Regulation of leptin by agouti.
Dominant mutations at the mouse Agouti locus lead to ectopic expression of the Agouti gene and exhibit diabetes, obesity, and yellow coat color. Obese yellow mice are hyperinsulinemic and hyperleptinemic, and we hypothesized that Agouti directly induces leptin secretion. Accordingly, we used transgenic mice expressing agouti in adipocytes (under the control of aP2 promoter, aP212) to examine changes in leptin levels. Agouti expression in adipose tissue did not significantly alter food intake, weight gain, fat pad weight, or insulinemia; however, the transgenic mice were hyperglycemic. We demonstrated that plasma leptin levels are approximately twofold higher in aP212 transgenic mice compared with their respective controls, whereas ubiquitous expression of agouti (under the control of beta-actin promoter, BAP20) led to a sixfold increase in leptin. Insulin treatment of aP212 mice increased adipocyte leptin content without affecting plasma leptin levels. These findings were further confirmed in vitro in 3T3-L1 adipocytes treated with recombinant Agouti protein and/or insulin. Agouti but not insulin significantly increased leptin secretion, indicating that insulin enhances leptin synthesis but not secretion while Agouti increases both leptin synthesis and secretion. This increased leptin synthesis and secretion was due to increased leptin mRNA levels by Agouti. Interestingly, agouti regulation of leptin was not mediated by melanocortin receptor 4, previously implicated in agouti regulation of food intake. These results suggest that increased leptin secretion by agouti may serve to limit agouti-induced obesity, independent of melanocortin receptor antagonism, and indicate that interaction between obesity genes may play a key role in obesity.


Role of lipid microdomains in P/Q-type calcium channel (Cav2.1) clustering and function in presynaptic membranes.
Lipid microdomains can selectively include or exclude proteins and may be important in a variety of functions such as protein sorting, cell signaling, and synaptic transmission. The present study demonstrates that two different voltage-gated calcium channels, which both interact with soluble N-ethyl-maleimide-sensitive fusion protein attachment protein receptor (SNARE) proteins but have distinct subcellular distributions and roles in synaptic transmission, are differently distributed in lipid microdomains; presynaptic P/Q (Cav2.1) but not Lc (Cav1.2) calcium channel subtypes are mainly accumulated in detergent-insoluble complexes. The immunoisolation of multiprotein complexes from detergent-insoluble or detergent-soluble fractions shows that the alpha1A subunits of Cav2.1 colocalize and interact with SNARE complexes in lipid microdomains. The altered organization of these microdomains caused by saponin and methyl-beta-cyclodextrin treatment largely impairs the buoyancy and distribution of Cav2.1 channels and SNAREs in flotation gradients. On the other hand, cholesterol reloading partially reverses the drug effects. Methyl-beta-cyclodextrin treatment alters the colocalization of Cav2.1 with the proteins of the exocytic machinery and also impairs calcium influx in nerve terminals. These results show that lipid microdomains in presynaptic terminals are important in organizing membrane sites specialized for synaptic vesicle exocytosis. The cholesterol-enriched microdomains contribute to optimizing the compartmentalization of exocytic machinery and the calcium influx that triggers synaptic vesicle exocytosis.


Aerogels in Chemical Engineering: Strategies Toward Tailor-Made Aerogels.
The present review deals with recent advances in the rapidly growing field of aerogel research and technology. The major focus of the review lies in approaches that allow tailoring of aerogel properties to meet application-driven requirements. The decisive properties of aerogels are discussed with regard to existing and potential application areas. Various tailoring strategies, such as modulation of the pore structure, coating, surface modification, and post-treatment, are illustrated by results of the last decade. In view of commercialization of aerogel-based products, a panorama of current industrial aerogel suppliers is given, along with a discussion of possible alternative sources for raw materials and precursors. Finally, growing points and perspectives of the aerogel field are summarized.


Immigrant and non-immigrant women's experiences of maternity care: a systematic and comparative review of studies in five countries.
Understanding immigrant women's experiences of maternity care is critical if receiving country care systems are to respond appropriately to increasing global migration. This systematic review aimed to compare what we know about immigrant and non-immigrant women's experiences of maternity care. Medline, CINAHL, Health Star, Embase and PsychInfo were searched for the period 1989-2012. First, we retrieved population-based studies of women's experiences of maternity care (n = 12). For countries with identified population studies, studies focused specifically on immigrant women's experiences of care were also retrieved (n = 22). For all included studies, we extracted available data on experiences of care and undertook a descriptive comparison. What immigrant and non-immigrant women want from maternity care proved similar: safe, high quality, attentive and individualised care, with adequate information and support. Immigrant women were less positive about their care than non-immigrant women. Communication problems and lack of familiarity with care systems impacted negatively on immigrant women's experiences, as did perceptions of discrimination and care which was not kind or respectful. Few differences were found in what immigrant and non-immigrant women want from maternity care. The challenge for health systems is to address the barriers immigrant women face by improving communication, increasing women's understanding of care provision and reducing discrimination.


[Intake of food products by obese inhibitans from Wroclaw].
The aim of the study was to asses food products intake in food ratio of women (n = 70) and men (n = 30) with BMI 27-40 from Wroclaw, which were patients of endocrynological section in Clinic Hospital in 2004. The 24 - hours recall and album of photographs of food products and dishes were used to estimate food products intake. Results of the study were compared with recommendation for adults in age 26-60 with low physical activity. In average food ratio the improperly high intake of meat and meat products (women 152% and men 198% of recommended level), fat (respectively 336% and 250%) and sugar and sweets (180%) were observed. The low intake of milk and milk products (women 71% and men 38% of recommendation) and vegetables and fruit (respectively 70% and 64%) were noticed. The way of nutrition of examined adults had many abnormalities predicted to increase body mass. The most errors including incorrect distribution of meals during the day, incorrect number of meals with snacks between them and too low physical activity was observed.


Chronic hepatitis virus infection in patients with multiple myeloma: clinical characteristics and outcomes.
Cytotoxic agents and steroids are used to treat lymphoid malignancies, but these compounds may exacerbate chronic viral hepatitis. For patients with multiple myeloma, the impact of preexisting hepatitis virus infection is unclear. The aim of this study is to explore the characteristics and outcomes of myeloma patients with chronic hepatitis virus infection. From 2003 to 2008, 155 myeloma patients were examined to determine their chronic hepatitis virus infection statuses using serologic tests for the hepatitis B (HBV) and C viruses (HCV). Clinical parameters and outcome variables were retrieved via a medical chart review. The estimated prevalences of chronic HBV and HCV infections were 11.0% (n = 17) and 9.0% (n = 14), respectively. The characteristics of patients who were hepatitis virus carriers and those who were not were similar. However, carrier patients had a higher prevalence of conventional cytogenetic abnormalities (64.3% vs. 25.0%). The cumulative incidences of grade 3-4 elevation of the level of alanine transaminase, 30.0% vs. 12.0%, and hyperbilirubinemia, 20.0% vs. 1.6%, were higher in carriers as well. In a Kaplan-Meier analysis, carrier patients had worse overall survival (median: 16.0 vs. 42.4 months). The prognostic value of carrier status was not statistically significant in the multivariate analysis, but an age of more than 65 years old, the presence of cytogenetic abnormalities, a beta-2-microglobulin level of more than 3.5 mg/L, and a serum creatinine level of more than 2 mg/ dL were independent factors associated with poor prognosis. Myeloma patients with chronic hepatitis virus infections might be a distinct subgroup, and close monitoring of hepatic adverse events should be mandatory.


An adult tissue-specific stem cell in its niche: a gene profiling analysis of in vivo quiescent and activated muscle satellite cells.
The satellite cell of skeletal muscle provides a paradigm for quiescent and activated tissue stem cell states. We have carried out transcriptome analyses on satellite cells purified by flow cytometry from Pax3(GFP/+) mice. We compared samples from adult skeletal muscles where satellite cells are mainly quiescent, with samples from growing muscles or regenerating (mdx) muscles, where they are activated. Analysis of regulation that is shared by both activated states avoids other effects due to immature or pathological conditions. This in vivo profile differs from that of previously analyzed satellite cells activated after cell culture. It reveals how the satellite cell protects itself from damage and maintains quiescence, while being primed for activation on receipt of the appropriate signal. This is illustrated by manipulation of the corepressor Dach1, and by the demonstration that quiescent satellite cells are better protected from oxidative stress than those from mdx or 1-week-old muscles. The quiescent versus in vivo activated comparison also gives new insights into how the satellite cell controls its niche on the muscle fiber through cell adhesion and matrix remodeling. The latter also potentiates growth factor activity through proteoglycan modification. Dismantling the extracellular matrix is important for satellite cell activation when the expression of proteinases is up-regulated, whereas transcripts for their inhibitors are high in quiescent cells. In keeping with this, we demonstrate that metalloproteinase function is required for efficient regeneration in vivo.


Effects of breed and region on longevity traits through five years of age in Brown Swiss, Holstein, and Jersey cows in the United States.
The objective of this study was to assess breed, and breed x region interactions for several longevity-related traits, measured up to 5 yr of age in Brown Swiss, Holstein, and Jersey cows in 7 regions of the United States. Data were analyzed using logistic, poisson, and linear models, and survival analyses. The traits were stayability (yes/no survived to 5 yr of age), number of completed lactations, days lived, herd-life, and days in milk (DIM) to 5 yr of age. Probable lifetime DIM were also estimated using data from the first 5 yr of age of the cows. Herd-life was defined as the days lived up to 5 yr of age minus the age at first calving. Days in milk consisted of herd-life up to 5 yr of age minus the dry periods. Three data files were analyzed: herds with one breed of cows, herds with Holstein and Brown Swiss, and herds with Holstein and Jersey cows. Breed x region interaction was usually significant, with larger effects for the southern regions. Jerseys obtained largest values for the ratio of DIM to days lived, and for the number of completed lactations to 5 yr of age. Brown Swiss had the largest probabilities of surviving to 5 yr of age (stayabilities) in all regions. For the other traits, the results for Brown Swiss were inconsistent, but usually the cows of this breed had shorter herd-life and DIM to 5 yr of age than Holsteins. Brown Swiss cows were expected to have more total DIM in their lifetime in the Southeast than Holsteins. Survival analysis gave the most readily interpretable information, although the linear, poisson, and logistic analyses answered slightly different questions. Adjustment for herd size did not modify the results.


