Cobra cardiotoxin-induced cell death in fetal rat cardiomyocytes and cortical neurons: different pathway but similar cell surface target.
Cobra cardiotoxins (CTXs) are basic polypeptides with diverse pharmacological functions that are cytotoxic to many different cell types through both necrotic and apoptotic cell death pathways. In this comparative study of the action of CTX A3 from the Taiwan cobra (Naja atra) on fetal rat cardiomyocytes and cortical neurons, it was shown that CTX A3 induced different patterns of elevation of intracellular Ca2+ concentration ([Ca2+]i), CTX internalization, caspase-3 activity and viability. Application of an anti-sulfatide monoclonal antibody, O4 specific for 3-sulfo-galactose lipid, but not in the control experiments using anti-GM3 monoclonal antibody, reduces CTX-induced [Ca2+]i elevation, CTX internalization and toxicity. Therefore, CTX may target similar sulfo-containing cell surface receptors in both fetal rat cardiomyocytes and cortical neurons, but induce cell death through different pathways specific to each cell type.


Catecholaminergic System of Invertebrates: Comparative and Evolutionary Aspects in Comparison With the Octopaminergic System.
In this review we examined the catecholaminergic system of invertebrates, starting from protists and getting to chordates. Different techniques used by numerous researchers revealed, in most examined phyla, the presence of catecholamines dopamine, noradrenaline, and adrenaline or of the enzymes involved in their synthesis. The catecholamines are generally linked to the nervous system and they can act as neurotransmitters, neuromodulators, and hormones; moreover they play a very important role as regards the response to a large number of stress situations. Nevertheless, in some invertebrate phyla belonging to Protostoma, the monoamine octopamine is the main biogenic amine. The presence of catecholamines in some protists suggests a role as intracellular or interorganismal signaling molecules and an ancient origin of their synthetic pathways. The catecholamines appear also involved in the regulation of bioluminescence and in the control of larval development and metamorphosis in some marine invertebrate phyla.


The influence of body position on autonomic nervous system function.
Five physiological measurements were recorded while 20 males Ss listened to a series of tones in two body positions (horizontal and vertical). Half the Ss were tested in the horizontal position, then raised to a vertical position. The other half were tested vertically first. The results showed body position significantly influenced basal levels for heart rate (HR), finger volume (FV), skin resistance (SR) and blood pressure (BP). In the vertical position, sympathetic arousal was higher than in the horizontal position. In addition, the sequence in which a S was tested influenced physiological activity in the two body positions. It was concluded that both resting levels and pretest activity levels are important variables to consider in research on physiological differences in psychiatric populations.


Distribution of the Brief Male Sexual Inventory in community men.
The objectives of the study were to characterize male sexual functioning as related to age in community-dwelling older men. In 1989, a random sample of men aged 40-79 y (n=2115) without prior prostate surgery, prostate cancer, or other conditions known to affect voiding function (except benign prostatic hyperplasia) was invited (55% agreed) to participate in the Olmsted County Study of Urinary Symptoms and Health Status Among Men. In 1996, a previously validated male sexual function questionnaire was administered to the cohort. The questionnaire has 11 questions measuring sexual drive (two questions); erectile function (three) and ejaculatory function (two), as well as assessing problems with sex drive, erections, or ejaculation (three); and overall satisfaction with sex life (one). Each question is scored on a scale of 0-4, with higher scores indicating better functioning. Cross-sectional age-specific means (+/-s.d.) for drive, erections, ejaculation, problems, and overall satisfaction declined from 5.2 (+/-1.5), 9.8 (+/-2.5), 7.4 (+/-1.4), 10.7 (+/-2.2), and 2.6 (+/-1.0), respectively, for men in their 40s to 2.4 (+/-1.6), 3.3 (+/-3.4), 3.6 (+/-3.2), 7.7 (+/-3.8), and 2.1 (+/-1.2) for men 70 y and older (all P<0.001). The cross-sectional decline in function with age was not constant, with age-related patterns differing by domain. The percentage of men reporting erections firm enough to have intercourse in the past 30 days declined from 97% (454/468) among those in their 40s to 51% (180/354) among those in their 80s (P&<0.001). In age-adjusted analyses, men reporting regular sexual partners had statistically significantly higher levels of sex drive, erectile function, ejaculatory function, and overall satisfaction than those who did not report regular sexual partners. Sexual drive, erectile functioning, ejaculatory functioning, and overall sexual satisfaction in men show somewhat differing cross-sectional patterns of decline with advancing age. Active sexual functioning is maintained well into the 80s in a substantial minority of community-dwelling men.


Antimicrobial effect of resveratrol on dermatophytes and bacterial pathogens of the skin.
The phytoalexin resveratrol is commonly found in food and drinks, including red wine, grapes, and peanuts. Many studies have shown that this compound has anti-inflammatory properties, and it has been ascribed as having health benefits that help to prevent cancer and coronary heart disease. A treatment that combines antimicrobial and anti-inflammatory actions may be desirable for alleviating many skin conditions that range in severity. Therefore, we evaluated the antimicrobial activity of resveratrol against bacteria and dermatophytes that are major etiologic agents of human skin infections. Using the broth microdilution protocol of the National Committee for Clinical Laboratory Standards (NCCLS) M7-A5, growth of the bacterial species Staphylococcus aureus, Enterococcus faecalis, and Pseudomonas aeruginosa was inhibited at 171-342 microg/mL of resveratrol in the solvent dimethyl sulfoxide. Using the NCCLS protocol M38-P, activity against the fungal species Trichophyton mentagrophytes, Trichophyton tonsurans, Trichophyton rubrum, Epidermophyton floccosum, and Microsporum gypseum was also tested. The growth of dermatophytes was inhibited at 25-50 microg/mL of resveratrol. Thus, this study indicates a novel application for resveratrol, a molecule of plant defense, to combat human fungal pathogens. Resveratrol and its analogs may have wide application to skin conditions that afflict a significant portion of our population, and may also have promising clinical potentials in diabetic wounds.


Medulloblastoma and primitive neuroectodermal tumors.
Medulloblastomas and sPNETs remain highly problematic tumors to treat. Prognosis has improved over the past two decades, but many children who survive treatment have significant long-term sequelae. The improvements in outcome have been due to advances in surgical techniques, the wider use of chemotherapy, and the more judicious use of radiotherapy. For further improvements,the recent impressive discoveries concerning molecular mechanisms of embryonal tumor origin, development,and growth will need to be translated into molecularly based, risk-adapted therapy.


Effect of pulse dose cyclophosphamide on the anamnestic immune response in NZB/W mice.
Mice exhibiting a spontaneous SLE-like lethal autoimmunity (female NZB/W hybrids) were given monthly doses of cyclophosphamide (CPA) 240 mg/kg p.o. starting at four months of age. Antibodies to DNA and sheep red blood cells (SRBC) were measured as well as general well being of the mice. The CPA-treated group demonstrated a marked increased in survival compared to the untreated controls with reduction of anti-DNA antibody levels but only a slight inhibition of the anamnestic response to SRBC immunization.


Saturated and monounsaturated fatty acids in membranes are determined by the gene expression of their metabolizing enzymes SCD1 and ELOVL6 regulated by the intake of dietary fat.
We investigated the effect of dietary fats on the incorporation of saturated (SAFAs) and monounsaturated dietary fatty acids (MUFAs) into plasma phospholipids and the regulation of the expression of lipid-metabolizing enzymes in the liver. Mice were fed different diets containing commonly used dietary fats/oils (coconut fat, margarine, fish oil, sunflower oil, or olive oil) for 4 weeks (n = 6 per diet group). In a second experiment, mice (n = 6 per group) were treated for 7 days with synthetic ligands to activate specific nuclear hormone receptors (NHRs) and the hepatic gene expression of CYP26A1 was investigated. Hepatic gene expression of stearoyl-coenzyme A desaturase 1 (SCD1), elongase 6 (ELOVL6), and CYP26A1 was examined using quantitative real-time PCR (QRT-PCR). Fatty acid composition in mouse plasma phospholipids was analyzed by gas chromatography (GC). We found significantly reduced hepatic gene expression of SCD1 and ELOVL6 after the fish oil diet compared with the other diets. This resulted in reduced enzyme-specific fatty acid ratios, e.g., 18:1n9/18:0 for SCD1 and 18:0/16:0 and 18:1n7/16:1n7 for ELOVL6 in plasma phospholipids. Furthermore, CYP26A1 a retinoic acid receptor-specific target was revealed as a new player mediating the suppressive effect of fish oil-supplemented diet on SCD1 and ELOVL6 hepatic gene expression. Plasma levels of MUFAs and SAFAs strongly reflect an altered hepatic fatty acid-metabolizing enzyme expression after supplementation with different dietary fats/oils.


Relationship between RNA synthesis and the Ca2+-filled state of the nuclear envelope store.
RNA synthesis and ATP-dependent (45)Ca(2+) uptake were measured simultaneously in isolated nuclear fraction of rat liver nuclei. Maximal level of RNA synthesis was obtained under ATP-dependent (45)Ca(2+)-uptake conditions (1 microM free [Ca(2+)] and 1 mM ATP in the bathing solution). This experimental condition was defined as "stimulated nuclei" condition. ATP-dependent (45)Ca(2+) uptake was inhibited using different strategies including: (a) eliminating Ca(2+) (1 mM EGTA); (b) lowering the ATP concentration; (c) modifying nuclear envelope membranes Ca(2+) permeability (Ca(2+) ionophores); or (d) inhibiting the nuclear Ca(2+) pump (thapsigargin and 3',3'',5',5''-tetraiodophenolsulfonephthalein). Under all the above conditions, RNA synthesis was lower than in "stimulated nuclei" condition. In the presence of ionomycin, RNA synthesis was significantly higher at 500 nM free [Ca(2+)], as compared with RNA synthesis in a Ca(2+)-free medium or at 1muM free [Ca(2+)]. However, even in such condition (500 nM free [Ca(2+)]), RNA synthesis was lower than RNA synthesis obtained in "stimulated nuclei" condition. We suggest two components for the effect of Ca(2+) on RNA synthesis: (A) a direct effect of nucleoplasmic [Ca(2+)]; and (B) an effect dependent on the accumulation of Ca(2+) in the nuclear envelope store mediated by the SERCA nuclear Ca(2+) pump.


