for polymorphisms rs2282679, rs4588, and rs7041. Serum 25(OH)D levels were determined in a subset of 102 participants. Women with PCOS were younger and had significantly higher body mass index, blood pressure, and insulin resistance than the control group (p<0.05). The prevalence of MetS in PCOS and controls was 26.5% and 4.8% respectively. Levels of 25(OH)D were lower in PCOS women with MetS, even after adjustment for age (p = 0.033). No associations were observed between PCOS and the polymorphisms or their haplotypes. A higher frequency of genotype TT of rs7041 was found in PCOS participants with MetS (OR: 2.21, 95%CI:1.08-4.52; p = 0.027). This same genotype was associated with lower 25(OH)D levels in both PCOS and control women (OR: 4.40, 95%CI:1.62-12.00; p = 0.002). In conclusion, these findings indicate that DBP gene polymorphisms and their haplotypes are not directly associated with PCOS. In contrast, the TT genotype of SNP rs7041 was associated with MetS in PCOS women, and with lower 25(OH)D levels in both PCOS and control groups.


Cultural Differences in Visual Search for Geometric Figures.
While some studies suggest cultural differences in visual processing, others do not, possibly because the complexity of their tasks draws upon high-level factors that could obscure such effects. To control for this, we examined cultural differences in visual search for geometric figures, a relatively simple task for which the underlying mechanisms are reasonably well known. We replicated earlier results showing that North Americans had a reliable search asymmetry for line length: Search for long among short lines was faster than vice versa. In contrast, Japanese participants showed no asymmetry. This difference did not appear to be affected by stimulus density. Other kinds of stimuli resulted in other patterns of asymmetry differences, suggesting that these are not due to factors such as analytic/holistic processing but are based instead on the target-detection process. In particular, our results indicate that at least some cultural differences reflect different ways of processing early-level features, possibly in response to environmental factors.


β-HCG secretion by a non-small cell lung cancer: a case report.
Paraneoplastic secretion of beta human chorionic gonadotropin (β-HCG) in non-small cell lung cancer (NSCLC) has been rarely reported. A 43-year old male patient was admitted with dyspnea and chest pain. Thorax computed tomography (CT) revealed bilateral multiple masses and pleural effusion at right hemithorax. Positron emission tomography (PET)-CT showed pathologic 18 FDG uptake at mass lesions and mediastinal lymph nodes. The serum β-HCG level was elevated. A bronchoscopy was performed and endobronchial lesion was observed. Since a definitive diagnosis was not achieved by pathologic examination of biopsy specimen, bronchoscopy was repeated and a sample was taken by cryobiopsy. The pathologic examination revealed non-small cell lung cancer.In conclusion, the case was presented because of extremely rare occurence of NSCLC secreting β-HCG.


Polymer brush and inorganic oxide hybrid nanodielectrics for high performance organic transistors.
A novel covalence-linked PMMA-SiO(2) hybrid nanodielectrics was prepared by grafting approximately 10 nm PMMA brush onto the SiO(2) (approximately 9 nm) surface, which effectively combines the respective merits of PMMA and SiO(2). As a result, the hybrid nanodielectrics exhibit excellent dielectric performance (e.g., low leakage density (<10(-7) A/cm(2) at 6 MV/cm), high breakdown voltage (7 MV/cm), high capacitance (142 nF/cm(2)), good operational stability, and good compatibility with organic semiconductors), and enable organic field-effect transistors (OFETs) to work with high performance and low voltage. These results may open a way to build ultrathin dielectrics for high performance transistor and circuit, as well as for microelectronics, nanoelectronics, and organic electronics.


Directional hyperacuity in ganglion cells of the rabbit retina.
Biological visual systems can detect positional changes that are finer than these systems' acuity to sine-wave gratings, a property known as hyperacuity. Some systems can even detect changes finer that the photoreceptor spacing. We report here that rabbit's directionally selective ganglion cells not only detect positional changes in the hyperacuity range, but also discriminate the direction of their motion. Our experiments show that directional selectivity occurs for edges of light moving as little as 1.1 microns (26" of visual angle) across the retina. This distance corresponds to a hyperacuity, since the acuity to sine-wave gratings of rabbit's On-Off DS ganglion cells is about 125 microns (50'). In addition, this distance is smaller than the minimal spacing between rabbit photoreceptors (1.9 microns or 46"), as estimated from cell-density studies (Young & Vaney, 1991). Such a hyperacuity suggests low-noise high-gain signal transmission from photoreceptors to ganglion cells and that directional selectivity can arise in small portions of retinal dendritic processes.