[Pyoderma gangrenosum: a complication following surgery for carpal tunnel syndrome].
Pyoderma gangrenosum is a rare condition with an unpredictable disease course. The condition is accompanied by tissue decay and recognition often comes late. Pyoderma gangrenosum has clinical features similar to an infection, but does not react to antibiotics. The condition can develop following a surgical procedure or can be worsened by one. To date, only one other case of pyoderma gangrenosum following surgery for carpal tunnel syndrome has been described in the literature. A 60-year-old man developed painful ulcers shortly after surgery for carpal tunnel syndrome, a clinical picture representing a serious infection. Antibiotics and surgical debridement did not lead to improvement. Cultures from the wound did not contain micro-organisms. Following histological investigation a diagnosis of pyoderma gangrenosum was made. Administration of a high dosage of prednisone led to a swift improvement and the wound healed. Timely recognition of pyoderma gangrenosum is essential to prevent unnecessary surgical treatment and worsening of the condition. Systemic glucocorticoids are the treatment of first choice for pyoderma gangrenosum.


Mycotic disease in the common New Zealand gecko (Hoplodactylus maculatus).
Two adult female geckoes (Hoplodactylus maculatus) from the National Wildlife Centre, Mt Bruce, Masterton, died within the period of a month and were presented to the Department of Veterinary Pathology and Public Health at Massey University for necropsy. The first gecko had numerous 1-2 mm diameter punctate ulcers of the skin over the ventral and dorsal regions of the body. The second animal had slight discolouration of some of the scales. Skin swabs were taken from each case for culture. There were no other gross lesions apparent at necropsy. Histologically, the only lesions in the first gecko were areas of epidermal and dermal ulceration involving fungi and bacteria. In the second gecko, there was limited inflammation in the skin, but in the lungs there was necrosis of the pulmonary septae and constituent muscle bundles caused by fungi whose septate mycelia extended into adjacent large blood vessels and caused mycotic thrombi; hyphae were also found in the spleen and liver. Paecilomyces sp. septate fungus was recovered from both geckoes and Pseudomonas spp. and a mixed Gram-negative flora were recovered from the cutaneous lesions on culture. The death of the first gecko was considered to be due to widespread ulcerative dermatitis, while that of the second gecko was thought to be due to mycotic pneumonitis and mycotic septicaemia. It is believed that environmental factors, such as cold temperature and high humidity, contributed to a reduction in the immune response in the affected geckoes, with the consequent development of overwhelming fungal infections.


Effect of clinical mastitis on the lactation curve: a mixed model estimation using daily milk weights.
The objective of this study was to estimate the milk production losses associated with clinical mastitis using mixed linear models and correlation structures that have not been available previously. Data used included computer-recorded daily milk yields and detailed and accurate recordings of clinical mastitis cases. Two commercial Holstein dairy farms in New York State participated in the study, one with 650 lactating cows and another that began the study with 830 lactating cows and increased to 1120 cows by the end of the study. Cows on both farms were housed in free stall barns and milked 3 times daily in milking parlors. Electrical conductivity was used as a diagnostic aid for clinical mastitis on both farms. Date of clinical onset was recorded for every episode of clinical mastitis as well as for 8 other diseases defined using standardized case definitions (dystocia, milk fever, retained placenta, metritis, ketosis, displaced abomasum, lameness, and cystic ovarian disease) during the study period of October 1, 1999 to July 31, 2001. The mixed linear model for explaining variation in the outcome variable daily milk yield relative to non-mastitic herdmates found the terms for all 9 diseases studied, including clinical mastitis, significant. The model with an autoregressive correlation structure was preferred based on -2 * log likelihood, Akaike's information criterion, and Bayesian information criterion as well as savings in degrees of freedom. Separate analyses were run for first lactation cows and for second-plus lactation cows because their lactation curves were shaped differently. Adjusting for the effects of the other 8 diseases, milk production loss from clinical mastitis during the whole lactation was estimated as approximately 598 kg for second-plus lactation cows. However, cows that contracted mastitis had a daily production advantage of 2.6 kg over their herdmates until they contracted the disease. When compared with this potentially higher milk production, the total loss from clinical mastitis was estimated as 1181 kg.


Secretoneurin is a potential paracrine factor from lactotrophs stimulating gonadotropin release in the goldfish pituitary.
Secretoneurin (SN) is a functional neuropeptide derived from the evolutionarily conserved part of precursor protein secretogranin II (SgII). In the time course study, SN (10 nM) stimulates luteinizing hormone (LH) production and secretion after 6 h of static incubation of goldfish pituitary cells. Due to the existence of SN-immunoreactivity (SN-IR) in goldfish lactotrophs, endogenous SN might exert a paracrine effect on LH in the pituitary. In an in vitro immunoneutralization experiment, coincubation with anti-SN antiserum reduces the stimulatory effect of salmon gonadotropin-releasing hormone (sGnRH) on LH release by 64%. Using Western blot analysis, we demonstrate that sGnRH significantly increases the expression of the major SgII-derived peptide (∼57 kDa, with SN-IR) and prolactin (PRL) after 12 h in the static culture of goldfish pituitary cells. Furthermore, there exists a significant correlation between the levels of these two proteins (R = 0.76, P = 0.004). Another ∼30 kDa SgII-derived peptide containing SN is only observed in sGnRH-treated pituitary cells. Consistent with the Western blot analysis results, real-time RT-PCR analysis shows that a 12-h treatment with sGnRH induced 1.6- and 1.7-fold increments in SgII and PRL mRNA levels, respectively. SgII gene expression was also associated with PRL gene expression (R = 0.66; P = 0.02). PRL cells loaded with the calcium-sensitive dye, fura 2/AM, respond to sGnRH treatment with increases in intracellular Ca(2+) concentration level, suggesting a potential mechanism of GnRH on PRL cells and thus SgII processing and SN secretion. Taken together, endogenous lactotroph-generated SN, under the control of hypothalamic GnRH, exerts a paracrine action on neighboring gonadotrophs to stimulate LH release.


Visible-light-mediated, nitrogen-centered radical amination of tertiary alkyl halides under metal-free conditions to form α-tertiary amines.
A mild and operationally convenient amino-functionalization of a range of tertiary alkyl halides by reaction with iminoiodinanes (PhI[double bond, length as m-dash]NNs) and I2 has been developed. According to the mechanistic experiments described within, the reaction is speculated to proceed through a light-promoted, N-centered radical pathway involving a N,N-diiodosulfonamide reactive species. This method of direct N-incorporation offers an attractive alternative to the production of α-tertiary amines, a synthetically challenging structural class found in a variety of bioactive molecules.


Isolation of Arcobacter spp. from retail meats and cytotoxic effects of isolates against vero cells.
A survey of Arcobacter spp. was conducted over a 12-month period in Guadalajara, Mexico. A total of 135 samples (45 lean ground beef samples, 45 lean ground pork samples, and 45 chicken samples, including drumsticks, gizzards, and ground or chopped breast) were collected from local butcheries. The samples were enriched in Johnson-Murano enrichment medium and then streaked onto Johnson-Murano agar plates. Typical colonies were subjected to microscopic and biochemical identification followed by polymerase chain reaction confirmation of the genus Arcobacter. All isolates confirmed to be Arcobacter isolates were then inoculated into Eagle's minimum essential medium to determine their cytotoxicity against Vero cells. Arcobacter spp. were detected in 28.8, 51.1, and 40.0% of beef, pork, and chicken samples, respectively. From these samples, 101 isolates were confirmed to be Arcobacter spp. by polymerase chain reaction. Overall, the species most frequently identified was A. butzleri, followed by A. skirrowii. A. cryaerophilus was isolated only from pork meat. Ninety-five (95%) of the Arcobacter isolates produced a virulence mechanism against Vero cells, and 38 of them induced cell elongation, indicating enterotoxin production. Eighteen isolates produced the formation of vacuoles, and 39 produced both vacuolization and elongation. The vacuolization effect may be related to a vacuolizing toxin. The production of a vacuolizing toxin by Arcobacter spp. has not previously been reported. Results obtained in this study indicate that Arcobacter spp. may show cytotoxic effects other than the recognized enterotoxin production.


Comparison of handmarks in manual strangulation: an experimental study.
A police case with a strangulated woman with fingermarks on the neck and two suspects identifying each other as the perpetrator set off a laboratory experiment. Twenty-one males participated in the study. Blue paint was applied to their fingers, after which they grasped a neck dummy and pressed hard as if strangulating someone. The imprint was removed from the dummy, and their hands were photographed. Five imprints were randomly chosen and superimposed on the hand photographs in blind trials. In no cases did we match an imprint to the correct hand. However, in four cases we matched the imprint with several hands, one of which was the correct one. This means we were able to exclude nonmatches in 4/5 cases. Overall, matching of hands and fingermarks is difficult and inconclusive. Objective criteria for matching are difficult to establish, and matching is probably best suited for cases with specific anatomical features.


Glucocorticoid modulation of extracellular signal-regulated protein kinase 1/2 and p38 in human ovarian cancer HO-8910 cells.
To investigate the signaling pathway through testing the effects of dexamethasone (Dex) on the activation of the extracellular signal-regulated protein kinase 1/2 (ERK1/2) and p38 kinase (p38) in HO-8910 cells. Activation of the ERK1/2 and p38 was detected by Western blotting using the antibodies against the total ERK1/2 and p38 mitogen-activated protein kinases (MAPKs) protein and the phosphorylated forms of them. Dex could suppress the activation of ERK1/2, while enhance the activation of p38 rapidly and strongly in a dose- and time- dependent manner. Neither effect could be blocked by RU486, the antagonist of glucocorticoid receptor (GR). Dex has rapid effects on the activation of ERK1/2 and p38, and these effects are not mediated by GR.


A Case of Dermatomyositis Along with Esophageal Cancer and Screening of Serum Transcriptional Intermediary Factor 1 Gamma Antibodies in Various Cancer Patients.
BACKGROUND Dermatomyositis (DM) is occasionally associated with malignancy, which is so-called cancer-associated myositis. The cancer screening in patients with dermatomyositis is an important clinical issue. That is because malignant disease underlying dermatomyositis is potentially life-threatening. Transcriptional intermediary factor 1γ (TIF1γ) antibodies (anti-TIF1γ Abs) are one of the myositis-specific autoantibodies, which are investigated as potential predictors of malignancy in patients with dermatomyositis. However, the etiology of anti-TIF1γ Abs generations in various cancer patients is not known. CASE REPORT A 70-year-old male patient was admitted for muscle pain and weakness in both legs. Erythematous on the face, eruption, and a V sign were also observed. Laboratory tests showed the elevation of creatine kinase, myoglobin, and aldolase. He was diagnosed as dermatomyositis. Cancer screening was performed, and esophageal cancer was detected in the lower esophagus. Despite the symptoms of dermatomyositis were improved with steroid, methotrexate, and radical esophagectomy, he died with esophageal cancer 3 years after the onset of dermatomyositis. TIF1γ is frequently overexpressed in cancer tissues. Therefore, some cancer patients without dermatomyositis could be positive for anti-TIF1γ Abs. We retrospectively analyzed anti-TIF1γ Abs in cancer patients (n=131). However, the screening of anti-TIF1γ Abs in cancer patients without dermatomyositis (n=130) showed there were no seropositive patients. Only this cancer-associated myositis patient was positive for anti-TIF1γ Abs. CONCLUSIONS Our result suggested the generation of anti-TIF1γ Abs is specific for cancer associated myositis, not for tumorigenesis.