Sex difference in appropriate shocks but not mortality during long-term follow-up in patients with implantable cardioverter-defibrillators.
Implantable cardioverter-defibrillators (ICDs) have been shown to improve survival, although a considerable number of patients never receive therapy. Implantable cardioverter-defibrillators are routinely implanted regardless of sex. There is continuing controversy whether major outcomes differ between men and women. In this retrospective single-centre study, 1151 consecutive patients (19% women) undergoing ICD implantation between 1998 and 2010 were followed for mortality and first appropriate ICD shock over 4.9 ± 2.7 years. Sex-related differences were investigated using multivariable Cox models adjusting for potential confounders. During follow-up, 318 patients died, a rate of 5.9% per year among men and 4.6% among women (uncorrected P = 0.08); 266 patients received a first appropriate ICD shock (6.3% per year among men vs. 3.6% among women, P = 0.002). After multivariate correction, independent predictors of all-cause mortality were age (hazard ratio, HR = 1.04 per year of age, 95% confidence interval (CI) [1.03-1.06], P < 0.001), left ventricular ejection fraction (HR = 0.98 per %, 95% CI [0.97-1.00], P = 0.025), renal function (HR = 0.99 per mL/min/1.73 m(2), 95% CI [0.99-1.00], P = 0.009), use of diuretics (HR = 1.81, 95% CI [1.29-2.54], P = 0.0023), peripheral arterial disease (HR = 2.21, 95% CI [1.62-3.00], P < 0.001), and chronic obstructive pulmonary disease (HR = 1.48, 95% CI [1.13-1.94], P = 0.029), but not sex. Female sex (HR = 0.51, 95% CI [0.33-0.81], P = 0.013), older age (HR = 0.98, 95% CI [0.97-0.99], P < 0.001), and primary prophylactic ICD indication (HR = 0.69, 95% CI [0.52-0.93], P = 0.043) were independent predictors for less appropriate shocks. Women receive 50% less appropriate shocks than men having similar mortality in this large single-centre population. These data may pertain to individually improved selection of defibrillator candidates using risk factors, e.g. sex as demonstrated in this study.


Taming PRRSV: revisiting the control strategies and vaccine design.
Porcine reproductive and respiratory syndrome virus (PRRSV) continues to be a threat, causing economically significant impacts on the swine industry worldwide. In this article, we share the information related to the Thai PRRSV and review the available options for PRRS control strategies. Unfortunately, the traditional control strategies and conventional vaccines fail to provide sustainable disease control, as they suffer from both antigenic heterogeneity and various immune evasion strategies of PRRSV. Induction of interleukin (IL)-10 following PRRSV infection is believed to be a focal mechanism leading to the unique immunological outcomes and interference of PRRS vaccine efficacy. It is likely that the nucleocapsid protein plays an important role in induction of IL-10 following PRRSV infection. We propose that removal or reduction of the PRRSV-induced, negative immunomodulatory effects especially during the first 2 weeks following infection is essential to establish proper anti-PRRSV immunity. In other word, incorporation of the "taming strategy" will be needed to reduce PRRSV-induced immunomodulatory effects, and to ensure maximal vaccine-induced immunity in the face of viral exposure. Any PRRSV vaccine that can induce cross-protective immunity and simultaneously eliminate the immunoinhibitory effects of PRRSV would be ideal. In addition, tracking of the inhibitory parameters, following the PRRSV challenge should be included in the vaccine testing protocol. Therefore, the future of PRRSV vaccine development relies tremendously on the basic knowledge of host-virus interactions and the communication between the basic and clinical PRRSV research fields.


Associations between use of electric cow-trainers and clinical diseases, reproductive performance and culling in Swedish dairy cattle.
The aims of this follow-up study were: (a) to evaluate the role of ECT technology as a risk factor for several diseases; and (b) to determine if the effects of these diseases on cows' reproductive performance and as risk factors for culling are influenced by exposure to ECTs. Diseases considered were retained placenta, metritis, ketosis, cystic ovaries, silent heat, milk fever, clinical mastitis, and foot and leg problems. We used historical and contemporary controls (with control herds selected to match the experimental herds for size and location). Data consisted of 10,264 Swedish Red and White (SRB) and 5461 Swedish Friesian (SLB) lactation records in 150 herds of which 33 used cow-trainers. Logistic regression was used to estimate the effects of parity and exposure to electric cow-trainers on the risks of diseases and the effects of diseases and exposure to electric cow-trainers on risk of culling. The least-squares procedure was used to estimate the effects of diseases on reproductive performance. The dominant effects associated with use of electric cow-trainers were an increased risk for silent heat, clinical mastitis, ketosis and culling relative to cows in herds not using cow-trainers. Diseases had negative effects on reproductive performance and the effects were larger for cows in herds using cow-trainers. In herds using electric cow-trainers, the largest increase in the interval from first service to conception (58 days) was caused by the occurrences of silent heat, cystic ovaries and the combination of two or more diseases. Retained placenta, metritis, cystic ovaries, clinical mastitis and a combination of two or more diseases increased the risk of culling about two times relative to healthy primiparous cows with the increase being greater for cows in herds using cow-trainers. Silent heat did not increase risk of culling in control groups, but was the largest risk factor for culling in the exposed group. We concluded that exposure to electric cow-trainers increased the incidence risk of silent heat, clinical mastitis, and ketosis and changed silent heat from a neutral disease with respect to culling to a major risk factor. Finally, exposure to cow-trainers increased the general negative effect of diseases on the cows' reproductive performance and risk for culling.


Implemented indoor airborne transmission mitigation strategies during COVID-19: a systematic review.
The COVID-19 pandemic has inflicted major economic and health burdens across the world. On the other hand, the potential airborne transmission of SARS-COV-2 via air can deeply undermine the effectiveness of countermeasures against spreading the disease. Therefore, there is an intense focus to look for ways to mitigate the COVID-19 spread within various indoor settings. This work systematically reviewed articles regarding airborne transmission of SARS-COV2 in various indoor settings since the onset of the pandemic. The systematic search was performed in Scopus, Web of Science, and PubMed databases and has returned 19 original articles carefully screened with regard to inclusion and exclusion criteria. The results showed that the facilities, such as dormitories and classrooms, received the most attention followed by office buildings, healthcare facilities, residential buildings, and other potential enclosed spaces such as a metro wagon. Besides, the majority of the studies were conducted experimentally while other studies were done using computer simulations. United States (n = 5), Spain (n = 4) and China (n = 3) were the top three countries based on the number of performed research. Ventilation rate was the most influential parameter in controlling the infection spread. CO2 was the primary reference for viral spread in the buildings. The use of natural ventilation or a combination of mechanical and natural ventilations was found to be highly effective in the studies. The current work helps in furthering research on effective interventions to improve indoor air quality and control the spread of COVID-19 and other respiratory diseases. The online version contains supplementary material available at 10.1007/s40201-023-00847-0.


The effect of 5-hydroxytryptamine and epinephrine on newborn platelets.
Blood levels of 5-hydroxytryptamine (5-HT) and epinephrine are increased in conditions such as severe hypoxia, and hypovolemic or septic shock. The effect of these agents, which influence the blood coagulation system, were studied in vitro on platelets from newborns. 5-HT was determined in platelets from 18 newborns and 28 adults. The 5-HT content was 0.305 +/- 0.144 microgram/10(9) platelets in newborns and 0.675 +/- 0.212 microgram/10(9) platelets in the adult controls, a difference which is statistically significant (P less than 0.001). The 5-HT content of newborn platelets proved to be higher than that reported in the literature. Further studies on platelet aggregation due to 5-HT and epinephrine were then carried out. These demonstrated first-phase aggregation in 40% of cases when both 5-HT and epinephrine were applied simultaneously, while in the majority of the newborns no reaction was encountered when each of these substances was applied separately. However, in 2 cases, simultaneous application of 5-HT and epinephrine produced both first- and second-phase platelet aggregation. The reduced response of the platelets in the newborn to these aggregating agents can be considered as a protection against disseminated intravascular coagulation (DIC), particularly in high-risk situations.


[The heart-hand syndrome. A new variant of disorders of heart conduction and syndactylia including osseous changes in hands and feet].
A male infant was born at the 36th week of gestation by cesarean section because of an intrauterine bradycardy. There was a 2nd degree a. v.-bloc postnatal. The heart rate was normal after the 5th day of life with a QT-interval of 150 percent resp. 120 percent after the 15th day. Additionally there were syndactylies of hands and feet. The infant suddenly died at the age of 5 months. Examination of the parents revealed a QT-interval of 115 percent as well as synostoses of the carpus in the father. These microsymptoms are very important for genetic counseling of the family. There is a recurrence risk of 50 percent for further children because a dominant trait is to be suggested.


A time-course study of immune response in Japanese flounder Paralichthys olivaceus exposed to heavy oil.
The immunotoxicities of oil and its components on fish immunities have been investigated, but there is little literature on the recovery of the fish from the immune suppression. Therefore, the recovery of Japanese flounder Paralichthys olivaceus from an immunosuppressive effect due to heavy oil (HO) exposure was investigated in this study. Fish were exposed to HO at a concentration of 0.385 g/L for 2 days, while control fish received no exposure. Seven fish were sampled at 0, 3, 7, and 14 days post-exposure. The respiratory rate was measured everyday as an indicator of the acute effect of HO exposure. Fish serum was collected and used for antibacterial activity assay against Edwardsiella tarda. Expression changes of respiratory and immune-related genes were evaluated by real-time PCR. The respiratory rate was significantly increased in the HO-exposed group until 4 days post-exposure. A respiratory-related gene, β-hemoglobin, was also significantly downregulated in the spleen both at 0 and 7 days post-exposure and kidney at 3 days post-exposure in HO-exposed fish. Immunotoxicity, including suppression of antibacterial activities and downregulation of the IgM gene, was observed in HO-exposed fish until 3 days post-exposure, but not after that time. From these results, we conclude that the fish likely return to normal status around 1 week.


Diagnosis of female bladder outlet obstruction and relevance of the parameter area under the curve of detrusor pressure during voiding: preliminary results.
The diagnosis of bladder outlet obstruction in women by pressure flow study may be difficult because there are several definitions of bladder outlet obstruction, several parameters and no standard cutoffs. We evaluated the ability of pressure flow studies to separate women into unobstructed, equivocal and obstructed groups. In a prospective study 85 women with lower urinary tract symptoms underwent clinical evaluation, including physical examination, voiding cystourethrography, endoscopy, flow rate and post-void residual volume measurement. A pressure flow study was performed 15 days later. The pressure flow study parameters were maximum flow, post-void residual volume, detrusor pressure at maximum flow, vesical pressure at maximum flow, area under the curve of detrusor pressure during voiding and area under the curve of detrusor pressure during voiding adjusted for voided volume. After considering the clinical evaluation 2 urologists classified the patients into 3 groups, namely unobstructed, equivocal and obstructed, as the traditional classification. Linear discriminant analysis was then performed using the traditional classification and pressure flow study data. Mean patient age was 55 years (range 18 to 83). According to the traditional classification there were 36 unobstructed, 28 equivocal and 21 obstructed cases. Significant differences were noted in all pressure flow study parameters (analysis of variance p <0.05). Linear discriminant analysis showed that area under the curve of detrusor pressure during voiding adjusted for voided volume was the most statistically discriminating parameter. Of the cases 86%, 36% and 57% were identically categorized by the traditional and area under the curve of detrusor pressure during voiding adjusted for voided volume parameter classifications in the unobstructed, equivocal and obstructed groups, respectively. The other pressure flow study parameters showed less satisfactory results. Area under the curve of detrusor pressure during voiding adjusted for voided volume appears to be the most discriminating urodynamic parameter of female bladder outlet obstruction. Other studies are needed to test the reliability and validity of this new parameter.