Creation of a client goal-setting framework.
During the past decade, there has been a noticeable shift in the philosophical approach to health care. This change in thinking, from problem-focused to goal-oriented and from discipline-specific to team driven, has been apparent in rehabilitation as well. The Spinal Cord Program at G. F. Strong Rehab Centre in Vancouver, Canada, has developed a goal-setting framework to define and meet clients' needs by promoting a partnership between the client and family and the clinical team. Donabedian's paradigm provides the model on which the interdisciplinary goal-setting framework is based. The purpose of the framework is to clearly outline clients' and staffs' expectations of the rehabilitation program, identify responsibilities, ensure accountability of clients and staff, and facilitate measurement of goal achievement. Evaluation of the framework indicates that most staff and clients believe the framework provides more structure and direction to the client's rehabilitation program than the previous approach; others believe the use of a goal checklist imposes too much structure and compromises the specificity of goals. This paper will discuss the design, implementation, and evaluation of the framework and recommendations for improvement.


The neonatal resuscitation training project in rural South Africa.
A paediatrician trainer from Australia (JT) spent 3 months in South Africa to assist with the development of neonatal resuscitation training in rural areas, particularly in district hospitals. The project was initiated by the Rural Health Unit at the University of the Witwatersrand and coordinated through the Family Medicine Education Consortium (FaMEC). The Rural Workforce Agency of Victoria together with General Practice and Primary Health Care Northern Territory covered the salary and international travel costs of the trainer, while local costs were funded by provincial departments of health, participants and a Belgian funded FaMEC project. The trainer developed an appropriate one-day skills training course in neonatal resuscitation (NNR), using the South African Paediatric Association Manual of Resuscitation of the Newborn as pre-reading, and a course to train trainers in neonatal resuscitation. From July to October 2004 he moved around the country running the neonatal resuscitation course, and, more importantly, training and accrediting trainers to run their own courses on an ongoing basis. The neonatal resuscitation course involved pre- and post-course multiple-choice question tests to assess knowledge and application, and, later, pre- and post-course skills tests to assess competence. A total of 415 people, including 215 nurses and 192 doctors, attended the neonatal resuscitation courses in 28 different sites in eight provinces. In addition, 97 trainers were trained, in nine sites. The participants rated the course highly. Pre- and post-course tests showed a high level of learning and improved confidence. The logistical arrangements, through the departments of family medicine, worked well, but the programme was very demanding of the trainer. Lessons and experiences were not shared between provinces, leading to repetition of some problems. A clear issue around the country was a lack of adequate equipment in hospitals for neonatal resuscitation, which needs to be addressed by health authorities. A process of ongoing training has been established, with provincial coordinators taking responsibility for standards and the roll-out of training. A formal evaluation of the project is planned. The project serves as a model for skills training in rural areas in South Africa, and for collaboration between organisations. A number of specific recommendations are made for the future of this NNR training project, which offer lessons for similar programmes.


Professional caregivers' work with the dying in nursing homes--a Foucault-inspired analysis of discourses in the last decade in a Danish context.
International studies on the death of elderly nursing home residents show the complexity in the understanding of the professionals who care for the dying. The aim of this study is to explore the discourses about professional caregivers caring for those dying in Denmark in the last decade. A discourse analysis inspired by Foucault was constructed. The material consists of different source documents: research articles, newspaper articles, theses, books, websites - 35 sources in total. There are constructed six positions of speech, five discourses and three themes: (1) 'the work of the professional caregivers - a complex low-status work'; (2) 'the education of the professionals - the way to ensure a good death or possessing the right qualifications' and (3) 'the vulnerable professionals'. The study concludes that an economical/political discourse is dominating and sets up the frames within which the professionals care for dying residents, although the medical, the social/critical and the religious discourses attempt to speak against it. All positions articulate that the professional caregivers' job has a low status and that it is not possible to provide an optimal care due to lack of time, resources and education. Psychical or mental demands make the professionals vulnerable. The meaning of optimal care varies according to the positions of speech.


Body mass index in amputees.
Whereas estimates of percent deviation of body weight from ideal (F delta weight) are corrected for amputation, those of body mass index (BMI) are not, creating discrepancies in evaluating obesity. A correction of the BMI formula for amputation is proposed. The formula for BMI was corrected for amputation mathematically. The mathematical model predicts that the uncorrected BMI formula underestimates body fat in unilateral amputees and overestimates body fat in subjects with bilateral amputations at the same length of the legs. F delta weight and corrected and uncorrected BMI estimates were computed in 15 subjects with unilateral leg amputation and in 8 subjects with multiple amputations. BMI estimates were as follows: in unilateral amputees, corrected 24.1 +/- 4.1 kg/m2, uncorrected 22.2 +/- 3.9 kg/m2 (p < .001); and in multiple amputees, corrected 21.6 +/- 2.4 kg/m2, uncorrected 32.6 +/- 11.8 kg/m2 (p = .043). Linear regressions of F delta weight obtained from standard nutrition assessment on F delta weight computed from uncorrected and corrected BMI values were as follows: in unilateral amputees, uncorrected F delta weight = -0.079 + 0.932 x actual F delta weight, r = .974, p < .01, and corrected F delta weight = 0.002 + 1.005 x actual F delta weight, r = .997, p < .01; in multiple amputees, uncorrected F delta weight = 0.528 + 1.930 x actual F delta weight, r = .607, p is not significant, and corrected F delta weight = -0.010 + 0.920 x actual F delta weight, r = .936, p < .01.(ABSTRACT TRUNCATED AT 250 WORDS)