Incidence of prenatal alcohol exposure in Prince Edward Island: a population-based descriptive study.
Fetal alcohol spectrum disorder (FASD) is a leading preventable cause of neurodevelopmental disability in North America. The stigma associated with alcohol use and abuse during pregnancy makes it difficult to obtain information on prenatal alcohol use through self-reporting. We assessed the incidence of prenatal alcohol exposure in Prince Edward Island to facilitate future public health initiatives addressing FASD. Prenatal alcohol exposure was examined via population-based collection of meconium and analysis of fatty acid ethyl esters (FAEEs). Fatty acid ethyl esters are nonoxidative metabolites of ethanol that are produced in the fetus. Meconium FAEE concentrations of 2.0 nmol/g or greater are indicative of frequent prenatal alcohol exposure during the last 2 trimesters of pregnancy. Samples were collected from 1307 neonates between Nov. 8, 2010, and Nov. 8, 2011, in hospitals in PEI, or from those born to mothers who resided in PEI but gave birth in Halifax, Nova Scotia. Samples were frozen and shipped for analysis. Fatty acid ethyl esters were analyzed by gas chromatography-mass spectrometry and quantified by means of deuterated internal standards. Of the 1307 samples collected, 1271 samples were successfully analyzed. Positive results for FAEEs were obtained in 3.1% (n = 39) of samples collected within the first 24 hours after birth. Not all neonates exposed to heavy prenatal alcohol in utero will exhibit FASD; based on current estimates of predictive value for disease by exposure, our findings suggest that 1.3% of neonates born in PEI during this 1-year period will have FASD. In its application to an entire provincial birth cohort, this study successfully implemented a public health-centred approach for evaluating population-based risk of FASD, with implications for practice across Canada.


Racial and ethnic minority participants in clinical trials of acute respiratory distress syndrome.
There is growing interest in improving the inclusiveness of racial and ethnic minority participants in trials of acute respiratory distress syndrome (ARDS). With our study we aimed to examine temporal trends of representation and mortality of racial and ethnic minority participants in randomized controlled trials of ARDS. We performed a secondary analysis of eight ARDS Network and PETAL Network therapeutic clinical trials, published between 2000 and 2019. We classified race/ethnicity into "White", "Black", "Hispanic", or "Other" (including Asian, American Indian or Alaskan Native, Native Hawaiian, or other Pacific Islander participants). Of 5375 participants with ARDS, 1634 (30.4%) were Black, Hispanic, or Other race participants. Representation of racial and ethnic minority participants in trials did not change significantly over time (p = 0.257). However, among participants with moderate to severe ARDS (i.e., partial pressure of arterial oxygen to fraction of inspired oxygen ratio < 150), the difference in mortality between racial and ethnic minority participants and White participants decreased over time. In the five most recent trials, including 2923 participants with ARDS, there were no statistically significant differences in mortality between racial/ethnic groups, even after adjusting for potential confounders. In these five most recent trials, mortality was 31% for White, 31.9% for Black, 30.3% for Hispanic, and 37.1% for Other race participants (p = 0.633). Representation of racial and ethnic minority participants in ARDS trials from North America, published between 2000 and 2019, did not change over time. Black and Hispanic participants with ARDS may have similar mortality as White participants within trials.


S-Equol Activates cAMP Signaling at the Plasma Membrane of INS-1 Pancreatic β-Cells and Protects against Streptozotocin-Induced Hyperglycemia by Increasing β-Cell Function in Male Mice.
Background:S-equol, which is enantioselectively produced from daidzein by gut microbiota, has been suggested as a chemopreventive agent against type 2 diabetes mellitus (T2DM), but the underlying mechanisms remain unclear.Objective: We investigated the effects of S-equol on pancreatic β-cell function.Methods: β-Cell growth and insulin secretion were evaluated with male Institute of Cancer Research mice and isolated pancreatic islets from the mice, respectively. The mechanisms by which S-equol stimulated β-cell response were examined in INS-1 β-cells. The effect of S-equol treatment on β-cell function was assessed in low-dose streptozotocin-treated mice. S-equol was used at 10 μmol/L for in vitro and ex vivo studies and was administered by oral gavage (20 mg/kg, 2 times/d throughout the experimental period) for in vivo studies.Results:S-equol administration for 7 d increased Ki67-positive β-cells by 27% (P < 0.01) in mice. S-equol enantioselectively enhanced glucose-stimulated insulin secretion in mouse pancreatic islets by 41% (P < 0.001). In INS-1 cells, S-equol exerted stronger effects than daidzein on cell growth, insulin secretion, and cAMP-response element (CRE)-mediated transcription. These S-equol effects were diminished by inhibiting protein kinase A. The effective concentration of S-equol for stimulating cAMP production at the plasma membrane was lower than that for phosphodiesterase inhibition. S-equol-stimulated CRE activation was negatively controlled by the knockdown of G-protein α subunit group S (stimulatory) and positively controlled by that of G-protein-coupled receptor kinase-3 and -6. Compared with vehicle-treated controls, S-equol gavage treatment resulted in an increase in β-cell mass of 104% (P < 0.05), a trend toward high plasma insulin concentrations (by 118%; P = 0.06), and resistance to hyperglycemia after streptozotocin treatment (78% of AUC after glucose challenge; P < 0.01). S-equol administration significantly increased the number of Ki67-positive proliferating β-cells by 62% (P < 0.01) and decreased that of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive apoptotic β-cells by 75% (P < 0.05).Conclusions: Our results show that S-equol boosts β-cell function and prevents hypoglycemia in mice, suggesting its potential for T2DM prevention.


Effects of integrated yoga on quality of life and interpersonal relationship of pregnant women.
The objective of this study was to investigate the effects of integrated yoga on the quality of life and interpersonal relationships in normal pregnant women. One hundred and two pregnant women between 18 and 20 weeks of gestation who met the inclusion criteria were recruited from the obstetric units in Bangalore and were randomly assigned to two groups of yoga (n = 51) and control (n = 51). Women with medical conditions that could potentially lead to pregnancy complications and those with abnormal fetal parameters were excluded. The yoga group received integrated yoga while control group received standard antenatal exercises, both for 1-h three times a week from 20th to 36th week of gestation. Pre and post assessments were done using WHOQOL-100 and FIRO-B questionnaires. Of the six domains of WHOQOL-100, between groups analysis showed significant improvements in the yoga group compared to the control in the physical (P = 0.001), psychological (P < 0.001), social (P = 0.003), and environmental domains (P = 0.001). In FIRO-B, the yoga group showed significant improvements in 'Expressed Inclusion' (P = 0.02) and 'Wanted Control' (P = 0.009) domains compared to the control group. The integrated yoga is an efficacious means of improving the quality of life of pregnant women and enhancing certain aspects of their interpersonal relationships.


Construction and characterization of a recombinant invertebrate iridovirus.
Chilo iridescent virus (CIV), officially named Insect iridescent virus 6 (IIV6), is the type species of the genus Iridovirus (family Iridoviridae). In this paper we constructed a recombinant CIV, encoding the green fluorescent protein (GFP). This recombinant can be used to investigate viral replication dynamics. We showed that homologous recombination is a valid method to make CIV gene knockouts and to insert foreign genes. The CIV 157L gene, putatively encoding a non-functional inhibitor of apoptosis (IAP), was chosen as target for foreign gene insertion. The gfp open reading frame preceded by the viral mcp promoter was inserted into the 157L locus by homologous recombination in Anthonomus grandis BRL-AG-3A cells. Recombinant virus (rCIV-Δ157L-gfp) was purified by successive rounds of plaque purification. All plaques produced by the purified recombinant virus emitted green fluorescence due to the presence of GFP. One-step growth curves for recombinant and wild-type CIV were similar and the recombinant was fully infectious in vivo. Hence, CIV157L can be inactivated without altering the replication kinetics of the virus. Consequently, the CIV 157L locus can be used as a site for insertion of foreign DNA, e.g. to modify viral properties for insect biocontrol.


Contrast sensitivity vision testing: new screening technology for family physicians.
Contrast sensitivity vision testing is the new technology in visual screening. Easy to administer and quick to perform, contrast sensitivity vision testing appears to be cost-effective for use by family physicians. It is a more sensitive indicator of ocular disease than traditional Snellen acuity testing and may detect ocular pathology at an early stage when Snellen acuity is still normal.


Mother-to-infant transmission of hepatitis B virus: a Chinese experience.
Over 90% of infants infected with hepatitis B virus (HBV) caused by mother-to-infant transmission will evolve to carrier status, and this cannot be prevented until widespread administration of the HB vaccine and hepatitis B immune globulin (HBIG) is implemented. This prospective study of 214 infants born to HBsAg-positive mothers was carried out to determine if either perinatal or intrauterine HBV transmission could be effectively prevented with HBIG and the HB vaccine. Peripheral blood was collected from mothers and from newborns before they received HBIG and the HB vaccine, as well as at 0, 1, 7, 24, and 36 months after birth. Infants born with an ratio of signal to noise(S/N) value of >5 for HBsAg (ABBOTT Diagnostic Kit) were defined as mother-to-infant transmission cases, those with an S/N between 5 and 50 were classified as perinatal transmission cases, and those with an S/N >50 were considered intrauterine transmission cases. Mother-to-infant transmission occurred in approximately 4.7% (10/214) of the infants; the perinatal transmission and intrauterine transmission rates were 3.7% (8/214) and 0.9% (2/214), respectively. The risk of mother-to-infant transmission increased along with maternal HBeAg or HBVDNA levels. After 36 months of follow-up, all perinatal cases became HBsAg-negative, whereas all intrauterine transmission cases evolved into carrier status. These results indicate that infants infected via intrauterine transmission cannot be effectively protected by HBIG and HB vaccine.