Enhancing pharmacy personnel immunization-related confidence, perceived barriers, and perceived influence: The We Immunize program.
Pharmacy personnel need practical strategies to incorporate nonseasonal vaccination services into pharmacy workflow. The objective of this study was to evaluate participants' confidence, perceived barriers and facilitators, and perceived influence on decision-making related to immunization services before and after the We Immunize program to assess program effectiveness. Randomized controlled trial. A total of 62 pharmacist-technician pairs from community pharmacies in Alabama and California participated in the randomized controlled trial. All participants were offered a 1-hour live immunization update. Intervention participants were also offered a 2-hour enhanced training at the beginning of the study period and tailored monthly feedback for 6 months. A survey was administered at baseline and after the intervention. Likert-type scales were used to rank level of agreement and differences were analyzed using paired-sample t tests and 2-way mixed analysis of variance. Sixty-seven participants completed both baseline and postintervention surveys (37 intervention; 30 control). Within the intervention group, participants' confidence in determining pneumococcal vaccine appropriateness (P = 0.027), confidence in pneumococcal vaccine-related patient interactions (P = 0.041), perceived external support (P = 0.016), and perceived influence on immunization services (P < 0.001) significantly improved. No change was observed within the control group. Compared to control participants, intervention participants showed a greater degree of change in perceived external support (P = 0.023) and influence on immunization services (P = 0.005) from baseline to post intervention. Neither confidence related to the herpes zoster vaccine nor marketing activities improved over the study period in either the intervention or control groups. Immunization training, including educational interventions and tailored feedback, can be used to positively impact pharmacy personnel's confidence in providing pneumococcal vaccinations and perceptions related to environmental support and influence on immunization services. This, in turn, may increase immunization activities within community settings.


Self-assembling amphiphilic peptides.
The self-assembly of several classes of amphiphilic peptides is reviewed, and selected applications are discussed. We discuss recent work on the self-assembly of lipopeptides, surfactant-like peptides and amyloid peptides derived from the amyloid-β peptide. The influence of environmental variables such as pH and temperature on aggregate nanostructure is discussed. Enzyme-induced remodelling due to peptide cleavage and nanostructure control through photocleavage or photo-cross-linking are also considered. Lastly, selected applications of amphiphilic peptides in biomedicine and materials science are outlined.


Matrix Metalloproteinase-9 in the Culprit Coronary Artery and Myocardial No-Reflow.
Matrix Metalloproteinases (MMPs) have been implicated in the pathogenesis of acute myocardial infarction (AMI). However, little is known about the association between MMP-9 and myocardial no-reflow. The aim of this study was to evaluate the role of MMP-9 in the culprit coronary artery as a predictor of no-reflow in patients with ST-elevation AMI. Ninety patients with ST-elevation AMI who underwent emergency percutaneous coronary intervention were consecutively recruited in this study. Blood samples were obtained from the extraction catheter placed distal to the culprit lesion at the beginning of percutaneous coronary intervention. No-reflow was defined as a coronary thrombolysis in myocardial infarction flow grade ≤2 after vessel reopening or thrombolysis in myocardial infarction flow 3 with a final myocardial blush grade ≤2. No-reflow was observed in 25 patients (27.8%). Using multiple logistic regression analysis, local MMP-9 levels (odds ratio [OR] = 3.356; confidence interval [CI]: 1.441-5.881; P = 0.007) were found to be a significant risk factor of no-reflow together with lesion length (OR = 6.985; CI: 2.574-11.533; P = 0.009) and time to balloon (OR = 2.143; CI: 1.216-5.901; P = 0.042). Elevation of MMP-9 level in the culprit coronary artery may predict no-reflow in patients with ST-elevation AMI.


Interrogation of electrocatalytic water oxidation mediated by a cobalt complex.
Examination of the aqueous electrochemistry of a Co(II) complex bearing a pentadentate ligand suggests that the catalytic current corresponding to water oxidation is molecular in origin, and does not emanate exclusively from Co-oxide phases formed in situ.


Micronutrient status during pregnancy is associated with child immune status in rural Bangladesh.
Poor immune function increases children's risk of infection and mortality. Several maternal factors during pregnancy may affect infant immune function during the postnatal period. We aimed to evaluate whether maternal micronutrients, stress, estriol, and immune status during the first or second trimester of pregnancy were associated with child immune status in the first two years after birth. We conducted observational analyses within the water, sanitation, and hygiene (WASH) Benefits Bangladesh randomized controlled trial. We measured biomarkers in 575 pregnant women and postnatally in their children. Maternal biomarkers measured during the first and second trimester of pregnancy included nutrition status via vitamin D (25-hydroxy-D [25(OH)D]), ferritin, soluble transferrin receptor (sTfR), and retinol-binding protein (RBP); cortisol; estriol. Immune markers were assessed in pregnant women at enrollment and their children at ages 14 and 28 mo, including C-reactive protein (CRP), alpha-1-acid glycoprotein (AGP), and 13 cytokines (including IFN-γ). We generated a standardized sum score of log-transformed cytokines. We analyzed IFN-γ individually because it is a critical immunoregulatory cytokine. All outcomes were prespecified. We used generalized additive models and reported the mean difference and 95% confidence intervals at the 25th and 75th percentiles of exposure distribution. At child age 14 mo, concentrations of maternal RBP were inversely associated with the cytokine sum score in children (-0.34 adjusted difference between the 25th and 75th percentile [95% confidence interval -0.61, -0.07]), and maternal vitamin A deficiency was positively associated with the cytokine sum score in children (1.02 [0.13, 1.91]). At child age of 28 mo, maternal RBP was positively associated with IFN-γ in children (0.07 [0.01, 0.14]), whereas maternal vitamin A deficiency was negatively associated with child AGP (-0.07 [-0.13, -0.02]). Maternal iron deficiency was associated with higher AGP concentrations in children at age 14 mo (0.13 [0.04, 0.23]), and maternal sTfR concentrations were positively associated with child CRP concentrations at age 28 mo (0.18 [0, 0.36]). Maternal deficiencies in vitamin A or iron during the first 2 trimesters of pregnancy may shape the trajectory of a child's immune status.


A Temporal PROTAC Cocktail-Mediated Sequential Degradation of AURKA Abrogates Acute Myeloid Leukemia Stem Cells.
AURKA is a potential kinase target in various malignancies. The kinase-independent oncogenic functions partially disclose the inadequate efficacy of the kinase inhibitor in a Phase III clinical trial. Simultaneously targeting the catalytic and noncatalytic functions of AURKA may be a feasible approach. Here, a set of AURKA proteolysis targeting chimeras (PROTACs) are developed. The CRBN-based dAurA383 preferentially degrades the highly abundant mitotic AURKA, while cIAP-based dAurA450 degrades the lowly abundant interphase AURKA in acute myeloid leukemia (AML) cells. The proteomic and transcriptomic analyses indicate that dAurA383 triggers the "mitotic cell cycle" and "stem cell" processes, while dAurA450 inhibits the "MYC/E2F targets" and "stem cell" processes. dAurA383 and dAurA450 are combined as a PROTAC cocktail. The cocktail effectively degrades AURKA, relieves the hook effect, and synergistically inhibits AML stem cells. Furthermore, the PROTAC cocktail induces AML regression in a xenograft mouse model and primary patient blasts. These findings establish the PROTAC cocktail as a promising spatial-temporal drug administration strategy to sequentially eliminate the multifaceted functions of oncoproteins, relieve the hook effect, and prevent cancer stem cell-mediated drug resistance.


Calcifying fibrous tumor of small intestine.
Calcifying fibrous tumor (CFT) is a rare benign tumor with a predilection for children and young adults that usually arises in the subcutaneous and deep soft tissues, pleura, or peritoneum. It presents histologically as a well-circumscribed mass consisting of hyalinized, hypocellular lamellar collagen, bland spindle cells, chronic inflammatory cell infiltrates, and psammomatous or dystrophic calcifications. Calcifying fibrous tumor of the gastrointestinal tract is exceedingly rare and therefore prone to confusion with other spindle cell lesions more commonly encountered in this location. We describe 4 cases of calcifying fibrous tumor arising in the terminal ileum, one of which caused the heretofore unreported complication of intestinal intussusception, and discuss the differential diagnosis with other common and uncommon spindle cell lesions.


Rax1, a protein required for the establishment of the bipolar budding pattern in yeast.
In Saccharomyces cerevisiae, cell type determines two distinct spatial budding patterns. Haploid cells exhibit an axial pattern, whereas diploid cells exhibit a bipolar pattern. Axl1, a member of the insulin-degrading enzyme (IDE) family, is the key morphological determinant for the haploid axial pattern. Here we identified a novel gene, RAX1, specifically required for the bipolar budding pattern. Loss of RAX1 alters the bipolar pattern of axl1 haploids resulting in reversion to the axial pattern, and also alters the bipolar patterns of bud3 and bud4 haploids. However, bud10 rax1 haploids exhibit a random budding pattern, suggesting Bud10 acts as the key proximal landmark in axial budding. Rax1 is required for the localization of Bud8, the distal bipolar budding landmark. Interestingly, Rax1 contains a C-terminal domain possessing some similarity to insulin-related peptides. Our results suggest that Rax1 is necessary for the establishment of the bipolar budding landmark.


Ca(2+)-channels and adrenoceptors in diabetic skeletal muscle.
The status of Ca(2+)-channels and adrenoceptors in the hind leg skeletal muscle was examined in rats 8 weeks after inducing diabetes by an intravenous injection of streptozotocin (65 mg/kg). Scatchard plot analysis of the data on specific binding of 3H-nitrendipine with crude membranes from diabetic muscle revealed an increase in the density of Ca(2+)-channels without any significant change in their affinity for the ligand. An increase in the density of beta-adrenoceptors without any alteration in their affinity, as measured by 3H-dihydroalprenolol binding, was also evident in the diabetic muscle. The observed increase in the number of Ca2+ channels or beta-adrenoceptors seems specific since no change in the alpha-adrenoceptor density or affinity, as measured by 3H-prazosin binding, was seen in the diabetic membranes. These results support the view that higher activities of Ca2+ transport systems or regulatory mechanisms may be associated with hyperfunction of the diabetic skeletal muscle.


