Impact of drinking of saline water on hemato-biochemical parameters of Black Bengal goats in the selected areas of Bangladesh.
Global climatic changes are contaminating ground and surface water sources around the world, resulting in increased salinity. Knowing the animals' typical physiological capability for salinity tolerance without compromising their health is a necessity. The research was undertaken to determine the impacts of drinking water salinity on hemato-biochemical parameters of Black Bengal goats. A total of 40 Black Bengal goats (20 male and 20 female), age ranging from 1 to 5 years, were randomly selected and divided into 2 groups. The animals of group 1 received higher saline water (12 ppt) and those in group 2 received lower saline water (1 ppt) as regular drinking water. Blood parameters of all selected goats were measured. Serum creatinine, uric acid, urea, potassium, sodium, and chloride were significantly higher (P< 0.05) in the animals of group 1 compared with group 2, although serum phosphorous was significantly lower (P < 0.05) in group 1 compared with group 2. There were no significant differences in serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), glucose, magnesium, and calcium between the animals of group 1 and 2. AST and magnesium differed significantly (P < 0.05) between young and adult goats in group 1. Glucose and urea levels were slightly higher (P < 0.05) in young goats. In both groups, male goats had significantly higher (P < 0.05) serum potassium and urea levels than female goats. The results suggest that Black Bengal goats of the coastal areas have different salt tolerance capacities based on their age and sex, and adapt to higher salinity by changing kidney functions.


Sorting Out Identities: An Educational Primer for Use with "Novel Tools for Genetic Manipulation of Follicle Stem Cells in the Drosophila Ovary Reveal an Integrin-Dependent Transition from Quiescence to Proliferation".
Organisms are made up of thousands of different cell types that must migrate, proliferate, and interact with each other to yield functional organ systems and ultimately a viable organism. A characteristic that distinguishes one cell type from another is the set of genes that it expresses. An article by Hartman et al. in the April 2015 issue of GENETICS identified methods to uniquely identify different cell populations during oogenesis, providing valuable tools for future studies. This Primer article provides background information on the Drosophila ovary as a system in which to study stem cell regulation, mechanisms for regulating gene expression, and the techniques used by Hartman et al. to identify specific cell populations and study their function.


Word recognition and orthographic context effects in a letter-by-letter reader.
The performance of letter-by-letter readers when attempting to decipher written material gives the impression that words fail to directly evoke any higher-level representation. As a consequence, spelling patterns appear to be treated perceptually as if they were a collection of random letters. We tested the hypothesis that words are no longer mapped onto orthographic descriptions by examining the ability of a letter-by-letter reader to identify letters in familiar words, pseudowords, and random strings. A clear effect of orthographic context was obtained on the accuracy of letter recognition, indicating that spelling patterns do gain access to more central components of the reading mechanism. The implications of this result for our understanding of the syndrome are discussed.


HIV pre-exposure prophylaxis in transgender women: a subgroup analysis of the iPrEx trial.
Pre-exposure prophylaxis (PrEP) with oral emtricitabine and tenofovir disoproxil fumarate is used to prevent the sexual acquisition of HIV in groups at high risk such as transgender women. We used data from the iPrEx study to assess PrEP efficacy, effectiveness, and adherence in transgender women. The iPrEx trial was a randomised controlled trial of PrEP with oral emtricitabine plus tenofovir disoproxil fumarate compared with placebo in men who have sex with men (MSM) and transgender women, followed by an open-label extension. Drug concentrations were measured in blood by liquid chromatography and tandem mass spectroscopy. We did unplanned exploratory analyses to investigate differences in PrEP outcomes among transgender women and between transgender women and MSM. Of the 2499 participants enrolled in the randomised controlled trial, 29 (1%) identified as women, 296 (12%) identified as trans, 14 (1%) identified as men but reported use of feminising hormones, such that 339 (14%) reported one or more characteristics and are classified as transgender women for the purpose of this study. Compared with MSM, transgender women more frequently reported transactional sex, receptive anal intercourse without a condom, or more than five partners in the past 3 months. Among transgender women, there were 11 HIV infections in the PrEP group and ten in the placebo group (hazard ratio 1·1, 95% CI 0·5-2·7). In the PrEP group, drug was detected in none of the transgender women at the seroconversion visit, six (18%) of 33 seronegative transgender women (p=0·31), and 58 (52%) of 111 seronegative MSM (p<0·0001). PrEP use was not linked to behavioural indicators of HIV risk among transgender women, whereas MSM at highest risk were more adherent. PrEP seems to be effective in preventing HIV acquisition in transgender women when taken, but there seem to be barriers to adherence, particularly among those at the most risk. Studies of PrEP use in transgender women populations should be designed and tailored specifically for this population, rather than adapted from or subsumed into studies of MSM. US National Institutes of Health and the Bill & Melinda Gates Foundation.


Clinical application of RT-nested PCR integrated with RFLP in Hantavirus detection and genotyping: a prospective study in Shandong Province, PR China.
The aim of the present study was to evaluate the clinical usefulness of applying RT-nested PCR along with RFLP as a method for diagnosis and genotypic differentiation of Hantavirus in the acute-stage sera of HFRS patients as compared to the ELISA technique. A prospective study of patients with suspected HFRS patients was carried out. Sera were collected for serological evaluation by ELISA and RT-nested PCR testing. Primers were selected from the published sequence of the S segment of HTNV strain 76-118 and SEOV strain SR-11, which made it possible to obtain an amplicon of 403 bp by RT-nested PCR. The genotypic differentiations of the RT-nested PCR amplicons were carried out by RFLP. Sequence analyses of the amplicons were used to confirm the accuracy of the results obtained by RFLP. Of the 48 acute-stage sera from suspected HFRS patients, 35 were ELISA-positive while 41 were positive by RT-nested PCR. With Hind III and Hinf I, RFLP profiles of the RT-nested PCR amplicons of the 41 positive sera exhibited two patterns. 33 had RFLP profiles similar to the reference strain R22, and thus belonged to the SEOV type. The other 8 samples which were collected during October-December had RFLP profiles similar to the reference strain 76-118, and thus belonged to the HTNV type. Sequence phylogenetic analysis of RT-nested PCR amplicons revealed sdp1, sdp2 YXL-2008, and sdp3 as close relatives of HTNV strain 76-118, while sdp22 and sdp37 as close relatives of SEOV strain Z37 and strain R22 located in two separate clusters in the phylogenetic tree. These results were identical to those acquired by RFLP. RT-nested PCR integrated with RFLP was a rapid, simple, accurate method for detecting and differentiating the genotypes of Hantavirus in the acute-stage sera of suspected HFRS patients. In Shandong province, the main genotypes of Hantavirus belonged to the SEOV types, while the HTNV types were observed during the autumn-winter season.


Reaching Out to Send a Message: Proteins Associated with Neurite Outgrowth and Neurotransmission are Altered with Age in the Long-Lived Naked Mole-Rat.
Aging is the greatest risk factor for developing neurodegenerative diseases, which are associated with diminished neurotransmission as well as neuronal structure and function. However, several traits seemingly evolved to avert or delay age-related deterioration in the brain of the longest-lived rodent, the naked mole-rat (NMR). The NMR remarkably also exhibits negligible senescence, maintaining an extended healthspan for ~75 % of its life span. Using a proteomic approach, statistically significant changes with age in expression and/or phosphorylation levels of proteins associated with neurite outgrowth and neurotransmission were identified in the brain of the NMR and include: cofilin-1; collapsin response mediator protein 2; actin depolymerizing factor; spectrin alpha chain; septin-7; syntaxin-binding protein 1; synapsin-2 isoform IIB; and dynamin 1. We hypothesize that such changes may contribute to the extended lifespan and healthspan of the NMR.


EUS and EUS-FNA diagnosis of suspected pancreatic cystic neoplasms: Is the sum of the parts greater than the CEA?
Carcinoembryonic antigen (CEA) is suggested as the single most useful EUS/EUS-FNA derived test for the diagnosis of mucinous pancreatic cysts. To investigate the yield and diagnostic performance of EUS/EUS-FNA on an intention to diagnose basis and to determine the utility of the recommended CEA and amylase cut-off values. A retrospective study of a prospectively maintained database of 433 procedures performed in a 10 year period. Diagnostic performance of EUS-FNA was determined in 133 procedures with a definite diagnosis. CEA value was determined in significantly fewer procedures (58.6%) than EUS diagnosis was stated (83.4%; p < 0.0001), cyst fluid appearance recorded (89.4%) or adequate sample for cytology obtained (76.7%; p < 0.005). Median CEA was significantly higher in mucinous cysts than non-mucinous (175 ng/ml vs 3 ng/ml, p < 0.0001) and in malignant cysts compared to benign (8945 ng/ml vs 93 ng/ml, p < 0.001). On an intention-to-diagnose analysis, a CEA cut-off of 110 ng/ml was significantly less accurate (42.8%) than EUS diagnosis (67.7%), cytology (58.6%) or aspirate appearance (66.9%; p < 0.05 for all comparisons). However, the combination of EUS diagnosis, cytology and CEA provided higher sensitivity (91%), specificity (75%) and accuracy (85.7%) than each component test alone (p < 0.05 for all comparisons). Median amylase was significantly higher in benign compared to high-risk mucinous cysts ((11,429IU/L vs. 113IU/L; p < 0.05. The combination of EUS, cytology and CEA performed well. Malignant cysts had a higher CEA value than benign cysts. On an intention to diagnose basis a CEA cut-off of 110 ng/ml performed poorly.


Differential antiproliferative actions of 2',5' oligo A trimer core and its cordycepin analogue on human tumor cells.
The antiproliferative effect of 2',5' A3 core and 2',5'-3'dA3 (cordycepin trimer) core was measured in 8 human tumor cell lines. Cells were treated in a dose-response manner for 72 hr and the concentration of drug necessary to inhibit cell growth 50% (GI50) was determined. A wide range of sensitivities to these drugs was found, even among tumors of the same histological type. The cell lines showed different sensitivities and dose-response curves to the 2',5'A3 and 2',5'-3'dA3 cores. Uptake studies of the 2',5'A3 and 2',5'-3'dA3 cores, using high-pressure liquid chromatography, demonstrated that both cores were rapidly degraded in the tissue culture medium and taken up as adenosine or cordycepin, respectively. There was a direct correlation between the uptake of cordycepin and the antiproliferative effect. In contrast, there was no correlation between cell sensitivity and the uptake of the 2',5'A3 core degradation products. Analysis of intracellular nucleosides and nucleotides indicated that differences in intracellular metabolism of adenosine might explain the different sensitivities of the various cell lines to 2',5'A3 core. Molar equivalent concentrations of adenosine and cordycepin inhibited cell growth; however, equimolar concentrations of these nucleosides were not effective. In addition, the antiproliferative effect of both core compounds and their corresponding nucleosides could be potentiated by the addition of the adenosine deaminase inhibitor, deoxycoformycin. The results indicate that these cores act as prodrugs and that the active metabolites are their corresponding nucleosides.