Using tumor registry resources in analyzing concordance with guidelines and outcomes.
Collection and analysis of standardized multi-institutional outcomes data is a labor-intensive process. As the National Comprehensive Cancer Network (NCCN) seeks to expand its Outcomes Database to include multiple primary tumor types, the amount of time and effort required for detailed data abstraction and transmission will become an obstacle for many primary institutions. In addition, as the NCCN Guidelines become more widely distributed and adopted in the oncology community, it would be appealing to evaluate guideline concordance and quality of care in community hospitals and community-based physician practices vs major cancer centers. However, methods for case finding and collection of detailed outcomes data in the community setting are not well established. Most cancer centers and community hospitals have already set aside resources for maintaining a local tumor registry that includes limited information on demographics, diagnosis, staging, treatment, and survival for all new cancer patients treated at the specific institution. One strategy that can be used to facilitate a global outcomes program within the NCCN community calls for capitalizing on existing local database resources and experienced coding and data management staff.


Evaluation of a Pseudotyped Virus Neutralisation Test for the Measurement of Equine Influenza Virus-Neutralising Antibody Responses Induced by Vaccination and Infection.
Equine influenza is a major respiratory disease of horses that is largely controlled by vaccination in some equine populations. Virus-neutralising antibodies, the mainstay of the protective immune response, are problematic in assaying for equine influenza virus, as most strains do not replicate efficiently in cell culture. Surrogate measures of protective antibody responses include the haemagglutination inhibition (HI) test and single radial haemolysis (SRH) assay. For this study, a pseudotyped virus, bearing an envelope containing the haemagglutinin (HA) from the Florida clade 2 equine influenza virus strain A/equine/Richmond/1/07 (H3N8), was generated to measure HA-specific neutralising antibodies in serum samples (n = 134) from vaccinated or experimentally-infected ponies using a pseudotyped virus neutralization test (PVNT). Overall, the results of PVNT were in good agreement with results from the SRH assay (100% sensitivity, 68.53% specificity) and HI test (99.2% sensitivity, 49.03% specificity). The PVNT was apparently more sensitive than either the SRH assay or the HI test, which could be advantageous for studying the antibody kinetics, particularly when antibody levels are low. Nevertheless, further studies are required to determine whether a protective antibody level can be defined for the SRH assay and to ascertain the inter-laboratory reproducibility. In conclusion, the PVNT efficiently measures neutralising antibodies after immunization and/or experimental infection in the natural host, and may complement existing antibody assays.


[RAPD-PCR analysis of the variability of spring common wheat cultivar genomes and their androclinal double haploid form].
Based on RAPD-PCR analysis with 15 primers including those homologous to particular loci, the level of genetic polymorphism in the collection of spring common wheat genotypes and their androclinal double haploid (ADH) lines was determined. Intraspecific polymorphism of the original wheat forms was 20%. By the absence of polymorphism in the molecular patterns of ADH lines and original forms, it was shown that, under the conditions used, no genetic changes in the genomic DNA of spring common wheat in anther culture occurred. Thus, the technology of direct in vitro androgenesis does not lead to genome rearrangements and may be used for rapid production of pure lines of such a complex allopolyploid as spring common wheat.


Prevalence of antibiotics prescription amongst patients with and without COVID-19 in low- and middle-income countries: a systematic review and meta-analysis.
Antimicrobial resistance (AMR) poses a substantial risk to public health. In low-income and middle-income (LMICs) nations, the impact of AMR is significantly more severe. The absence of data from low-income countries (LMICs) causes this topic to be frequently overlooked. Additionally, the COVID-19 pandemic could make the AMR issue even worse. Earlier guidelines recommended antibiotic use in patients with COVID-19, even in those without bacterial coinfection. This study aims to investigate the proportion of antibiotic prescriptions in LMICs among patients with and without coronavirus disease-2019 (COVID-19), the proportion of inappropriate antibiotics, and multi-antibiotic prescribing. We followed the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA). We retrieved data through online databases, including PubMed, Scopus, and ScienceDirect. Amongst COVID-19 patients, the meta-analytic estimate of antibiotic prescription was 0.80 (95% CI: 0.72-0.88), whereas antibiotic use among patients with non-COVID-19 infections was 0.54 (95% CI: 0.49-0.58). Half of those prescribed antibiotics (0.52, 95% CI: 0.32-0.72) are inappropriate prescriptions. In addition, we found that one-third of antibiotics prescriptions consisted of more than one antibiotic (0.32, 95% CI: 0.21-0.43). In conclusion, antibiotics are highly prescribed across LMICs, and their use is increased in patients with COVID-19. Amongst those prescriptions, inappropriate and multiple use was not uncommon. This study has several limitations, as it included two studies in an ambulatory setting, and some of the studies included in the analysis were conducted on a small scale. Nevertheless, our findings suggest that urgent action to improve prescribing practices is essential.


The WERO group stop smoking competition: main outcomes of a pre- and post- study.
One potential promising strategy for increasing smoking cessation for Māori (Indigenous New Zealanders) and New Zealand resident Pacific Island people is Quit and Win competitions. The current uncontrolled pre and post study, WERO (WERO in Māori language means challenge), differs from previous studies in that it aims to investigate if a stop smoking contest, using both within team support, external support from a team coach and cessation experts, and technology, would be effective in prompting and sustaining quitting. Fifteen teams, recruited from urban Māori, rural Māori and urban Pacific communities, competed to win a NZ$5000 (about € 3,000, £ 2600) prize for a charity or community group of their choice. People were eligible if they were aged 18 years and over and identified as smokers. Smoking status was biochemically validated at the start and end of the 3 month competition. At 3-months post competition self-reported smoking status was collected. Fourteen teams with 10 contestants and one team with eight contestants were recruited. At the end of the competition the biochemically verified quit rate was 36%. The 6 months self-reported quit rate was 26%. The Pacific and rural Māori teams had high end of competition and 6 months follow-up quit rates (46% and 44%, and 36% and 29%). WERO appeared to be successful in prompting quitting among high smoking prevalence groups. WERO combined several promising strategies for supporting cessation: peer support, cessation provider support, incentives, competition and interactive internet and mobile tools. Though designed for Māori and Pacific people, WERO could potentially be effective for other family- and community-centred cultures.


Emotional Maltreatment and Psychosocial Functioning in Preadolescent Youth Placed in Out-of-Home Care.
This paper examines the impact of emotional maltreatment on the psychosocial functioning of youth placed in out-of-home care as a result of maltreatment. Participants included 243 children participating in a randomized controlled trial of a preventive intervention for preadolescent youth placed in out-of-home care. This study analyzed baseline data collected pre-randomization from interviews with children and their out-of-home caregivers and data from child welfare records. Bivariate and regression analyses were used to explore the relationships between emotional maltreatment and interpersonal functioning, self-perception, mental health, and behavioral problems for the total sample and by gender. Findings suggest that subtypes of emotional maltreatment are associated with different outcomes and that males are more negatively impacted by emotional maltreatment than are females.


Glycogen phosphorylase as a target for type 2 diabetes: synthetic, biochemical, structural and computational evaluation of novel N-acyl-N´-(β-D-glucopyranosyl) urea inhibitors.
Glycogen phosphorylase (GP), a validated target for the development of anti-hyperglycaemic agents, has been targeted for the design of novel glycopyranosylamine inhibitors. Exploiting the two most potent inhibitors from our previous study of N-acyl-β-D-glucopyranosylamines (Parmenopoulou et al., Bioorg. Med. Chem. 2014, 22, 4810), we have extended the linking group to -NHCONHCO- between the glucose moiety and the aliphatic/aromatic substituent in the GP catalytic site β-cavity. The N-acyl-N´-(β-D-glucopyranosyl) urea inhibitors were synthesized and their efficiency assessed by biochemical methods, revealing inhibition constant values of 4.95 µM and 2.53 µM. Crystal structures of GP in complex with these inhibitors were determined and analyzed, providing data for further structure based design efforts. A novel Linear Response - Molecular Mechanics Coulomb Surface Area (LR-MM-CBSA) method has been developed which relates predicted and experimental binding free energies for a training set of N-acyl-N´-(β-D-glucopyranosyl) urea ligands with a correlation coefficient R(2) of 0.89 and leave-one-out cross-validation (LOO-cv) Q(2) statistic of 0.79. The method has significant applications to direct future lead optimization studies, where ligand entropy loss on binding is revealed as a key factor to be considered. ADMET property predictions revealed that apart from potential permeability issues, the synthesized N-acyl-N´-(β-D-glucopyranosyl) urea inhibitors have drug-like potential without any toxicity warnings.


Phorbol myristate acetate-activated keratinocytes stimulate proliferation of resting peripheral blood mononuclear lymphocytes via a MHC-independent, but protein kinase C- and intercellular adhesion molecule-1-dependent, mechanism.
Recent attention has focused on the role keratinocytes (KC) may play in the induction of T cell-mediated inflammatory responses in skin, particularly because KC, when activated by immunologic stimuli, express MHC class II Ag and secrete immunomodulatory cytokines. We tested the capacity of normal human KC that were stimulated with PMA to induce PBMC proliferation. PMA-treated, but not untreated, KC induced proliferation of allogeneic as well as autologous PBMC; in addition, when purified CD4+ or CD8+ T cells were used as responders, each subset proliferated. PBMC proliferation was not due to direct action of PMA on PBMC, nor to contamination of KC cultures with Langerhans cells (LC) or dermal APC. Pretreatment with different protein kinase C inhibitors abrogated the capacity of PMA-stimulated KC to induce proliferation. Paraformaldehyde-fixed PMA-KC stimulated PBMC proliferation, whereas supernatants from PMA-treated KC failed to do so, indicating that a membrane-associated activity on PMA-KC contributes to the induction of PBMC proliferation. PMA induced intercellular adhesion molecule-1 (ICAM-1) expression on KC; furthermore, mAb against ICAM-1 or against its ligand lymphocyte function-associated Ag (LFA-1) (CD11a/CD18) significantly, but incompletely, reduced the stimulatory capacity of PMA-treated KC, indicating that ICAM-1/LFA-1 interaction contributed to PBMC proliferation. IFN-gamma or TNF-alpha also induced ICAM-1 on KC, but these KC failed to stimulate proliferation, suggesting that PMA induces additional signals from KC, which act in concert with ICAM-1 to promote proliferation. Finally, mAb against HLA-ABC or HLA-DR did not inhibit proliferation. We conclude that PMA can activate KC to stimulate T cell proliferation in a MHC-independent fashion. This activation is mediated by protein kinase C and in part by the induction of ICAM-1 expression on KC.


