The in vivo and in vitro effects of chicken interferon alpha on infectious bursal disease virus and Newcastle disease virus infection.
The in vitro and in vivo effects of chicken interferon alpha on infectious bursal disease virus (IBDV) infection were investigated in this study. A cDNA of interferon alpha was first cloned from a Chinese strain chicken Shiqi by reverse transcription-polymerase chain reaction. The deduced amino acid sequence has one amino acid substitution with chicken interferon alpha 1 at residue 65 (N to S) and two amino acid substitutions with chicken interferon alpha 2 at residues 50 (N to S) and 58 (P to L), respectively. A prokaryotic expression system was employed to produce a large quantity of recombinant protein. Recombinant interferon was purified in a one-step process, and an optimal refolding process was devised. About 51% recombinant protein from inclusion bodies was refolded, and the final yield of the recombinant interferon reached 24.66 mg/liter culture. The recombinant interferon suppressed IBDV plaque formation in a dose-dependent manner and ameliorated IBDV and Newcastle disease virus infection in both specific-pathogen-free (SPF) and commercial chickens. The antiviral effect of interferon alpha is more significant in commercial chickens than in SPF chickens, and the route of administration affects the efficacy of interferon therapy. This is the first reported study of the effects of interferon alpha on IBDV infection.


Risk Factors for Candidemia in Intensive Care Unit: A Matched Case Control Study from North-Western India.
Candidemia is one of the significant causes of mortality amongst critically ill patients in Intensive Care Units (ICUs). This study aimed to assess the incidence, risk factors and antifungal susceptibility pattern in candidemia cases admitted in ICU in a tertiary care hospital in Jaipur, Rajasthan from June 2021 to November 2021. Candida species isolated from blood culture of clinically suspected patients of sepsis were defined as candidemia cases. Blood culture and antifungal susceptibility testing were performed as per standard laboratory protocol. Analyses of risk factors was done between candidemia cases and matched controls in a ratio of 1 : 3. Forty-six candidemic cases and 150 matched controls were included in the study. C. tropicalis was the most prevalent species (22/46; 48%) followed by C. auris (8/46; 17%) and C. albicans (7/46; 15%). Candida species showed good sensitivity to echinocandins (97%) followed by amphotericin B (87%) and voriconazole (80%). In multivariate analysis, longer stay in ICU, presence of an indwelling device, use of immunosuppressive drugs and positive SARS-CoV-2 infection were associated with increased risk of candidemia. The constant evaluation of risk factors is required as prediction of risks associated with candidemia may help to guide targeted preventive measures with reduced morbidity and mortality.


Effect of Solution and Aging Temperatures on Microstructure and Mechanical Properties of 10Cr13Co13Mo5Ni3W1VE(S280) Steel.
The article investigated the effects of solution and ging temperatures on microstructure and mechanical properties of ultra-high strength stainless steel 10Cr13Co13Mo5Ni3W1VE(S280). Higher solution temperatures can improve impact toughness because of the quantity reduction of submicron-sized particles which act as microporous nucleation sites. S280 has the best mechanical properties at 1080 °C solution temperature. After quenching, the steel is completely martensite with almost no retained austenite. Aging at 560 °C results in peak strength due to the precipitation of fine carbides coherent zones. The loss of precipitates/matrix coherency and precipitates coarsening cause a decrease in strength at higher aging temperatures. Good strength and toughness obtained at 540 °C aging temperature are attributed to fine and dispersed strengthening phases such as Cr2C and Fe2Mo, and the recovery of austenite in high-density dislocation martensite matrix. The details of electron microscopy research, strengthening and toughening mechanisms are discussed.


Establishing compliance with liquid medication administration in a child with autism.
Children with autism often display difficulty with swallowing pills and liquid medications. In the current study, stimulus fading and positive reinforcement established compliance with liquid medication administration in a young boy with autism. The boy's mother eventually administered liquid medication on her own.


Organellar Calcium Handling in the Cellular Reticular Network.
Ca2+ is an important intracellular messenger affecting diverse cellular processes. In eukaryotic cells, Ca2+ is handled by a myriad of Ca2+-binding proteins found in organelles that are organized into the cellular reticular network (CRN). The network is comprised of the endoplasmic reticulum, Golgi apparatus, lysosomes, membranous components of the endocytic and exocytic pathways, peroxisomes, and the nuclear envelope. Membrane contact sites between the different components of the CRN enable the rapid movement of Ca2+, and communication of Ca2+ status, within the network. Ca2+-handling proteins that reside in the CRN facilitate Ca2+ sensing, buffering, and cellular signaling to coordinate the many processes that operate within the cell.


Identification of two Fas-associated phosphatase-1 (FAP-1) promoters in human cancer cells.
Fas-associated phosphatase-1 (FAP-1) has been reported as a negative regulator of Fas-mediated signal transduction in human cancer cells. To obtain insights into the potential carcinogenesis of the FAP-1 gene, we investigated its transcriptional regulation in normal and cancerous cells. To identify the FAP-1 promoter sequences, we first isolated P1 and cosmid clones that contained the regulatory region upstream from the FAP-1 gene by using the PCR products of 5' rapid amplification of cDNA end (5'-RACE) as probes. Genomic analysis of positive clones revealed that the major FAP-1 mRNA was transcribed from its proximal promoter (pPRM) in all human cancer cell lines tested, but 1 additional large transcript derived from its distal promoter (dPRM) was found in the human colon cancer cell line DLD-1. This suggests that the FAP-1 gene may be aberrantly dysregulated in some types of human cancers, including colon carcinoma. Sequence analysis of the region upstream from the FAP-1 gene strongly suggests that the transcript of the FAP-1 gene may be controlled by a variety of transcriptional regulatory elements, including NF-kappa B, NF-IL6, and p53 in its 2 promoters. These results imply that the FAP-1 gene may be a target gene under the control of important apoptosis-related nuclear factors in human cancers.


[The Role of Endothelial Dysfunction in the Development of Cardiotoxic Action of Cytostatics in Patients with Lymphoproliferative Diseases].
Understanding mechanisms of chemotherapy cardiotoxicity is an important problem due to the lack of clear understanding of its occurrence. Development of endothelial dysfunction is considered to be one of possible ways in implementation of these side effects. The analysis of endothelin-1 and e-selectin levels in 26 patients with lymphoproliferative diseases before and after the completion of the treatment program was been performed. The results of the study showed normal values of E-selectin level and increased level of endothelin-1 in the whole group of patients before treatment. After completion of chemotherapy program, in the whole group, there was a decrease of these two markers. However, values of level of endothelin-1 with vasoconstrictor effect remained high even after the end of therapy. It is imp ortant that at detailed analysis the dynamics of investigated markers in patients of older age group (median age 64 years) was associated with worsening of endothelial dysfunction.


Leisure-time physical activity is associated with a reduced risk for metabolic syndrome.
The objective of this study was to evaluate the cross-sectional relationship between leisure-time physical activity and the prevalence of metabolic syndrome in the Korean population. The study population included 11,925 participants (6,878 men and 5,047 women), aged 30-79 years. Metabolic syndrome was defined based on the National Cholesterol Education Program criteria of having three or more cardiovascular risk factors, with a modified obesity index. Self-reported leisure-time physical activity was calculated using metabolic equivalents (MET) scores. Logistic regression was used to estimate the association between leisure-time physical activity and the prevalence of metabolic syndrome, with adjustment for other risk factors. The prevalence of metabolic syndrome was 18.2% in men and 8.5% in women. After adjustments for age and education levels, household income, smoking status, and alcohol consumption, the prevalence of metabolic syndrome among participants in the middle and top tertiles of leisure-time physical activity was significantly lower than that among those with no physical activity; the odds ratios (95% confidence intervals) were 0.84 (0.71-0.99) and 0.75 (0.62-0.89), respectively, in men and 0.54 (0.39-0.76) and 0.65 (0.48-0.88), respectively, in women. These results suggest that increasing levels of leisure-time physical activity, in terms of duration or intensity, are linearly associated with a reduced risk for metabolic syndrome.


High-cost users of medical care.
Cost characteristics of hospital patients were analyzed in 2238 medical records randomly selected from 42,880 dicharges in six contrasting hospital populations in the year 1976. Total hospital billings were concentrated on a few patients. On average, the high-cost 13% of patients consumed as many resources as the low-cost 87%. Repeated hospitalizations for the same disease were more characteristic of the expensive patients than were single cost-intensive stays, "intensive care," or prolonged single hospitalizations. Potentially harmful personal habits (e.g., drinking and smoking) were indicated in the records of high-cost patients substantially more often than in those of low-cost patients. Unexpected complications during treatment were five times more frequent in the high-cost group. Public policy programs for health insurance or cost control should include provisions based on the special characteristics of high-cost patients.


Pharmaceutical and preclinical evaluation of Advax adjuvant as a dose-sparing strategy for ant venom immunotherapy.
A major challenge in broader clinical application of Jack Jumper ant venom immunotherapy (JJA VIT) is the scarcity of ant venom which needs to be manually harvested from wild ants. Adjuvants are commonly used for antigen sparing in other vaccines, and thereby could potentially have major benefits to extend JJA supplies if they were to similarly enhance JJA VIT immunogenicity. The purpose of this study was to evaluate the physicochemical and microbiological stability and murine immunogenicity of low-dose JJA VIT formulated with a novel polysaccharide adjuvant referred to as delta inulin or Advax™. Jack Jumper ant venom (JJAV) protein stability was assessed by UPLC-UV, SDS-PAGE, SDS-PAGE immunoblot, and ELISA inhibition. Diffraction light scattering was used to assess particle size distribution of Advax; pH and benzyl alcohol quantification by UPLC-UV were used to assess the physicochemical stability of JJAV diluent, and endotoxin content and preservative efficacy test was used to investigate the microbiological properties of the adjuvanted VIT formulation. To assess the effect of adjuvant on JJA venom immunogenicity, mice were immunised four times with JJAV alone or formulated with Advax adjuvant. JJA VIT formulated with Advax was found to be physicochemically and microbiologically stable for at least 2 days when stored at 4 and 25 °C with a trend for an increase in allergenic potency observed beyond 2 days of storage. Low-dose JJAV formulated with Advax adjuvant induced significantly higher JJAV-specific IgG than a 5-fold higher dose of JJAV alone, consistent with a powerful allergen-sparing effect. The pharmaceutical data provides important guidance on the formulation, storage and use of JJA VIT formulated with Advax adjuvant, with the murine immunogenicity studies providing a strong rationale for a planned clinical trial to test the ability of Advax adjuvant to achieve 4-fold JJAV dose sparing in JJA-allergic human patients.