Contextual factors and spatial trends of childhood malnutrition in Zambia.
Understanding the national burden and epidemiological profile of childhood malnutrition is central to achieving both national and global health priorities. However, national estimates of malnutrition often conceal large geographical disparities. This study examined the prevalence of childhood malnutrition across provinces in Zambia, changes over time, and identified factors associated with the changes. We analyzed data from the 2013/4 and 2018 Zambia demographic and health surveys (ZDHS) to examine the spatial heterogeneity and mesoscale correlates of the dual burden of malnutrition in children in Zambia. Maps illustrating the provincial variation of childhood malnutrition were constructed. Socio-demographic and clinical factors associated with childhood malnutrition in 2013 and 2018 were assessed independently using a multivariate logistic model. Between 2013/4 and 2018, the average prevalence of stunting decreased from 40.1% (95% CI: 39.2-40.9) to 34.6% (95% CI:33.6-35.5), wasting decreased from 6.0% (95% CI: 5.6-6.5) to 4.2% (95% CI: 3.8-4.7), underweight decreased from 14.8% (95% CI: 14.1-15.4) to 11.8% (95% CI: 11.2-12.5) and overweight decreased from 5.7% (95% CI: 5.3-6.2) to 5.2% (95% CI: 4.8-5.7). High variability in the prevalence of childhood malnutrition across the provinces were observed. Specifically, stunting and underweight in Northern and Luapula provinces were observed in 2013/14, whereas Lusaka province had a higher degree of variability over the two survey periods. The study points to key sub-populations at greater risk and provinces where malnutrition was prevalent in Zambia. Overall, these results have important implications for nutrition policy and program efforts to reduce the double burden of malnutrition in Zambia.


Variations in the postnatal maternal environment in mice: effects on maternal behaviour and behavioural and endocrine responses in the adult offspring.
According to the maternal mediation hypothesis, brain and behavioural development in rodents is affected by environment-dependent variations in maternal care. Thus, it has been shown that early handling results in reduced behavioural and neuroendocrine responses to stressors and that these effects are associated with increased maternal care received during infancy. To investigate this further in mice, we chose a less artificial paradigm that is not confounded by human manipulation and reflects a more natural form of early environmental variation. We housed lactating C57BL/6 dams and their litters in cage systems composed of a nest cage (NC) and a foraging cage (FC) connected by a tunnel, and varied the dams' access to food by providing food either in the NC (NC dams) or FC (FC dams) until postnatal day 14. FC dams were more frequently observed in the FC than NC dams, and although the frequency of the dams being in physical contact with the pups did not differ between the two treatments, FC dams showed lower levels of active nursing than NC dams during the first week of lactation. These environment-dependent variations in maternal behaviour had sex-specific effects on the adult offspring's behavioural and HPA responses to stressors and altered their social behaviour in the home cage, with NC offspring showing higher levels of socio-positive behaviours than FC offspring. These results provide further independent evidence for the maternal mediation hypothesis and demonstrate that even subtle variations of the maternal environment can affect maternal care and induce persistent changes in offspring phenotype.


Right Atrial Pressure Predicts Mortality Among LVAD Recipients: Analysis of the INTERMACS Database.
Risk stratifying candidates for left ventricular assist device (LVAD) is challenging. While INTERMACS profiles provide some prognostic insights, there is an ongoing search for better tools. We studied pre-LVAD haemodynamic parameters in predicting post-LVAD mortality. We analysed the INTERMACS dataset for the ability of right atrial pressure (RAP), pulmonary capillary wedge pressure (PCWP), pulmonary arterial systolic (PASP) and diastolic pressures (PADP), mean pulmonary artery pressure, transpulmonary gradient, cardiac output, cardiac power output and INTERMACS profiles, all recorded before LVAD implantation, to predict mortality. Among 18,733 patients in the INTERMACS dataset, we found that, RAP was the main significant haemodynamic predictor of mortality (13.1 vs. 14.4 mmHg in survivors and non-survivors, respectively, p<0.001), and a higher RAP also predicted the need for extra-corporeal membrane oxygenation (ECMO) support (p<0.001) and intra-aortic balloon pump (p<0.001). Right atrial pressure had a significantly higher area under the curve (AUC) in predicting mortality compared with PASP (difference between areas 0.0338, p<0.0001), PADP (difference between areas 0.0414, p<0.0001), PCWP (difference between areas 0.0290, p=0.0001) and pulmonary artery pulsatility index (difference between areas 0.0105, p=0.0052). Kaplan Meier survival curves showed that RAP≥13 mmHg was the optimal cut-off value to predict mortality (log-rank p<0.001). On Cox regression analysis, RAP remained an independent predictor of mortality (hazard ratio 1.008, 95% confidence interval 1.003-1.013, p=0.003) after covariate adjustment. According to time of death, a higher RAP remained a significant predictor of mortality at 1 month, 3 months, 6 months, 1 year, and beyond 1 year (all p<0.001). RAP remained a predictor for mortality within INTERMACS profiles. After excluding early deaths (first 3 months), the RAP remained a significant predictor of mortality, while INTERMACS profiles were no longer significant. In general, haemodynamic variables, as well as other criteria including INTERMACS profiles, are weak predictors of mortality. Right atrial pressure is the main consistent haemodynamic predictor of mortality in LVAD recipients. It outperforms other haemodynamic parameters, and keeps its value within each INTERMACS profile.


Chmp1A acts as a tumor suppressor gene that inhibits proliferation of renal cell carcinoma.
Renal cell carcinoma (RCC) is a highly malignant and often fatal disease of the kidney. Chmp1A is a member of the Endosomal Sorting Complex Required for Transport (ESCRT-III) family, and plays a role in the cytoplasm in sorting proteins to the multivesicular body (MVB). Chmp1A functions as a tumor suppressor gene and has been reported in pancreatic tumor cells. Here, we examined the expression level of Chmp1A in human RCC tissues and renal tumor cells by real-time quantitative RT-PCR and western blot. We found that the expression level of Chmp1A is significantly lower in RCC tissues and renal tumor cells compared with adjacent non-tumorous tissues and normal renal cells. Additionally, inhibition of Chmp1A expression by shRNA induced tumor formation in normal renal cells. However, inhibition of Chmp1A did not significantly affect tumor cell proliferation in vitro and tumor progression in vivo. Interestingly, overexpression of Chmp1A using a eukaryotic plasmid inhibited the proliferation of renal tumor cells in vitro and the growth of renal tumor in vivo. Thus, our results demonstrate that Chmp1A functions as a tumor suppressor gene in renal cells and may be a useful target for treatment of RCC.


Risk factors for coexisting deep endometriosis for patients with recurrent ovarian endometrioma.
The aim of this study was to assess the risk factors for coexisting deep endometriosis (DE) in patients with recurrent ovarian endometrioma (OE). We retrospectively reviewed 151 recurrent OE patients who had been diagnosed of OE but not DE at the time of their first surgery and then received a second surgery for recurrent endometriosis with or without DE. Their clinical characteristics at the time of the first and second surgeries were collected. Univariate and multivariate logistic regression analyses were conducted to identify potential risk factors for coexisting DE in patients with recurrent OE. Among the 151 recurrent OE patients, 46 were diagnosed of DE during the recurrent surgery and included in the DE group, while the remaining 105 patients were included in the non-DE group. In univariate analysis, there were significant differences in terms of uterine retroversion during the primary surgery and the follow-up time after the primary surgery between the DE and non-DE groups. The multivariate analysis also showed that both uterine retroversion and the follow-up time (≥5 years) were associated with the coexistence of DE during the recurrent surgery. The odds ratio (OR) for uterine retroversion was 3.72 [95% confidence interval (CI) 1.62-8.53], and the OR for follow-up time (≥5 years) was 5.03 (95% CI 2.29-11.02). Our study suggested that for recurrent OE patients, uterine retroversion during the first surgery and a follow-up time of at least 5 years are risk factors for the coexistence of DE in recurrent surgery, early prevention and full preparation before the recurrent surgery should be emphasized in these conditions.


Mimicking Enzymatic Non-Covalent Interactions with Functionalized Covalent Organic Frameworks for Improved Adsorption and Hydrolysis of Cellobiose.
Tuning catalytic centers in heterogeneous catalyst, both in a chemical and a spatial manner, is a powerful approach to improve the stability and the efficiency of catalysts. While the chemical aspects are largely understood, the spatial interactions around active sites, comprised of non-covalent interactions, are difficult to maintain and challenging to study. Herein, the unique properties of covalent organic frameworks (COFs) are utilized to establish an ideal reaction environment for the hydrolysis of cellobiose and other common disaccharides in mild, metal-free, and neutral aqueous conditions. The chosen COF, HCl-PSA-IM-COF-OMe ("HCl" for hydrochloric acid, "PSA" for propyl sulfonic acid, "IM" for imidazole, and "OMe" for methoxy), is modified to be ultra-stable in aqueous conditions and possesses sulfonic acid groups for general acid catalysis and for enhanced hydrogen bonding with reactants as well as intraporous chloride anions for oxocarbenium intermediate stabilization. In addition, the system also relies on the differences in adsorptive binding behavior, Kads , of the reactants and the products to the functionalized framework and benefits from a separate physical, kinetic process to boost the catalytic cycle. Due to its stability in aqueous conditions, HCl-PSA-IM-COF-OMe can be recycled and maintains its hydrolytic properties for five cycles before regeneration is needed.


A new bifunctional chelator enables facile biocoupling and radiolabeling as the basis for a bioconjugation kit.
A new tridentate bifunctional chelator, N-(-2-picolyl)(-4-hydroxy)(-3-amino)benzoic acid (PHAB), was designed to efficiently coordinate the [(99m)Tc(CO)3](+) core and facilitate coupling reactions to biomolecules. The chelator can be procured in the form of the corresponding benzotriazole ester (PHAB-OBT), which can be stored and used as a bioconjugation kit. PHAB-OBT reacts with modified carbohydrates with high selectivity and efficiency in a single step in both aqueous and organic media. As is desirable for a kit, no complicated chemical bench work is required. Glycoconjugate postlabeling resulted in neutral radiolabeled glycans with high radiochemical yields. Prelabeling approaches were assessed by successive reaction of PHAB-OBT with the [(99m)Tc(CO)3](+) core and a modified galactose model. The radiolabeled galactose was obtained in 84% yield as defined by HPLC analysis. Biodistribution of the radioactive (99m)Tc-labeled chelator, as well as the glycoconjugates, were examined in mice. Noticeably different biodistribution patterns were observed that reflect trends in the uptake of carbohydrate analogues by various organs.


Cerebral malaria and the hemolysis/methemoglobin/heme hypothesis: shedding new light on an old disease.
Malaria causes more than 1 million deaths every year with cerebral malaria (CM) being a major cause of death in Sub-Saharan African children. The nature of the malaria-associated pathogenesis is complex and multi-factorial. A unified hypothesis involving sequestration of infected red blood cells, systemic host inflammatory response and hemostasis dysfunction has been proposed to explain the genesis of CM. In this review, we discuss the role of hemolysis, methemoglobin and free heme in CM, brought to light by our recent studies in mice as well as by other studies in humans.