The -2549 insertion/deletion polymorphism in the promoter region of VEGF is associated with the risk of recurrent spontaneous abortion.
Recurrent spontaneous abortion (RSA) is a common health problem affecting women of reproductive age. Altered expression of vascular endothelial growth factor (VEGF) has been associated with spontaneous abortion. The present case-control study aimed to evaluate the impact of the 18-bp insertion/deletion (ins/del) polymorphism (rs35569394) in the promoter region of the VEGF gene on idiopathic RSA. Genomic DNA from 93 patients with RSA and 93 healthy fertile women of southeastern Iran was isolated using the salting-out method. Genotyping of the rs35569394 variant was performed by a polymerase chain reaction (PCR) method. The findings indicated that the VEGF 18-bp ins/del variant significantly increased the risk of RSA under codominant (ins/ins vs. del/del; OR=2.85, 95% CI=1.31-6.22, P=0.019), dominant (del/ins+ins/ins vs. del/del; OR=2.19, 95% CI=1.20-4.01, P=0.015) and allelic (ins vs. del; OR=1.90, 95% CI=1.25-2.88, P=0.003) inheritance models. In summary, the findings propose a significant association between the VEGF 18-bp ins/del polymorphism and risk of RSA in a sample of the southeast Iranian population. Further studies on larger sample sizes and different ethnicities are required to validate the present findings.


Haplotype-GGGT in long non-coding RNA MALAT1 inhibits brain metastatic lung cancer and lymph nodes of lung cancer via the MALAT1/miR-328/KATNB1.
The up-regulation of katanin P80 has been reported to be correlated with a larger tumor size and lymph node metastasis in non-small-cell lung cancer (NSCLC) patients. And lncRNA MALAT1 was demonstrated to promote the proliferation of chronic myeloid leukemia cells via modulating miR-328. 135 lung cancer patients were divided into 6 groups according to their genotypes of MALAT1. The expression of KATNB1 was negatively correlated with the GGGT genotype of MALAT1. Decreased lymph node size and tumor size of brain metastatic lung were observed in patients with GGGT genotype of MALAT1. The luciferase activities of MALAT1 and KATNB1 were remarkably suppressed by miR-328 in A549 and H460. And the down-regulation of MALAT1 or up-regulation of miR-328 significantly repressed the KATNB1 expression in A549 and H460 cells. MALAT1 expression was reduced in patients carrying haplotype GGGT. A signaling pathway of MALAT1/miR-328/KATNB1 was established to explain the down-regulation of KATNB1 mRNA in patients carrying haplotype GGGT and reduced lymph node size in lung cancer and tumor size in brain metastatic lung cancer.


Lanthanide-Potassium Biphenyl-3,3'-disulfonyl-4,4'-dicarboxylate Frameworks: Gas Sorption, Proton Conductivity, and Luminescent Sensing of Metal Ions.
A novel sulfonate-carboxylate ligand of biphenyl-3,3'-disulfonyl-4,4'-dicarboxylic acid (H4-BPDSDC) and its lanthanide-organic frameworks {[LnK(BPDSDC)(DMF)(H2O)]·x(solvent)}n (JXNU-2, where JXNU denotes Jiangxi Normal University, DMF indicates dimethylformamide, and Ln = Sm(3+), Eu(3+), and Pr(3+)) were synthesized and structurally characterized. The three isomorphous lanthanide compounds feature three-dimensional frameworks constructed from one-dimensional (1D) rod-shaped heterometallic Ln-K secondary building units and are an illustration of a Kagome-like lattice with large 1D hexagonal channels and small 1D trigonal channels. The porous material of the representive JXNU-2(Sm) has an affinity to quadrupolar molecules such as CO2 and C2H2. In addition, the JXNU-2(Sm) compound exhibits humidity- and temperature-dependent proton conductivity with a large value of 1.11 × 10(-3) S cm(-1) at 80 °C and 98% relative humidity. The hydrophilic sulfonate group on the surface of channels facilitates enrichment of the solvate water molecules in the channels, which enhances the proton conductivity of this material. Moreover, the JXNU-2(Eu) material with the characteristic bright red color shows the potential for recognition of K(+) and Fe(3+) ions. The enhancing Eu(3+) luminescence with the K(+) ion and quenching Eu(3+) luminescence with the Fe(3+) ion can be associated with the functional groups of the organic ligand.