The Impact of Thermal Stress on Cognition and the Use of Cooling Wear for Alleviation-An Explorative Study.
Increased ambient temperatures during the care of severely burned patients are essential for mitigating hypothermia and minimizing the impact of consecutive hypermetabolism. For involved medical staff, those conditions may lead to impaired concentration, possibly negatively affecting optimal patient care. Yet, alleviation strategies are lacking. As a novel coping strategy, cooling wear may be an effective means. This explorative study aimed to investigate the effect of high ambient temperatures on the concentration capacity and cooling wear to alleviate thermal stress. The effects of high ambient temperatures and the additional use of cooling wear on the concentration capacity of medical staff were investigated in six subjects during two simulated burn surgeries. Each individual served as his/her own control undergoing one simulation with and one without cooling wear. Concentration capacity was measured before and after each simulation with a standardized test. The results suggested that high ambient temperatures, as used in burn medicine, negatively affect human concentration capacity. The initial assessment of concentration capacity yielded homogenous values. After heat exposure, subjects wearing cooling wear showed a higher concentration capacity and a lower error rate compared to subjects without cooling wear. Summing up, temperature-related decrements in vigilance and performance among medical personnel may impair the patients' outcome. As an opportunity to withstand thermal stress and improve medical care and safety, cooling wear showed promising results and may be used as a heat alleviator. Burn medicine may particularly benefit from further development and rigorous investigation of cooling strategies.


Comparative effects of high and low-dose simvastatin on prostate epithelial cells: the role of LDL.
Epidemiological studies have linked statin use with a decreased risk of advanced prostate cancer and an improved recurrence-free survival after radical therapy. It is unclear, however, whether statins could have direct effects against prostate cancer in a clinical setting, as their growth-inhibiting effects on prostate cancer cells have been demonstrated at drug concentrations which exceed the level in plasma during standard clinical dosing. We compared responses to high-dose and therapeutic-dose simvastatin in normal and cancerous prostate epithelial cells. Simvastatin was more effective at inhibiting the growth of normal prostate epithelial cells than of cancer cells. At therapeutic 100 nM concentration simvastatin had a cytostatic effect on normal cells: apoptosis was only slightly induced, but a decrease in cell cycle activity and an increase in senescence were observed. At therapeutic concentrations, lipophilic simvastatin caused a stronger growth inhibition than did hydrophilic rosuvastatin. In contrast, 10 μM simvastatin had a cytotoxic effect both on normal and cancer cells. Addition of LDL-cholesterol effectively reversed the cytostatic effect in all cell lines, but overcoming the cytotoxicity of 10 μM simvastatin required a combination of LDL-cholesterol and mevalonate. As LDL-cholesterol completely prevented the growth-inhibiting effect of therapeutic-dose simvastatin already at low, subphysiological concentrations it is unlikely that statins have direct effects on growth of prostate epithelial cells in vivo. Statins' possible benefits against prostate cancer could be due to systemic cholesterol-lowering, as suggested by epidemiological studies. Future clinical studies evaluating the effects of statins on prostate cancer prevention should monitor serum LDL and should probably administer statins at higher concentrations than those currently used in the treatment of hypercholesterolemia.


The effects of tetrahydrobiopterin on intracerebral hemorrhage-induced brain injury in mice.
Tetrahydrobiopterin (BH4) is an essential cofactor for nitric oxide synthase (NOS) and is presently used clinically to treat forms of phenylketonuria. BH4 has been reported to restrain superoxide generation of NOS and chemically reduce superoxide. However, there has been no report concerning the effects of BH4 in intracerebral hemorrhage (ICH). In the present study, we investigated the neuroprotective effect of BH4 against ICH-induced brain injury in a mouse model.A total of 26 male CD1 mice (31-39 g) were divided into sham, ICH-vehicle, and ICH-treated with BH4 groups (n = 8 in each group). ICH was induced by collagenase injection into the right basal ganglia. BH4 (20 mg/kg) was administrated intraperitoneally at 1 h after ICH. The effect of BH4 was measured by neurological score and brain water content at 24 h after ICH.Our data demonstrates that ICH caused significant neurological deficit that is associated with brain edema. Treatment with BH4 did not reduce brain edema and neurological deficits at 24 h after ICH in mice. Further study is required to investigate the long-term effect of BH4 in ICH-induced brain injury.


Detection of infective poliovirus by a simple, rapid, and sensitive flow cytometry method based on fluorescence resonance energy transfer technology.
The rapid and effective detection of virus infection is critical for clinical management and prevention of disease spread during an outbreak. Several methods have been developed for this purpose, of which classical serological and viral nucleic acid detection are the most common. We describe an alternative approach that utilizes engineered cells expressing fluorescent proteins undergoing fluorescence resonance energy transfer (FRET) upon cleavage by the viral 2A protease (2A(pro)) as an indication of infection. Quantification of the infectious-virus titers was resolved by using flow cytometry, and utility was demonstrated for the detection of poliovirus 1 (PV1) infection. Engineered buffalo green monkey kidney (BGMK) cells expressing the cyan fluorescent protein (CFP)-yellow fluorescent protein (YFP) substrate linked by a cleavage recognition site for PV1 2A(pro) were infected with different titers of PV1. After incubation at various time points, cells were harvested, washed, and subjected to flow cytometry analysis. The number of infected cells was determined by counting the number of cells with an increased CFP-to-YFP ratio. As early as 5 h postinfection, a significant number of infected cells (3%) was detected by flow cytometry, and cells infected with only 1 PFU were detected after 12 h postinfection. When applied to an environmental water sample spiked with PV1, the flow cytometry-based assay provided a level of sensitivity similar to that of the plaque assay for detecting and quantifying infectious virus particles. This approach, therefore, is more rapid than plaque assays and can be used to detect other viruses that frequently do not form clear plaques on cell cultures.


Phosphine-catalyzed remote β-C-H functionalization of amines triggered by trifluoromethylation of alkenes: one-pot synthesis of bistrifluoromethylated enamides and oxazoles.
An unprecedented phosphine-catalyzed remote β-CH functionalization of amine derivatives triggered by trifluoromethylation of an alkene with Togni's reagent was disclosed. This reaction proceeded through the highly selective and concomitant activation of an unactivated alkene and the β-C sp 3H bond of an amine derivative, providing bistrifluoromethylated enamides in excellent yields with good regio-, chemo-, and stereoselectivity. Furthermore, the newly developed one-pot protocol provides a facile and step-economical access to valuable trisubstituted 5-(trifluoromethyl)oxazoles. Mechanistic studies showed that this reaction may initiate with a novel phosphine-catalyzed radical trifluoromethylation of unactivated alkene via a phosphorus radical cation.


Evaluation of sun protection factor of cosmetic formulations by a simple visual in vitro method mimicking the in vivo method.
A new concept for in vitro visual evaluation of sun protection factor (SPF) of cosmetic formulations based on a supramolecular ultraviolet (UV) dosimeter was clearly demonstrated. The method closely parallels the method validated for in vivo evaluation and relies on the determination of the slightest perceptible bleaching of an iron-complex dye/nanocrystalline-titanium dioxide interface (UV dosimeter) in combination with an artificial skin substrate simulating the actual human skin in the presence and absence of a cosmetic formulation. The successful evaluation of SPF was ensured by the similarity of the erythema response of our dosimeter and human skin to UV light irradiation. A good linear correlation of in vitro and in vivo data up to SPF 40 confirmed the effectiveness of such a simple, cheap, and fast method. In short, here we unravel a convenient and accessible visual FPS evaluation method that can help improving the control on cosmetic products contributing to the reduction of skin cancer, one of the critical public health issues nowadays.


Effect of transforming growth factor-beta1 on microglial MHC-class II expression.
In the present report, the effects of IFN-gamma and transforming growth factor beta1 (TGF-beta1) on major histocompatibility complex class II (MHC-II) gene expression in isolated mouse brain microglial cells, in the MH-S macrophage cell line and in the primary mouse macrophage cultures were examined. IFN-gamma is a potent inducer of MHC-II gene and this induction was further elevated in microglia by TGF-beta1, while TGF-beta1 inhibited IFN-gamma, induction in macrophages. The enhancing effect of TGF-beta1 was also detected in microglia at the protein level. Transient transfection of microglia with 5' deletional mutants of the MHC-II IAalpha promoter linked to the chloramphenicol acetyltransferase reporter gene demonstrated that TGF-beta1 acts at the transcriptional level to enhance the MHC-II expression induced by IFN-gamma.


Atypical Cogan's syndrome associated with coronary disease.
Cogan's syndrome (CS) is a rare inflammatory disorder characterized by interstitial keratitis and vestibuloauditory abnormalities often associated with various systemic manifestations. Involvement of cardiovascular system resembling systemic vasculitis may lead to severe complications and death. The present report describes a case of a female patient with atypical Cogan's syndrome presented with systemic manifestations and severe coronary and femoral artery stenosis. Despite the clinical improvement after glucocorticoids and cyclophosphamide, the patient required double aortocoronal bypass grafting one year letter. During three years follow-up, she was in stable condition, without stenocardial symptoms and claudication and her inflammatory parameters remain normal. This case highlights the rare involvement of coronary arteries without associated large-vessel vasculitis of the aortic arch in CS.


Superoxide overproduction and kidney fibrosis: a new animal model.
To establish whether the mutation in the Immp2L gene induces renal fibrosis and whether aging exacerbates renal morphology in mice. Female mutant mice with mutation in the inner mitochondrial membrane peptidase 2-like protein at 3 and 18 months of age were used. Renal fibrosis was analyzed using classic fibrosis score, Masson's trichrome staining, and analysis of profibrotic markers using real time polymerase chain reaction (superoxide dismutase 1, metalloproteinase-9, erythropoietin, transforming growth factor beta), and immunostaining (fibroblasts and Type IV collagen). Oxidative stress markers were determined by immunohistochemistry. The number of renal apoptotic cells was determined. Renal function was estimated by serum creatinine. Young mutant mice had significantly more glomerulosclerosis than age-matched mice (p=0.034). Mutant mice had more tubular casts (p=0.025), collagen deposition (p=0.019), and collagen type IV expression (p<0.001). Superoxide dismutase 1 expression was significantly higher in young mutants (p=0.038). Old mutants exhibited significantly higher expression of the fibroblast marker and macrophage marker (p=0.007 and p=0.012, respectively). The real time polymerase chain reaction of metalloproteinase-9 and erythropoietin were enhanced 2.5- and 6-fold, respectively, in old mutants. Serum creatinine was significantly higher in old mutants (p<0.001). This mutation altered renal architecture by increasing the deposition of extracellular matrix, oxidative stress, and inflammation, suggesting a protective role of Immp2L against renal fibrosis.