Association between subthalamic nucleus deep brain stimulation and weight gain: Results of a case-control study.
To evaluate whether weight change in patients with Parkinson's disease (PD) is different in those undergoing deep brain stimulation (DBS) of the subthalamic nucleus (STN) compared to those not undergoing DBS. A retrospective case-control study was performed in PD patients who had undergone STN DBS (cases) compared to matched PD patients without DBS (controls). Demographic and clinical data including Unified Parkinson's Disease Rating Scale (UPDRS) motor scores were collected. Repeated measures mixed model regression was used to identify variables associated with weight gain. Thirty-five cases and 34 controls were identified. Baseline age, gender, diagnosis and weight were similar. Duration of diagnosis was longer in cases (6.3 vs 4.9 years, p=0.0015). At 21.3 months, cases gained 2.9 kg (+4.65%) while controls lost 1.8 kg (-3.05%, p<0.02). Postoperative UPDRS motor scores improved by 49% indicating surgical efficacy. Only younger age (p=0.0002) and DBS (p=0.008) were significantly associated with weight gain. In this case-control study, PD patients undergoing STN DBS experienced post-operative weight gain that was significantly different from the weight loss observed in non-DBS PD controls. Patients, especially overweight individuals, should be informed that STN DBS can result in weight gain.


Intranasal corticosteroids: the development of a drug delivery device for fluticasone furoate as a potential step toward improved compliance.
Devices for the aqueous delivery of intranasal corticosteroids to patients with allergic rhinitis have been available since 1984, so there is a need for new devices to be developed to provide ease of use, efficacy and safety. A novel drug delivery system has been developed for fluticasone furoate (FF; GlaxoSmithKline): a new enhanced-affinity glucocorticoid with a scent-free formulation. The FF system was developed, giving attention to patients' unmet needs, in order to promote acceptance and compliance. It demonstrates a number of key features including its ergonomic design, side-actuation system and short delivery nozzle. Exploiting issues with present devices highlighted the need for the FF system. This review reports data from key studies and surveys conducted by GlaxoSmithKline during development, to determine ease of use and acceptance of the FF system. Findings suggest that the FF system should aid in improving attitudes to the use of intranasal corticosteroids amongst physicians and patients.


Health-related quality of life in Parkinson's: impact of 'off' time and stated treatment preferences.
Long-term levodopa therapy and related fluctuating plasma concentrations are associated with between-dose periods of 'off time' resulting in substantial variation in symptoms and functioning throughout the day in people with Parkinson's (PwP). PwP across UK, France, Spain and Italy completed an online survey to explore: the impact of 'off time' on (1) health-related quality of life (HRQL) and (2) on functioning and ability to undertake usual activities; (3) the value of 'off time' relative to other factors associated with Parkinson's through a stated preference discrete choice experiment (SPDCE). In total, 305 PwP completed the online survey. Overall mean HRQL (utility) score was significantly lower for 'off time' (0.37) than for 'on time' (0.60). All attributes within the SPDCE were significant predictors of treatment choice, although increased duration of 'on time' (per hour per day: odds ratio (OR) = 1.40) and predictability of 'off time' to within 30 min (OR = 1.42) were valued most highly. 'On time' and predictability of 'off time' are highly valued by PwP. Due to substantial diurnal variation of Parkinson's symptoms, standard patient-reported outcome (PRO) assessments may not adequately capture the impact of 'off time' on HRQL and participation in daily activities.


Comparison of Emla cream and lidocaine injection for local anaesthetic before radiofrequency reduction of the inferior turbinates.
We compared the effectiveness of local anaesthetic with Emla cream with that of an injection of lidocaine for radiofrequency reduction of the inferior turbinates. We studied 98 consecutive patients with hypertrophied inferior turbinates, 46 of whom were given Emla cream and 52 lidocaine injection. The procedure began five minutes after the injection of lidocaine and 10minutes after the Emla cream had been applied. Patients were asked to indicate on a visual analogue scale (VAS) the degree of perioperative pain, anxiety, sensation of choking, and discomfort on swallowing that they felt after the procedure. Patients treated with Emla had significantly lower VAS scores for discomfort on swallowing than those treated with lidocaine (p=0.001), but there were no other significant differences between the two groups. We conclude that Emla cream is an efficacious alternative to infiltration of lidocaine for radiofrequency reduction of the inferior turbinates.


On the ecogenetics of Stellaria media (L.) Vill. and Stellaria pallida (Dum.) pire from abandoned arable field.
Isoenzyme analyses were carried out on the hypotetraploid Stellaria media and the diploid Stellaria pallida occurring on abandoned sandy fields in the coastal dunes of the Netherlands. Amylase isoenzymes in germinating seeds of Stellaria media showed a striking intrapopulational variability, which is in accordance with the germination behaviour of the different subpopulations. In contrast to these findings no intrapopulational variation nor developmental change in isoenzyme pattern could be detected on basis of 14 other analysed leaf enzymes. For five enzymes there was a difference in isoenzyme pattern between the species Stellaria media and Stellaria pallida. Of these five enzymes two showed an interpopulational variation in Stellaria media. The fact that there was almost no variability of the isoenzyme pattern in Stellaria pallida could be explained by the permanent autogamous (cleistogamous) state of the species. Effects of polyploidy on the isoenzyme pattern and its activity could not be demonstrated. Consequences of the extreme difference between the monomorphic pattern of the leaf enzymes as opposed to the polymorphism of the amylase are discussed in view of the difference in germination ecology and lifecycle strategy of Stellaria media subpopulations.


Autologous peripheral blood mononuclear cell implantation for patients with peripheral arterial disease improves limb ischemia.
Implantation of bone marrow mononuclear cells, including endothelial progenitor cells, into ischemic limbs has been shown to improve collateral vessel formation. In the present study the safety and feasibility of autologous peripheral blood mononuclear cells (PBMNCs) implantation after granulocyte-colony stimulating factor (G-CSF)-induced mobilization was investigated in patients with severe peripheral arterial disease. Six cases were enrolled: 5 of thromboangitis obliterans and 1 of arteriosclerosis obliterans. Following administration of G-CSF (10 microg . kg(-1) . day(-1)), PBMNCs were harvested and injected intramuscularly (5 legs and 1 arm) for 2 days for the patients with ischemia of the legs. No serious adverse events related to G-CSF administration, harvest or implantation were observed during this study period. Improvement in the ankle - brachial pressure index (ABI: >0.1) was seen in 4 patients at 4 weeks and ischemic ulcers improved in 3 of 3 patients. The mean maximum walking distance significantly increased from 203 m to 559 m (p=0.031) at 4 weeks and was sustained for 24 weeks. Significant improvement was seen in physiological functioning subscale of Short Form-36. Implantation of PBMNCs collected after G-CSF administration could be an alternative to therapeutic angioplasty in patients with severe peripheral arterial disease.


Genome-wide noninvasive prenatal screening for carriers of balanced reciprocal translocations.
Balanced reciprocal translocation carriers are at increased risk of producing gametes with unbalanced forms of the translocation leading to miscarriage, fetal anomalies, and birth defects. We sought to determine if genome-wide cell-free DNA based noninvasive prenatal screening (gw-NIPS) could provide an alternative to prenatal diagnosis for carriers of these chromosomal rearrangements. This pilot series comprises a retrospective analysis of gw-NIPS and clinical outcome data from 42 singleton pregnancies where one parent carried a balanced reciprocal translocation. Gw-NIPS was performed between August 2015 and March 2018. Inclusion criteria required at least one translocation segment to be ≥15 Mb in size. Forty samples (95%) returned an informative result; 7 pregnancies (17.5%) were high risk for an unbalanced translocation and confirmed after diagnostic testing. The remaining 33 informative samples were low risk and confirmed after diagnostic testing or normal newborn physical exam. Test sensitivity of 100% (95% confidence interval [CI]: 64.6-100%) and specificity of 100% (95% CI: 89.6-100%) were observed for this pilot series. We demonstrate that gw-NIPS is a potential option for a majority of reciprocal translocation carriers. Further confirmation of this methodology could lead to adoption of this noninvasive alternative.


PVP encapsulated MXene coated on PET surface (PMP)-based photocatalytic materials: A novel photo-responsive assembly for the removal of tetracycline.
Tetracycline (TC) antibiotic that is effective against wide-range micro-organisms, thereby used to control bacterial infection. The partial metabolism of TC antibiotics in humans and animals leads to the contamination of TC in the environments like water bodies. Thus, requirements to treat/remove/degrade TC antibiotics from the water bodies to control environmental pollution. In this context, this study focuses on fabricating PVP-MXene-PET (PMP) based photo-responsive materials to degrade TC antibiotics from the water. Initially, MXene (Ti2CTx) was synthesized using a simple etching process from the MAX phase (Ti3AlC2). The synthesized MXene was encapsulated using PVP and cast onto the surface of PET to fabricate PMP-based photo-responsive materials. The rough surface and micron/nano-sized pores within the PMP-based photo-responsive materials might be improved the photo-degradation of TC antibiotics. The synthesized PMP-based photo-responsive materials were tested against the photo-degradation of TC antibiotics. The band gap value of the MXene and PMP-based photo-responsive materials was calculated to be ∼1.23 and 1.67 eV. Incorporating PVP within the MXene increased the band gap value, which might be beneficial for the photo-degradation of TC, as the minimum band gap value should be ∼1.23 eV or more for photocatalytic application. The highest photo-degradation of ∼83% was achieved using PMP-based photo-degradation at 0.1 mg/L of TC. Furthermore, ∼99.71% of photo-degradation of TC antibiotics was accomplished at pH ∼10. Therefore, the fabricated PMP-based photo-responsive materials might be next-generation devices/materials that efficiently degrade TC antibiotics from the water.


Electrophoretic elution of proteins from polyacrylamide gel slices.
A method for electrophoretic elution of proteins from polyacrylamide gel slices is described. Eluted proteins were retained by a discontinuous conductivity gradient (M. Otto and M. Snejdárková, Anal. Biochem. 111, 111-114 (1981)). The method has been adapted to slices from slab gels and gels that have been stained and destained. Proteins were eluted as their sodium dodecyl sulfate complexes. Minute amounts of proteins (0.1 microgram) were recovered in high yield (85-95%) in 2 h in less than 0.1 ml volume.


Development of a sterile cold-smoked fish model.
It is difficult to create a successful sterile cold-smoked fish model, particularly when very fresh fish are not readily available. This study tested a low-dose ionization technique (1.5 and 3.0 kGy) as a means of eliminating residual flora and ensuring sterility without altering sensory qualities. Ionized cold-smoked salmon displayed no bacterial contamination during an 11 week storage period and was not considered as spoiled by a sensory panel. In comparison, non-ionized smoked salmon, although aseptically processed, contained a bacterial flora responsible for its spoilage. This model allows assessment of the spoilage potential or activity of isolated bacterial strains as well as independent studies of bacterial and non-bacterial reactions in cold-smoked fish.