Taking blood cultures from a newly established intravenous catheter in the emergency department does not increase the rate of contaminated blood cultures.
It has been suggested that blood cultures drawn from vascular catheters have a higher false positive rate than those drawn by venepuncture. In the face of institutionally imposed practice change prohibiting obtaining blood cultures from intravenous (i.v.) catheters in the ED, our aim of was to compare the rate of contaminated blood cultures between those taken from recently placed i.v. catheters and those taken by direct venepuncture. Prospective, non-randomised, observational study comparing the rate of contaminated blood cultures for specimens taken from recently placed (<1 h) i.v. catheters and direct venepuncture in adult ED patients. Outcome of interest was the rate of false positive cultures. Analysis was by comparison of proportions (χ(2) -test). Four hundred seventy-two blood culture sets were studied. There were 65 positive cultures, of which 49 (75%; 95% confidence interval [CI], 63-85%) were classified as true positive. The overall rate of contaminated blood cultures was 3.4% (95% CI, 2.0-5.6%). There was no difference in false positive rate between blood cultures taken via venepuncture and those taken from a recently placed i.v. cannula (P = 0.52; odds ratio, 0.9; 95% CI, 0.33-2.44). We found no difference in contaminated blood culture rate between recently placed i.v. catheters and direct venepuncture when infection control procedures were followed.


Safe use of hazardous chemicals.
This appendix provides protocols for some commonly used disposal and decontamination procedures along with analytical techniques that are used to verify that reagents have been decontaminated. Some of the specific reagents covered are diaminobenzidine, ethidium bromide, cyanogen bromide and chloromethylsilane. With modification, these assays may also be used to determine the concentration of a particular chemical. Precautions are also detailed for routine handling of viable pathogenic microorganisms, as well as all human-derived materials, because they may harbor dangerous pathogens such as human immunodeficiency virus (HIV), hepatitis B virus (HBV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), and a host of bacterial pathogens.


Effects of cryopreservation on cAMP-dependent protein kinase and AMP-activated protein kinase in Atlantic salmon (Salmo salar) spermatozoa: Relation with post-thaw motility.
Sperm motility in fish with external fertilization is critical for reproductive efficiency in aquaculture, especially in salmonids. Gamete preservation techniques, such as cryopreservation, however, reduce sperm motility and fertilizing capacity. Very few studies have addressed cryodamage from energetic and cell signalling approaches. In this study, cAMP-dependent protein kinase (PKA) and AMP-activated kinase (AMPK) activities were quantified in fresh and cryopreserved spermatozoa of Atlantic salmon (Salmo salar); and the relation with motility was analysed. Results indicate there was a decrease in membrane integrity and motility in post-thawed spermatozoa compared to fresh samples, however, there was about 30% of cells with intact plasma membrane but incapable of motility. The PKA and AMPK activities were less after cryopreservation, indicating that loss of motility may be related to alteration of these key enzymes. Furthermore, PKA and AMPK activities were positively correlated with each other and with motility; and inhibition decreased motility, indicating there is a functional relationship between PKA and AMPK. The PKA inhibition also decreased AMPK activity, but results from protein-protein docking analyses indicated AMPK activation directly by PKA is unlikely, thus an indirect mechanism may exist. There have been no previous reports of these kinase actions in fish spermatozoa, making these findings worthy of assessment when there are future studies being planned, and may serve as base knowledge for optimization of cryopreservation procedures and development of biotechnologies to improve reproduction efficiency in the aquaculture industry.


Simulation can replace part of speech-language pathology placement time: A randomised controlled trial.
Simulation is increasingly used within speech-language pathology education. Research has primarily explored students' perceptions of learning in simulation. The aim of this study was to determine if speech-language pathology students achieved a statistically-equivalent level of competency when a mean of 20% of placement time was replaced with simulation compared to placements without a simulation component. This non-inferiority randomised controlled trial involved students from six Australian universities. Students were randomised to either a simulation + traditional placement group attending 5 days of simulation prior to their traditional placement, or a traditional only placement group. Their end-placement clinical competency was assessed using Competency Assessment in Speech Pathology (COMPASS®). Final data were available for 325 students: 150 students in traditional placements, 138 students in protocol-compliant simulation + traditional placements, and 37 students in non-protocol simulation + traditional placements. There were no statistically significant differences between groups (traditional vs protocol-compliant simulation + traditional Mann-Whitney-Wilcoxon z = 1.23, df = 286, p = 0.22; traditional vs intention-to-treat simulation + traditional Mann-Whitney-Wilcoxon z = 0.23, df = 323, p = 0.81). This research contributes to the evidence base which suggests that simulation can partially replace traditional placement time for speech-language pathology students without loss of competency, substantiating its value as an alternative placement model in speech-language pathology programmes.


The effects of different exercise intensity on myokine and angiogenesis factors.
Myokines and angiogenesis factors, studies on trainings according to the difference of exercise intensity are not sufficient, and it has not been elucidated. Particularly, studies on the effect of resistance exercise according to the intensity of resistance exercise on blood myokines and angiogenesis may be essential in the metabolic process of angiogenesis and the formation of muscle. The subjects of our studies were healthy male college students (N.=30) randomly assigned to the high intensity exercise group (N.=10), the moderate intensity exercise group (N.=10), and the control group (N.=10). The study was performed after obtaining a consent in advance, and the approval from the Institutional Review Board of Dong-A University Hospital. In the body composition test, height, weight, BMI (body mass index), %fat, and LBM (lean body mass) were measured by electric impedance. In blood analysis, myokines (interleukin (IL)-6, IL-8, IL-15) and angiogenesis factors (vascular endothelial growth factor (VEGF), angiopoietin (Ang)1, follistatin (FLRG)) were analyzed by ELISA methods. The results show %body fat and LBM of the three groups were significantly different (P<0.05). IL-6 and IL-8 of the three groups were significantly different (P<0.05). Particularly, IL-8 of RE60 (60% of 1RM) was shown to be significantly higher than other groups (P<0.05). IL-15 also showed significant differences with time (P<0.05). In addition, VEGF and Ang 1 showed significant differences with time (P<0.05), nonetheless, FLRG did not showed statistical differences. Many of muscle contraction through 8 weeks resistance exercise exerted positive effects on the concentration of blood myokines as well as angiogenesis. Particularly, in regard to blood myokines, moderate intensity exercise were more effective than high intensity exercise, which is considered to be due to that continuous muscle contraction of moderate intensity exercises exerted more positive effects on the elevation of the concentration of myokines than less muscle contraction of high intensity exercise.


Scalp infection after fetal monitoring in labour.
Neonatal scalp infection was reviewed over a four year period. The occurrence of such infection was found to be 0.14% of those infants monitored in labour using a spiral scalp electrode and 0.16% of those infants undergoing instrumental delivery. The duration of labour and the membrane-rupture delivery interval did not differ significantly from the total population. Scalp infection after monitoring occurred significantly later (day seven) than after instrumental delivery (day three) and was less often associated with positive bacterial cultures. Scalp damage is probably important in the aetiology of scalp infection, and the course of infection related to the degree of trauma.


Methamphetamine increases dopamine transporter higher molecular weight complex formation via a dopamine- and hyperthermia-associated mechanism.
Multiple high-dose administrations of methamphetamine (METH) both rapidly (within hours) decrease plasmalemmal dopamine (DA) uptake and cause long-term deficits in DA transporter (DAT) levels and other dopaminergic parameters persisting weeks to months in rat striatum. In contrast, either a single administration of METH or multiple administrations of methylenedioxymethamphetamine (MDMA) cause less of an acute reduction in DA uptake and little or no persistent dopaminergic deficits. The long-term dopaminergic deficits caused by METH have been suggested, in part, to involve the DAT. Hence, this study assessed the impact of METH and MDMA administration on the DAT protein per se. Results revealed that multiple administrations of METH promoted formation of higher molecular weight (>170 kDa) DAT-associated protein complexes 24-48 hr after treatment. This increase was attenuated by either preventing hyperthermia or pretreatment with the tyrosine hydroxylase inhibitor alpha-methyl-p-tyrosine; notably, each of these manipulations has also been demonstrated previously to prevent the persistent deficits in dopaminergic function caused by METH treatment. In contrast, either a single injection of METH or multiple injections of MDMA caused little or no formation of these DAT complexes. The addition of the reducing agent beta-mercaptoethanol to samples prepared from METH-treated rats diminished the intensity of these complexes. Taken together, these data are the first to demonstrate higher molecular weight DAT complex formation in vivo and that such formation can be altered by both pharmacological and physiological manipulations. The implications of this phenomenon with regard to the neurotoxic potential of these stimulants are discussed.


Grape seed extract attenuates dexamethasone-induced testicular and thyroid dysfunction in male albino rats.
This study scrutinised the ameliorative properties of grape seed extract (GSE) in dexamethasone (DEX)-induced testicular and thyroid dysfunction associated with oxidative stress in male albino rats. Thirty-two healthy adult male albino rats were divided into four groups of eight animals each: normal, DEX control, DEX + GSE (200 mg/kg body weight) group and DEX + GSE (400 mg/kg body weight) group. The body weight gain and testes weight were assessed. Plasma testosterone and thyroid profile were determined. Testicular glucose-6-phosphate dehydrogenase (G-6-PDH), acid phosphatase (ACP), total protein and glutathione (GSH) levels, as well as catalase (CAT) activity also histopathological changes of the testis were evaluated. DEX treatment caused a significant decrease in body weight gain and weight of testes. Significant alterations in enzymatic and nonenzymatic antioxidants were observed. Moreover, a marked reduction in plasma testosterone levels and thyroid profile was observed. The administration of GSE significantly attenuated the deleterious effects of oxidative stress induced by DEX, as well as attenuated DEX-induced testicular and thyroid damage. Furthermore, DEX induced histological alterations in the testis. GSE ameliorated the injurious effects of DEX and improved the histological alterations in the testis.


Synergistic tumor suppression by coexpression of FHIT and p53 coincides with FHIT-mediated MDM2 inactivation and p53 stabilization in human non-small cell lung cancer cells.
Aberrations of the tumor suppressor genes FHIT and p53 are frequently associated with a wide range of human cancers, including lung cancer. We studied the combined effects of FHIT and p53 proteins on tumor cell proliferation and apoptosis in human non-small cell lung carcinoma (NSCLC) cells in vitro and on tumor growth in animal models by adenoviral vector-mediated cotransfer of wild-type FHIT and p53 genes. We found that the coexpression of FHIT and p53 synergistically inhibited tumor cell proliferation in NSCLC cells in vitro and suppressed the growth of human tumor xenografts in nude mice. Furthermore, we found that this synergistic inhibition of tumor cell growth corresponded with the FHIT-mediated inactivation of MDM2, which thereby blocked the association of MDM2 with p53, thus stabilizing the p53 protein. Our results therefore reveal a novel molecular mechanism consisting of FHIT-mediated tumor suppression and the interaction of FHIT with other cellular components in the pathways regulating p53 activity. These findings show that combination treatment with synergistic tumor-suppressing gene therapy such as Ad-FHIT and Ad-p53 may be an effective therapeutic strategy for NSCLC and other cancers.