How microsurgery can assist in tubal reconstruction.
Despite the fact that gynecologists were very early users of the operating microscope to observe the possible pathology of the cervical mucosa by brilliant lighting and magnification, the advent of in vitro fertilization (IVF) seems to have stopped this specialty from using the benefits of microsurgery in female tubal reconstruction. Now having performed and followed up for at least 2 years nearly 1000 microsurgical tubal reconstructions after sterilizations, with an endpoint being the birth of a baby in the time following, it is obvious that there are real benefits in pursuing these techniques, because no single IVF Unit in the world gets even half as many live birth results from their best practices. Apart from a genuine 82.7% baby result from all comers, of any child-bearing age and "sterilization age," with an ectopic pregnancy rate of <1%, there are the benefits of (i) a single procedure, (ii) normal intercourse to become pregnant is the way to go, (iii) psychological trauma of the women involved is not a problem, and (iv) the next baby after the first is "free." In our opinion, it is sensible to scientifically attempt to reconstruct a deliberately blocked tube in the first instance because it is healthier (for mother and children), less expensive, more satisfying and psychologically acceptable, and is certainly far more reliable in its results than any other baby-promoting proceedure now available. It is regretted that gynecologists who flocked to workshops teaching microsurgical gynecological techniques before IVF was established now do not even seem to consider giving the operative reconstruction as a first alternative to their couples that come to them with sterilization as the cause of infertility.


Practical memory concerns in adulthood.
In this article, we focus on practical memory concerns in adulthood. Young, middle-aged, and community-dwelling older adults responded to seven open-ended questions covering the topics of memory self-efficacy, memory management, memory remediation, and fears about memory aging in adulthood. The results revealed several similarities among the age groups. All groups reported the same types of information as easy to recall, and responses across age groups were also largely alike in terms of mnemonics usage, forgetting that is bothersome, and forgetting that is not bothersome. Differences between the age groups were most evident in responses related to types of information that are difficult to recall, areas of memory where improvement is desired, and fears of memory aging. Implications for understanding adult memory concerns and memory beliefs across the adult lifespan are discussed.


Kinase-independent functions of TEL1 in telomere maintenance.
TEL1 is important in Saccharomyces cerevisiae telomere maintenance, and its kinase activity is required. Tel1p associates with telomeres in vivo, is enriched at short telomeres, and enhances the binding of telomerase components to short telomeres. However, it is unclear how the kinase activity and telomere association contribute to Tel1p's overall function in telomere length maintenance. To investigate this question, we generated a set of single point mutants and a double point mutant (tel1(KD)) of Tel1p that were kinase deficient and two Xrs2p mutants that failed to bind Tel1p. Using these separation-of-function alleles in a de novo telomere elongation assay, we found, surprisingly, that the tel1(KD) allele and xrs2 C-terminal mutants were both partially functional. Combining the tel1(KD) and xrs2 C-terminal mutants had an additive effect and resembled the TEL1 null (tel1Delta) phenotype. These data indicate that Tel1p has two separate functions in telomere maintenance and that the Xrs2p-dependent recruitment of Tel1p to telomeres plays an important role even in the absence of its kinase activity.


Electrophysiological and echocardiographic parameters predisposing to atrial fibrillation in patients with a structurally normal heart.
The electroanatomical substrate of dilated atria is characterised by increased non-uniform anisotropy and macroscopic slowing of conduction, which promote reentrant circuits. To analyse the relationship between electrophysiological properties of atria and echocardiographic markers of dilatation and increased filling pressure. The study group consisted of 79 patients without structural heart disease, aged 53+/-22 years, who were referred for electrophysiological study. In order to examine the atrial electrophysiological characteristics we studied interatrial conduction time (iaCT), double potentials and fragmented atrial activity during premature stimulation of the high right atrium (HRA). The analysed parameters included: duration of atrial activity, baseline iaCT (iaCTb) between HRA and distal coronary sinus (CS), iaCT during HRA pacing S1S1 600 ms (iaCTS1), maximum prolongation of iaCT during S2 and S3 delivery (iaCTS2, iaCTS3). We also calculated the decremental index (DI)=iaCT S3- iaCTS1/iaCTS1%. The following echocardiographic parameters were assessed: left atrial (LA) dimensions, surface (LAs), volume using ellipse formula (LAv), right surface (RAs), total atrial surface (TAs=LAs+RAs), and global myocardial index (GMI). Patients were divided into two groups. Group 1 consisted of 37 patients with evidence of slow atrial conduction (atrial fragmentation/iaCTb>80 ms/DI>50%/double atrial potentials), whereas group 2 was composed of 42 patients without slow conduction properties. There were no significant differences concerning age, body mass index or LA parasternal dimensions between the groups. Thirty-seven patients, of whom 32 were from group 1, had documented episodes of paroxysmal atrial fibrillation. GMI, LAs, LAv and TAs values were significantly higher in patients from group 1 than in group 2 subjects. A statistically significant linear correlation between iaCTb and TAs (r=0.52 p <0.0001)/LAv (r=0.38 p <0.0001) was found. There was also a trend toward a correlation between DI and TAs. This study supports the role of stretch and dilated atria in electrophysiological changes which occur in structurally normal hearts. The iaCT value may be indirectly and non-invasively evaluated using echocardiographic measurements.


Factor structure and predictive utility of the Binge Eating Scale in bariatric surgery candidates.
Screening for binge eating before bariatric surgery is a component of the recommended clinical practice for bariatric surgery candidates. The Binge Eating Scale (BES) is 1 of the most commonly used self-report measures of eating behaviors in preoperative evaluations; however, the factor structure of this measure has not been evaluated in the bariatric population. The aims of the present study were to report the mean, standard deviation, and reliability of the BES for patients seeking bariatric surgery; to evaluate the 2-factor structure of the BES using confirmatory factor analysis; and to investigate the association between the BES and its factors with surgical weight loss. The setting was an academic medical center. A total of 530 patients completed the BES as a component of their psychological evaluation before undergoing Roux-en-Y gastric bypass surgery. Approximately one third of patients reported at least mild to moderate binge eating, with 9% of patients reporting severe binge eating on the BES. The BES demonstrated good internal consistency. The results of the confirmatory factor analysis indicated that a 2-factor structure, consisting of feelings/cognitions related to binge eating and behavioral manifestations of binge eating, was the best fit to the data. Nonsignificant correlations were found between the BES and its 2 factors with short-term postoperative weight loss. The BES measures 2 aspects of binge eating in bariatric surgery candidates, feelings/cognitions and behavioral manifestations of binge eating. Consideration of these factors in patients presenting for bariatric surgery could allow for a more detailed understanding of binge eating in this population.


Occurrence of Vibrio parahaemolyticus in estuarine waters and oysters of New Hampshire.
Vibrio parahaemolyticus was isolated from water and oysters collected from seven different sampling stations in the Great Bay and Little Bay estuarine areas of New Hampshire. The morphological and biochemical characteristics of 50 isolates conformed in general to those described for this organism in the literature. All isolates produced hemolysis on blood-agar. To date, there have been no reports of V. parahaemolyticus food poisoning outbreaks due to the consumption of fish or shellfish harvested from this estuarine region.


Circulating dendritic cells in early and advanced cancer patients: diminished percent in the metastatic disease.
Despite the well demonstrated fundamental role of dendritic cells (DC) in generating antitumor immunity in experimental conditions, to date there are only few preliminary studies which investigate the percent of DC in the peripheral blood of cancer patients. Several cell surface markers have now been described which are specific to cultured DC, however their expression in vivo is still controversial. Recently, however, two DC subsets, consisting of immature and mature DC, have been shown to be present in peripheral blood, which can be recognized as CD123+ and CD11c+ cells, respectively. On this basis, we decided to investigate the presence of both mature and immature DC in the peripheral blood of early or advanced cancer patients. The study included 40 solid tumor patients, 18 of whom had a locally limited disease, while the other 22 showed distant organ metastases. CD123+ and CD11c+ cells were detected by FACS using monoclonal antibodies, and expressed as the percent of total leukocytes. The control group consisted of 50 healthy subjects. The mean percent of both CD123+ and CD11c+ cells was significantly lower in cancer patients than in controls. Moreover, the mean percent of both DC subsets was significantly lower in metastatic patients than in the non-metastatic ones. This study, demonstrating significantly lower percents of both immature and mature DC in the peripheral blood of cancer patients, particularly in those with distant organ metastases, suggests that DC deficiency may play a role in inducing cancer-related immunosuppression. Therefore, the demonstration of a diminished percent of DC in peripheral blood may represent a new interesting biological marker predicting a poor prognosis in human neoplasms, as with lymphocytopenia, the unfavourable prognostic significance of which has been well demonstrated.


Arterial stiffness and progressive neurological deficit in patients with acute deep subcortical infarction.
The mechanism of progressive neurological deficit (PND) in patients with ischemic stroke remains unclear. The aim of this study was to clarify whether arterial stiffness, a marker of vascular endothelial impairment and arteriosclerosis, is associated with PND in patients with acute deep subcortical infarction. We evaluated 156 consecutive first-ever ischemic stroke patients with acute deep subcortical infarction. PND was defined as an increment of ≥2 points in the National Institute of Health Stroke Scale score or an increase of ≥1 point in the limb weakness score within 7 days of stroke onset. Patients were assessed for risk factors, and infarct size was measured on initial diffusion-weighted magnetic resonance imaging. We measured brachial-ankle pulse wave velocity (baPWV) as a marker of arterial stiffness. We divided patients into 2 groups according to the presence or absence of PND to compare their clinical characteristics. Fifty-two patients (33%) had PND, and baPWV was significantly higher in patients with than in those without PND. The baPWV cut-off value for PND was 18.24 m/s, with 90% sensitivity and 47% specificity. In multivariable logistic regression analysis, high baPWV (≥18.24 m/s; odds ratio, 8.22; 95% confidence interval, 2.55-31.9), large infarct size (≥15 mm; odds ratio, 2.76; 95% confidence interval, 1.01-7.92), and ≥3 infarct slices on serial axial diffusion-weighted imaging (odds ratio, 3.38; 95% confidence interval, 1.22-10.0) were independently associated with PND. Arterial stiffness indicated by baPWV is independently associated with PND in patients with acute deep subcortical infarction.