Leaf palatability, life expectancy and herbivore damage.
Observations on leaves from plants with a wide range of life-forms, ruderals to trees, indicate that palatability to insect herbivores is strongly correlated with the life-expectancy of the leaves. The amount of damage suffered in the field is however inversely correlated with palatability; although the rate of damage is less on unpalatable leaves, their longer life means that they accumulate damage over a longer period. It is only with extremely well-defended evergreen leaves, that the total damage is less than that experienced by less palatable (but short-lived) leaves. These observations are related to the current theories on relative palatability (the apparency theory and the resource availability theory), within the framework of the habitat templet.


bla(OXA-51)-type beta-lactamase genes are ubiquitous and vary within a strain in Acinetobacter baumannii.
We investigated the spread of bla(OXA-51)-type beta-lactamase genes in 200 Acinetobacter spp. clinical strains isolated in Argentina from 1982 to 2005. bla(OXA-51)-type genes were present in all Acinetobacter baumannii isolates tested (n=194), whereas they were not detected in two Acinetobacter haemolyticus, two genomic species 10 or two Acinetobacter lwoffii isolates. The bla(OXA-51)-type alleles varied within a strain and were found in six different A. baumannii pulsed-field gel electrophoresis clones that were susceptible or resistant to imipenem, suggesting a controversial role in imipenem resistance. Our findings agree with previous reports showing that bla(OXA-51)-type genes are naturally harboured by A. baumannii isolates from various geographical origins and support the presence of a direct reservoir of beta-lactam resistance genes within the nosocomial environment.


In vitro antioxidant and free-radical scavenging activities of polar leaf extracts of Vernonia amygdalina.
Plants are able to deliver a huge number of differing bioactive compounds which may supplement the requirements of the human body by acting as natural antioxidants. Antioxidants are mindful for the defense component of the life form against the pathologies related to the assault of free radicals. The main purpose of this study was to investigate the qualitative phytochemical composition of Vernonia amygdalina leaf extract and its antioxidant activity. The powdered plant sample was successively extracted with aqueous, methanol and ethanol solvents using Soxhlet apparatus. The antioxidant activities of the crude leaf extract were determined using 1, 1- diphenyl-2-picryl hydrazyl (DPPH) radical, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical, phosphomolybdate (PM) and hydrogen peroxide (H2O2) scavenging assay. All the examinations were drained triplicates and average values of each test were taken. Phytochemical investigation of the plant revealed that the three solvent extracts contained numerous bioactive compounds namely alkaloids, tannins, saponins, phenols, terpenoids, steroids, glycosides and sugars. The result showed that, the leaf extracts of V. amygdalina obtained from methanol extract exhibit the maximum antioxidant activity compared ethanol and aqueous extracts. The IC50 values of DPPH assay for the H2O, MeOH and EtOH extracts were 111.4, 94.92 and 94.83 μg/ml; of ABTS assay were 334.3, 179.8 and 256.9 μg/ml; of H2O2 assay were 141.6, 156 and 180.6 μg/ml, respectively. The maximum radical scavenging activity was obtained in DPPH assay while the lowest scavenging activity was obtained in ABTS assay method. The data obtained in the in vitro models clearly suggest that methanol extract has higher antioxidant activity due to a higher presence of phenolic constituents in the extract. This study revealed that V. amygdalina leaf has a noteworthy antioxidant and free radical scavenging activity mitigating the traditional use of the plant for different aliments.


Breast reconstruction after neoadjuvant radio chemotherapy: review and personal technique IDEAL concept REV-EJMR-D-15-00268.
Neoadjuvant radio chemotherapy and immediate reconstruction for breast cancer are still under debate. But there are recent abstracts and articles which show that neoadjuvant radio chemotherapy is feasible and could improve the clinical outcome of breast cancer patients. The aim of this review is to present the authors' techniques and approaches with regard to neoadjuvant radiation of breast cancer patients. It seems that the concept of immediate implant delayed autologous breast reconstruction could be a safe procedure that is at least equivalent to primary autologous reconstruction.


Direct catalytic asymmetric alkynylation of ketoimines.
An efficient protocol for direct catalytic alkynylation of ketoimines is described. The simultaneous activation of a soft Lewis basic terminal alkyne and a ketoimine bearing a thiophosphinoyl group by soft Lewis acid Cu(I) is crucial for high conversion. The reaction can be rendered asymmetric with a chiral bisphosphine ligand (S,S)-Ph-BPE.


Cancer patient survival in Estonia 1995-2009: time trends and data quality.
Survival from most cancers in Estonia has been consistently below European average. The objective of this study was to examine recent survival trends in Estonia and to quantify the effect on survival estimates of the temporary disruption of the Estonian Cancer Registry (ECR) practices in 2001-2007 when death certificates could not be used for case ascertainment. ECR data on all adult cases of 16 common cancers diagnosed in Estonia during 1995-2008 and followed up for vital status until 2009 were used to estimate relative survival ratios (RSR). We used cohort analysis for patients diagnosed in 1995-1999 and 2000-2004; and period hybrid approach to obtain the most recent estimates (2005-2009). We compared five-year RSRs calculated from data sets with and without death certificate initiated (DCI) cases. A total of 64328 cancer cases were included in survival analysis. Compared with 1995-1999, five-year age-standardized RSR increased 20 percent units for prostate cancer, reaching 76% in 2005-2009. A rise of 10 percent units or more was also seen for non-Hodgkin lymphoma (five-year RSR 51% in 2005-2009), and cancers of rectum (49%), breast (73%) and ovary (37%). The effect of including/excluding DCI cases from survival analysis was small except for lung and pancreatic cancers. Relative survival continued to increase in Estonia during the first decade of the 21st century, although for many cancers, a gap between Estonia and more affluent countries still exists. Cancer control efforts should aim at the reduction of risk factors amenable to primary prevention, but also at the improvement of early diagnosis and ensuring timely and optimal care to all cancer patients.


[Esthetic restorations in conservative dentistry].
The AA. discuss how to use some esthetic materials, as the Masking Agents and Tints, considering their technique characteristics and tackling the problem of right dental color remark.


Purification and characterization of a carbohydrate: acceptor oxidoreductase from Paraconiothyrium sp. that produces lactobionic acid efficiently.
A carbohydrate:acceptor oxidoreductase from Paraconiothyrium sp. was purified and characterized. The enzyme efficiently oxidized beta-(1-->4) linked sugars, such as lactose, xylobiose, and cellooligosaccharides. The enzyme also oxidized maltooligosaccharides, D-glucose, D-xylose, D-galactose, L-arabinose, and 6-deoxy-D-glucose. It specifically oxidized the beta-anomer of lactose. Molecular oxygen and 2,6-dichlorophenol indophenol were reduced by the enzyme as electron acceptors. The Paraconiothyrium enzyme was identified as a carbohydrate:acceptor oxidoreductase according to its specificity for electron donors and acceptors, and its molecular properties, as well as the N-terminal amino acid sequence. Further comparison of the amino acid sequences of lactose oxidizing enzymes indicated that carbohydrate:acceptor oxidoreductases belong to the same group as glucooligosaccharide oxidase, while they differ from cellobiose dehydrogenases and cellobiose:quinone oxidoreductases.


The efficacy of selenium dioxide as a selenium supplement for dairy cattle.
The efficacy of selenium dioxide (SeO2) was similar to sodium selenate (Na2SeO4 x 10H2O), in terms of increasing and maintaining blood Se concentrations, when administered orally twice daily to give 0.64 mg of Se/day to grazing dairy cows for 55 days.


Enhancement of intramammary lymph nodes with lymphoid hyperplasia: a potential pitfall in breast MRI.
We present three cases of breast lesions labeled as probable intramammary lymph nodes that showed an increase in size on follow-up mammography. Contrast-enhanced MRI was performed and the three lesions showed strong and rapid uptake of the intravenous contrast. Core needle biopsy established the diagnosis of lymphoid hyperplasia in all three patients. Because intramammary lymph nodes affected by benign processes can present findings similar to malignant lesions, the usefulness of contrast-enhanced MRI in these cases is controversial.


Contribution of the E2 transitions to the opacity of hot and dense plasmas of heavy elements by an average-atom approach.
The contribution of electric quadrupole (E2) transitions to the opacity of hot and dense plasmas is taken into account by using an average-atom model. As an example, the increase of the opacity of Au due to the E2 transition is shown to range from less than 1% to more than 10% depending on density and temperature. It reaches 15% when the density and temperature are, respectively, 100 g/cm(3) and 5000 eV. The most significant influence comes from the E2 photoionization processes.


Estimation of extracellular fluid volume from plasma clearance on technetium-99m DTPA by a single-injection, two-sample method.
A simple method is presented for estimating extracellular fluid volume from the plasma clearance of [99mTc])DTPA or [169Yb]DTPA. Two plasma samples are required, at 1 and 3 hr, following a single intravenous injection. (The same plasma samples can be used for measurement of glomerular filtration rate.) Using the complete plasma clearance curve as a reference (eight samples at 10 to 240 min), the error of the two-sample method in 40 patients was 1.5 I for [99mTc]DTPA, 2.1 I for [169Yb]DTPA (residual standard deviation).


Listeria monocytogenes in Gorgonzola cheese: Study of the behaviour throughout the process and growth prediction during shelf life.
As reported on RASFF's portal, in the first 9months of 2016, a total of 13 "alerts/information for attention" were issued concerning the presence of Listeria monocytogenes in mould cheeses throughout Europe. This study analyzes the behaviour of L. monocytogenes in Gorgonzola cheese, a typical Italian soft blue-veined cheese, when contaminated at different time points. In the first challenge test, the pasteurized milk was contaminated and the complete cheese manufacture (cheesemaking, ripening) and shelf life was simulated. After a decrease during the first days of the cheesemaking, the pH remained constant for 35days (5weeks) and then it increased rapidly reaching the final values of 6.8±0.02 in the core and 5.8±0.4 on the rind. At the same time, the pathogen concentration decreased (about 2logCFU/g), although during the last week a rapid pathogen growth was observed after the rise in pH values. When the cheese was stored at thermal abuse condition (8-12°C), the pathogen concentration on the rind was 4.8±0.3 log CFU/g and after 66days (about 9weeks) no significant difference (p>0.05) was observed; whereas, a growth from 5.4±0.4 to 7.1±0.5logCFU/g was observed in the core. A second challenge test was performed using three batches of commercial slices of Gorgonzola cheese inoculated by L. monocytogenes and stored at 8°C. The maximum specific growth rates (μmax, 1/h) of L. monocytogenes estimated ranged from 0.007 to 0.061. The square root model was used to predict the μmax at others temperature and to establish the time necessary to reach the European critical legal limit of 2logCFU/g, in different storage scenarios. The predictions obtained in this study can be applied to any time-temperature profile, and in particular to the conditions to which the product is most likely to be subject in normal use, up to its final consumption. This study can be considered a valuable contribution also aimed at supporting the monitoring surveys carried out by officers of the Regional Veterinary Authority.


