Palladium- or iridium-catalyzed allylic substitution of guanidines: convenient and direct modification of guanidines.
As a convenient and direct functionalization of guanidines, the transition metal-catalyzed allylic substitution of guanidines was studied. The guanidine derivatives bearing two electron-withdrawing substituents acted as reactive nucleophiles in the allylic substitution to give the monoallylated products. The double allylic substitution was achieved by using tri-Boc-guanidine bearing three electron-withdrawing substituents as a nucleophile to give the diallylated products. The regiocontrol in the allylic substitution of unsymmetrical allylic substrates has been investigated by employing the palladium or iridium catalysts. The iridium complex of chiral pybox ligand allowed the regio- and enantioselective allylic substitution. Asymmetric double allylic substitution of tri-Boc-guanidine with phosphate bearing the 1-naphthyl group gave the diallylated product with high diastereo-, regio-, and enantioselectivities.


Surface phytolith and pollen assemblages of a low-latitude subtropical region in Southwest China and their implications for vegetation and climate.
Phytoliths, as a newly developing plant proxy, have broad application prospects in paleoclimate and paleoethnobotany. However, the shortage of studies regarding tropical-subtropical plants and topsoil phytoliths interferes with the research progress on primitive humanity's utilization of plant resources and paleoclimate in the region. This research focuses on the subtropical mountainous region with a monsoon climate of low latitudes in Southwest China to conduct phytolith morphology analysis of living plants and phytolith/pollen assemblages of topsoil to reveal the indicative significance of vegetation and climate. A total of 111 species from 50 families, including 73 species from 33 tree/shrub families, 31 species from 12 herb families and 7 species from 5 fern families, were collected for morphological characteristics analysis, as well as 19 topsoil specimens for phytolith and pollen assemblage analysis. The results suggest that phytoliths are mainly deposited in situ, with assemblages of topsoil corresponding well with plant types in the quadrat and being able to exhibit constructive species in small regions. In comparison, pollen assemblages of topsoil dominantly respond to regional vegetation due to their long-distance transportation and widespread presence, in addition to their characteristics that correspond to the vegetation in the quadrat. The topsoil phytolith assemblages are mainly based on the elongate-bulliform flabellate-square/rectangle-broadleaf-types (including spheroid echinate), and the vegetation types indicate the subtropical climate. In addition, phytolith assemblages of Poaceae are dominated by collapsed saddle-bulliform flabellate square/rectangle-elongate-point, reflecting warm and humid conditions. The pollen assemblages mainly consist of Pinus, Betula, Alnus, deciduous Quercus, Euphorbiaceae, Rhamnaceae and Polygonum, reflecting tropical-subtropical plant communities and indicating warm and humid conditions. Overall, phytolith and pollen assemblages have unique characteristics and are thus explicitly representative of the low-latitude subtropical monsoon climate.


[Effect of ultrasound contrast agent targeting gelatin on uptake of mouse ascites hepatocellular carcinoma cell lines with high lymphatic metastasis].
Objective: To analyze the effect of ultrasound contrast agent targeting gelatin on uptake of high lymphatic metastasis cell lines of mouse hepatocellular carcinoma with peritoneal effusion. Methods: The modified double emulsifying solvent evaporation method was used to construct the macromolecule contrast agent PLGA-Cooh. The carbodiimide was used to connect the monoclonal antibody of gelatin with the contrast agent PLGA-Cooh, and the targeted ultrasound contrast agent Gsn-PLGA was established. The particle size and Zeta potential of the targeted ultrasound contrast agent were measured by laser particle size analyzer. The surface binding of the contrast agent to the gelatin monoclonal antibody was evaluated by immunofluorescence. Hca-F cells with high lymphatic metastasis were cultured in mice with peritoneal effusion hepatocellular carcinoma. Target-seeking ability in vitro was evaluated by in vitro uptake test, and the imaging effect of the contrast agent in vitro was evaluated by in vitro developing test. Results: The contrast agent is white powder with good water solubility. The average particle size and surface potential were (569.68±6.96) nm and (-10.95±2.43) mV, respectively. The fluorescent antibody binding rate of non-targeted and targeted ultrasound contrast agent labeled with DiI were 0.84% and 95.89%, respectively. The results showed that the targeted ultrasound contrast agent Gsn-PLGA had a better of developing effect in vitro. Hca-F cells with high expression of gelsolin protein had stronger uptake ability of targeted ultrasound contrast agent and stronger green fluorescence in vitro than those with low expression of gelsolin protein (P<0.05). Moreover, targeted ultrasound contrast agent Gsn-PLGA had stronger targeting to the gelsolin protein. The echo of the targeted ultrasound contrast agent Gsn-PLGA was uniform and fine, without attenuating echo of the back. Simultaneously, the development effect was more obvious with the increase of contrast agent concentration (P<0.05). Conclusion: Ultrasound contrast agent Gsn-PLGA targeting gelatin can bind Hca-F cells with high expression of gelatin and display a good imaging effect in vitro.