Prevalence of Colorectal Neoplasms and Mortality in New Users of Low-Dose Aspirin With Lower Gastrointestinal Bleeding.
Aspirin inhibits platelet function and may therefore accelerate early lower gastrointestinal bleeding (LGIB) from colorectal cancer (CRC) precursor polyps. The bleeding may increase endoscopic polyp detection. To estimate the prevalence of polyps and CRC comparing new users of low-dose aspirin with nonusers who all received a diagnosis of LGIB and to investigate the mortality among these patients. Using Danish nationwide health registries, we conducted a cohort study (2006-2013) of all new aspirin users who also received a diagnosis of LGIB (n = 40,578). Each new user was matched with 5 nonusers with LGIB by gender and age at the LGIB diagnosis date. We computed the prevalence and prevalence ratios (PRs) of colorectal polyps and CRCs, and the mortality ratios within 6 months after the LGIB, comparing new users with nonusers. We identified 1038 new aspirin users and 5190 nonusers with LGIB. We observed 220 new users and 950 nonusers recorded with endoscopically detected polyps. New aspirin users had a higher prevalence of conventional {PR = 1.28 [95% confidence interval (CI): 1.06-1.55]} and serrated [PR = 1.31 (95% CI: 0.95-1.80)] polyps. New users and nonusers had a similar prevalence of CRC [PR = 1.04 (95% CI: 0.77-1.39)]. However, after stratifying by location of CRC, the prevalence of proximal tumors was lower [PR = 0.71 (95% CI: 0.35-1.43)] in new users than in nonusers. No difference in mortality was observed. These findings indicate that new use of low-dose aspirin is associated with an increased detection of colorectal polyps compared with nonuse.


Flavobacterium heparinum 2-O-sulphatase for 2-O-sulphato-delta 4,5-glycuronate-terminated oligosaccharides from heparin.
The glycosulphatase which hydrolyses the 2-O-sulphate of the disaccharide, 4-deoxy-2-O-sulphato-alpha-L-threohex-4-enopyranosyl uronic acid-(1----4)-2-deoxy-2-sulphamido-6-O-sulphato-D-glucose (delta UA-2S----GlcNS-6S), has been isolated from the soluble fraction of disrupted Flavobacterium heparinum. The activity was purified 3300-fold by chromatography on CM-Sepharose CL-6B, hydroxyapatite, taurine-Sepharose CL-4B and blue-Sepharose CL-6B. From sodium dodecylsulphate/polyacrylamide gel electrophoresis, the enzyme was homogeneous and of 62000 Mr. A novel assay was devised using the de-N-sulphonated [1-3H]alditol, 4-deoxy-2-O-sulphato-alpha-L-threo-hex-4-enopyranosyl uronic acid-(1----4)-2-amino-2-deoxy-6-O-sulphato-D-[1-3H]glucitol (delta UA-2S----[1-3H]GlcNH2-ol-6S). This alditol was shown by 13C-NMR to be desulphated in the analogous manner to the original reducing trisulphated disaccharide. The purified 2-O-sulphatase was completely free of heparinase I, heparinase II (heparitinase), chondroitinases AC, chondroitinase B, the delta 4,5-glycuronidase for heparin delta 4,5-disaccharides, the 6-O-sulphatase and the 2-sulphamidase. It was optimally active over the range pH 5.5-6.5 and was practically unaffected by Na, K, Ca or Mg ions. Inorganic phosphate inhibited the activity. The Km value for the alditol substrate was 1.22 mmol dm-3. Using 13C-NMR, the 2-O-sulphatase was found to hydrolyse the analogous esters of higher delta 4,5-oligosaccharides from heparin. This contrasts with the findings of other authors [Dietrich, C. P., Silva, M. E., and Michelacci, Y. M. (1973) J. Biol. Chem. 248, 6408-6415].


The prediction of therapy-benefit for individual cardiovascular disease prevention: rationale, implications, and implementation.
We aim to outline the importance and the clinical implications of using predicted individual therapy-benefit in making patient-centered treatment decisions in cardiovascular disease (CVD) prevention. Therapy-benefit concepts will be illustrated with examples of patients undergoing lipid management. In both primary and secondary CVD prevention, the degree of variation in individual therapy-benefit is large. An individual's therapy-benefit can be estimated by combining prediction algorithms and clinical trial data. Measures of therapy-benefit can be easily integrated into clinical practice via a variety of online calculators. Lifetime estimates (e.g., gain in healthy life expectancy) look at therapy-benefit over the course of an individual's life, and are less influenced by age than short-term estimates (e.g., 10-year absolute risk reduction). Lifetime estimates can thus identify people who could substantially benefit from early initiation of CVD prevention. Compared with current guidelines, treatment based on predicted therapy-benefit would increase eligibility for therapy among young people with a moderate risk-factor burden and individuals with a high residual risk. The estimation of individual therapy-benefit is an important part of individualized medicine. Implementation tools allow for clinicians to readily estimate both short-term and lifetime therapy-benefit.


Flipping the Photoswitch: Ion Channels Under Light Control.
Nature has incorporated small photochromic molecules, colloquially termed 'photoswitches', in photoreceptor proteins to sense optical cues in phototaxis and vision. While Nature's ability to employ light-responsive functionalities has long been recognized, it was not until recently that scientists designed, synthesized and applied synthetic photochromes to manipulate many of which open rapidly and locally in their native cell types, biological processes with the temporal and spatial resolution of light. Ion channels in particular have come to the forefront of proteins that can be put under the designer control of synthetic photochromes. Photochromic ion channel controllers are comprised of three classes, photochromic soluble ligands (PCLs), photochromic tethered ligands (PTLs) and photochromic crosslinkers (PXs), and in each class ion channel functionality is controlled through reversible changes in photochrome structure. By acting as light-dependent ion channel agonists, antagonist or modulators, photochromic controllers effectively converted a wide range of ion channels, including voltage-gated ion channels, 'leak channels', tri-, tetra- and pentameric ligand-gated ion channels, and temperature-sensitive ion channels, into man-made photoreceptors. Control by photochromes can be reversible, unlike in the case of 'caged' compounds, and non-invasive with high spatial precision, unlike pharmacology and electrical manipulation. Here, we introduce design principles of emerging photochromic molecules that act on ion channels and discuss the impact that these molecules are beginning to have on ion channel biophysics and neuronal physiology.


The effect of body weight compression on axillo-femoral by-pass patency.
The influence of external compression on extra-anatomic bypass patency is still debated. The specific purpose of this study is the evaluation of ankle Pressure Index (P.I.) and Pulse Volume Recorder (P.V.R.) wave amplitude changes after 5 and 10 minutes of external bypass compression by body weight, lying on the side of the reconstruction. Eight patients with axillo-femoral bypass (mean follow-up 15.5 months) have been evaluated. The external body weight compression caused important changes of graft haemodynamics: (1) decrease in ankle Pressure Index at 5 min (p less than 0.005) or 10 min (p less than 0.0005); (2) decrease in P.V.R. wave amplitude at 5 min (p less than 0.005) and 10 min (p less than 0.025).


Drug safety and the impact of drug warnings: An interrupted time series analysis of diabetes drug prescriptions in Germany and Denmark.
To analyse the impact of drug safety warnings from the European Medicines Agency (EMA) on drug utilisation and their interaction with information released through national reimbursement bodies. Insurance claims data on anti-diabetic drug prescriptions in primary care in Germany and Denmark were analysed using interrupted time series analysis, with EMA drug warnings for thiazolidinediones (TZDs) in 2007 and 2011 as the intervention. Monthly drug utilisation data per substance in defined daily dosages (DDD) consumed per 1000 insurees were retrieved from the Danish national drug prescriptions register and one large statutory sickness fund in Germany. TZDs were generally reimbursed in Germany but restricted to individual reimbursement in Denmark. Consequently, utilisation of TZDs was much higher in Germany in 2007 compared with Denmark. For rosiglitazone, the drug warning had a significant impact on utilisation, reducing the number of DDD per 1000 insurees per day by -0.0105 in Denmark and -0.0312 in Germany (p-values<0.05). For pioglitazone, neither of the drug warnings had a significant effect on utilisation. The impact of EMA drug warnings differed across countries and might be mediated by information released through national reimbursement bodies and physician associations. Increasing complexity of new drugs and modified approval procedures require a strengthening of information exchange between drug regulation bodies and physicians to ensure patient safety.


Mice deficient in MIM expression are predisposed to lymphomagenesis.
Missing in metastasis (MIM) is a member of newly emerged inverse Bin-Amphiphysin-Rvs (BAR) domain protein family and a putative metastasis suppressor. Although reduced MIM expression has been associated with bladder, breast and gastric cancers, evidence for the role of MIM in tumor progression remains scarce and controversial. Herein we characterized a MIM knockout mouse strain and observed that MIM-deficient mice often developed enlarged spleens. Autopsy and histological analysis revealed that nearly 78% of MIM(-/-) mice developed tumors with features similar to diffuse large B lymphoma during a period from 1 to 2 years. MIM(-/-) mice also exhibited abnormal distribution of B cells in lymphoid organs with decrease in the spleen but increase in the bone marrow and the peripheral blood. Furthermore, the bone marrow of MIM(-/-) mice contained a higher percentage of pre-B2 cells but fewer immature B-cells than wild-type mice. In response to CXCL13, a B-cell chemokine released from splenic stromal cells, MIM-deficient B-cells did not undergo chemotaxis or morphological changes in response to the chemokine and also did not internalize CXCR5, the receptor of CXCL13. Microarray analyses demonstrated that MIM is the only member of the I-BAR domain family that was highly expressed in human B cells. However, low or absent MIM expression was common in either primary B-cell malignancies or established B-cell acute lymphocytic leukemia or lymphomas. Thus, our data demonstrate for the first time an important role for MIM in B-cell development and suggest that predisposition of MIM-null mice to lymphomagenesis may involve aberrant interactions between B lineage cells and the lymphoid microenvironment.


Transition to Parenthood and Marital Satisfaction: A Meta-Analysis.
The transition to parenthood is a major life event characterized by profound changes for a considerable number of people. Previous meta-analyses summarized the results obtained by various researchers in the first year and, respectively, in the first 2 years postpartum, globally. The current studyadds to the literature by testing the changes from 12 to 24 months, the cross-partner associations and the analysis of different moderators. The aims of thispresent meta-analysis are to investigate the decrease in marital satisfaction during the first and second year postpartum, to examine cross-partner associations of the decline in postpartum marital satisfaction, and to investigate the potential moderating variables of this decrease. Forty-nine studies (97 samples of parents and 9 samples of non-parents) that fit our criteria are included in the meta-analysis. The data analysis was performed using meta-analytic techniques. Marital satisfaction has a medium decrease between pregnancy and 12 months postpartum, and a small decline between 12 and 24 months postpartum for both genders. In a similar period with first year postpartum, non-parents present a small decline in marital satisfaction. Moreover, the analysis of the dyadic studies data shows cross-partner associations, confirming that one partner's satisfaction has a steeper decline when the other partner's satisfaction presents a steep decrease. The decrease in marital satisfaction does not stop after the first postpartum year, and the coss-partners associations are present. Theoretical and therapeutic implications are also discussed.