Structural mapping of chloroplast coupling factor.
Fluorescence resonance energy transfer measurements have been used to investigate the spatial relationships between the nucleotide binding sites and the gamma-subunit of the H+-ATPase from chloroplasts and the orientation of these sites with respect to the membrane surface. Fluorescent maleimides reacted covalently at specific sulfhydryl sites on the gamma-subunit served as energy donors. One sulfhydryl site can be labeled only under energized conditions on the thylakoid membrane surface (light site). The two gamma-sulfhydryls exposed after catalytic activation served as a second donor site (disulfide site). In one set of experiments, the nucleotide analogue 2'(3')-(trinitrophenyl)adenosine triphosphate, selectively bound at each of the three nucleotide binding sites of the solubilized coupling factor, was used as an energy acceptor; in another, octadecylrhodamine with its acyl chain inserted in the vesicle bilayer and the rhodamine fluorophore exposed along the membrane surface was the energy acceptor. The distance between the sulfhydryl and disulfide sites was also obtained by sequentially labeling the sites with coumarin (donor) and fluorescein (acceptor) maleimide derivatives, respectively. The results indicate that all three nucleotide sites are approximately equal to 50 A from the light-labeled gamma-sulfhydryl. Two of the nucleotide sites are very far from the gamma-disulfide (greater than 74 A), while the third site, which binds nucleotides reversibly under all conditions, is 62 A from this sulfhydryl. The light-labeled sulfhydryl and disulfide sites are about 42-47 A apart. Finally, the distance of closest approach between the membrane surface of the reconstituted system and the gamma-disulfide is 31 A.(ABSTRACT TRUNCATED AT 250 WORDS)


Consequences of work group manpower and expertise understaffing: A multilevel approach.
Complaints of chronic understaffing in organizations have become common among workers as employers face increasing pressures to do more with less. Unfortunately, despite its prevalence, there is currently limited research in the literature regarding the nature of workplace understaffing and its consequences. Taking a multilevel approach, this study introduces a new multidimensional conceptualization of subjective work group understaffing, comprising of manpower and expertise understaffing, and examines both its performance and well-being consequences for individual workers (Study 1) and work groups (Study 2). Results show that the relationship between work group understaffing and individual and work group emotional exhaustion is mediated through quantitative workload and role ambiguity for both levels of analysis. Work group understaffing was also related to individual job performance, but not group performance, and this relationship was mediated by role ambiguity. Results were generally similar for the 2 dimensions of understaffing. Implications for theory and research and future research directions are discussed. (PsycINFO Database Record


[Update on the treatment with platelet antiaggregation agents].
Antiplatelet agents are primarily used to prevent and treat arterial thrombosis. Their mechanism of action is related to the interaction with metabolism of arachidonic acid, the increase of intraplatelet cAMP or the antagonism of ADP or GP IIb/IIIa receptors. Aspirin was one of the first agents to be adopted and it remains as the standard therapy with the higher amount of available clinical information. Following aspirin, ADP receptor antagonists like ticlopidine and more recently clopidogrel have been introduced. In the CAPRIE study, clopidogrel was shown to be more effective than aspirin in the prevention of vascular events in patients with atherothrombotic disease. The newer antiplatelet agents are GP IIb/IIIa receptor antagonists like eptifibatide, tirofiban and abciximab, which act at the end of the common pathway of platelet aggregation. Their benefits after intravenous administration have been shown in the treatment of acute coronary syndrome and percutaneous coronary angioplasty. The potential application of GIIb/IIIa targeted therapy might theortically be expanded by the new class of oral GP IIb/IIIa antagonists. However, their performance in clinical trials has been disappointing.


Risk factors for anastomotic leak and postoperative morbidity after right hemicolectomy for colon cancer: results from a prospective, multi-centre, snapshot study in China.
Right hemicolectomy is the standard treatment for right-sided colon cancer. There is variation in the technical aspects of performing right hemicolectomy as well as in short-term outcomes. It is therefore necessary to explore best clinical practice following right hemicolectomy in expert centres. This snapshot study of right hemicolectomy for colon cancer in China was a prospective, multicentre cohort study in which 52 tertiary hospitals participated. Eligible patients with stage I-III right-sided colon cancer who underwent elective right hemicolectomy were consecutively enrolled in all centres over 10 months. The primary endpoint was the incidence of postoperative 30-day anastomotic leak. Of the 1854 patients, 89.9 per cent underwent laparoscopic surgery and 52.3 per cent underwent D3 lymph node dissection. The overall 30-day morbidity and mortality were 11.7 and 0.2 per cent, respectively. The 30-day anastomotic leak rate was 1.4 per cent. In multivariate analysis, ASA grade > II (P < 0.001), intraoperative blood loss > 50 ml (P = 0.044) and D3 lymph node dissection (P = 0.008) were identified as independent risk factors for postoperative morbidity. Extracorporeal side-to-side anastomosis (P = 0.031), intraoperative blood loss > 50 ml (P = 0.004) and neoadjuvant chemotherapy (P = 0.004) were identified as independent risk factors for anastomotic leak. In high-volume expert centres in China, laparoscopic resection with D3 lymph node dissection was performed in most patients with right-sided colon cancer, and overall postoperative morbidity and mortality was low. Further studies are needed to explore the optimal technique for right hemicolectomy in order to improve outcomes further.


Coronavirus replication in the intestinal and respiratory tracts during infection of calves.
Coronaviruses have been isolated from cases of neonatal calf diarrhoea in many parts of the world and were revealed in the respiratory tract recently, during a study of calf pneumonia. In experiments on gnotobiotic calves an enteric coronavirus replicated in the nasal epithelium and a respiratory isolate was shed in faeces. The enteric coronavirus prevented subsequent infection with either homologous enteric or the respiratory isolate. A dual tropism for this agent was emphasized by the detection of coronavirus antigen in intestinal and respiratory epithelium of naturally-infected calves.


Effect of beta-carotene on cell cycle progression of human fibroblasts.
The uptake of beta-carotene (BC) and its effect on the cell cycle progression of normal human fibroblasts in primary culture were investigated by using two different delivery methods: exposure to BC solubilized in the organic solvent tetrahydrofuran (THF) or to BC incorporated into dipalmitoylphosphatidylcholine (DPPC) liposomes. Cell cycle progression was evaluated by immunofluorescence detection and flow cytometric analysis of the proliferating cell nuclear antigen (PCNA). In contrast to THF, which induced a marked reduction in the number of cells in S phase and in the extent of PCNA immunolabeling, DPPC liposomes proved to be an effective delivery system that does not interfere with cell proliferation. Cellular uptake of 0.23 nmol/10(6) cells was found after 24 h incubation in BC-containing DPPC liposomes. This value increased to 1.2 nmol/10(6) cells after 72 h. After the first day of incubation, the number of cells in S phase was reduced by approximately 50%, with a consequent accumulation of cells in G1 phase. This effect was maintained up to 3 days incubation, with no detectable effects on cell viability. This cell cycle delay was found to be reversible, returning the percentage of cells in S phase to the control value 24 h after removal of BC from the medium. In order to determine whether the activity of BC could be attributed to the molecule itself or to its conversion into retinoids, the production of BC metabolites was assessed. Analysis of cellular levels of retinoids failed to demonstrate the presence of retinal, retinol, retinoic acid or retinyl esters during an incubation period of 6 days. These results suggest that in normal human fibroblasts, BC induces a cell cycle delay in the G1 phase and that this effect is independent of conversion to known retinoids.


Self-collimation phenomena of surface waves in structured perfect electric conductors and metal surfaces.
We demonstrate that surface waves in structured perfect electric conductor surfaces can be self-collimated using the finite-difference time-domain method. The self-collimation frequency is obtained from the equi-frequency contours of a perfect electric conductor patterned with an array of square holes. The field patterns of the self-collimated surface wave, obtained using the periodic boundary conditions, show that the surface waves propagate with almost no spreading. We also show that self-collimation phenomena can be observed for the hybrid surface plasmon waves in structured metal surfaces using the finite-difference time-domain method with the Drude model. It is shown that for a structured silver surface the self-collimation can be achieved at the frequencies in the infrared region.


Random technique to encode complex valued holograms with on axis reconstruction onto phase-only displays.
A new technique for encoding the amplitude and phase of diffracted fields in digital holography is proposed. It is based on a random spatial multiplexing of two phase-only diffractive patterns. The first one is the phase information of the intended pattern, while the second one is a diverging optical element whose purpose is the control of the amplitude. A random number determines the choice between these two diffractive patterns at each pixel, and the amplitude information of the desired field governs its discrimination threshold. This proposed technique is computationally fast and does not require iterative methods, and the complex field reconstruction appears on axis. We experimentally demonstrate this new encoding technique with holograms implemented onto a flicker-free phase-only spatial light modulator (SLM), which allows the axial generation of such holograms. The experimental verification includes the phase measurement of generated patterns with a phase-shifting polarization interferometer implemented in the same experimental setup.


Knock-in rats with homozygous PSEN1L435F Alzheimer mutation are viable and show selective γ-secretase activity loss causing low Aβ40/42 and high Aβ43.
Familial forms of Alzheimer's disease (FAD) are caused by mutations in the gene encoding amyloid precursor protein, whose processing can result in formation of β-amyloid (Aβ). FAD can also result from mutations in the presenilin 1/2 (PSEN1/2) genes, whose protein products partially compose the γ-secretase complex that cleaves Aβ from amyloid precursor protein fragments. Psen1 KO mice and knock-in (KI) mice with homozygous FAD-associated L435F mutations (Psen1LF/LF ) are embryonic and perinatally lethal, precluding a more rigorous examination of the effect of Alzheimer's disease-causing Psen1 mutations on neurodegeneration. Given that the rat is a more suitable model organism with regard to surgical interventions and behavioral testing, we generated a rat KI model of the Psen1LF mutation. In this study, we focused on young Psen1LF rats to determine potential early pathogenic changes caused by this mutation. We found that, unlike Psen1LF/LF mice, Psen1LF/LF rats survive into adulthood despite loss of γ-secretase activity. Consistent with loss of γ-secretase function, Psen1LF/LF rats exhibited low levels of Aβ38, Aβ40, and Aβ42 peptides. In contrast, levels of Aβ43, a longer and potentially more amyloidogenic Aβ form, were significantly increased in Psen1LF/LF and Psen1LF/w rats. The longer survival of these KI rats affords the opportunity to examine the effect of homozygous Psen1 Alzheimer's disease-associated mutations on neurodegeneration in older animals.