Hsa_circ_0001550 impairs decidualization by regulating the proliferation and apoptosis of endometrial stromal cells.
What is the molecular function of hsa_circ_0001550 in decidualization? Human endometrial stromal cells (HESC) were isolated from the endometrium tissues to build an in-vitro decidualization model. Different concentrations of medroxyprogesterone acetate (MPA) were used to observe whether the expression level of hsa_circ_0001550 was related to progesterone. Biological characteristics and distribution of hsa_circ_0001550 were determined by RNase R, actinomycin D (Act D) assay and cytoplasmic/nuclear fraction assay. Then the overexpression of hsa_circ_0001550 was achieved by adenovirus vector. Cell proliferation was determined by Cell Counting Kit-8 (CCK-8) assays. The cell cycle was assessed by flow cytometry analyses. Cell apoptosis was determined by annexin-V/propidium iodide double staining experiment and western blotting. The expression of hsa_circ_0001550 was decreased in decidua and decidualized HESC (P < 0.001, P = 0.014). Hsa_circ_0001550 is a covalently closed RNA molecule that was verified by RNase R assay and Act D assay (P = 0.012). Nuclear and cytoplasmic separation experiments confirmed that hsa_circ_0001550 was mainly distributed in the cytoplasm. Overexpression of hsa_circ_0001550 inhibited decidualization of HESC (P < 0.0001). Furthermore, overexpression of hsa_circ_0001550 inhibited proliferation by decreasing the number of S phase cells (P = 0.033). Annexin-V/propidium iodide double staining experiment and western blotting revealed that overexpression of hsa_circ_0001550 promoted HESC apoptosis (P < 0.001, P = 0.0139). Hsa_circ_0001550 impairs decidualization of HESC. Progesterone decreases the expression of hsa_circ_0001550. The results may provide new insights into the cause of decidualization.


Oropharyngeal complications of suspension laryngoscopy: a prospective study.
This study was designed to evaluate the oropharyngeal complications of suspension laryngoscopy (SL). We prospectively analyzed 56 consecutive SLs for intervention-related complications. Oropharyngeal symptoms and physical examination abnormalities were recorded before and after SL. SL-related problems were graded in severity and followed over time (weekly) until resolution was achieved. All patients had SL with either a gallows suspension or a manual technique and not a rotation-oriented (fulcrum) laryngoscope holding device. Oropharyngeal minor complications after SL occurred at a rate of 37.5%, and all these were temporary. No dental injuries occurred in the study cohort. There were no major complications after SL. Minor alterations related to taste occurred in 18% of the patients, 16% of patients had subjective swallowing complaints, and 12.5% had partial tongue numbness. Average duration of the post-SL complaints was 11 (6-34) days. A correlation between duration of suspension, size of laryngoscope, and risk of developing a minor oropharyngeal complication was present. SL carries a higher risk for lingual and glossopharyngeal nerve injuries than previously recognized. All of these complications were temporary. On the basis of comparison with historic data, SL by gallows suspension technique may pose a lower risk of dental injuries. This information should be used to improve preoperative SL patient education and informed consent.


Personnel for the office surgical facility.
Ambulatory surgery in a private plastic surgery office is a practical and desirable reality. This can be achieved only in a properly staffed facility. A small number of employees are needed but each must be carefully selected for proper qualifications and attributes, appropriate training and skills necessary to execute the assigned duties, the correct attitude toward patient care, and a sense of responsibility to the surgeon. The facility must be appropriately built and job descriptions organized so as to achieve efficient and good patient care and high employee satisfaction. This common sense approach has proved effective in our experience and should serve the prospective office-based plastic surgeon well.


Phosphodiesterase 2 inhibitor Hcyb1 reverses corticosterone-induced neurotoxicity and depression-like behavior.
Currently available PDE2 inhibitors have poor brain penetration that limits their therapeutic utility in the treatment of depression. Hcyb1 is a novel selective PDE2 inhibitor that was introduced more lipophilic groups with polar functionality to the scaffold pyrazolopyrimidinone to improve the blood-brain barrier (BBB) penetration. Our previous study suggested that Hcyb1 increased the neuronal cell viability and exhibited antidepressant-like effects, which were parallel to the currently available PDE2 inhibitor Bay 60-7550. The present study investigated whether Hcyb1 protected HT-22 cells against corticosterone-induced neurotoxicity and produced antidepressant-like effects in behavioral tests in stressed mice. The neuroprotective effects of Hcyb1 against corticosterone-induced cell lesion were examined by cell viability (MTS) assay. The enzyme-linked immunosorbent assay (ELISA) and immunoblot analysis were used to determine the levels of cAMP or cGMP and expression of pCREB or BDNF, respectively, in the corticosterone-treated HT-22 cells. The antidepressant-like effects of Hcyb1 were determined in the tail suspension and novelty suppressed feeding tests in stressed mice. In the cell-based assay, Hcyb1 significantly increased cell viability of HT-22 cells against corticosterone-induced neurotoxicity in a time- and dose-dependent manner. Hcyb1 also rescued corticosterone-induced decreases in both cGMP and cAMP levels, pCREB/CREB and BDNF expression. These protective effects of Hcyb1 were prevented by pretreatment with either the PKA inhibitor H89 or the PKG inhibitor KT5823. Moreover, Hcyb1 reversed acute stress-induced increases in immobility time and the latency to feed in the tail suspension and novelty suppressed feeding tests, respectively, which were prevented by pretreatment with H89 or KT5823. These findings provide evidence that the neuroprotective effects of Hcyb1 are mediated by PDE2-dependent cAMP/cGMP signaling.


Screening chemical and physical stability of drug substances.
General multistep methods are described for the screening of the chemical and the physical stability and/or reactivity of new drug candidates. The chemical reactivity is studied in aqueous buffer solutions; the rate of degradation is measured as a function of pH. The products of the reaction mixture are evaluated at selected pH-values as a function of time and key reaction products are identified. Strategies for testing degradation products in stability studies are discussed. The purpose of the physical reactivity test is to obtain information on the existing solid-state form in relation to the thermodynamically stable form. A method for finding the stable form is described. When polymorphism is observed a search for additional polymorphs is performed and the different solid phases are characterized. Special tests are described for hydrates and anhydrous forms.


Plexin-B3 interacts with EB-family proteins through a conserved motif.
Plexins are transmembrane receptors that are highly expressed in the central nervous system. They participate in the patterning of neural connections and regulation of cell adhesion and motility in many cell types. The aim of this study was to characterize novel protein-protein interactions of plexin-B3 intracellular portion. To identify new interactors of plexin-B3 yeast two-hybrid screen was performed. We used GST pull-down and co-immunoprecipitation to verify those results. Deletion mutants were used to map the interacting regions. The physiological relevance of this interaction was assessed with neurite outgrowth assay in Neuro2A cell line. We show that the N-terminal segment of intracellular domain of plexin-B3 interacts with microtubule plus end-binding proteins EB1, EB2 and EB3. The corresponding region in human plexin-A2, B1 and B3 contains the conserved EB-binding motif SxIP and these plexins also associate with EBs indicating the specificity of plexin-EB binding. As to the EB proteins, their N-terminal microtubule-binding domain is dispensable for plexin interaction. Plexin-EB interaction is involved in neurite growth as the synthetic peptide corresponding to the EB-binding region of plexin-B1 increases significantly the number of neurite tips in Neuro2A cells. Microtubule end-binding proteins EB1, EB2 and EB3 interact with plexin-A2, B1 and B3 through a conserved EB-binding motif, which is located in their intracellular domain N-terminal segment. The observed interaction between plexin intracellular domain and EBs suggests a novel function for plexins in regulating EB-mediated changes in microtubule dynamics and neurite growth.


A Review of Sustainability Enhancements in the Beef Value Chain: State-of-the-Art and Recommendations for Future Improvements.
The beef sector is working towards continually improving its sustainability in order to achieve environmentally, socially and economically desirable outcomes, all of which are of increasing concern to consumers. In this context, the Global Roundtable for Sustainable Beef (GRSB) provides guidance to advance the sustainability of the beef industry, through increased stakeholder engagement and the formation of national roundtables. Recently, the 2nd Global Conference on Sustainable Beef took place in Banff, Alberta, Canada, hosted by the GRSB and the Canadian Roundtable for Sustainable Beef. Conference attendees discussed the various initiatives that are being developed to address aspects of beef sustainability. This paper reviews the main discussions that occurred during this event, along with the key lessons learned, messages, and strategies that were proposed to improve the sustainability of the global beef industry.


Catastrophic associations predict level of change in anxiety sensitivity in response to cognitive-behavioural treatment for panic.
The aim of the present study was to elucidate one of the factors that might be responsible for the maintenance of panic patients' harmful beliefs about anxiety. Specifically, it was hypothesized that harmful beliefs about anxiety, i.e. anxiety sensitivity, is maintained in panic patients by automatic activation of idiographic catastrophic cognitions. To test this prediction, panic patients participated in a one-session cognitive-behavioural treatment of 4-8h to reduce anxiety sensitivity. The strength of automatic catastrophic cognitions in response to idiographic anxiety symptoms, measured with a modified semantic priming task, as well as the strength of the consciously accessible catastrophic meaning of these symptoms were assessed before treatment. In accordance with the hypothesis, stronger automatic catastrophic cognitions predicted a smaller reduction of anxiety sensitivity independently of the strength of conscious catastrophic cognitions. Moreover, in a first exploration, the strength of catastrophic associations was also shown to have an incremental predictive value for change in anxiety sensitivity beyond that of a number of demographic, clinical, treatment and assessment variables. The theoretical and clinical implications are discussed.


Evidence of discontinuous transcription in the trypanosomatid Crithidia fasciculata.
In an effort to exploit the advantages of Crithidia fasciculata for detailed analysis of the mechanisms of discontinuous transcription in the trypanosomatid family, we have cloned, sequenced, and characterized the mini-exon gene repeat in Crithidia and mapped the termini of its primary transcript. We find that Crithidia contains approximately 500 mini-exon genes, present almost exclusively as tandemly repeated arrays on a single chromosome. Transcripts derived from these genes are approximately 90 bases in length with heterogeneity at both the 5' and 3' ends. Primer extension experiments reveal a putative splicing intermediate. Specific inhibition of in vitro translation of Crithidia mRNAs by an oligonucleotide complementary to the mini-exon suggests that all Crithidia mRNAs contain the mini-exon at their 5' termini. Comparison of mini-exon gene sequences from various trypanosomatids reveals several regions of conservation that imply functional constraints on the transcription of mini-exon genes and the processing of their transcripts.