Comparative study of the ability of three xanthobacter species to metabolize cycloalkanes.
The ability of three species of Xanthobacter to metabolize cyclohexane and its derivatives has been compared. Xanthobacter flavus was unable to utilize any of the cycloalkanes under investigation. X. autotrophicus was unable to utilize cyclohexane but was able to grow with a limited range of substituted cycloalkanes, including cyclohexanol and cyclohexanone. Comparison of a previously isolated cyclohexane growing Xanthobacter sp. with X. flavus and X. autotrophicus indicated it to be closely related to X. autotrophicus. Studies with cell-free extracts have indicated that the route of metabolism for cyclohexanol by X. autotrophicus is the same as that shown for the cyclohexane growing Xanthobacter sp., proceeding via cyclohexanol-->cyclohexanone--> epsilon-caprolactone-->--> adipic acid. A comparison of the cyclohexanol dehydrogenase found in X. autotrophicus with that found in the cyclohexane-growing Xanthobacter sp. indicated these enzymes to be distinctly different from one another on the basis of substrate specificity, molecular weight, and pH optima. The cyclohexanone monooxygenase enzymes found in the two bacteria were also found to be different when the pH optima and cofactor specificity of the two enzymes were compared. Preliminary genetic studies on the cyclohexane-growing Xanthobacter sp. have indicated that there are no plasmids present in this bacterium. The presence of RP4 in the Xanthobacter sp. can be detected following its conjugation with an RP4-carrying Escherichia coli strain.


Where the exception confirms the rule: The cyclones of 1982-1983 in French Polynesia.
The island groups of French Polynesia, which had not experienced any really devastating cyclones since the beginning of the century, were hard hit several times between December 1982 and April 1983. This paper reviews the cost of damage from these cyclones and shows how lowered public awareness of the hazard in a low-frequency area combined with the special economic conditions prevailing in the Territory to make the total cost much higher than it need have been. Ways and means of rehabilitation are analyzed. The development of the thermal imbalance in the Pacific, which appears to have triggered this series of natural disasters, only seemingly exceptional, is briefly discussed.


Left ventricular dyssynchrony predicts right ventricular remodeling after cardiac resynchronization therapy.
The purpose of this research was to evaluate right ventricular (RV) remodeling after six months of cardiac resynchronization therapy (CRT). Cardiac resynchronization therapy is beneficial in patients with end-stage heart failure. The effect of CRT on RV size is currently unknown. Accordingly, the effects of CRT on RV size, severity of tricuspid regurgitation, and pulmonary artery pressure were evaluated. Fifty-six consecutive patients with end-stage heart failure (52% ischemic cardiomyopathy), left ventricular (LV) ejection fraction (EF) < or =35%, QRS duration >120 ms, and left bundle branch block were included. Clinical parameters, LV volumes, LVEF, LV dyssynchrony, and RV chamber size were assessed at baseline and after six months of CRT; LV dyssynchrony was assessed using tissue Doppler imaging. Clinical parameters improved significantly; LV dyssynchrony was acutely reduced after CRT and remained unchanged at six-month follow-up. Left ventricular EF improved significantly from 19 +/- 6% to 26 +/- 8% (p < 0.001), and LV end-diastolic volume decreased from 257 +/- 98 ml to 227 +/- 86 ml (p < 0.001). Right ventricular annulus decreased significantly from 37 +/- 9 mm to 32 +/- 10 mm, RV short-axis from 29 +/- 11 mm to 26 +/- 7 mm, and RV long-axis from 89 +/- 11 mm to 82 +/- 10 mm (all p < 0.001). Left ventricular and RV reverse remodeling were only observed in patients with substantial LV dyssynchrony at baseline. Finally, significant reductions in severity of tricuspid regurgitation and pulmonary artery pressure were observed. Cardiac resynchronization therapy results in significant reverse LV and RV remodeling after six months of CRT in patients with LV dyssynchrony. Moreover, CRT leads to a reduction of the severity of tricuspid regurgitation and a decrease in pulmonary artery pressure.


Two-wave longitudinal findings from the Berlin aging study: introduction to a collection of articles.
We provide background information for a collection of articles that describe two-wave longitudinal findings derived from the first intensive follow-up of participants of the Berlin Aging Study (BASE). Multidisciplinary data were collected during 1995-1996 from 206 survivors approximately 4 years after baseline assessment (1990-1993). The strengths of the initial BASE design, in terms of a focus on very old age, multidisciplinary intensive assessment, and an examination of selectivity issues, were maintained in this longitudinal extension of the study.


A rare case of arrhythmogenic right ventricular cardiomyopathy associated with LAMA2 mutation: A case report and literature review.
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a heritable heart muscle disorder that predominantly affects the right ventricle. Mutations in genes that encode components of desmosomes, the adhesive junctions that connect cardiomyocytes, are the predominant cause of ARVC. A case with novel heterozygous mutation in the LAMA2 gene is reported here. The protein encoded by LAMA2 gene is the α2 chain of laminin-211 protein, which establishes a stable relationship between the muscle fiber membrane and the extracellular matrix. We explored the potential mechanism and the relationship between the mutation and ARVC. At the age of 8, the patient developed syncope and palpitation after exercise. Dynamic electrocardiogram recorded continuous premature ventricular beats, and MRI showed the right ventricle was significantly enlarged and there were many localized distensions at the edge of the right ventricular wall. The patient was diagnosed with ARVC and received heart transplantation at the age of 14 due to severe heart dysfunction. The myocardial histological pathological staining revealed a large amount of fibrosis and adipose migration. Whole exome sequencing (WES) identified the heterozygous mutation in the LAMA2 gene [NM_000426.3: c.8842G > A (p.G2948S)]. This is the first report of these variants. Analysis was performed on genetic disorders to reveal splice site changes and damage to protein structure. LAMA2 p.G2948S predicted unstable protein structure and impaired function. Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) were established. RNA-seq and the western blot were performed on IPSC-CMs to explore the ARVC-related signaling pathway. This is the first case report to describe an ARVC phenotype in patients possessing a novel LAMA2 c.8842G > A (p.G2948S) mutation. Our results aid in understanding of the pathogenesis of ARVC. The molecular mechanism of LAMA2 leading to ARVC disease still needs further study.


Use of electronic medical records in Oman and physician satisfaction.
The Electronic Medical Record (EMR) is a computerized record of clinical, demographic and management information. EMR is an enabling technology that allows physicians to utilize quality improvement processes in the practice of medicine. Oman is one of the Middle Eastern Countries that has implemented an integrated electronic hospital information system at government health care institutions. The system was first applied in primary health care centers and then implemented in hospitals. Survey research highlights factors that affect physician satisfaction and utilizing of this new technology in a hospital setting. Outcome survey data suggests areas for improvement. Specific concerns about patient confidentiality are discussed as well as quality improvement in patient care.


Response to initial treatment of low and intermediate risk gestational trophoblastic disease with methotrexate and folinic acid.
To evaluate the response and toxicity of methotrexate and folinic acid given as primary treatment of low and intermediate risk gestational trophoblastic disease (GTD). Medical records review was performed in patients who received methotrexate and folinic acid as a primary treatment of low and intermediate risk persistent GTD between January 1992 and December 2001. Response was defined as decline of beta human chorionic gonadotropin (hCG) to < or = 5 mlU/ml (remission) after methotrexate and folinic acid treatment. Response rate was estimated and factors associated with response were evaluated. Ninety four eligible patients were treated with intramuscular methotrexate and folinic acid. Complete remission was achieved in 64 cases (68%, 95% CI 58-78%). Mucositis (6.4%) and hepatotoxicity (6.4%) were the most common toxicity of methotrexate in the present study and none of these toxic effects was life threatening. Factors associated with response were initial serum hCG < or = 10,000 mlU/ml and stage I disease. Methotrexate with folinic acid is effective treatment for low and intermediate risk GTD with minimal severe toxicity.


[Coronary microvascular resistance and its relevant factors in patients with moderate coronary stenosis and chest pain].
Objective: To evaluate the impact of cardiovascular risk factors on index of microvascular resistance (IMR) and coronary flow reserve (CFR) and to explore the characteristics of IMR and CFR and the relationship between IMR and angiographic features in patients with intermediate coronary stenosis and chest pain. Methods: Fractional flow reserve (FFR), CFR, and IMR were measured in patients who underwent invasive coronary angiography with 40%-70% stenosis by visual assessment. All patients with FFR>0.75 were enrolled and grouped with the cut-off points of IMR≥25 and CFR≤2.0. Patients with IMR≥25 were group H, including two sub-groups (high IMR-low CFR, group H1 and high IMR-high CFR, group H2), while those with IMR<25 were group N. The thrombolysis in myocardial infarction (TIMI) frame were counted. Results: A total of 34 patients with FFR>0.75 were enrolled with 61.8%(21 cases) of males and 38.2% (13 cases) of females. The mean age was (57.3±8.1) years old. High IMR accounted for 47.1% of all cases. There was significant difference between group H and N in TIMI frame (33.0 vs. 20.8, P=0.031). There were significant differences between group H1 and H2 in homocysteine (17.8 µmol/L vs. 12.0 µmol/L, P=0.005) and IMRcorr (58.0 vs. 36.1, P=0.002). IMRcorr was correlated to TIMI frame (r=0.40, P=0.012) for all cases. The sensitivity and specificity of inferring IMR≥35.3 by TIMI frame were 0.75 and 0.65 (P=0.049) with TIMI frame over 40.5. Conclusions: High IMR may be one of the reasons for chest pain in patients with intermediate coronary stenosis. There is no correlation between vascular risk factors and IMR or CFR, while there is positive correlation between TIMI frame and IMR. The specificity is 65% for inferring IMR rise with TIMI frame over 40.5.


Predictors of left atrial volume index reduction following cryoballoon-based pulmonary vein isolation.
Ablation for atrial fibrillation (AF) has been suggested to be associated with 'reverse left atrial remodelling'. Reduction in left atrial volume index (LAVIR) is regarded as a determinant of reverse remodelling following pulmonary vein isolation (PVI). However, there is paucity on data about the predictors for LAVIR after PVI. In this study, we aimed to investigate predictors of LAVIR at 12 months in AF patients undergoing cryoballoon-based PVI. Patients with symptomatic paroxysmal or persistent AF despite ≥1 antiarrhythmic drug(s), who were scheduled for cryoballoon-based AF ablation procedure per the recent consensus recommendations, were enrolled and followed-up for 12 months in this prospective observational study. Left atrial volume was derived using the biplane area-length method. A total of 160 patients (54.25 ± 7.66 years, 44.40% female) were involved in the study. Reduction in left atrial volume index occurred in 120 patients. Age [hazard ratio (HR): 0.901, 95% confidence interval (CI): 0.828-0.981, P = 0.017], hypertension (HR: 0.151, 95% CI: 0.048-0.471, P = 0.001), mild mitral regurgitation (MR) (HR: 5.327, 95% CI: 1.489-19.058, P = 0.010), and AF recurrence (HR: 0.017, 95% CI: 0.005-0.065, P< 0.001) were found to be independent predictors for LAVIR. To the best of our knowledge, this is the largest study in the literature investigating the predictors of LAVIR following AF ablation. According to this data, younger patients without hypertension or moderate MR are most likely to experience LAVIR following ablation.