In vitro drug susceptibility using a parasite-rescue and transformation assay of Leishmania (Mundinia) martiniquensis and Leishmania (Mundinia) orientalis amastigotes against antileishmanial drugs.
Leishmaniasis is an emerging infectious disease in Thailand, with Leishmania martiniquensis and Leishmania orientalis identified as the primary causative agents among immunocompetent and immunocompromised individuals. Variations in drug susceptibility among different Leishmania species have been reported in different regions. Therefore, drug susceptibility assays are essential to assess the effectiveness of antileishmanial drugs used or potentially used in the affected areas. This study investigated the in vitro drug sensitivity of L. martiniquensis and L. orientalis, along with two reference species causing VL, namely L. donovani and L. infantum, against six antileishmanial drugs. Using a parasite-rescue and transformation assay, the results demonstrated that the IC50 values of amphotericin B (AmB), miltefosine (MIL), and sodium stibogluconate (Sb(III)) against all Leishmania species tested were within the sensitive range of each drug. On the contrary, the IC50 values of artemisinin (ART) and dihydroartemisinin (DHA), drugs primarily used for malaria treatment, were outside the sensitive range of the Leishmania species tested except L. infantum. This in vitro study highlights that AmB could effectively exhibit good sensitivity against the intracellular amastigotes of L. martiniquensis and L. orientalis. Also, MIL and Sb(III) could be considered alternative drugs for antileishmanial treatment in Thailand.


Gene expression and trace elements in Greenlandic ringed seals (Pusa hispida).
Marine top predators such as ringed seals biomagnify environmental contaminants; and with the increasing human activities in the Arctic, ringed seals are exposed to biologically significant concentrations of trace elements resulting in reproductive impairment, immunosuppression, and neurological damages. Little is known about the molecular effects of heavy metals on these vulnerable apex predators suffering from a rapid changing Arctic with significant loss of sea-ice. In the present study, concentrations of cadmium (Cd), mercury (Hg) and selenium (Se) were measured in liver of sixteen Greenlandic ringed seals (nine adults and seven subadults) together with molecular biomarkers involved in bio-transformation, oxidative stress, endocrine disruption and immune activity in blood and blubber. The concentrations of trace elements increased in the following order: Hg > Se > Cd with levels of mercury and selenium being highest in adults. Aryl hydrocarbon receptor nuclear translocator (ARNT), peroxisome proliferator activated receptor alpha (PPARα, estrogen receptor alpha (ESR1), thyroid hormone receptor alpha (TRα) and interleukin - 2 (IL-2) mRNA transcript levels were significantly highest in blubber, while heat shock protein 70 (HSP70) and interleukin - 10 (IL-10) were higher in blood. There were no significant correlations between the concentrations of trace elements and mRNA transcript levels suggesting that stressors other than the trace elements investigated are responsible for the changes in gene expression levels. Since Hg seem to increase in Greenlandic ringed seals, there is a need to re-enforce health monitoring of this ringed seal population.


NMR experiments for the analysis of mixtures: beyond 1D 1H spectra.
State-of-the-art technologies and methodologies in NMR spectroscopy make it possible to obtain very informative and high-quality spectra in much less experimental time than classical methods by making better choices of NMR pulse sequences and acquisition parameters. This review presents some recent NMR methods allowing rapid identification, assignment and structural characterization of the components in mixtures. The relative merits of the different NMR pulse sequences are briefly discussed and recommendations are made for the preferred choice of sequences to obtain rapidly artifact-free data. This review covers diffusion experiments (DOSY), HSQC and HMBC experiments, ultra-resolved 2D spectra exploiting the property of aliasing and NOESY/ROESY experiments. It will be in particular shown that selective 1D NOESY/ROESY sequences can be more informative and reach higher resolution in less experimental time than the corresponding 2D sequences.


Establishing the Roles of the Dorsal and Ventral Striatum in Humor Comprehension and Appreciation with fMRI.
Humor comprehension (i.e., getting a joke) and humor appreciation (i.e., enjoying a joke) are distinct, cognitively complex processes. Functional magnetic resonance imaging (fMRI) investigations have identified several key cortical regions but have overlooked subcortical structures that have theoretical importance in humor processing. The dorsal striatum (DS) contributes to working memory, ambiguity processing, and cognitive flexibility, cognitive functions that are required to accurately recognize humorous stimuli. The ventral striatum (VS) is critical in reward processing and enjoyment. We hypothesized that the DS and VS play important roles in humor comprehension and appreciation, respectively. We investigated the engagement of these regions in these distinct processes using fMRI. Twenty-six healthy young male and female human adults completed two humor-elicitation tasks during a 3 tesla fMRI scan consisting of a traditional behavior-based joke task and a naturalistic audiovisual sitcom paradigm (i.e., Seinfeld viewing task). Across both humor-elicitation methods, whole-brain analyses revealed cortical activation in the inferior frontal gyrus, the middle frontal gyrus, and the middle temporal gyrus for humor comprehension, and the temporal cortex for humor appreciation. Additionally, with region of interest analyses, we specifically examined whether DS and VS activation correlated with these processes. Across both tasks, we demonstrated that humor comprehension implicates both the DS and the VS, whereas humor appreciation only engages the VS. These results establish the role of the DS in humor comprehension, which has been previously overlooked, and emphasize the role of the VS in humor processing more generally.SIGNIFICANCE STATEMENT Humorous stimuli are processed by the brain in at least two distinct stages. First, humor comprehension involves understanding humorous intent through cognitive and problem-solving mechanisms. Second, humor appreciation involves enjoyment, mirth, and laughter in response to a joke. The roles of smaller subcortical brain regions in humor processing, such as the DS and VS, have been overlooked in previous investigations. However, these regions are involved in functions that support humor comprehension (e.g., working memory ambiguity resolution, and cognitive flexibility) and humor appreciation (e.g., reward processing, pleasure, and enjoyment). In this study, we used neuroimaging to demonstrate that the DS and VS play important roles in humor comprehension and appreciation, respectively, across two different humor-elicitation tasks.


Cytological Diagnostic Procedures in Malignant Mesothelioma.
Malignant mesotheliomas (MM) are rare tumors with high mortality rates, whose incidence varies regionally and nationally, and the diagnosis is difficult. Histology-based diagnosis is considered the gold standard despite its low sensitivity of 57-84%. However, recent advances in cytological analysis offer promise for diagnostic advancements. In this study, we reappraised the current cytological guidelines for the MM diagnosis and concluded on their practicability and reliability. The study included 5731 consecutive specimens of pleural effusions from 4552 patients (3026 males of the average age of 67.5 years and 1526 females of the average age of 65.4 years) between December 2017 and January 2000. Out of these patients, 444 (9.8%) were diagnosed with MM. The effusions were examined by immunocytochemistry using routine Giemsa staining. Additionally, hyaluronic acid (HA) was assessed. Cytological findings confirmed 223 out of the 444 MM. The additional 88 cases with negative cytology were corroborated by supplemental assessments of HA above 30 mg/L. Cytological evaluation accomplished the sensitivity of 0.50, specificity of 0.99, and a positive predictive value (PPV) of 0.97 for MM diagnosis. The use of HA determination raised the sensitivity to 0.70 without affecting the specificity or PPV. We conclude that cytological evaluation of effusions aided by the assessment of HA demonstrates the diagnostic sensitivity and specificity for MM no less than the hitherto standard histological evaluation. The cytology-based MM diagnosis may thus be routinely considered when MM is suspected and may offer confirmatory advantages in difficult or doubtful diagnostic cases.


Posttraumatic stress disorder: epidemiology and health-related considerations.
Epidemiologic studies show that prevalence of trauma and posttraumatic stress disorder (PTSD) is substantial in modern society. Most people will experience a traumatic event at some point in their life, and up to 25% of them will develop the disorder. Demographic and socioeconomic factors also play a role in the risk for exposure to traumatic experiences and subsequent PTSD. Psychiatric history, both personal or in family members, increases the likelihood of being exposed to trauma and of developing PTSD once exposed. Traumatic exposure and PTSD have an impact on the individual's health, health care service utilization, and general functioning. Such effects provoke a considerable economic burden not only for those persons experiencing trauma and PTSD, but also for the health care system and society as a whole.


[Common channel syndrome--2 case reports].
The common channel syndrome is a disease mostly of young girls. To demonstrate the problems of diagnosis and therapy we report on 2 cases operated on in 1987 and 1989. The long delay of several years between the onset of symptoms and the diagnosis might be shortened by improved diagnostic possibilities (Ultrasound, ERCP). In any case of hyperamylasemia or chronic pancreatitis in childhood an obstruction of the biliary tract should be excluded. The common channel syndrome can be treated by means of sphincteroplasty or a bilidigestive anastomosis.


Effect of leisure time physical activity on blood lipid levels: the ATTICA study.
We aimed to evaluate the effect of leisure time physical activity on blood lipid levels, in a random sample of cardiovascular disease-free individuals from the Attica basin. The ATTICA study is a population-based cohort, which during 2001-2002 randomly enrolled 2772 men (n = 1376, 45 +/- 12 years old) and women (n = 1396, 45 +/- 13 years old). Physical activity status was evaluated through intensity (kcal/min expended per day), frequency (per week) and duration (min). Multivariate data analysis evaluated the association of blood lipids with physical activity levels. 578 (42%) men and 584 (40%) women were physically active. Compared to sedentary women, physically active women had lower levels of total cholesterol (P < 0.05), low-density lipoprotein (LDL) (P < 0.05), oxidized LDL-cholesterol (P < 0.05), triglycerides (P < 0.05) and apolipoprotein B (P < 0.05) and higher levels of high-density lipoprotein (HDL)-cholesterol (P < 0.05) and apolipoprotein A1 (P < 0.05). Similar associations were observed in men, but they did not reach statistical significance. However, after adjustments for age, smoking habits, body mass index and dietary intake were made, the effect of physical activity on blood lipids remained statistically significant only for HDL-cholesterol (P < 0.05) and apolipoprotein A1 (P < 0.05) levels in women. Moreover, physical activity was associated with lower total cholesterol levels both in nonsmoker men (-7%, P = 0.032) and nonsmoker women (-2%, P = 0.064) and lower triglyceride levels in nonsmoker men (-15%, P = 0.086) and nonsmoker women (-9%, P = 0.036). Although almost all blood lipids were inversely associated with physical activity status, only HDL-cholesterol and apolipoprotein A1 concentrations were significantly affected by exercise in women.