A cytotoxic effect associated with 9-(1,3-dihydroxy-2-propoxymethyl)-guanine is observed during the selection for drug resistant human cells containing a single herpesvirus thymidine kinase gene.
A cytotoxic effect associated with 9-(1,3-dihydroxy-2-propoxymethyl)-guanine (DHPG) was discovered while searching for spontaneous mutations in a single copy, integrated HSV-1 thymidine kinase (TK) gene in the human 143 TK- cell line. It was found that spontaneous DHPGR mutations could not be selected while other anti-TK drugs resulted in selectable mutation frequencies of 10(-4) to 10(-3). When 143 TK- cells were mixed with these HSV-1 TK+ cells and subjected to DHPG, a 90% to 100% decrease in recoverable TK- colonies was observed. In addition, the media from the HSV-1 TK+ cells metabolizing DHPG was shown to inhibit the growth of the TK- cells.


Surgical management of otitis media and otitis interna.
Surgical management of otitis media and otitis interna includes the following options: lateral bulla osteotomy, ventral bulla osteotomy, or curettage of the tympanic cavity. Because otitis media frequently accompanies chronic nonresponsive otitis externa, one of the above procedures may be combined with operative procedures of the external ear canal. Also, gentle selective curettage of the tympanic cavity may be combined with either lateral or ventral bulla osteotomy in the treatment of otitis media and interna. The choice of surgical procedure(s) should be based on the condition of the external ear canal (vertical and horizontal parts), the duration of clinical signs, response to previous surgery, and the familiarity of the surgeon with the different approaches and techniques. With the increased reporting of long-term results following surgical management of otitis externa, media, and interna, more meaningful conclusions concerning selection of surgical procedure may be made in the future.


The prevalence of chronic conditions in patients diagnosed with one of 29 common and rarer cancers: A cross-sectional study using primary care data.
Pre-existing chronic conditions (morbidities) influence the diagnosis and management of cancer. The prevalence of specific morbidities in patients diagnosed with common and rarer cancers is inadequately described. Using data from the English National Cancer Diagnosis Audit 2014, we studied 11 pre-existing morbidities recorded as yes/no items by participating general practitioners based on information included in primary care records. We examined the number and type of morbidities across socio-demographic and cancer site strata, and subsequently estimated observed and age/sex standardised prevalence of each morbidity by cancer. Over three-quarters (77 %; 11,429/14,774) of non-screen-detected patients had at least one chronic condition before diagnosis, while nearly half (47 %) had two or more. Hypertension (39 %) and physical disability (2%) were the most and least common conditions. Male, older and more socio-economically deprived patients were more likely to have at least one morbidity (p < 0.001 for all between variable group comparisons). For most morbidities, the standardised prevalence was similar across different cancers with a few exceptions, including respiratory disease prevalence being greatest among lung cancer patients and diabetes prevalence being greatest among liver, pancreatic, and endometrial cancer patients. Most cancer patients have at least one morbidity, while almost one in two have two or more. The findings highlight the need to take certain morbidity- and cancer-site combinations into account when examining associations between morbidity and cancer outcomes.


Salsolinol-neurotoxic or Neuroprotective?
Salsolinol (6,7-dihydroxy-1-methyl-1,2,3,4-tetrahydroisoquinoline), widely available in many edibles, is considered to alter the function of dopaminergic neurons in the central nervous system and thus, multiple hypotheses on its either physiological and/or pathophysiological role have emerged. The aim of our work was to revisit its potentially neurotoxic and/or neuroprotective role through a series of both in vitro and in vivo experiments. Salsolinol in the concentration range 10-250 μM did not show any significant release of lactate dehydrogenase from necrotic SH-SY5Y cells and was able in the concentration of 50 and 100 μM to rescue SH-SY5Y cells from death induced by H2O2. Its neuroprotective effect against neurotoxin 6-hydroxydopamine was also determined. Salsolinol was found to decrease significantly the reactive oxygen species level in SH-SY5Y cells treated by 500 μM H2O2 and the caspase activity induced by 300 μM of H2O2 or 100 μM of 6-hydroxydopamine. Serum levels of TNFα and CRP of salsolinol-treated rats were not significantly different from control animals. Both TNFα and CRP served as indirect markers of neurotoxicity and/or neuroprotection. Although the neurotoxic properties of salsolinol have numerously been emphasized, its neuroprotective properties should not be neglected and need greater consideration.


Determination of free acetaldehyde in total blood for investigating the effect of aspartate on metabolism of alcohol in mice.
To explore the effect of sodium L-aspartate monohydrate (aspartate) as a NAD+ regenerating agent for acetaldehyde in alcohol metabolism, a simple HPLC method has been developed for the measurement of free acetaldehyde in total mice blood digested with alcohol and aspartate. The blood samples were collected in EDTA Vacutainer tubes, and treated with 2,4-dinitrophenylhydrazine (DNP hydrazine) reagent in total blood. Acetaldehyde DNP hydrazone was extracted from total blood and analyzed by HPLC using an Ultrasphere ODS column. The compounds were separated using acetonitrile-water (50:50, v/v) as mobile phase and detected at 356 nm. The detection limit for acetaldehyde DNP hydrazone was 0.1 ppm. A blank determination was carried out for each analysis and subtracted from the results. The amount of acetaldehyde in blood has been determined as a function of time lapse after sole alcohol administration and aspartate ingestion followed by alcohol administration, respectively. This comparative analysis demonstrates that the ingestion of aspartate before the administration of alcohol dramatically decreases the aldehyde level in blood, and aspartate may be utilized as a prospective antagonist for acceleration of ethanol metabolism and prevention of acetaldehyde toxicity.


Variations in occurrences of nutrition-related diseases in Sub-Saharan Africans in stages of transition: what of the future?
In many Sub-Saharan African populations, in particular urban dwellers, there have been marked rises in the prevalences of obesity in women, hypertension, diabetes, and cerebral vascular disease. Yet there have been only slight rises in coronary heart disease. To learn more of the roles of the various influencing factors in the puzzling situations described, some aspects of the past and present occurrences of these diseases are described and discussed, with comparisons being made with corresponding situations in African Americans, as well as in certain white populations. Despite increases in the knowledge of influencing factors, such fail to explain fully the epidemiologic situations described. As to the future, judging from the experiences of other populations, despite continuing indigence, within the next generation significant rises in coronary heart disease in certain African populations seem to be inevitable. However, in many of those populations, in particular those in the South, the extent of changes, apart from those linked with level of socioeconomic state, will be strongly affected by the rising epidemic of human immunodeficiency virus and acquired immunodeficiency syndrome.


Dielectric and electrical properties of electrorheological carbon suspensions.
Measurements of electrorheological (ER) effects, dielectric properties, and electrical conductivity are made on an ER suspension composed of carbonaceous particles and silicone oil to understand the mechanism which governs the ER effect. In the frequency dependence of the dielectric permittivities, a dielectric dispersion is observed in the first-order dielectric permittivity, while in the third-order dielectric permittivity a resonance peak, which is due to shear-induced particle rotation, is recognized, showing that such dielectric properties are closely related to ER properties of the suspension. An electrical conduction mechanism, which is responsible for the ER effect, is also investigated from the dependence of dc electrical conductivity on electric-field strength and temperature.


Essential and Toxic Metals in Oral Fluid-a Potential Role in the Diagnosis of Periodontal Diseases.
Recently, many studies have investigated the relationship between the level of metals in the body and various diseases. The objective of this study was to examine any possible influence of periodontal disease upon the concentration of metals in oral fluid and blood and to explore the usability of applying cluster analysis coupled with the analysis of selected elements in oral fluid, calcium (Ca), copper (Cu), iron (Fe), magnesium (Mg), manganese (Mn), zinc (Zn), cadmium (Cd) and lead (Pb), for effectively distinguishing people affected by periodontitis from healthy individuals. The quantification of eight metals in oral fluid and blood samples was performed by two inductively coupled plasma techniques-inductively coupled plasma mass spectrometry (ICP-MS) and inductively coupled plasma optical emission spectrometry (ICP-OES). Most of the examined elements were detected at elevated concentration in the oral fluid of periodontal patients. However, the differences were statistically significant in the case of three metals: Cu, Mg and Mn (p < 0.05). Approximately, fivefold increase in the concentration of Cu, threefold-elevated levels of Mn and a twofold increase in the concentration of Mg were found in the oral fluid of the periodontal patients compared to the controls. Cluster analysis confirmed the statistical significance of the differences in the level of metals in the oral fluid between the two groups in most cases, plus enabled the correct classification of the subjects into patients and controls. The relationship between concentrations of metals and periodontal disease may in the future serve to prevent the development of such disease.


A novel fast T1-mapping method.
The authors present a novel fast T1-mapping technique that allows a T1 map to be reconstructed from data acquired in less than 3 seconds. Data were acquired by using two modified TurboFLASH (fast low-angle shot) sequences and were processed with a combination of one-dimensional Fourier transforms and a parameter-fitting routine, instead of a standard two-dimensional Fourier transform. Apparent T1 (T1*) maps were obtained, from which T1 maps were calculated. Comparisons of T1 values obtained in phantoms and the human brain by using this technique with those obtained with multipoint inversion-recovery T1 mapping showed that the new method yielded accurate T1 values. Optimization of the method will further improve speed and accuracy. The general approach of this T1-mapping technique is believed to be also applicable to other problems, such as T2 and T2* mapping.


Time dependency and irreversibility of water desorption by drinking-water treatment residuals: implications for sorption mechanisms.
Drinking-water treatment residuals (WTRs) are being evaluated as cost-effective sorption media for use in environmental remediation. Data from previous work have suggested that intraparticle phosphorus (P) diffusion into micropores is the rate-limiting mechanism of P sorption by WTRs. We used isothermal thermogravimetric analysis (TG) to study water desorption/resorption dynamics as they relate to steric diffusion rate limitations for prospective sorbates. Results showed that air-dried WTR particles contain significant amounts of water. Only about 40% of water desorbed isothermally (70 degrees C) for 10 h was readsorbed when particles were reexposed to ambient temperature and moisture conditions. This hysteresis related closely with time dependency of water loss, suggesting steric diffusional hindrance of water re-adsorption by meso- and micropores. The irreversibly desorbed water may be the component requiring increased kinetic energy to overcome diffusional resistance. Another possible factor in irreversibility could be pore shrinkage. Samples incubated for 12 months at 70 degrees C prior to TG analysis showed no hysteresis at 70 degrees C. Isothermal water losses with time fit well (r2 = 0.95) the diffusion model of Kabai. These results are consistent with an aqueous pore network that would account for high phosphorus sorption capacity and hysteresis that has been recently documented for WTRs.