Microtubule-associated protein-4 controls nanovesicle dynamics and T cell activation.
The immune synapse (IS) is a specialized structure formed at the contact area between T lymphocytes and antigen-presenting cells (APCs) that is essential for the adaptive immune response. Proper T cell activation requires its polarization towards the APC, which is highly dependent on the tubulin cytoskeleton. Microtubule-associated protein-4 (MAP4) is a microtubule (MT)-stabilizing protein that controls MTs in physiological processes, such as cell division, migration, vesicular transport or primary cilia formation. In this study, we assessed the role of MAP4 in T cell activation. MAP4 decorates the pericentrosomal area and MTs of the T cell, and it is involved in MT detyrosination and stable assembly in response to T cell activation. In addition, MAP4 prompts the timely translocation of the MT-organizing center (MTOC) towards the IS and the dynamics of signaling nanovesicles that sustains T cell activation. However, MAP4 acts as a negative regulator of other T cell activation-related signals, including diacylglycerol (DAG) production and IL2 secretion. Our data indicate that MAP4 acts as a checkpoint molecule that balances positive and negative hallmarks of T cell activation.


Albumin is the major plasma protein target of oxidant stress in uremia.
Patients with uremia are exposed to increased oxidative stress. Examination of the oxidation of individual plasma proteins may be useful in establishing specific pathways of oxidative stress in vivo and in determining functional consequences of oxidant stress exposure. We therefore examined oxidative modification of plasma proteins by carbonyl formation using Western blot immunoassay and enzyme-linked immunosorbent assay (ELISA) techniques in patients with chronic renal failure (CRF) and on chronic hemodialysis therapy (HD). Plasma was obtained from 25 HD, 20 CRF, and 20 healthy volunteers, derivatized with 2,4 dinitrophenylhydrazine (DNP) and electrophoresed on duplicate 4 to 12% gradient sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) gels, transferred to nitrocellulose, and stained for DNP for carbonyls and amido black for protein content. Data are recorded as DNP area/protein area and are reported in densitometry units. Total plasma carbonyls were determined by ELISA. Plasma albumin is substantially more oxidized in HD than in healthy volunteers (1.22 +/- 0.14 densitometry units vs. 0.60 +/- 0.08, P = 0.002). There were no significant differences in oxidation of plasma transferrin, immunoglobulin, and fibrinogen in HD versus healthy volunteers. In CRF patients, plasma albumin is more oxidized compared with normal volunteers (1.36 +/- 0.20 densitometry units vs. 0.94 + 0.08, P = 0.09). There were no differences in oxidation of plasma transferrin, fibrinogen, and immunoglobulin in CRF patients versus healthy volunteers. An increased plasma protein carbonyl concentration in CRF patients compared with healthy volunteers was confirmed by ELISA (0.31 +/- 0.07 vs. 0.04 +/- 0.01 nmol/mg protein (P = 0.001). Albumin is the major plasma protein target of oxidant stress in CRF and HD patients.


Coexistence of Cervical Leiomyosarcoma and Gastric-Type Adenocarcinoma In Situ with Extensive Extension to the Endometrium and Fallopian Tube.
Cervical leiomyosarcoma is known to be rare from the previous reviews of a large number of malignant cervical tumors. The patient was a 66-year-old woman with irregular vaginal bleeding. She underwent modified radical hysterectomy and bilateral salpingooophorectomy. Histopathologically, we diagnosed the coexistence of uterine cervical leiomyosarcoma and cervical gastric-type adenocarcinoma in situ with endometrial lesions that had continuous and skip patterns and fallopian tubal lesions with a partial lesion. To the best of our knowledge, cases of synchronous leiomyosarcoma and cancers have not often been reported; only two cases of synchronous cervical leiomyosarcoma and cervical squamous cell carcinoma have been published. This case is the first presentation of coincidental primary cervical leiomyosarcoma and cervical gastric-type adenocarcinoma in situ. Additionally, we considered cervical gastric-type adenocarcinoma in situ with continuous lesions on the endometrium and skip lesions on the left fallopian tube.


Diversity of Ochrobactrum species in food animals, antibiotic resistance phenotypes and polymorphisms in the blaOCH gene.
Twenty-six lactose non-fermenting, oxidase, urease and citrate-positive Gram-negative rods, isolated from broiler chickens, pigs and cattle at slaughter, were subjected to the matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry and 16S rDNA sequencing for identification. Susceptibility to 14 antimicrobials was determined by the disc diffusion method. Ochrobactrum isolates resistant to third-generation cephalosporins were PCR-screened for the presence of the Ochrobactrum anthropi ampC gene (blaOCH). A 547-bp internal segment of blaOCH in the Ochrobactrum spp isolates was amplified with a newly designed primer set, and a phylogenetic reconstruction based on the complete amino acid sequence of blaOCH obtained from nine Ochrobactrum strains in our collection and 20 O. anthropi available in the GenBank was undertaken. All the Ochrobactrum isolates were resistant to the expanded-spectrum beta-lactams and streptomycin. None of the isolates was resistant to imipenem while 41.7% to 50.0% of them were resistant to fluoroquinolones. The blaOCH gene was detected in 16 (66.7%) and 20 (83.3%) of the 24 Ochrobactrum isolates (O. intermedium/O. tritici species), using primers designed for O. anthropi and the newly designed primer set, respectively. Six blaOCH variants grouped into two divergent clusters were identified. This is the first report of the complete nucleotide sequence of the blaOCH gene in non-antropi Ochrobactrum species.


The effect of demographic, clinical, and pathological data on quality of life in rectum cancer.
The aims of the current study are to describe the quality of life among patients with rectal cancer and to determine the clinical and demographic correlation that influences the quality of life of rectal cancer patients. In this study, 50 patients with rectal cancer treated in the Radiation Oncology Department of Kayseri City Education and Research Hospital were included. Ethics committee approval was received for the study. Data collection form was used to determine the demographic and clinicopathological characteristics of the patients. To assess the quality of life, the European Committee of Cancer Treatment and Organization Quality of Life Scale (EORTC QLQ-C30) question-answer scale was used. The data were collected by interviewing the patients face to face. Mann-Whitney U and Kruskal-Wallis tests were used to analyze the data. Spearman correlation analysis was performed to reveal the relationship between dependent variables. As a result of this study, 52% of patients were 65 years and older and 54% were male patients. The most common surgery was low anterior resection and the most common type of pathology was adenocarcinoma. According to American Cancer Committee (AJCC) 7th edition 2009 staging, 80% stage 3 was the most common. In EORTC C30 Cancer Quality of Life Scale Functional Scale Subscale, the highest score is from the physical function and the lowest score is from the emotional function. In the symptom scale subscale, the most common symptom was nausea/vomiting. Performance status (ECOG) was found to be significantly associated with T stage, N stage, TNM stage, and symptom scores. There was a moderately significant positive correlation between symptom scales and global health status scales (ρ = 0.51; p < 0.001). There was a perfectly positive and significant relationship between symptom scales and functional scales (ρ = 0.83; p < 0.001). As a result of this study we conducted, it was observed that rectal cancer patients decreased performance status and increased symptoms in the presence of advanced disease. Accordingly, it was found that the quality of life of the patient decreased.


Study on the correlation between maternal serum uric acid and foetal birth weight in Naqu, Tibet.
In high-altitude regions, low birth weight is mainly caused by hypoxia. We aimed to determine whether maternal serum uric acid (SUC) level was associated with decreased foetal birth weight. The relevant data of individual pregnant women who delivered between 37 and 40 weeks in the People's Hospital of Naqu City, Tibet were retrospectively collected. The correlation between maternal SUC and birth weight was examined using multivariate linear regression analysis and subgroup analysis. The results showed that there was a significant negative correlation between SUC and birth weight in pregnant women with proteinuria, female foetuses, and primiparas. Fitting smoothing curve analysis showed that there was a negative linear correlation between SUC and birth weight in primiparas and female foetuses. Maternal SUC is negatively associated with foetal birth weight in a single pregnancy with proteinuria, primipara, or female foetuses in the Naqu region of Tibet, China.IMPACT STATEMENTWhat is already known on this subject? Preeclampsia associated with hyperuricaemia can affect foetal birth weight, foetal birth weight in plains area is negatively correlated with maternal hyperuricaemia.What do the results of this study add? Maternal SUC was negatively correlated with foetal birth weight, especially in primipara, mothers with proteinuria, and pregnant girls.What are the implications of these findings for clinical practice and/or further research? The results suggest that attention should be paid to SUC in pregnant women, especially in primipara, mothers with proteinuria, and pregnant girls, in the prevention of low birth weight infants in Naqu Plateau area of Tibet.


HDL re-examined.
To summarize the current evidence concerning the role of HDL-C and HDL-associated parameters in the risk for cardiovascular disease (CVD). Numerous population studies have shown that plasma levels of HDL-C are inversely associated with CVD risk; in patient care HDL-C levels are therefore widely implemented in risk estimation models. A number of antiatherogenic properties have been ascribed to the HDL particle, but the hypothesis that HDL is causally related to CVD has been seriously challenged by recent data obtained from both human genetic studies and clinical trials. The final word on HDL-C as a therapeutic target is pending, as a number of clinical endpoint trials specifically focusing on the effect(s) of HDL-C increasing agents are underway. Moreover, recent data show that HDL efflux capacity could hold independent predictive value for CVD events, which clearly highlights the potential need to focus on HDL functionality, rather than on HDL-C levels. The dogmatic concept that HDL-C levels predict future CVD events is undisputed, but the role of HDL-C as a causal factor in atherosclerosis has been challenged by a number of different types of studies. In recent years, a paradigm shift toward 'HDL functionality' is apparent. Whether or not optimizing these markers of HDL functionality actually does reduce CVD risk requires formal testing in prospective controlled studies.