The evaluation of ocular refractive error and axial length changes after scleral buckle removal.
The present study aimed to evaluate refractive error and axial length changes after buckle removal due to buckle complications. A total of 15 patients involved in this study. The enrolled patients who had history of scleral buckling (SB) for rhegmatogenous retinal detachment referred to clinic for buckle removal due to buckle-related complications. Complete ophthalmic examinations and IOLMaster (Carl Zeiss) device performed prior and 3 months after buckle removal. Also best corrected visual acuity (BCVA), refractive error and axial length changes evaluated after buckle removal. BCVA, refractive error, and axial length changes were not statistically significant (P value: 0.24, 0.23, 0.33, respectively). No redetachment or any other complication was observed after buckle removal. The study displayed induced globe shape changes due to SB are irreversible after buckle removal. In addition, it is a safe procedure and does not raise any risk of retinal redetachment.


Influence of vitamin A status and DDT on vitamin A-dependent protein mannosylation in rat liver.
Male Wistar rats of different vitamin A status (total depletion to moderate deficiency) were administered DDT (5 mg/kg/day) or vehicule (corn oil) i.p. daily for 14 days. Vitamin A-dependent protein mannosylation was measured either by in vivo incorporation of [3H]mannose into liver glycoprotein or by in vitro assay of incorporation of [14C]mannose into mannosylretinyl phosphate. Vitamin A deficiency resulted in a significantly impaired in vivo incorporation of mannose in liver glycoprotein but had no effect on the in vitro transport of mannose via retinyl phosphate. Although DDT induced an increase synthesis of liver proteins in smooth endoplasmic reticulum and caused a diminution of the hepatic vitamin A content, it did not affect vitamin A-dependent protein mannosylation.


Jumonji/ARID1 B (JARID1B) protein promotes breast tumor cell cycle progression through epigenetic repression of microRNA let-7e.
MicroRNAs (miRs) function as tumor suppressors or oncogenes in multiple tumor types. Although miR expression is tightly regulated, the molecular basis of miR regulation is poorly understood. Here, we investigated the influence of the histone demethylase Jumonji/ARID1 B (JARID1B) on miR regulation in breast tumor cells. In MCF-7 cells with stable RNAi-mediated suppression of JARID1B expression we identified altered regulation of multiple miRs including let-7e, a member of the let-7 family of tumor suppressor miRs. Chromatin immunoprecipitation analysis demonstrated JARID1B binding to the let-7e promoter region as well as removal of the of H3K4me3 histone mark associated with active gene expression. These results suggest that JARID1B epigenetically represses let-7e expression. JARID1B stimulates tumor cell proliferation by promoting the G(1) to S transition. As predicted, suppression of JARID1B resulted in an accumulation of MCF-7 cells in G(1). We confirmed that cyclin D1, which also promotes G(1) progression, is a direct target of let-7e, and we show that cyclin D1 expression is suppressed in JARID1B knockdown cells. Cyclin D1 expression and cell cycle progression were restored following inhibition of let-7e, suggesting that JARID1B repression of let-7e contributes to cyclin D1 expression and JARID1B-mediated cell cycle progression. Our results indicate that the JARID1B demethylase contributes to tumor cell proliferation through the epigenetic repression of a tumor suppressor miR.


Impact of nosocomial infections on patient mortality following cardiac surgery.
To determine the rate of nosocomial infection among patients undergoing cardiac surgery and to identify risk factors and the impact of these infections on patient mortality. Prospective observational study. Intensive Care Unit (ICU). 1097 adult patients who underwent cardiac surgery at Hospital Clínico Universitario de Valladolid between January 2011 and January 2016. None. Preoperative, intraoperative and postoperative medical, surgical and anaesthetic variables. A total of 111 patients (10.1%) acquired a nosocomial infection in the postoperative period. Pneumonia was the most frequent (4.2%) nosocomial infection. Three independent risk factors for the development of a nosocomial infection were identified: cardiopulmonary bypass time, kidney failure and emergency surgery. The stay in the ICU was significantly higher in patients who developed a nosocomial infection (16.6 ± 38.8 vs. 4.4 ± 17.8, P < 0.001). The mortality rate of patients who acquired a nosocomial infection was significantly greater (18%) than that of patients who did not acquire a nosocomial infection (5%) (P < 0.001). The 90-day survival was greater in the group of patients without nosocomial infection (log rank 27.55, P < 0.001). The dynamic modelling of 90-day mortality revealed that in the first week, cardiopulmonary bypass time (HR = 1.00, 95% CI 1.00-1.02, P < 0.001) and emergency surgery (HR = 0.12, 95% CI 0.04-0.37, P < 0.001) were the most important risk factors for mortality, while after the first week, nosocomial infection (HR = 6.23, 95% CI 2.49-15.63, P < 0.001) was the main risk factor, followed by cardiopulmonary bypass time (HR = 1.01, 95% CI 1.00-1.01, P = 0.001) and EuroSCORE (HR = 1.03, 95% CI 1.00-1.06, P = 0.008). Nosocomial infections after cardiac surgery constitute the main independent risk factor for mortality after the first week of surgery. These data suggest that its prevention following cardiac surgery must be prioritised to improve patient outcomes.


STRA6 and Placental Retinoid Metabolism in Gestational Diabetes Mellitus.
Recent reports indicate the potential role of the stimulated by retinoic acid 6 (STRA6) protein in developing insulin resistance. The study's objective was to assess placental STRA6 expression and staining pattern in human pregnancy complicated by gestational diabetes mellitus (GDM). The expression pattern of further relevant genes involved in retinoid metabolism was also evaluated. A retrospective case-control study on paraffin-embedded placental tissue. Twenty-two human pregnancies affected by GDM, namely, 11 insulin-treated (iGDM) and 11 diet-controlled (dGDM), were compared with 22 normal-developed pregnancies (controls). An RT-PCR was performed in a random sample of 18 patients (six iGDM, six dGDM, and six controls) to assess RNA expression of STRA6 and further markers of retinoid metabolism. A semi-quantitative intensity evaluation at immunohistochemistry was performed for STRA6 in all 44 recruited patients. STRA6 showed a decreased placental staining (9.09% vs. 68.18% positively stained samples, p < 0.05) and augmented RNA expression in dGDM patients than controls (ΔCT expression 0.473, IQR 0.403-0.566 vs. 0.149, IQR 0.092-0.276, p < 0.05). The protein staining pattern in patients affected by iGDM was comparable to controls. A reduced RNA expression of LPL, LRP1, VLDLR, and MTTP besides an augmented expression of LDLR was found in dGDM, while overexpression of LRP1 and LPL was found in iGDM patients. Unlike in the control group, significant positive correlations were found between RXRα and the proteins involved in the intracellular uptake of ROH, such as STRA6, LRP1, LRP2, and VLDLR. An altered placental expression and staining pattern of STRA6 were found in pregnancies complicated by GDM compared to the controls. These changes were coupled to an altered expression pattern of several other genes involved in the retinoid metabolism.


Gastrointestinal damage induced by platelet-activating factor. Inhibition by the corticoid, dexamethasone.
Intravenous infusion of platelet-activating factor (PAF-acether) induces extensive vasocongestion and damage in the stomach and small intestine of the rat. The effect of pretreatment with the corticoid dexamethasone (2 mg/kg) on such gastrointestinal damage in the rat has now been investigated, using macroscopic observation and the release of acid phosphatase, as an enzyme marker of cell disruption. Administration of PAF-acether (100 ng/kg/min intravenously, for 10 min) induced focal, intense hyperemia and hemorrhage in all the regions of the gastrointestinal tract, with the exception of the distal colon. This damage was associated with an increase in the release of acid phosphatase into the lumen of the stomach, duodenum, jejunum, and ileum following incubation in vitro. Pretreatment with dexamethasone reduced the macroscopically apparent gastrointestinal damage following PAF-acether administration and abolished the intraluminal release of acid phosphatase. Dexamethasone also significantly suppressed the hemoconcentration, as determined by changes in platelet and erythrocyte count and hematocrit, 30 min after PAF-acether infusion. Thus, as in endotoxin shock, this glucocorticoid can reduce the gastrointestinal damage associated with PAF-acether administration.


Peripheral blood NK cell cytotoxicities are negatively correlated with CD8(+) T cells in fertile women but not in women with a history of recurrent pregnancy loss.
We aim to investigate NK cell cytolytic activities and its relationship to other lymphocyte subsets in peripheral blood of women with a history of recurrent pregnancy loss (RPL). Women with a history of RPL (n = 48) comprised RPL group, and 15 fertile women served as controls. Lymphocyte subsets such as T (CD3(+)), T helper (CD3(+)/4(+)), cytotoxic T (CD3(+)/8(+)), NK (CD3(-)/56(+)), and peripheral blood NK cell cytolytic activities at three different effector to target cell ratios (E/T ratio, 50:1, 25:1 and 12.5:1) are measured by flow cytometric analysis. Peripheral blood NK cell levels are significantly increased in women with RPL as compared to controls (P = 0.001). NK cell cytolytic activities in RPL group are significantly increased as compared to those of controls at E/T ratio of 50:1 (42.5 ± 16.3 versus 29.9 ± 13.8, P = 0.009), 25:1 (31.6 ± 15.0 versus 19.4 ± 10.1, P = 0.004), and 12.5:1 (20.1 ± 10.9 versus 12.3 ± 7.5, P = 0.011). In RPL group, peripheral blood NK cell levels (%) showed a significant positive correlation with NK cell cytolytic activities at E/T ratio of 50:1 (r = 0.522, P < 0.001), 25:1 (r = 0.588, P < 0.001), and 12.5:1 (r = 0.604, P < 0.001). In controls, CD3(+)/8(+) cells (%) show a negative correlation with NK cell cytolytic activities at E/T ratio of 50:1 (r = -0.566, P = 0.028), 25:1 (r = -0.60., P = 0.017), and 12.5:1 (r = -0.602, P = 0.018). Ratios of T-helper cell to T-cytotoxic cell are positively correlated with NK cell cytolytic activities at E/T ratio of 50:1 (r = 0.601, P = 0.018), 25:1 (r = 0.632, P = 0.012), and 12.5:1 (r = 0.637, P = 0.011). NK cell-mediated immunopathology plays a role in RPL. Women with RPL have a disrupted immune regulation between cytotoxic T and NK cells. Failure of immune modulation by CD8(+) T cells may exert NK cell activation and reproductive failures in women with RPL.