Sarcoidosis and tuberculosis in South Croatia: are there epidemiological similarities or not?
Tuberculosis and sarcoidosis are chronic granulomatous diseases. Clinical, pathologic and immunologic aspects are similar although different. The authors were interested to highlight possible epidemiological similarities of these two granulomatous diseases. The objective of this study was to evaluate incidence rate as well as age, sex and geographic distribution of sarcoidosis in South Croatia and to compare it with these epidemiological characteristics of tuberculosis. Retrospective. The study was including ten years follow up period (1997-2006), and was performed in Split-Dalmatia County, Croatia. All data were collected retrospectively and analyzed using Statistica 7 programme. The mean annual incidence of sarcoidosis was 3.3/100,000 inhabitants with a mean of 15,6 cases per year. Woman accounted for 61% of all sarcoidosis cases. The mean sarcoidosis patient age was 44.94 ± 11.85 years. The peak age group was 40-49 years (31%). Significant difference according to incidence rate on the islands comparing to the rates on the coast and the mainland was observed (P = 0.003). The mean sarcoidosis mortality rate was 1.2/100,000. Statistically significant differences between sarcoidosis and tuberculosis were observed according the higher number of tuberculosis patients (P < 0.000), among males (P < 0.000), and females, too (P < 0.000) as well as in mortality rates (P = 0.401). Significantly more patients had tuberculosis on the mainland (P < 0.000) and on the coast (P < 0.000), but not in the islands (P = 0.260). The results from this study showed dissimilarities in classic epidemiological patterns between sarcoidosis and tuberculosis, incidence rates, as well as sex and geographic distribution. Our findings resulted from this study might be starting point for the future epidemiological, genetic, and immunological studies.


BMSCs Promote Differentiation of Enteric Neural Precursor Cells to Maintain Neuronal Homeostasis in Mice With Enteric Nerve Injury.
Our previous study showed that transplantation of bone marrow-derived mesenchymal stem cells (BMSCs) promoted functional enteric nerve regeneration in denervated mice but not through direct transdifferentiation. Homeostasis of the adult enteric nervous system (ENS) is maintained by enteric neural precursor cells (ENPCs). Whether ENPCs are a source of regenerated nerves in denervated mice remains unknown. Genetically engineered mice were used as recipients, and ENPCs were traced during enteric nerve regeneration. The mice were treated with benzalkonium chloride to establish a denervation model and then transplanted with BMSCs 3 days later. After 28 days, the gastric motility and ENS regeneration were analyzed. The interaction between BMSCs and ENPCs in vitro was further assessed. Twenty-eight days after transplantation, gastric motility recovery (gastric emptying capacity, P < .01; gastric contractility, P < .01) and ENS regeneration (neurons, P < .01; glial cells, P < .001) were promoted in BMSCs transplantation groups compared with non-transplanted groups in denervated mice. More importantly, we found that ENPCs could differentiate into enteric neurons and glial cells in denervated mice after BMSCs transplantation, and the proportion of Nestin+/Ngfr+ cells differentiated into neurons was significantly higher than that of Nestin+ cells. A small number of BMSCs located in the myenteric plexus differentiated into glial cells. In vitro, glial cell-derived neurotrophic factor (GDNF) from BMSCs promotes the migration, proliferation, and differentiation of ENPCs. In the case of enteric nerve injury, ENPCs can differentiate into enteric neurons and glial cells to promote ENS repair and gastric motility recovery after BMSCs transplantation. BMSCs expressing GDNF enhance the migration, proliferation, and differentiation of ENPCs.


Effect of alfacalcidol on natural course of renal bone disease in mild to moderate renal failure.
To determine whether alfacalcidol--used in management of overt renal bone disease--may safely prevent renal bone disease when used earlier in course of renal failure. Double blind, prospective, randomised, placebo controlled study. 17 nephrology centres from Belgium, France, the Netherlands, and the United Kingdom. 176 patients aged 18-81 with mild to moderate chronic renal failure (creatinine clearance 15-50 ml/min) and with no clinical, biochemical, or radiographic evidence of bone disease. Alfacalcidol 0.25 micrograms (titrated according to serum calcium concentration) or placebo given for two years. Quantitative histology of bone to assess efficacy of treatment and renal function to assess safety. 132 patients had histological evidence of bone disease at start of study. Biochemical, radiographic, and histological indices of bone metabolism were similar for the 89 patients given alfacalcidol and the 87 controls given placebo. After treatment, mean serum alkaline phosphatase activity and intact parathyroid hormone concentration had increased by 13% and 126% respectively in controls but had not changed in patients given alfacalcidol (P < 0.001). Hypercalcaemic episodes occurred in 10 patients given alfacalcidol (but responded to decreases in drug dose) and in three controls. Histological indices of bone turnover significantly improved in patients given alfacalcidol and significantly deteriorated in controls: among patients with abnormal bone histology before treatment, bone disease resolved in 23 (42%) of those given alfacalcidol compared with two (4%) of the controls (P < 0.001). There was no difference in rate of progression of renal failure between the two groups. Early administration of alfacalcidol can safely and beneficially alter the natural course of renal bone disease in patients with mild to moderate renal failure.


Structural and functional effects of hemiretinal endodiathermy axotomy in cynomolgus macaques.
Outer retinal injury has been well described in glaucoma. To better understand the source of this injury, we wanted to develop a reliable model of partial retinal ganglion cell (RGC) axotomy. Endodiathermy spots were placed along the inferior 180° adjacent to the optic nerve margin in the right eyes of four cynomolgus monkeys. Fluorescein angiography, spectral domain optical coherence tomography (SD-OCT), and multifocal electroretinography (mfERG) were performed at various intervals. Two animals were sacrificed at 3 months. Two animals were sacrificed at 4 months, at which time they underwent an injection of fluorescent microspheres to measure regional choroidal blood flow. Retinal immunohistochemistry for glial fibrillary acidic protein (GFAP), rhodopsin, S-cone opsin, and M/L-cone opsin were performed, as were axon counts of the optic nerves. At 3 months, there was marked thinning of the inferior nerve fiber layer on SD-OCT. The mfERG waveforms were consistent with inner but not outer retinal injury. Greater than 95% reduction in axons was seen in the inferior optic nerves but no secondary degeneration superiorly. There was marked thinning of the nerve fiber and ganglion cell layers in the inferior retinas. However, the photoreceptor histology was similar in the axotomized and nonaxotomized areas. Regional choroidal blood flow was not affected by the axotomy. Unlike experimental glaucoma, hemiretinal endodiathermy axotomy (HEA) of the RGCs produces no apparent anatomic, functional, or blood flow effects on the outer retina and choroid.


Synthesis, Characterization and Role of Anions (Nitrate, Sulphate, Oxalate and Acetate) \in the Biological Activity of Hydrazine Derived Compounds and Their Metal Chelates.
Hydrazine derived compounds and its Co(II), Cu(II) and Ni(II) chelates having the same metal ion but different anions (e.g., nitrate, sulphate, oxalate and acetate) have been synthesised and characterised by their physical, spectral and analytical data. In order to evaluate the participating role of anions in the antibacterial activity, these synthesised ligands and its metal chelates have been screened against bacterial species such as Staphylococcus aureous, pseudomonas aeruginosa, Klebsiella pneumonae and Proteus vulgarus, and the results are reported.


Cholangiovenous reflux pathways as defined by corrosion casting and scanning electron microscopy.
Using corrosion casting and scanning electron microscopy of the rat biliary tree, we investigated the site and size of the pathways that allow bacteria to reflux from bile to blood. Nonobstructed rat biliary trees were injected retrograde with methylmethacrylate resin at a constant rate of 0.04 ml/min to volumes of 40, 60, 80, 120, 160, and 200 microliters. The infusion pressure was monitored and a pressure-volume curve was constructed. After polymerization and corrosion in 30 percent potassium hydroxide, the casts were examined with scanning electron microscopy. In addition, to identify the size of the reflux pathways, ceramic particles of 150 A, 1.7 mu, or 10 mu were added to the resin, and the studies were repeated. Finally, intact livers with casted biliary trees were processed and studied by scanning electron microscopy without corrosion. Scanning electron microscopy demonstrated fine anatomic detail of the cholangiovenous reflux pathway. At 40 microliters (20 cm water pressure), normal biliary radicals were filled. Between 40 and 80 microliters (20 to 50 cm water pressure), the cast material refluxed from the bile ductules into the spaces of Mall and Disse and then into the hepatic sinusoids. Filling of sinusoids continued at volumes between 80 to 160 microliters, and filling of collecting veins was seen above 160 microliters. Particles of 1.7 mu and smaller readily refluxed, but there was no sinusoidal reflux of casting material that contained particles of 10 mu. Casting without corrosion showed that the liver parenchyma remained intact. There was no evidence of reflux across hepatocytes. This study shows that cholangiovenous reflux occurs directly from bile ductules through the spaces of Mall and Disse into the hepatic sinusoids. The pathways measure between 1.7 and 10 mu. Since this is the path of least resistance, it may be of greater importance in the reflux of bacteria and toxins than other high-resistance pathways, for example, biliary canaliculi, tight junctions, or hepatocytes.


Efficacy of atomoxetine in adult attention-deficit/hyperactivity disorder: a drug-placebo response curve analysis.
The objective of this study was to evaluate the efficacy of atomoxetine, a new and highly selective inhibitor of the norepinephrine transporter, in reducing symptoms of attention-deficit/hyperactivity disorder (ADHD) among adults by using drug-placebo response curve methods. We analyzed data from two double-blind, placebo-controlled, parallel design studies of adult patients (Study I, N = 280; Study II, N = 256) with DSM-IV-defined ADHD who were recruited by referral and advertising. Subjects were randomized to 10 weeks of treatment with atomoxetine or placebo, and were assessed with the Conners Adult ADHD Rating Scales and the Clinical Global Impression of ADHD Severity scale before and after treatment. Those treated with atomoxetine were more likely to show a reduction in ADHD symptoms than those receiving placebo. Across all measures, the likelihood that an atomoxetine-treated subject improved to a greater extent than a placebo-treated subject was approximately 0.60. Furthermore, atomoxetine prevented worsening of most symptom classes. From these findings, we conclude that atomoxetine is an effective treatment for ADHD among adults when evaluated using several criteria.