[Accelerated transepithelial corneal collagen cross-linking for progressive keratoconus with a thin cornea: one-year results].
Objective: To evaluate the clinical results of keratoconic eyes with a thin cornea treated with accelerated transepithelial corneal collagen cross-linking (A-TE-CXL) within 1 year. Methods: Nineteen eyes of 19 patients with progressive keratoconus with a minimum corneal thickness from 380 μm to 420 μm (including the epithelium) were included in this prospective, nonrandomized clinical study and treated with A-TE-CXL. Scoring of pain and foreign body sensation, slit lamp examination, uncorrected visual acuity, best corrected distance visual acuity, corneal topography, anterior segment optical coherence tomography, in vivo corneal confocal microscopy and endothelial cell count were assessed before surgery and at 1, 3, 6 and 12 months postoperatively. Paired t test was applied for statistical analysis. Results: Mild pain and moderate foreign body sensation were reported by most patients within postoperative 24 hours, but rapidly disappeared on day 2. Extremely mild epithelial damage was observed within postoperative 24 hours, and the epithelium fully recovered on day 2. Improvement of visual acuity was recorded at 3 and 12 months. Pentacam corneal topography revealed a significant reduction of the thickness of the thinnest location from(395.2±13.8)μm preoperatively to (378.9±17.1)μm at 1 month postoperatively (t=2.982, P<0.01). Front curvature values were reduced postoperatively. K(MAX) was significantly decreased at 12 months (55.67±4.91) compared with (57.35±5.54) preoperatively, while K2 was also significantly decreased at 12 months (52.18±3.70) compared with (52.70±3.56) preoperatively (K(MAX), t=3.044, P<0.01. K2, t=2.384, P<0.05) . Within 1 month postoperatively, optical coherence tomography exhibited an increase of reflectance with a demarcation line in the anterior stroma. In vivo confocal microscopy also showed significant thickening and increased connections of collagen fibers with a maximal depth at about 90 to 120 μm. The corneal endothelial cell density remained stable (t=0.692, P>0.05). None of the patients showed postoperative complications such as corneal infection, scarring and ulceration. Conclusions: Within 1 year postoperatively, A-TE-CXL was effective and safe for the management of progressive keratoconus with a thin cornea. A-TE-CXL showed the advantages of very short time consuming in surgery, rapid recovery and very few complications, and had the potential to become a valid alternative for the treatment of keratoconus. (Chin J Ophthalmol, 2017, 53: 694-700).


Pattern and determinants of contraceptive usage among women of reproductive age in the United Arab Emirates.
Women in the UAE and Muslim countries are a largely understudied population with significant disparities in knowledge to most basic health concerns and family planning. Our objective was to identify UAE contraceptive knowledge similarities and variances to other world regions, and to inform efforts to improve contraceptive care at Arab world and Muslim countries. Structured questionnaire consisting of socio-demographic characteristics, knowledge, beliefs and attitudes related to contraception methods. The use of effective contraception methods was associated with higher educational levels of UAE national women who desired to conceive. These women had knowledge of contraception that was associated with an identified impact of their spouse on their choice of contraception. Religion plays an essential role in knowledge on the risk of contraception and safe type of contraceptive methods in the UAE. Statistically significant predictors of having knowledge on different methods of contraception were nationality, P < 0.002; education level, P < 0.03; number of marriages P < 0.002; monthly income, P < 0.04; and the number of children, P < 0.015. Our results demonstrate that higher education and communication of the benefits and risks of different types of contraceptive methods are needed to improve the use of contraception in the UAE population. We recommend additional training in this area for healthcare providers. The involvement of the spouse in the mutual understanding of contraception and its choice coupled with third party insurance coverage may decrease knowledge and utilization gaps further assisting in providing a best contraceptive method.


The impact of an emergency motorcycle response vehicle on prehospital care in an urban area.
Faster emergency response times are generally considered to have a positive effect on life expectancy of patients with a life-threatening event, leading many communities to determine response time intervals. However, worldwide, increasing urbanization and traffic congestion threatens ambulance response times. An emergency motorcycle response vehicle (MRV) can overcome these hurdles more easily than a larger ambulance. It also offers dispatch flexibility in responding to calls estimated to have a low likelihood of a patient who needs transport. The first aim of this study was to determine whether an MRV can shorten response times and impact on resuscitation outcomes in a heavily urbanized and densely populated region in the Netherlands. The second aim was to evaluate differences in dispatch and transport between MRV and ambulance. This was a nonrandomized, prospective cohort study comparing an MRV unit with regular ambulances in a Dutch city of 265 000 people. Included were all 'urgent patient' cases within operating time of the MRV between January 2003 and August 2003. A total of 1664 patients was evaluated, including 468 motorcycle and 1196 ambulance responses. Use of MRVs led to a decrease in response time of 54 s (P≤0.01). We could not show a decrease in mortality risk in cases of resuscitation [relative risk (RR): 2.50, confidence interval (CI): 0.17-36.21]. There was a slightly improved 1-year survival in other life-threatening cases (RR: 1.13, CI: 1.03-1.24). However, this is most likely because of differences in dispatch decisions (the MRV is sent to 'lighter' cases) and not because of faster assistance. The MRV paramedic was more likely to treat and release the patient (RR: 2.21, CI: 1.80-2.73) or refer them to a general practitioner (RR: 2.11, CI: 1.73-2.58) and much less likely to refer them to the hospital emergency department (41.2 vs. 72.6%). Referrals to the hospital by the MRV were mostly by the patient's own means of transportation (RR: 13.14, CI: 5.89-29.32) rather than by ambulance. Using motorcycles in a Dutch setting lead to better emergency medical service response times. The MRV serves a different population. Resulting in a higher treat and release rate and less transportation to hospital.


Breakage of the Grosse-Kempf nail: causes and remedies.
Eleven cases of breakage of the Grosse-Kempf nail were observed in a series of 297 operations performed at the Rizzoli Orthopaedic Institute in Bologna. Seven of the 9 femoral nails were not the latest available model, which is capable of supporting more stress because areas of less resistance have been eliminated. However, breakage is still a possibility as a result of errors of technique and incorrect planning of weightbearing.


Summation of sinoaortic baroreflexes depends on size of input signals.
We studied sinoaortic baroreflex summation in seven anesthetized rabbits by paying special attention to the sigmoidal nature of the open-loop characteristic curve of the two reflexes. Carotid sinuses were isolated to control carotid sinus pressure (CSP). Aortic nerves were cut, and the left aortic nerve was electrically stimulated. Initially, CSP was set between 75 and 95 mmHg, and the parameters for aortic nerve stimulation (ANS) were chosen so that mean arterial pressure (MAP) was between 80 and 100 mmHg. We then increased CSP and ANS mildly so that MAP would fall by 10-20 mmHg in each case. Comparison of the sum of these decreases with the decrease caused by simultaneous increases in CSP and ANS showed no statistical difference, indicating a simply additive summation. With mild decreases in CSP and ANS, a similar additive summation was observed in the reflex increases in MAP. When we input slightly larger changes in CSP and ANS so that MAP fell by 20-30 mmHg for each stimulus, comparison of the sum of the separate effects with the combined effect on MAP indicated a mildly inhibitory summation. By analyzing the total peripheral resistance calculated from aortic flow data, we found this inhibitory summation occurred in the reflex controls of the total peripheral resistance. We conclude that the summation of the sinoaortic reflex controls of arterial pressure can be regarded as simply additive when small input signals are given in the physiological range of both reflexes, but the summation is mildly to moderately inhibitory when moderately larger input signals are given.


Delayed feedback control of periodic orbits without torsion in nonautonomous chaotic systems: theory and experiment.
We demonstrate theoretically and experimentally that the unstable delayed feedback controller is an efficient tool for stabilizing torsion-free unstable periodic orbits in nonautonomous chaotic systems. To improve the global control performance we introduce a two-step control algorithm. The problem of a linear stability of the system under delayed feedback control is treated analytically. Theoretical results are confirmed by electronic circuit experiments for a forced double-well oscillator.


Discovery and verification of urinary peptides in type 2 diabetes mellitus with kidney injury.
Varying degrees of renal injury could lead to different changes in urinary protein composition. We want to find urinary candidate peptide biomarkers in type 2 diabetic patients with different extents of kidney injury. Two sets of patients were recruited. Discovery set: weak cationic-exchange magnetic beads coupled with matrix-assisted laser desorption ionization time-of-flight mass spectrometry were used to profile the low-molecular weight peptidome in urine samples from type 2 diabetes patients with normoalbuminura and microalbuminuria. The differently expressed urinary peptides were screened by ClinProTools2.1 bioinformatics software and identified through nano-liquid chromatography-tandem mass spectrometry. Verification set: the above screened urinary peptides were validated by use matrix-assisted laser desorption ionization time-of-flight mass spectrometry on another group of type 2 diabetes patients with different extents use of kidney injury. In the screening and identification stages, seven urinary peptides were selected as the most promising biomarker candidates, and they were identified as fragments of vitronectin precursor, isoform 1 of fibrinogen alpha chain precursor, prothrombin precursor and inter-alpha-trypsin inhibitor heavy chain H4. The diagnostic efficacy of these urinary peptides was evaluated by area under the receiver operating characteristic curve, and they were 0.767, 0.768, 0.868, 0.910, 0.860, 0.843, and 0.865, respectively. In the verification stage, m/z 1743.9, 2154, 2175.5, and 2184.9 were decreased as albumin-to-creatinine (Alb/Cre) increased and m/z 2231.1, 2430.8, and 2756.1 were elevated as Alb/Cre rose. These small molecule peptides are related to type 2 diabetes kidney damage, and they may play an important role in monitoring type 2 diabetes.


Astragaloside IV supplementation attenuates cognitive impairment by inhibiting neuroinflammation and oxidative stress in type 2 diabetic mice.
Although diabetic cognitive impairment is one of the most common complications of type 2 diabetes mellitus (T2DM), optimized therapeutic strategies are not available yet. Astragalosides IV (AS-IV) is a traditional Chinese medicine possessing diverse pharmacological properties including anti-inflammatory and antioxidant effects. However, the effects of AS-IV on diabetes-related cognitive impairment and its precise mechanisms remain largely unknown. T2DM mice, induced by a high-fat diet (HFD) and an intraperitoneal injection of low-dose streptozotocin (STZ) were administrated with AS-IV every other day for eight consecutive weeks. Learning and memory abilities were assessed subsequently using the Ymaze test and the anxious behavior was evaluated using an open field test. Then, the morphology and number of neurons and microglia were observed by HE staining or immunohistochemistry. Oxidative stress biomarkers and pro-inflammatory cytokines were determined using relevant kits. In addition, the expression levels of Nrf2, Keap1, HO-1, and NQO1 were determined by Western blot analyses. The results indicated that AS-IV administration significantly improved neuronal damage and cognitive deficit in T2DM mice. Meanwhile, oxidative stress and neuroinflammation were also ameliorated in T2DM mice, which might be attributed to the regulation of Nrf2/Keap1/HO-1/NQO1 pathway in T2DM mice. Taken together, these data suggested that AS-IV ameliorates cognitive impairment in T2DM mice by attenuating oxidative stress and neuroinflammation, possibly through modulating the Nrf2/Keap1/HO1/NQO1 pathway.