Immunomodulatory effects of dietary β-1,3-glucan from Euglena gracilis in rainbow trout (Oncorhynchus mykiss) immersion vaccinated against Yersinia ruckeri.
Potential immunostimulatory effects of orally administered β-glucan were investigated in combination with immersion vaccination against enteric redmouth disease caused by Yersinia ruckeri in rainbow trout (Oncorhynchus mykiss). A linear, unbranched and pure (purity ≥98%) β-1,3-glucan (syn. paramylon) from the alga Euglena gracilis was applied at an inclusion level of 1% β-glucan in feed administered at a rate of 1% biomass day(-1) for 84 consecutive days. Fish were vaccinated after two weeks of experimental feeding and bath challenged with live Y. ruckeri six weeks post-vaccination. Blood and head kidney were sampled at day 0, 13 (1 day pre-vaccination), 15, 55, 59 (day 3 post-challenge (p.c.)), 70 and 84. Vaccination induced significantly increased survival p.c., whereas the β-glucan had no effect on survival in either unvaccinated or vaccinated fish. Expression in head kidney of genes related to the acute phase response, i.e. interleukin-1β (IL-1β), serum amyloid A (SAA), precerebellin, and hepcidin, was significantly different in vaccinated fish receiving β-glucan compared to vaccinated controls at day 3 p.c., while no effect of β-glucan was observed among unvaccinated fish. Significant interaction between β-glucan and vaccination was found for the regulation of IL-1β, tumour necrosis factor-α, interferon-γ, SAA, precerebellin and hepcidin p.c. For SAA, the significant effect of β-glucan in vaccinated fish persisted at day 14 p.c. and 28 p.c. The difference in gene expression among vaccinated fish was mainly observed as down-regulations in vaccinated, β-glucan fed fish compared to up-regulations or no regulation in vaccinated controls. Slightly increased levels of plasma lysozyme activity were found in fish (both unvaccinated and vaccinated) receiving β-glucan at day 3 p.c. compared to control fed groups. This was associated with a faster clearance of Y. ruckeri in unvaccinated fish receiving β-glucan. In contrast to the trend towards a beneficial effect of β-glucan on plasma lysozyme activity, a trend towards suppression of plasma antibodies was seen in both unvaccinated and vaccinated fish receiving β-glucan. However, the effects of β-glucan were not reflected in the survival curves, and the differences seen in plasma lysozyme activity and antibody levels may have counteracted and set off each other as well as counteracted any potential effect represented by the differences in gene expression found.


Paratesticular leiomyosarcoma: A clinical case report.
We present you a Case of 62 year old man with Paratesticular leiomyosarcoma (LMS) localized to the right sctotal half. Detailed pathological and immunohistochemistry characteristic of the tumor was done. For staging was used the classification of French Federation of Cancer Centres Sarcoma Grading System. The final grading of the tumor is grade 3. Paratesticular LMS is rare identity and serves as a diagnostic and treatment challenge.


Dynamic changes in antibiotic resistance genes and gut microbiota after Helicobacter pylori eradication therapies.
Short-term antibiotics exposure is associated with alterations in microbiota and antibiotic resistance genes (ARGs) in the human gut. While antibiotics are critical in the successful eradication of Helicobacter pylori, the short-term and long-term impacts on the composition and quantity of antibiotics resistance genes after H. pylori eradication are unclear. This study used whole-genome shotgun metagenomic of stool samples to characterize the gut microbiota and ARGs, before and after H. pylori eradication therapy. Forty-four H. pylori-infected patients were recruited, including 21 treatment naïve patients who received clarithromycin-based triple therapy (CLA group) and 23 patients who failed previous therapies, in which 10 received levofloxacin-based quadruple therapy (LEVO group) and 13 received other combinations (OTHER group). Stool samples were collected at baseline (before current treatment), 6 week and 6 month after eradication therapy. At baseline, there was only a slight difference among the three groups on ARGs and gut microbiota. After eradication therapy, there was a transient but significant increase in gut ARGs 6 week post-therapy, among which the LEVO group had the most significant ARGs alteration compared to other two groups. For treatment naïve patients, those with higher ErmF abundance were prone to fail CLA eradication and gain more ARGs after treatment. For gut microbiota, the bacteria richness decreased at 6 week and there was a significant difference in microbiota community among the three groups at 6 week. Our findings demonstrated the dynamic alterations in gut microbiota and ARGs induced by different eradication therapies, which could influence the choices of antibiotics in eradication therapy.


Subendocardial resection for sustained ventricular tachycardia in the early period after acute myocardial infarction.
One hundred nineteen patients with drug-refractory ventricular tachycardia (VT) underwent mapping-guided subendocardial resection for control of their arrhythmias from 3 weeks to 10 years after acute myocardial infarction (AMI). Patients were separated into 2 groups: those treated early (within 4 months, group I) and those treated later (after 1 year, group II) after AMI. There were 32 patients in group I and 72 patients in group II. Both groups of patients had similar clinical, angiographic and hemodynamic characteristics. Patients in group I had VT with a shorter mean cycle length than patients in group II (322 +/- 71 vs 349 +/- 88 ms, p less than 0.05). The groups did not differ with respect to operative mortality (12% vs 7%), late mortality (31% vs 33%, mean follow-up 23 months), or frequency with which subendocardial resection without any adjunctive therapy prevented postoperative spontaneous or inducible VT (21% vs 34%). Group I was further separated into patients who underwent subendocardial resection within 1 month of AMI (n = 7) and those who underwent subendocardial resection with 2 months of AMI (n = 14). Although patients in group I were characterized by having more spontaneous morphologically distinct tachycardias, their operative mortality, total mortality and surgical success rates were comparable to those of patients in group II.(ABSTRACT TRUNCATED AT 250 WORDS)


Vector analysis of high astigmatism (≥ 2.0 diopters) correction after small-incision lenticule extraction with stringent head positioning and femtosecond laser-assisted laser in situ keratomileusis with compensation of cyclotorsion.
The purpose of this study was to compare the astigmatic correction by vector analysis in patients with high myopic astigmatism after femtosecond laser-assisted laser in situ keratomileusis (FS-LASIK) with cyclotorsion compensation or small-incision lenticule extraction (SMILE) with stringent head positioning. Beijing Aier-Intech Eye Hospital, Beijing, China. A retrospective case series. Patients who had correction of myopic astigmatism of 2 diopters (D) or more treated with either FS-LASIK with cyclotorsion compensation or SMILE with stringent head positioning were included. The results of vision and refraction were analyzed and compared between groups with the right eye. The study enrolled 94 patients (41eyes in an FS-LASIK with compensation of cyclotorsion group and 53 eyes in a SMILE with stringent head positioning control group. The mean preoperative manifest cylinder was -2.65 ± 0.77D in the FS-LASIK group and 2.51 ± 0.56D in the SMILE group (P = 0.302). At 12 months, there was no significant between-group difference in uncorrected distance visual acuity (UDVA, P = 0.274) and postoperative spherical equivalent (SEQ) (P = 0.107). 46.3% and 24.5% of eyes in the FS-LASIK and SMILE groups were within 0.25 D were within 0.25D postoperative cylinder, respectively, and 78% and 66% of eyes in these two groups were within 0.5 D postoperative cylinder (P = 0.027, P = 0.202). The vector analysis showed comparable between-group target-induced astigmatism (TIA) (P = 0.114), surgically induced astigmatism (SIA) (P = 0.057), difference vector (DV, P = 0.069), and the angle of error (AE) (P = 0 .213) values. The index of success (IOS) was 0.18 in the FS-LASIK group and 0.24 in the SMILE group (P = 0.024), with a significant difference between the two groups. FS-LASIK with compensation of cyclotorsion showed a favorable correction of high myopic astigmatism (≥ 2.0 D) compared to SMILE with stringent head positioning at 12 months.


Frequency and genetic diversity of Blastocystis subtypes among patients attending to health centers in Mazandaran, northern Iran.
Blastocystis hominis is a common intestinal protozoan with global distribution. The prevalence of B. hominis is extremely diverse in different countries. Molecular studies show that there is a great deal of genetic variation in the Blastocystis parasite isolated from humans and animals. Therefore, this study was conducted to determine B. hominis genotypes in patients attending to health centers of Sari, Mazandaran Province, north of Iran. 420 fecal specimens were collected from individuals in health centers of Sari from April to December 2017. The samples were examined by direct methods, parasite test (formalin ether) and Giemsa staining. In order to determine the genotypes of Blastocystis parasite, all positive samples in direct methods were tested by PCR using SSU rDNA gene. Eventually, seven positive molecular samples were sequenced and recorded in the gene bank. The phylogenetic analysis was done by drawing a gene tree using the neighbor-joining procedure. B. hominis was detected in 60 stool specimens by microscopic method. All these 60 samples were positive by PCR and the bands 310 bp were observed. According to the phylogenetic tree, it was revealed that B. hominis isolates of Mazandaran Province are more similar to subtype ST3 (ST type) that reported in Khorramabad in Lorestan Province (West of Iran). The present study showed that, like most studies, ST3 is the dominant genotype of protozoan in Sari. Improvement of public health awareness, relative improvement in environmental health, urban wastewater treatment, proper clothing coverage and the use of gloves during dealing with livestock and the use of domestic water treatment devices can reduce the Blastocystis infection in this area.


The expression and correlation of Hsp 70 and Hsp 27 in serous middle ear effusion fluids of pediatric patients-a preliminary study.
Several cytokines and innate immune-associated molecules are present in middle ear effusions, but damage-associated molecular patterns (DAMPs) in middle ear effusion have not been studied. Therefore, we evaluated the role of heat shock proteins (Hsps) in the development of otitis media with effusion (OME). Serous middle ear effusions from 22 pediatric patients who were diagnosed with OME and underwent ventilation tube insertion from June 2015 to March 2017 were evaluated in our study. The levels of Hsp 90, 70, 27, IL-8, and TNF-α in effusion fluids were evaluated by enzyme-linked immunosorbent assays. The associations between the levels of these molecules and the degree of tympanic membrane inflammation were statistically evaluated. Finally, the relationships among these molecules were also evaluated. Hsp 70 and Hsp 27 were detected in all middle ear effusions, but Hsp 90 was detected in only five effusion fluid samples. IL-8 was also detected in all middle ear effusions, but TNF-α was detected in only four effusion fluid samples. When we compared the degree of tympanic membrane inflammation with the levels of Hsp 70, Hsp 27, and IL-8, which were detected in all effusion fluids, we could not find statistical significance. However, Hsp 70, Hsp 27, and IL-8 were significantly associated with each other (p < 0.05). Hsp 70 and Hsp 27 were expressed in middle ear effusions. Furthermore, the levels of Hsp 70 and Hsp 27 were positively correlated with each other, and were also positively associated with the neutrophil chemoattractant, IL-8. Our findings suggested that Hsp 70 and Hsp 27 might be involved in the pathophysiology of pediatric OME.