Determination by high-performance liquid chromatography with electrochemical detection of free and conjugated N-acetyldopamine excretion in urine of children with neuroblastoma and nephroblastoma.
A simple method for the determination of N-acetyldopamine (NADA) (both free and conjugated) in children's urine by high-performance liquid chromatography with electrochemical detection has been developed. Conjugated NADA was measured as the free compound after enzymatic hydrolysis and purification on alumina. The total analysis time is 25 min. The results show a linearity of the whole assay from 0.005 to 20 mumol/l NADA; the sensitivity is 0.2 pmol per 20 microliters injected sample. Mean recoveries of 96.7 and 86.6% were obtained for free and total NADA, respectively. Modifications of the retention times (between 2 and 50 min) induced by changes in the eluent were determined. Conjugated NADA accounted for about 90% of the total excretion of NADA. These results suggest that this compound could play an important part in neuroblastoma; its concentration is thirteen times higher in children with neuroblastoma than in normal subjects.


Insulin Resistance and Endometrial Cancer: Emerging Role for microRNA.
Endometrial cancer (EC) remains one of the most common cancers of the female reproductive system. Epidemiological and clinical data implicate insulin resistance (IR) and its accompanying hyperinsulinemia as key factors in the development of EC. MicroRNAs (miRNAs) are short molecules of non-coding endogenous RNA that function as post-transcriptional regulators. Accumulating evidence has shown that the miRNA expression pattern is also likely to be associated with EC risk factors. The aim of this work was the verification of the relationships between IR, EC, and miRNA, and, as based on the literature data, elucidation of miRNA's potential utility for EC prevention in IR patients. The pathways affected in IR relate to the insulin receptors, insulin-like growth factors and their receptors, insulin-like growth factor binding proteins, sex hormone-binding globulin, and estrogens. Herein, we present and discuss arguments for miRNAs as a plausible molecular link between IR and EC development. Specifically, our careful literature search indicated that dysregulation of at least 13 miRNAs has been ascribed to both conditions. We conclude that there is a reasonable possibility for miRNAs to become a predictive factor of future EC in IR patients.


Spinal muscular atrophy (SMA) type I (Werdnig-Hoffmann disease).
Spinal muscular atrophy type I, also called Werdnig-Hoffmann disease, is the most serious form. The disease appears before the age of 6 months and is characterized by major global hypotonia and abolition of tendon reflexes, with children never being able to sit unaided. Cognitive development is normal and the expressive gaze of these children contrasts with the paralytic attitude. Respiratory involvement predominates in the intercostal muscles, and sometimes brainstem involvement are all serious aspects of the disease. Type I spinal muscular atrophy has been subdivided into 3 groups: - type IA, the clinical signs of which set in between birth and 15 days of life with sudden severe motor impairment, sucking-swallowing disorders attesting to bulbar involvement, respiratory distress. - type IB with onset of symptoms before the age of 3 months, which implies no head control - type IC starting between 3 and 6 months with the possibility of checking head control, often referred to as "I bis" by French practitioners. The development and use of innovative therapies in recent years does actually change the natural course of this disease. But we do not know for sure what the long-term evolution of infants who received these new therapies will be. © 2020 French Society of Pediatrics. Published by Elsevier Masson SAS. All rights reserved.


An overview of only child family mental health in China.
This author reviewed most of the recent literature and research including three major studies in Shanghai, Changsha and Beijing as well as the authors' studies, including the 4 and 6 year follow-up studies in Nanjing. Most of the research undertaken in the USA and other Western countries and in China challenges the negative view of the only child described as 'selfish', 'lonely' or 'maladjusted'. The results showed no significant differences between the only child and the child with siblings, in terms of the prevalence of behavior problems except that certain items needed attention. In 4 and 6 year follow-up studies the developmental impact of being an only child or being a child without sibling was found to be different. However, the difference was not at a clinical level, but in behavior patterns or traits which clearly revealed many variables that were 'functional' in nature and related to child rearing. The data from these studies reflected only the comparison between groups of only children versus children with siblings. As individuals, behavior problems dominated in only a few children without siblings.


Comparison of cell culture and three enzyme-linked immunosorbent assays for the rapid diagnosis of respiratory syncytial virus from nasopharyngeal aspirate and tracheal secretion specimens.
A total of 211 specimens, including 144 nasopharyngeal aspirates and 67 tracheal secretions, were evaluated for the rapid detection of Respiratory Syncytial Virus (RSV) antigen by three commercial enzyme-linked immunosorbent assays (ELISA; Kallestad Diagnostic, Austin, TX; Ortho Diagnostics, Raritan, NJ, and Abbott Laboratories, North Chicago, IL) and by isolation of RSV in cell culture. Of the 61 RSV culture positive specimens, Kallestad ELISA, Ortho ELISA, and Abbott ELISA detected RSV antigen in 80%, 95%, and 92% of the specimens, respectively. An additional 28 specimens were found to be positive only by one or more RSV ELISA tests. A blocking assay confirmed the specificity of ELISA in 71% (20/28) of the RSV ELISA positive and the culture-negative specimens, and 29% were found to be false positive. Through the use of cell culture, with the resolution of ELISA positive and culture negative specimens by blocking assay, 81 specimens (61 + 20) were considered to be true positive. The sensitivity, specificity, and diagnostic accuracy were, for cell culture, 75%, 100%, and 91%; for Kallestad ELISA, 79%, 98%, and 91%; for Ortho ELISA, 95%, 99%, and 98%; and for Abbott ELISA, 93%, 96%, and 95% respectively. In our study, commercial ELISA tests have been shown to be rapid, reliable tests for the detection of RSV. Ortho ELISA and Abbott ELISA showed better sensitivity than the Kallestad ELISA for RSV detection directly in the clinical specimens.


Development and validation of the Affect in Play Scale-brief rating version (APS-BR).
The Affect in Play Scale (APS; Russ, 1987, 2004) is one of few reliable, standardized measures of pretend play, yet the fact that it requires videotaping and extensive training to score compromises its clinical utility. In this study, we developed and validated a brief rating version (APS-BR) that does not require videotaping. Construct validity was established by comparing scores from the original APS and the APS-BR using an existing data set of videotaped play (n = 46). We examined associations between scores on the APS-BR and theoretically relevant measures of divergent thinking and emotional memories. Scores on the APS-BR related strongly to those on the APS, and the pattern of correlations for each scale and relevant criterion measures was similar in strength and direction, supporting the APS-BR as an alternate form of the APS. In addition, we completed a pilot study to examine the efficacy of using the APS-BR in its intended in vivo format (n = 28). Results from both studies suggest that the APS-BR is a promising brief measure of children's pretend play that can be substituted for the APS in clinical and research settings.


The chemosensitizing potential of GF120918 is independent of the magnitude of P-glycoprotein-mediated resistance to conventional chemotherapeutic agents in a small cell lung cancer line.
GF120918, at 250 ng/ml, increased the sensitivity of a P-glycoprotein (P-gp)-mediated multidrug resistant (MDR) small cell lung cancer cell line (H69/LX4) to the P-gp substrates, paclitaxel, taxotere, vinblastine, vinorelbine, daunorubicin and etoposide to levels which were either greater (in the case of etoposide) or close to that of the parent cell line (H69/P). This was achieved in spite of the great variation in the levels of resistance of the MDR cell line for the various anti-cancer drugs tested. These data suggest that GF120918 is a potent antagonist of P-gp mediated multidrug resistance, even in the case of high levels of resistance, as was the case with paclitaxel and taxotere (2560 and 2215 fold more than the sensitive parent cell line respectively).


Enzyme termini of a phosphocreatine shuttle. Purification and characterization of two creatine kinase isozymes from sea urchin sperm.
Two isozymes of creatine kinase have been purified from sperm of the sea urchin, Strongylocentrotus purpuratus. One isozyme was purified from the sperm flagellum, and the other from the head. Both require nonionic detergent for extraction from sperm. The flagellar isozyme is a monomeric species with an Mr of 145,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and 126,000 from sucrose density gradient and gel filtration analyses. Creatine kinase from sperm heads was localized to the mitochondrion by an antibody raised against mouse muscle creatine kinase. This purified mitochondrial isozyme is multimeric, with an Mr of 47,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, but 240,000 for the native enzyme. Peptide mapping indicates that the two isozymes are not related. The following kinetic characteristics were observed for the purified flagellar and mitochondrial isozymes, respectively. In the direction of ATP formation, at pH 6.6 and 25 degrees C, specific activities were 235 and 180 units/mg; pH optima were 6.7 and 6.9 and Michaelis constants were 0.13 and 0.055 mM for ADP and 5.8 and 2.7 mM for phosphocreatine. In the direction of phosphocreatine formation, at pH 7.5 and 25 degrees C, specific activities were 29 and 47 units/mg; pH optima were 7.5 and 7.7 and Michaelis constants were 0.89 and 0.31 mM for ATP and 39 and 62 mM for creatine. These unique isozymes constitute the termini of the phosphocreatine shuttle of sea urchin sperm that is responsible for energy transport from the mitochondrion to the distal flagellum (Tombes, R. M., and Shapiro, B. M. (1985) Cell 41, 325-334; Tombes, R. M., Brokaw, C. J., and Shapiro, B. M. (1987) Biophys. J., 52, 75-86).


Therapeutic inhibition of PPARα-HIF1α-PGK1 signaling targets leukemia stem and progenitor cells in acute myeloid leukemia.
Treatment of acute myeloid leukemia (AML) with chemotherapeutic agents fails to eliminate leukemia stem cells (LSC),and thus patients remain at high risk for relapse. Therefore, the identification of agents that target LSC is an important consideration for the development of new therapies. Enhanced glycolysis in LSC contributes to the aggressiveness of AML, which is difficult to be targeted. In this study, we showed that targeting peroxisome-proliferator-activated receptor α (PPARα), a ligand-activated transcription factor by chiglitazar provided a promising therapeutic approach. We first identified that chiglitazar reduced cell viability and proliferation of the leukemia stem-like cells population in AML. Treatment with chiglitazar blocked the ubiquitination of PPARα and increased its expression, resulting in the inhibition of glucose metabolism and apoptosis of AML cells. Consistent with its anti-leukemia stem-like cells activity in vitro, chiglitazar treatment in vivo resulted in the significant killing of leukemia stem-like cells as demonstrated in AML patient-derived xenograft (PDX) models. Mechanistically, PPARα overexpression inhibited the expression and promoter activity of PGK1 through blocking HIF1-α interaction on the PGK1 promoter. Thus, we concluded that targeting PPARα may serve as a novel approach for enhancing stem and progenitor cells elimination in AML.