Impact of stone density on outcomes in percutaneous nephrolithotomy (PCNL): an analysis of the clinical research office of the endourological society (CROES) pcnl global study database.
This study aimed to explore the relationship between stone density and outcomes of percutaneous nephrolithotomy (PCNL) using the Clinical Research Office of the Endourological Society (CROES) PCNL Global Study database. Patients undergoing PCNL treatment were assigned to a low stone density [LSD, ≤ 1000 Hounsfield units (HU)] or high stone density (HSD, > 1000 HU) group based on the radiological density of the primary renal stone. Preoperative characteristics and outcomes were compared in the two groups. Retreatment for residual stones was more frequent in the LSD group. The overall stone-free rate achieved was higher in the HSD group (79.3% vs 74.8%, p = 0.113). By univariate regression analysis, the probability of achieving a stone-free outcome peaked at approximately 1250 HU. Below or above this density resulted in lower treatment success, particularly at very low HU values. With increasing radiological stone density, operating time decreased to a minimum at approximately 1000 HU, then increased with further increase in stone density. Multivariate non-linear regression analysis showed a similar relationship between the probability of a stone-free outcome and stone density. Higher treatment success rates were found with low stone burden, pelvic stone location and use of pneumatic lithotripsy. Very low and high stone densities are associated with lower rates of treatment success and longer operating time in PCNL. Preoperative assessment of stone density may help in the selection of treatment modality for patients with renal stones.


Microleakage under orthodontic brackets bonded with different adhesive systems.
This in vitro study aimed to compare the microleakage of orthodontic brackets between enamel-adhesive and adhesive-bracket interfaces at the occlusal and gingival margins bonded with different adhesive systems. A total of 144 human maxillary premolar teeth extracted for orthodontic reasons was randomly divided into four groups. Each group was then further divided into three sub-groups. Three total-etching bonding systems (Transbond XT, Greengloo and Kurasper F), three one-step self-etching bonding systems (Transbond Plus SEP, Bond Force and Clearfil S3), three two-step self-etching bonding systems (Clearfil SE Bond, Clearfil Protectbond and Clearfil Liner Bond), and three self-adhesive resin cements (Maxcem Elite, Relyx U 100 and Clearfil SA Cement) were used to bond the brackets to the teeth. After bonding, all teeth were sealed with nail varnish and stained with 0.5% basic fuchsine for 24 h. All samples were sectioned and examined under a stereomicroscope to score for microleakage at the adhesive-enamel and adhesive-bracket interfaces from both occlusal and gingival margins. Statistical analyses were performed with Kruskal-Wallis and Wilcoxon signed-rank tests. The results indicate no statistically significant differences between the microleakage scores of the adhesives; microleakage was detected in all groups. Comparison of the average values of the microleakage scores in the enamel-adhesive and adhesive-bracket interfaces indicated statistically significant differences (P < 0.05). The amount of the microleakage was higher at the enamel-adhesive interface than at the bracket-adhesive interface. All of the brackets exhibited some amount of microleakage. This result means that microleakage does not depend on the type of adhesive used.


Cholylglycine hydrolase and 7alpha-dehydroxylase optimum assay conditions in vitro and caecal enzyme activities ex vivo.
Increasing evidence implicates deoxycholic acid (DCA) in the pathogenesis of cholesterol-rich gallbladder stones. However, relatively little is known about the activities of the two intestinal bacterial enzymes (cholylglycine hydrolase and cholic acid 7alpha-dehydroxylase) responsible for the deconjugation and subsequent dehydroxylation of conjugated cholic acid (CA), to form DCA. We, therefore, established optimal reaction conditions for measuring the activities of these two enzymes in vitro, and applied these conditions to the determination of the enzymes in caecal aspirates from six subjects undergoing clinically-indicated colonoscopy. With respect to cholylglycine hydrolase activity: zero order kinetics were found over 20 min at 37 degrees C (pH optimum 4.0), with Km and Vmax values of 1.66 mmol/l and 0.90 mmol CA min(-1) mg prot(-1), respectively. For cholic acid 7alpha-dehydroxylation: zero order kinetics were found over 7.5 min at 37 degrees C, under anaerobic conditions (pH optimum 8.0), with Km and Vmax values of 5.23 x 10(-8) mol/l and 1.88 x 10(-7) mol DCA min(-1) mg prot(-1), respectively. Applying these reaction conditions to the caecal aspirates, endogenous cholylglycine hydrolase activities ranged from 0.49 to 2.43 units (mg protein[-1] min[-1]) and CA 7alpha-dehydroxylase activities from 1.75 to 5.82 x 10(-7) units (mg protein[-1] min[-1]). This study is unique in assaying quantitatively both the deconjugation and dehydroxylation enzyme activities in human caecal samples--an essential first step to further studies of intestinal bacterial enzymes in the pathogenesis of cholesterol gallstone disease.


[Localization of ATPase activity, respiration and ultrastructure of wheat root cells with modulated ion conductivity of plasma membrane].
Changes in the localization of ATPase activity, respiration and ultrastructure of wheat root cells with modulated ion conductivity of plasma membrane were studied. A 2 h treatment of excised root with valinomycin (20 microM), N,N-dicyclohexylcarbodiimid (100 microM), gramicidin S (20 microM) and chlorpromazine (100 microM) caused an increased loss of potassium by cells, a decreased respiration and changes in the localization of ATPase activity and in cell ultrastructure. Differences in the observed changes may be conditioned by different mechanisms of action of the membrane active compounds used. It is concluded that changes in the localization of ATPase activity and ultrastructure may indicate some early specific responses of root cells, whereas the increase in the ion conductivity and decrease in respiration under disruption of ion homeostasis caused by membrane active compounds indicate unspecific responses of cells.


Induction of c-fos transcripts in early postimplantation mouse embryos by TGF-alpha, EGF, PDGF, and FGF.
The activity of growth factor receptors in the early postimplantation mouse embryo was studied by analyzing changes in expression of mRNA transcripts of an early response gene, c-fos, after binding of specific ligands. Reverse transcription of mRNA coupled with the polymerase chain reaction was used to detect gene transcription in single embryos after exposure to growth factors. Postimplantation embryos (at 7.5 days of gestation) had physiologically active receptors for transforming growth factor-alpha (TGF-alpha), epidermal growth factor (EGF), human platelet-derived growth factor (PDGF), recombinant PDGF-AA homodimer, and basic fibroblast growth factor (FGF), as indicated by induced expression of c-fos mRNA, c-fos expression was not induced in untreated embryos or in embryos incubated with active recombinant PDGF-BB homodimer. These results show that growth factor receptors are functional during early mammalian embryogenesis.


Parental Support of Adult Children and Middle-Aged Couples' Marital Satisfaction.
Middle-aged adults commonly provide support to grown offspring. Yet little is known about how parental support may be related to parents' marital quality at midlife. This study explored couple patterns of support given to adult children and their implications for marital satisfaction. In a sample of 197 middle-aged couples from Wave 2 of the Family Exchanges Study, we estimated actor-partner interdependence models to evaluate the links between each spouse's reports of tangible and nontangible support given to adult children and their marital satisfaction. Wives and husbands were more satisfied with their marriage when they and their partner gave more frequent nontangible support to adult children. By contrast, wives and husbands were less satisfied with their marriage when they gave more frequent nontangible support to adult children and their partner gave low levels of this support. Findings shed light on the conditions under which support given to adult offspring may enhance or undermine marital quality. This study highlights the value of considering both individual and couple-level characteristics of parent-child relationships and their potential consequences for midlife couples.


Dietary Potassium Supplementation Reduces Chronic Kidney Lesions Independent of Blood Pressure in Deoxycorticosterone-Acetate and High Sodium Chloride-Treated Mice.
We have previously shown that an excess of deoxycorticosterone acetate and high sodium chloride intake (DOCA/salt) in one-renin gene mice induces a high urinary Na/K ratio, hypokalemia, and cardiac and renal hypertrophy in the absence of hypertension. Dietary potassium supplementation prevents DOCA/salt-induced pathological processes. In the present study, we further study whether DOCA/salt-treated mice progressively develop chronic inflammation and fibrosis in the kidney and whether dietary potassium supplementation can reduce the DOCA/salt-induced renal pathological process. Results showed that (1) long-term DOCA/salt-treated one-renin gene mice developed severe kidney injuries including tubular/vascular hypertrophy, mesangial/interstitial/perivascular fibrosis, inflammation (lymphocyte's immigration), proteinuria, and high serum creatinine in the absence of hypertension; (2) there were over-expressed mRNAs of plasminogen activator inhibitor-1 (PAI-1), fibronectin, collagen type I and III, interferon-inducible protein-10 (IP-10), monocyte chemotactic protein-1 (MCP1), transforming growth factor-β (TGF-β), tumor necrosis factor-alpha (TNF-α), osteopontin, Nuclear factor kappa B (NF-κB)/P65, and intercellular adhesion molecule (ICAM)-1; and (3) dietary potassium supplementation normalized urinary Na/K ratio, hypokalemia, proteinuria, and serum creatinine, reduced renal hypertrophy, inflammations, and fibrosis, and down-regulated mRNA expression of fibronectin, Col-I and III, TGF-β, TNF-α, osteopontin, and ICAM without changes in the blood pressure. The results provide new evidence that potassium and sodium may modulate proinflammatory and fibrotic genes, leading to chronic renal lesions independent of blood pressure.


Incidence of Peri-Implantitis and Relationship with Different Conditions: A Retrospective Study.
Articles on the prevalence of peri-implant diseases showed that 90% of peri-implant tissues had some form of inflammatory response and a prevalence of peri-implantitis from 28% to 51% according to various publications. Objective: To provide an overview of how risk factors can be related with peri-implantitis. Methods: A retrospective longitudinal study including 555 implants placed in 132 patients was evaluated based on the presence of peri-implantitis following the criteria of Renvert et al. 2018. Results: In total, 21 patients (15.9%) suffered peri-implantitis (PPG) and 111 patients (84.1%) did not suffer peri-implantitis (NPG). The results reveal that smokers have a high incidence of peri-implantitis (72.7%) compared to non-smokers (27.3%) (p < 0.0005). Another variable with significant results (p < 0.01) was periodontitis: 50% PPG and 23.9% NPG suffered advanced periodontitis. Systemic diseases such as arterial hypertension, diabetes mellitus, osteoporosis, and cardiovascular diseases do not show a statistically significant influence on the incidence of peri-implantitis. Patients who did not attend their maintenance therapy appointment had an incidence of peri-implantitis of 61.4%, compared to 27.3% in those who attend (p < 0.0001). From the results obtained, we can conclude that relevant factors affect peri-implantitis, such as tobacco habits, moderate and severe periodontitis, and attendance in maintenance therapy.