Changes of knowledge, attitudes, beliefs, and preference of bar owner and staff in response to a smoke-free bar law.
To examine attitudinal changes of bar owners and staff regarding a smoke-free bar law. Bar owners and staff were random selected and telephone interviewed in June 1998, shortly after a smoke-free bar law was enacted, and October 2002. Similar instruments were used in both surveys to collect data on attitudes related to secondhand smoke (SHS) and behaviours related to the smoke-free bar law. 651 and 650 respondents worked for either stand alone bars or combination bars. Preference of working in a smoke-free environment, concerns of the effect of SHS, and how to comply with the law. The percentage of bar owners or staff working in stand alone bars who prefer to work in a smoke-free environment increased from 17.3% in 1998 to 50.9% in 2002 (p < 0.001). Significantly more respondents (45.5%) working in stand alone bars were concerned about the effects of SHS on their health, comparing to 21.6% in 1998 (p < 0.001). When patrons smoked in the bar, 82.1% of stand alone bar owners or staff in the 2002 survey would ask them to stop or to smoke outside, increased from only 43.0% in the 1998 survey (p < 0.001). A positive and significant attitudinal change related to the smoke-free bar law occurred among California bars.


Ontogeny and immunocytochemical differentiation of the pituitary gland in a sea turtle, Caretta caretta.
In the sea turtle Caretta caretta the dorsal wall of the pituitary anlage and the apex of the hypophyseal angle are derived from stomodeal epithelium adherent to the neural epithelium of the diencephalon; a substantial part of the ventral wall of the anlage is derived from epithelium of mixed origin (stomodeum and foregut). Distribution of immunoreactive cells in the embryonic gland suggests that pituitary peptide hormones (adrenocorticotropin, ACTH; melanotropin, MSH; prolactin, PRL; growth hormone, GH) are synthesized in cells from the dorsal wall, while cells producing glycoprotein hormones (luteinizing hormone, LH; thyrotropin, TSH) trace their lineage to ventral and ventrolateral areas of the anlage that include some endoderm. Mesenchymal movements mold the epithelial anlage in two steps, delineating first the posterior and subsequently the anterior area of the gland. During the former process the lateral lobes are defined, and material immunoreactive with antiserum to ACTH appears in epithelial cells of presumptive pars distalis (PD) and pars intermedia (PI). Delineation of the anterior end of the pituitary gland occurs as the hypophyseal stalk forms, approximately one-fourth through ontogenesis. Shortly thereafter, immunoreactions demonstrate synthetic activity of distinctively distributed cells containing ACTH, PRL, GH, LH and TSH. In Caretta the lateral lobes of the pituitary anlage give rise to a distinct layer of tissue around the PD (pars tuberalis interna, PTint) and a thick layer on the floor of the hypothalamus (juxtaneural pars tuberalis, juxPT). In the pituitaries of late embryos, juxPT tissue proximal to the PD contains many cells immunoreactive with LH antiserum; whereas cells in distal areas of the juxPT do not react with any antisera tested. LH-cells also occur in large numbers in the PTint and in the posterior PD where tissues of the partes tuberalis and distalis are continuous. Cells reactive with antiserum to TSH are found in small numbers in the PTint, and in larger numbers along with the LH-cells in the posterior PD. PRL-cells occur in the anterior PD, GH-cells in the posterior. ACTH-cells are found primarily in the anterior two-thirds of the PD.


Rhabdomyosarcoma in Roberts syndrome.
A 23-month-old child diagnosed as having Roberts syndrome, born to consanguineous parents, developed a sarcoma botryoides. Cytogenetic evaluation of peripheral blood lymphocytes and tumor cells showed premature centromere separation, which is characteristic of Roberts syndrome.


Alien genes introgression and development of alien monosomic addition lines from a threatened species, Allium roylei Stearn, to Allium cepa L.
To produce alien monosomic addition lines (AMALs) of Allium cepa (genomes CC, 2n = 2x = 16) carrying extrachromosomes from Allium roylei (RR, 2n = 2x = 16), reciprocal backcrossing of allotriploids (2n = 24, CCR) with diploids (2n = 16, CC) and selfing of a single allotriploid were carried out. The chromosome numbers in the BC(2)F(1) and BC(1)F(2) progenies ranged from 16 to 32. Forty-eight plants were recorded to possess 2n = 17 among a total of 169 plants in observation. Through the analyses of isozymes, expressed sequence tag (EST) markers, and karyotypes, all eight possible types of A. cepa-A. roylei monosomic addition lines (CC+1R-CC+8R) could be identified. Seven types of representative AMALs (without CC+2R) were used for the GISH analysis of somatic chromosomes. Except for CC+6R, all AMALs showed an entire (unrecombined) extrachromosome from A. roylei in the integral diploid background of A. cepa. A single recombination between A. cepa and A. roylei was observed on the extrachromosome in the remaining type. All alloplasmic AMALs possessing A. roylei cytoplasm showed high or complete pollen sterility. Only the autoplasmic CC+4R with A. cepa cytoplasm possessed relatively high pollen fertility. The bulbs of CC+4R displayed the distinct ovoid shape that discriminates them from spherical or oval ones in other AMALs. Downy mildew screening in the field showed higher resistance in A. roylei, a hypo-allotriploid (CCR-nR, 2n = 23), and an allotriploid (CCR, 2n = 24). Meanwhile, no complete resistance was found in some AMALs examined. This was the first trial toward the establishment of a complete set of A. cepa-A. roylei monosomic additions.


Effects of laser polar-body biopsy on embryo quality.
To evaluate the effect of laser polar-body biopsy (PBB) for preimplantation genetic diagnosis on embryo quality. Retrospective case-control analysis. The quality of 145 embryos after PBB was compared to 276 embryos of the same group of women without biopsy. University-based tertiary-care medical center. Women with inherited genetics disease. Laser PBB of IVF embryos for genetic diagnosis. The study and control embryos were compared for fertilization rate, pronuclear grading, and cleavage-stage parameters on days 1, 2, and 3 after oocyte retrieval. The study embryos demonstrated higher rates of cleavage arrest (3.6% vs. 0.7%), higher rate of significant fragmentation on day 2 (9.5% vs. 3.0%), and lower rate of good cleavage embryos on day 2 (69.1% vs. 78.4%) compared with control embryos. On day 3, the study embryos had lower cleavage rates (six or more blastomeres; 56.5% vs. 74.5%), higher fragmentation (11.7% vs. 3.9%), higher rate of embryos presenting inferior cleavage pattern (57.2% vs. 38.5%), and lower mean blastomere number (5.8 ± 2.1 vs. 6.6 ± 1.9) compared with control embryos. Polar-body biopsy may have a negative effect on embryo quality.


[Construction of monovalent and compound nucleic acid vaccines against Toxoplasma gondii with gene encoding p30].
To construct a monovalent gene vaccine pcDNA3.1-p30 and a compound gene vaccine pcDNA3.1-p30-ROP2 and assess the protective effect of the two vaccines against Toxoplasma gondii. The sequences encoding p30 and ROP2 were amplified from the genomic DNA of T. gondii RH strain by polymerase chain reaction (PCR) and inserted into eukaryotic vector pcDNA3.1 to construct pcDNA3.1-p30 and pcDNA3.1-p30-ROP2. Mice were injected with the recombinant plasmid to observe the immunoprotectivity of the nucleic acid vaccine by using ELISA for detection of total IgG and observing the survival time after tachyzoites challenge. The recombinant plasmids pcDNA3.1-p30 and pcDNA3.1-p30-ROP2 were constructed. Mice in pcDNA3.1-p30-ROP2 group showed higher IgG (P < 0.05) and survived longer than those in pcDNA3.1-p30 group (P < 0.01) after challenged with T. gondii. Compound vaccine of genes from different stages of T. gondii elicits stronger immunoprotectivity in mice than a single gene vaccine.


Sucrose enhances colour formation in dry sausages by up-regulating gene expression of nitric oxide synthase in Staphylococcus vitulinus.
The effects of glucose and sucrose on the gene expression of nitric oxide synthase (NOS) in Staphylococcus vitulinus and colour formation in dry sausages were investigated. The results showed that sucrose addition promoted nitric oxide (NO) production in media when compared with glucose. In addition, sucrose could up-regulate nos (encoding NOS) and katA (encoding catalase KatA) gene expression by enhancing oxidative stress levels. In the sausages inoculated with S. vitulinus, a*-values (indicating redness) of the sausages with added sucrose were higher than those of samples with added glucose (P < 0.05) but did not differ from those in the nitrite treatment group (P > 0.05). The UV-vis spectra results showed that nitrosylmyoglobin (NO-Mb) was formed in the sausages with either S. vitulinus or nitrite added. In the S. vitulinus-inoculated sausages, sucrose addition led to a higher NO-Mb content than that after glucose addition, which was attributed to up-regulation of the nos gene. This study provides a potential method to enhance NO yield in S. vitulinus and colour formation in dry sausages without nitrite addition.


IgA nephropathy is associated with elevated urinary mitochondrial DNA copy numbers.
Mitochondrial injury plays important roles in the pathogenesis of various kidney diseases. However, mitochondrial injury in IgA nephropathy (IgAN) remains largely unexplored. Here, we examined the associations among mitochondrial injury, IgAN, and treatment outcomes. We prospectively enrolled patients with IgAN and age-/sex-matched healthy volunteers (HVs) as controls (n = 31 each). Urinary copy numbers of the mitochondrial DNA (mtDNA) genes cytochrome-c oxidase-3 (COX3) and nicotinamide adenine dinucleotide dehydrogenase subunit-1 (ND1) were measured. Urinary mtDNA levels were elevated in the IgAN group compared with that in HVs (p < 0.001). Urinary ND1 levels were significantly higher in the low proteinuria group than in the high proteinuria group (p = 0.027). Changes in urinary levels of ND1 and COX3 were positively correlated with changes in proteinuria (p = 0.038 and 0.024, respectively) and inversely correlated with changes in the estimated glomerular filtration rate (p = 0.033 and 0.017, respectively) after medical treatment. Mitochondrial injury played important roles in IgAN pathogenesis and may be involved in early-stage glomerular inflammation, prior to pathological changes and increased proteinuria. The correlation between changes in urinary mtDNA and proteinuria suggest that these factors may be promising biomarkers for treatment outcomes in IgAN.


Dihydrocapsaicin suppresses proinflammatory cytokines expression by enhancing nuclear factor IA in a NF-κB-dependent manner.
Atherosclerosis is a chronic inflammatory disease and represents the leading cause of morbidity and mortality throughout the world. Accumulating evidences have showed that Dihydrocapsaicin (DHC) has been found to exert multiple pharmacological and physiological effects. Nevertheless, the effects and possible mechanism of DHC on proinflammatory response remain largely unexplained. We found that DHC markedly upregulated NFIA and suppressed NF-κB expression in THP-1 macrophages. Up-regulation of proinflammatory cytokines induced by LPS including TNF-α, IL-1β and IL-6 were markedly suppressed by DHC treatment. We also observed that protein level of NFIA was significantly increased while NF-κB and proinflammatory cytokines were decreased by DHC treatment in apoE(-/-) mice. Lentivirus-mediated overexpression of NFIA suppressed NF-κB and proinflammatory cytokines expression both in THP-1 macrophages and plaque tissues of apoE-/- mice. Moreover, treatment with lentivirus-mediated overexpression of NFIA made the down-regulation of DHC on NF-κB and proinflammatory cytokines expression notably accentuated in THP-1 macrophages and apoE(-/-) mice. In addition, treatment with siRNA targeting NF-κB accentuated the suppression of proinflammatory cytokines by lentivirus-mediated overexpression of NFIA. These observations demonstrated that DHC can significantly decrease proinflammatory cytokines through enhancing NFIA and inhibiting NF-κB expression and thus DHC may be a promising candidate as an anti-inflammatory drug for atherosclerosis as well as other disorders.