Lunch energy density and the metabolic syndrome in patients with type 2 diabetes mellitus.
The aim of the present study was to investigate the possible associations between dietary energy density (ED) and the metabolic syndrome (MetS) in patients with type 2 diabetes. In the present case-control study, the dietary ED of 125 patients with type 2 diabetes (seventy-eight with (cases) the MetS and forty-seven without (controls) the MetS; mean age 62·0 (SD 9·4) years, mean diabetes duration 12·5 (SD 8·4) years and mean glycated Hb 7·2 (SD 1·3) %) was assessed by weighed diet records. The MetS was defined according to the 2009 Joint Interim Statement and ED by the amount of energy (kJ) in a given weight of food. Data are expressed as means (standard deviations) or medians (interquartile ranges). Patients with the MetS reported lower intakes of total energy and fibre, and a higher total food amount than the controls; the total ED did not differ, but the cases had a higher ED at lunch (mean 6·3 (SD 1·3) v. 5·9 (SD 0·8) kJ/g; P= 0·017). In this meal, patients with the MetS had lower intakes of beans (median 0·7 (interquartile range 0·4-1·1) v. 1·1 (interquartile range 0·6-1·6) g/kg; P= 0·020), vegetables (median 1·2 (interquartile range 0·6-1·7) v. 1·4 (interquartile range 1·0-2·0) g/kg; P= 0·046) and total meat (median 1·3 (interquartile range 1·0-1·6) v. 1·4 (interquartile range 1·2-1·8) g/kg; P= 0·034) than patients without the MetS. The associations between lunch ED (kJ/g) and food groups (g/kg) were confirmed for vegetables (r - 0·584; P< 0·001), fruits (r - 0·233; P= 0·070), beans (r - 0·189; P= 0·037) and oils (r 0·323; P< 0·001). In a multivariate logistic regression model, a high lunch ED was associated with the MetS (OR 6·89, 95 % CI 1·35, 35·15; P =0·020) after adjusting for confounders. In conclusion, a high ED at lunch increased the odds of the presence of the MetS in patients with type 2 diabetes. Beans and vegetables may be the major contributors to this association and their consumption might be considered to decrease ED.


Social support and depression in men during alcoholism treatment.
Psychiatric comorbidities have been shown to be important predictors of the outcome of alcoholism treatment. This study examines whether perceived lack of social support can be identified as an independent predictor of symptoms of depression experienced during alcoholism treatment over and above the effects of personality characteristics and the severity of alcohol and psychiatric history. We studied 189 alcoholic men in treatment at a rural midwestern Department of Veterans Affairs medical center. Multiple regression analyses found that reduced social support significantly predicted depression (measured by the Beck Depression Inventory) during treatment while controlling for personality characteristics and the alcoholism and psychiatric subscales of the Addiction Severity Index. Although self-esteem, neuroticism, and psychiatric severity also were significantly associated with depression in the hierarchical regression model, social support demonstrated the strongest unique contribution to depression of any of the predictors. These results suggest that social support has an independent association with depression and perhaps may play an important role in improving treatment compliance and the outcome of alcoholism treatment.


Mesoporous Silicon Microspheres Produced from In Situ Magnesiothermic Reduction of Silicon Oxide for High-Performance Anode Material in Sodium-Ion Batteries.
Sodium-ion batteries have been widely used in energy storage owing to its high sodium content and low cost. This study proves that mesoporous silicon microspheres (MSMs) with the homogeneously distributed mesopores ranging from 1 to 10 nm can be used as anodes of NIBs. In situ magnesiothermic reduction of silicon oxide was carried out to synthesize the MSM samples. An anode in NIBs was tested, and it was observed that the MSMs sample which was calcined at 650 °C had a good rate performance of 160 mAh g-1 at 1000 mAg-1 and a high reversible capacity of 390 mAh g-1 at 100 mAg-1 after 100 cycles. Moreover, its long-term cycling performance was 0.08 mAh g-1 decay per cycle for 100 cycles, which was quite excellent. MSMs have high reversibility, good cycling performance, and excellent rate capability, which are related to its ultrafine particle size and mesoporous morphology.


Neoadjuvant Therapy in Non-Small Cell Lung Cancer.
Locally advanced (stage IIIA) non-small cell lung cancer (NSCLC) is confined to the chest, but requires more than surgery to maximize cure. Therapy given preoperatively is termed neoadjuvant, whereas postoperative therapy is termed adjuvant. Trimodality therapy (chemotherapy, radiation, and surgery) has become the standard treatment regimen for resectable, locally advanced NSCLC. During the past 2 decades, several prospective, randomized, and nonrandomized studies have explored various regimens for preoperative treatment of NSCLC. The evaluation of potential candidates with NSCLC for neoadjuvant therapy as well as the currently available therapeutic regimens are reviewed.


Assessing the potential of change in institutions.
The present article discusses the importance of evaluating the strengths and weaknesses of key institutional personnel prior to attempting program innovations. The importance of such individuals in "making" or "breaking" effective programs is emphasized, and various key hospital staff members are described. A simple evaluation process is discussed with the purpose of better anticipating problem areas in program development. It was concluded that in some cases, project implementations should not be attempted when assessed personnel problems appear capable of seriously limiting the effectiveness of a program.


A case of intradural lumbar disc herniation.
MRI remains the best tool in the diagnosis of this disease entity however preoperative diagnosis remains a difficult task. A high degree of suspicion is raised when intraoperative findings and preoperative image description become incompatible. Lumbar disc herniation into the dural space is a rare phenomenon of lumbar disc degeneration with an unclear remaining pathogenesis. Intraoperative ultrasonography and histopathological examination of resected specimen help in the diagnosis of intradural disc herniation. Prompt surgery is recommended due to the high incidence of cauda equina syndrome.


[Induction of a menadione-dependent respiratory shunt by a platinum complex].
Submitochondrial particles (SMP) from the bovine heart were treated with platinum complex--K [C2H4 PtCl3] (Zeize's salt); there occurred a menadion-dependent shunt, this being expressed in menadion stimulation of oxygen consumption under conditions of electron transport block with rotenon. This effect was observed only with the use in the capacity of a substrate of NAD.N2, but not of succinate. Menadion-dependent respiration induced with Zeize's salt was dicoumarol-sensitive, but was not inhibited by antimycin and cyanide, this differentiating it from menadionreductase shunt in the intact hepatic mitochondria.


Direct anterior versus mini-anterolateral approach for primary total hip arthroplasty: early postoperative outcomes and complications.
Anterior-based approaches to primary total hip arthroplasty (THA) are being used more frequently, and several variations have been described. The supine direct anterior (DA) approach has been widely studied, but few studies have compared it with the mini-anterolateral (mini-AL) approach (abductor-sparing, Watson-Jones approach) in the lateral decubitus position. This study aims to compare early perioperative complications and outcomes between these 2 approaches. This study retrospectively reviewed 340 consecutive THAs (n = 170 DA, n = 170 mini-AL) performed by 3 arthroplasty surgeons at a single institution between January 2017 and May 2018. The primary outcome was reoperation for any reason within 1 year. Secondary outcomes included wound-healing complications and several perioperative factors. A Student's t-test was used for continuous variables, and a chi-squared test was used for categorical variables. In this cohort, 6 patients (4%) from the mini-AL group required reoperation within 1 year, compared with 2 patients (1%) from the DA group (P = .024). However, the DA group had 13 patients (8%) with wound-healing complications compared with 6 patients (4%) in the mini-AL group 4% (P = .036). Perioperative outcomes were similar for operative time, distance walked with physical therapy, morphine milligram equivalent consumed, length of stay, and discharge disposition. Pain scores during index hospitalization were also similar. Patients who underwent THA using the supine DA approach had fewer reoperations within 1 year, but more wound-healing complications compared with the mini-AL approach in the lateral decubitus position. For surgeons performing primary THA using an anterior-based approach, relative risks and benefits of these approaches must be understood. Level III.


CRISPR-based therapeutics: current challenges and future applications.
The discovery, only a decade ago, of the genome editing power of clustered regularly interspaced short palindromic repeats (CRISPR)-associated nucleases is already reinventing the therapeutic process, from how new drugs are discovered to novel ways to treat diseases. CRISPR-based screens can aid therapeutic development by quickly identifying a drug's mechanism of action and escape mutants. Additionally, CRISPR-Cas has advanced emerging ex vivo therapeutics, such as cell replacement therapies. However, Cas9 is limited as an in vivo therapeutic due to ineffective delivery, unwanted immune responses, off-target effects, unpredictable repair outcomes, and cellular stress. To address these limitations, controls that inhibit or degrade Cas9, biomolecule-Cas9 conjugates, and base editors have been developed. Herein, we discuss CRISPR-Cas systems that advance both conventional and emerging therapeutics.


The relationship between intelligence and reaction time varies with age: Results from three representative narrow-age age cohorts at 30, 50 and 69 years.
Reaction time (RT) has played a prominent part in research on mental ability for over a century. Throughout this time a number of questions have been repeatedly posed: what is the relationship of RT to general mental ability, and is this the same for simple and choice RT? Does the relationship change with age? How important is RT variability compared with mean values? Here we examine these questions in three population representative cohorts. Participants were drawn from the West of Scotland Twenty-07 study, a longitudinal population based study designed to investigate socially structured health inequalities. At the fourth wave of data collection, part I of the Alice Heim 4 (AH4) test of general intelligence was administered, and reaction times were measured using a portable device. Means and standard deviations were recorded for simple and 4-choice reaction time. Full data were available for 2196 participants, comprising 714 aged 30 years, 813 aged 50, and 669 aged 69. Correlations of simple RT means with AH4 scores were - 0.27, - 0.30 and - 0.32, for age 30, 50 and 69, respectively; and - 0.44, - 0.47 and - 0.53 for 4-choice RT. The underlying relationships showed evidence of non-linearity, particularly for simple RT, with stronger association at lower AH4 scores. This was more pronounced with age. RT variability was correlated with the mean at 0.57, 0.57, 0.58 for simple RT; and 0.53, 0.53, 0.47 for choice RT. Residuals from regressing the RT variability on the mean showed no association with AH4 in the case of simple RT but a weak association for choice RT which decreased with age. There is a strong correlation of RT means with general mental ability which increases with age. The underlying relationship is complex for SRT. RT variability shows little association with mental ability when its dependence on the mean is removed. Combining samples with disparate ages may overestimate the association.


Facial emotion recognition and sleep in mentally disordered patients: A natural experiment in a high security hospital.
We investigated the relationship between a change in sleep quality and facial emotion recognition accuracy in a group of mentally-disordered inpatients at a secure forensic psychiatric unit. Patients whose sleep improved over time also showed improved facial emotion recognition while patients who showed no sleep improvement showed no change in emotion recognition.