Neonatal metabolic acidosis caused by food proteininduced enterocolitis syndrome: a case report.
Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE mediated allergic reaction with gastrointestinal symptoms, such as vomiting and diarrhea. FPIES diagnosis is based on clinical criteria and on a food challenge test. It is an unknown disease in neonatal units due to its nonspecific symptoms in newborn infants. An elevated methemoglobin level is a simple way to approach diagnosis. Here we describe a clinical case of a newborn admitted to the emergency department because of dehydration, lethargy, vomiting, diarrhea, severe metabolic acidosis, and a high methemoglobin level. Clinical improvement and complete recovery was achieved after initiation of elemental formula. The diagnostic suspicion was confirmed after a positive challenge test.


Exercise treatment for osteoarthritis disability.
Osteoarthritis (OA) is a chronic prevalent condition that affects the synovial joints and can lead to disability. There is no single treatment that is known to cure OA. Most treatments have aimed at reducing symptoms or slowing the progression of the disease and its consequences. Exercise therapy is a common intervention in treating OA, with primary aims of improving functional movement and managing the problems associated with abnormal functional movement. We review the underlying process of exercise treatment and its importance for OA disability. A brief description of OA disease and an OA disability model are introduced, and then the importance of exercise and trends in prescribing exercises for OA are discussed. Finally, future directions and suggestions for research in this field are described.


Differential vulnerability of substantia nigra and corpus striatum to oxidative insult induced by reduced dietary levels of essential fatty acids.
Oxidative stress (OS) has been implicated in the etiology of certain neurodegenerative disorders. Some of these disorders have been associated with unbalanced levels of essential fatty acids (EFA). The response of certain brain regions to OS, however, is not uniform and a selective vulnerability or resilience can occur. In our previous study on rat brains, we observed that a two-generation EFA dietary restriction reduced the number and size of dopaminergic neurons in the substantia nigra (SN) rostro-dorso-medial. To understand whether OS contributes to this effect, we assessed the status of lipid peroxidation (LP) and anti-oxidant markers in both SN and corpus striatum (CS) of rats submitted to this dietary treatment for one (F1) or two (F2) generations. Wistar rats were raised from conception on control or experimental diets containing adequate or reduced levels of linoleic and α-linolenic fatty acids, respectively. LP was measured using the thiobarbituric acid reaction method (TBARS) and the total superoxide dismutase (t-SOD) and catalase (CAT) enzymatic activities were assessed. The experimental diet significantly reduced the docosahexaenoic acid (DHA) levels of SN phospholipids in the F1 (~28%) and F2 (~50%) groups. In F1 adult animals of the experimental group there was no LP in both SN and CS. Consistently, there was a significant increase in the t-SOD activity (p < 0.01) in both regions. In EF2 young animals, degeneration in dopaminergic and non-dopaminergic neurons and a significant increase in LP (p < 0.01) and decrease in the CAT activity (p < 0.001) were detected in the SN, while no inter-group difference was found for these parameters in the CS. Conversely, a significant increase in t-SOD activity (p < 0.05) was detected in the CS of the experimental group compared to the control. The results show that unbalanced EFA dietary levels reduce the redox balance in the SN and reveal mechanisms of resilience in the CS under this stressful condition.


Reteplase: Structure, Function, and Production.
Thrombolytic drugs activate plasminogen which creates a cleaved form called plasmin, a proteolytic enzyme that breaks the crosslinks between fibrin molecules. The crosslinks create blood clots, so reteplase dissolves blood clots. Tissue plasminogen activator (tPA) is a well-known thrombolytic drug and is fibrin specific. Reteplase is a modified nonglycosylated recombinant form of tPA used to dissolve intracoronary emboli, lysis of acute pulmonary emboli, and handling of myocardial infarction. This protein contains kringle-2 and serine protease domains. The lack of glycosylation means that a prokaryotic system can be used to express reteplase. Therefore, the production of reteplase is more affordable than that of tPA. Different methods have been proposed to improve the production of reteplase. This article reviews the structure and function of reteplase as well as the methods used to produce it.


Post-operative refractory cystoid macular edema in a vitrectomized eye treated with slow-release dexamethasone implant (Ozurdex).
The use of a slow-release dexamethasone implant (Ozurdex) for the treatment of post-operative macular edema (ME) in a vitrectomized eye has never been used before. We herein report a case of a 70-year-old woman with post-vitrectomy ME refractory to topical, sub-tenon's and intravitreal steroid administration that responded well to the implantation of a slow-release dexamethasone implant (Ozurdex) in a previously vitrectomized eye. Interventional case presentation. One week post-implantation, the central retinal thickness was reduced to 383 μm from 640 μm and the best corrected visual acuity (BCVA) improved to 6/36 from counting fingers (CF). At six months' follow-up visit, the improvement of the ME was sustained as indicated by the optical coherence tomography (OCT) measurements and the BCVA remained stable. No serious topical or systemic adverse events were observed from the implantation of Ozurdex in the vitrectomized eye. The use of Ozurdex in our case resulted in rapid improvement of the post-operative resistant ME. To the best of our knowledge, this is the first report in the literature demonstrating the use of the slow-release dexamethasone implant (Ozurdex) to treat post-operative ME in a vitrectomized eye.


Study of microfiltration behaviour of oily wastewater.
Crossflow microfiltration experiments were carried out with oily wastewater using alpha-Al(2)O(3) membranes with 0.05 microm pore size. The influence of parameters such as transmembrane pressure (TMP), crossflow velocity (CFV), oil concentration, pH and salt concentration on the microfiltration behaviors were studied based on the measurements of permeate flux, total organic carbon (TOC) removal efficiency, and size and zeta potential of the emulsion droplets. The results showed that there were different degrees of effect on the membrane separation performance by these parameters. The TOC removal efficiencies higher than 92.4% were achieved under all experimental conditions. A non-steady model of accumulation volume of permeation was developed. It was found that the calculated values were in good agreement with the experimental results. Sensitivity analysis was also conducted to identify the degree of influence of the parameters on the accumulation volume of permeation. The results indicated that the accumulation volume of permeation was significantly affected by the TMP.


Chiasmal high signal on magnetic resonance imaging in the atrophic phase of leber hereditary optic neuropathy.
A 30-year-old man with Leber hereditary optic neuropathy mutation 11778 displayed no magnetic resonance imaging abnormalities during the acute phase of visual loss in the right eye. Three months later, during the acute phase of visual loss in the left eye, magnetic resonance imaging showed T2 hyperintense signal changes on the right half of the optic chiasm. Six months later, magnetic resonance imaging revealed T2 hyperintense signal changes on both sides of the optic chiasm. This is the first reported case of optic chiasmal involvement on magnetic resonance imaging in the atrophic phase of Leber hereditary optic neuropathy.


Arthroscopic Repair in Tibial Spine Avulsion Fractures Using Polyethylene Terephthalate Suture: Good to Excellent Results in Pediatric Patients.
The objective of the arthroscopic treatment in tibial spine avulsion fractures (TSAF) is to achieve firm reduction and strong internal fixation while still having the patient undergo a minimally invasive procedure. The study was performed on 12 young patients with avulsion fracture of the anterior tibial spine. All 12 patients had type 3 Modified Meyers and McKeever fractures. The injury mechanism was direct anterior to posterior trauma in full leg length hyperextension with sport trauma reported in all cases. The physical examination revealed decreased range of motion, extension deficit, and pain during walking. Radiology, MRI, and CT pathologic findings described complete fracture of the anterior tibial spine with no clear signs of callus formation at the time of examination. All patients underwent arthroscopic suture surgical treatment. The Tegner, the Lysholm, and the International Knee Documentation Committee (IKDC) scores were used to evaluate subjective outcomes at three and six months after the surgery. Radiographs were used to assess callus formation and healing status of the fracture. The mean IKDC score was 33.4 ± 23.3 (p = 0.032) preoperatively and 84.2 ± 14.3 at final follow-up (p = 0.0032, CI = 95%). The mean Tegner score improved from 3.8 ± 1.1 pre-operatively to 6.7 ± 2.2 at six months follow-up (p = 0.0231, CI = 95%). The Lysholm score differed significantly at baseline compared to final follow-up (53.7 ± 17.3 vs. 87.7 ± 9.9; p = 0.0066, CI = 95%). In all cases (n = 12), the radiographs taken after six months revealed the healing of the fracture in the anatomic position without secondary displacement. No functional knee instability was detected at the end of the study. The study provides preliminary promising results regarding fracture healing, knee stability, and functional subjective scores. Patient selection was a major factor of success prediction for this technique.


Activation of bronchopulmonary vagal afferent nerves with bradykinin, acid and vanilloid receptor agonists in wild-type and TRPV1-/- mice.
The vanilloid receptor TRPV1 (formerly VR1) has been implicated in the activation of nociceptive sensory nerves by capsaicin, noxious heat, protons, bradykinin, cannabinoids such as anandamide, and certain metabolites of arachidonic acid. Using TRPV1 knockout mouse (TRPV1-/-) we address the question of whether TRPV1 is obligatory for action potential discharge in vagal C-fibre terminals evoked by capsaicin, anandamide, acid and bradykinin. The response of a defined subtype of the vagal afferent bronchopulmonary C-fibres (conduction velocity < 0.7 ms(-1)) to the putative TRPV1 activators was studied in vitro in the mouse isolated/perfused lung-nerve preparation. Capsaicin (1 microm) evoked action potential discharge of approximately 90% (28/31) of C-fibres in the TRPV1+/+ mice, but failed to activate bronchopulmonary C-fibres in TRPV1-/- animals (n = 10). Anandamide (3-100 microm) induced concentration-dependent activation of capsaicin-sensitive TRPV1+/+ C-fibres with a threshold of 3-10 microm, but failed to evoke substantive discharge in TRPV1-/- C-fibres. In the TRPV1+/+ mice, the B2 receptor-mediated activation by bradykinin (1 microm) was restricted to the capsaicin-sensitive C-fibres. Bradykinin was effective in evoking B2 receptor-mediated action potential discharge in TRPV1-/- C-fibres, but the response was significantly (P < 0.05) less persistent than in TRPV1+/+ C-fibres. Exposing the tissue to acid (pH = 5) excited both TRPV1+/+ and TRPV1-/- C-fibres. We conclude that TRPV1 is obligatory for vagal C-fibre activation by capsaicin and anandamide. By contrast, whereas TRPV1 may have a modulatory role in bradykinin and acid-induced activation of bronchopulmonary C-fibres, it is not required for action potential discharge evoked by these stimuli.