Effects of dietary restriction on radial-arm maze performance and flavor memory in aged rats.
Two groups of aged rats, a dietary restricted group fed approximately 10 g per day from 6 weeks of age and a group fed ad lib throughout their life span, were compared with a young adult group on an 8-arm radial maze and a flavor memory task. The young adult displayed efficient performance on the radial-arm maze within the 15 day test period. In contrast, both aged groups exhibited significantly poorer performance in the maze in comparison with the young adult group neither aged group differed from chance at the end of the 15 days. The flavor memory task required the animals to consume a novel flavor. Their loss of neophobia, as indexed by their subsequent consumption, was then taken as an indication of the extent to which they remembered the novel flavor and its effects. The young adult group lost their neophobia more rapidly than either of the aged groups, which did not appear to differ from each other. Taken together, this pattern of results indicates that dietary restriction does not protect animals from the memory loss observed in aged animals.


Caregiver socioemotional health as a determinant of child well-being in school-aged and adolescent Ugandan children with and without perinatal HIV exposure.
Caregiver socio-emotional attributes are major determinants of child well-being. This investigation in vulnerable school-aged Ugandan children estimates relationships between children's well-being and their caregiver's anxiety, depression and social support. Perinatally HIV-infected, HIV-exposed uninfected and HIV-unexposed Ugandan children and their caregivers were enrolled. Perinatal HIV status was determined by 18 months of age using DNA-polymerase chain-reaction test; status was confirmed via HIV rapid diagnostic test when children were 6-18 years old. Five indicators of child well-being (distress, hopelessness, positive future orientation, esteem and quality of life (QOL)) and caregivers' socioemotional status (depressive symptoms, anxiety and social support) were measured using validated, culturally adapted and translated instruments. Categories based on tertiles of each caregiver psychosocial indicator were defined. Linear regression analyses estimated percent differences (β) and corresponding 95% confidence intervals (CI) for child well-being in relation to caregiver's psychosocial status. As per tertile increment, caregiver anxiety was associated with 2.7% higher distress (95%CI:0.2%, 5.3%) and lower self-esteem/QOL (β = -1.3%/-2.6%; 95%CI: -5.0%,-0.2%) in their children. Child distress/hopelessness increased (β = 3.3%/7.6%; 95%CI:0.4%, 14.7%) and self-esteem/QOL decreased 2.3% (β = -2.3%/-4.4%; 95%CI: -7.2%, -1.3%) as per tertile increment in caregiver depression. Higher caregiver social support was associated with lower distress and higher positive outlook (β = 3%; 95%CI:1.4%, 4.5%) in their children. HIV-infected/exposed children had most caregiver depression-related QOL deficit (β = -5.2%/-6.8%; 95%CI: -12.4%, -0.2%) and HIV-unexposed children had most caregiver social support-related enhancements in positive outlook (β=4.5%; 95%CI:1.9%, 7.1%). Caregiver anxiety, depressive symptoms and low social support were associated with worse well-being in school-aged and adolescent children. Improvement of caregiver mental health and strengthening caregiver social support systems may be a viable strategy for improving well-being of vulnerable children and adolescents in this setting.


Implant-bone load transfer mechanisms in complete-arch prostheses supported by four implants: a three-dimensional finite element approach.
Complete-arch restorations supported by fewer than 5 dental implants can induce unbalanced load transfer and tissue overloading, leading to excessive bone resorption and possible clinical failure. This is primarily affected by the cantilever length, the implant design and positioning, and the morphology and properties of the bone. The purpose of this study was to compare 2 different restorative techniques for complete-arch rehabilitations supported by 4 implants. The primary purpose was to highlight the possible risks of excessive stress and unbalanced load transfer mechanisms and to identify the main biomechanical factors affecting loading transmission. Three-dimensional (3D) numerical models of edentulous maxillae and mandibles restored with 2 techniques using 4 implants were generated from computed tomography (CT) images and analyzed with linear elastic finite-element simulations with 3 different static loads. The first technique used 2 vertical mesial implants and 2 tilted distal implants (at a 30 degree angle), and the second used vertical implants that fulfilled platform switching concepts. Bone-muscle interactions and temporomandibular joints were included in the mandibular model. Complete implant osseous integration was assumed and different posthealing crestal bone geometries were modeled. Stress measures (revealing risks of tissue overloading) and a performance index (highlighting the main features of the loading partition mechanisms) were introduced and computed to compare the 2 techniques. Dissimilar load transfer mechanisms of the 2 restorative approaches when applied in mandibular and maxillary models were modeled. Prostheses supported by distally tilted implants exhibited a more effective and uniform loading partition than all vertical implants, except in the simulated maxilla under a frontal load. Tilted distal implants reduced compressive states at distal bone-implant interfaces but, depending on bone morphology and loading type, could induce high tensile stresses at distal crests. Overloading risks on mesial periimplant bone decreased when the efficient preservation of the crestal bone through platform switching strategies was modeled. Numerical simulations highlighted that the cantilever length, the implant design and positioning, and the bone's mechanical properties and morphology can affect both load transmission mechanisms and bone overloading risks in complete-arch restorations supported by 4 implants. Distally tilted implants induced better loading transmission than vertical implants, although the levels of computed stress were physiologically acceptable in both situations.


Inherent bacterial community response to multiple heavy metals in sediment from river-lake systems in the Poyang Lake, China.
Sediment is the one of most important storage of heavy metal. Microbiotas in sediment can be used as the effective indicators of heavy metals. The goal of this study was to understand the bacterial communities responding to heavy metal enrichment in sediments and prioritize some factors that affected significantly to bacterial community. Sediments were sampled from five river-lake systems in the Poyang Lake in dry season, and the bacterial community was analyzed using Illumina high-throughput sequencing. Relationships between sediment environment and the diversity and structure of bacterial communities were determined by correlation analysis and redundancy analysis (RDA). The result indicated that Cd and Sb were identified as the heavy metals of the great risk in sediments. Sediments from five river-lake systems shared 31.83% core operational taxonomic units (OTUs) of bacterial communities. Proteobacteria (33.54% of total sequences) and Actinobacteria (15.04%) were the dominant phyla across all sites. High enrichment of heavy metals (MRI and mCd) resulted in low diversity of bacterial communities (Simpson index). The RDA revealed pH, OC, mCd, and Efs of As, Pb, Cd were major factors related to bacterial community structure changes. The dominant phylum Actinobacteria was regarded as tolerant bacteria, while the dominant phylum Proteobacteria was named as resistant bacteria in sediment with high anthropogenic Cd enrichment.


Lymph node harvest in esophageal cancer after neoadjuvant chemoradiotherapy.
This study was designed to determine the effects of lymph node (LN) harvest on survival in esophageal cancer after neoadjuvant chemoradiation (nCRT). An analysis of surgically resected esophageal cancer patients after nCRT was performed to determine an association between the number of LNs resected and survival. Overall survival (OS) and disease-free survival (DFS) curves were calculated according to the Kaplan-Meier method and log-rank analysis. Multivariate analysis (MVA) was performed by the Cox proportional hazard model. We identified 358 patients with a mean follow-up of 27.3 months. The number of LN removed was not impacted by the type of surgical procedure. The number of LNs removed (<10 vs. ≥10, <12 vs. ≥12, and <15 vs. ≥15) did not impact OS or DFS. We found a significant difference in OS and DFS by pathologic response. The median and 5-year OS for patients with complete, partial, and no response was 65.6 months and 52.7%, 29.7 months and 30.4%, and 17.7 months and 25.4% (p=0.0002). However, the number of LN harvested did not impact OS and DFS when patients were stratified by pathologic response. MVA also revealed that the number of lymph nodes removed was not prognostic for OS or DFS. Higher age, higher stage, and less than a complete response were associated with a decreased OS. Higher stage and less than a complete response were prognostic for worse DFS. The number of LNs harvested during esophagectomy does not impact survival after nCRT. Stage and pathologic response continue to be the strongest prognostic factors for survival in esophageal cancer after nCRT.


Severe chronic Carboxyhemoglobinemia and polycythemia due to smoking hookah.
Acute carbon monoxide (CO) poisoning due to smoking hookah has been reported and may present similarly to other causes of acute carbon monoxide poisoning with nausea, headache, and loss of consciousness [1]. In the acute poisoned patient, immediate removal from the carbon monoxide source is paramount in addition to administration of oxygen and possible hyperbaric oxygen therapy (HBO) in certain situations. However, cases of chronic CO poisoning, treatment options, and long-term adverse health effects are far less reported but may include atherosclerosis and vague neurologic symptoms [2]. We present a case of a patient who chronically smoked hookah creating a condition of chronic carboxyhemoglobinemia which was discovered during work up for unexplained polycythemia. While being seen in the hematology clinic, he was found to have a blood carboxyhemoglobin of level 33.6% despite being asymptomatic. This is the highest recorded hookah-related carboxyhemoglobin concentration in the medical literature; and the significant chronic carboxyhemoglobinemia explained his polycythemia. This case illustrates that a social history is crucial when assessing the patient with severe carboxyhemoglobinemia as HBO is not indicated in chronic CO poisoning in an asymptomatic patient.


Importance of autophosphorylation at Ser186 in the A-loop of salt inducible kinase 1 for its sustained kinase activity.
Autophosphorylation is an important mechanism by which protein kinases regulate their own biological activities. Salt inducible kinase 1 (SIK1) is a regulator in the feedback cascades of cAMP-mediated gene expression, while its kinase domain also features autophosphorylation activity. We provide evidence that Ser186 in the activation loop is the site of autophosphorylation and essential for the kinase activity. Ser186 is located at the +4 position of the critical Thr residue Thr182, which is phosphorylated by upstream kinases such as LKB1. The relationship between phosphorylation at Ser186 and at Thr182 in COS-7 cells indicates that the former is a prerequisite for the latter. Glycogen synthase kinase-3beta (GSK-3beta) phosphorylates Ser/Thr residues located at the fourth position ahead of the pre-phosphorylated Ser/Thr residues, and inhibitors of GSK-3beta reduce the phosphorylation at Thr182. The results of an in vitro reconstitution assay also indicate that GSK-3beta could be the SIK1 kinase. However, overexpression and knockdown of GSK-3beta in LKB1-defective HeLa cells suggests that GSK-3beta alone may not be able to phosphorylate or activate SIK1, indicating that LKB1 may play a crucial role by phosphorylating SIK1 at Thr182, possibly as an initiator of the autophosphorylation cascade, and GSK-3beta may phosphorylate SIK1 at Thr182 by recognizing the priming-autophosphorylation at Ser186 in cultured cells. This may also be the case for the other isoform SIK2, but not for SIK3.