Obesity a communicable disease - A new age paradigm.
Obesity has reached pandemic proportions globally and is now also affecting developing countries in the south Asian region. Though conventionally described as a non-communicable disease, in certain ways it can be transmitted from one individual to another. In this paper we describe the different ways in which obesity has been considered as a communicable disease. The role of gut microbiota in causing obesity, transfer of microbes causing changes in body composition, viral infections associated with human obesity and above all it being a socially contagious disease in view of rapid globalization, are few of the communicable attributes of obesity. This framework has also led to development of novel treatment strategies for managing this rapidly increasing pandemic.


Measurement Properties of Smartphone Approaches to Assess Physical Activity in Healthy Young People: Systematic Review.
Physical inactivity is a preventable risk factor for several chronic diseases and one of the driving forces behind the growing global burden of disease. Recent evidence has shown that interventions using mobile smartphone apps can promote a significant increase in physical activity (PA) levels. However, the accuracy and reliability of using apps is unknown. The aim of our review was to determine the accuracy and reliability of using mobile apps to measure PA levels in young people. We conducted a systematic review guided by PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). Studies published from 2007 to 2020 were sourced from 8 databases-Ovid MEDLINE, Embase (Elsevier), Cochrane Library (Wiley), PsychINFO (EBSCOhost), CINAHL (EBSCOhost), Web of Science (Clarivate), SPORTDiscus (EBSCOhost), and IEEE Xplore Digital Library database. Studies were conducted in young people aged 10-24 years and without chronic illnesses, who evaluated a mobile app's ability to measure PA. Primary outcomes included validity, reliability, and responsiveness of the measurement approach. Duplicate screening was conducted for eligibility, data extraction, and assessing the risk of bias. Results were reported as a systematic review. The main physical activity measures evaluated for each study were the following: total PA time (min/day or min/week), total moderate to vigorous PA per week, daily step count, intensity measure (heart rate), and frequency measure (days per week). Of the 149 identified studies, 5 met the inclusion criteria (322 participants, 176 female; mean age 14, SD 3 years). A total of 3 studies measured criterion validity and compared PA measured via apps against PA measured via an Actigraph accelerometer. The 2 studies that reported on construct validity identified a significant difference between self-reported PA and the objective measure. Only 1 of the 5 apps examined was available to the public, and although this app was highly accepted by young people, the app recorded PA to be significantly different to participants' self-reported PA. Overall, few studies assess the reliability, validity, and responsiveness of mobile apps to measure PA in healthy young people, with studies typically only reporting on one measurement property. Of the 3 studies that measured validity, all concluded that mobile phones were acceptable and valid tools. More research is needed into the validity and reliability of smartphone apps to measure PA levels in this population as well as in populations with other characteristics, including other age groups and those with chronic diseases. PROSPERO CRD42019122242; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=122242.


Negative mobility induced by colored thermal fluctuations.
Anomalous transport of non-Markovian thermal Brownian particle dynamics in spatially periodic symmetric systems that is driven by time-periodic symmetric driving and constant bias is investigated numerically. The Brownian dynamics is modeled by a generalized Langevin equation with exponentially correlated Gaussian thermal noise, obeying the fluctuation-dissipation theorem. We study the role of nonzero correlation time of thermal fluctuations for the occurrence of absolute negative (linear) mobility (ANM) near zero bias, negative-valued, nonlinear mobility (NNM), and negative differential mobility (NDM) at finite bias away from equilibrium. We detect that a nonzero thermal correlation time can either enhance or also diminish the value of ANM. Moreover, finite thermal noise correlation can induce NDM and NNM in regions of parameter space for which such ANM and NNM behaviors are distinctly absent for limiting white thermal noise. In parts of the parameter space, we find a complex structure of regions of linear and nonlinear negative mobility: islands and tongues which emerge and vanish under parameters manipulation. While certain such anomalous transport regimes fade away with increasing temperature some specific regions interestingly remain rather robust. Outside those regimes with anomalous mobility, the ac/dc driven transport is either normal or the driven Brownian particles are not transported at all.


"We Tried to Take Care of Her, but it Got Too Exhausting": A Study of the Transition From Family Carer to Employer.
In Taiwan an increasing number of families are employing live-in carers from abroad to cope with care responsibilities, including the Indigenous Tayal. The aim of this research was to understand the transition from Indigenous family carer to employer with older family members who have extensive care needs. Six Indigenous employers were interviewed, and a narrative hermeneutic analysis was performed. The Tayal caregivers' cases revealed that their transition to employing live-in carers was complex and filled with ethical dilemmas due to their vulnerable positions. They tried to ensure person-centered care for their family members, but by doing this they risked reproducing vulnerability when transferring their own vulnerability to the live-in carer. The results indicate the interwoven nature of care dependency when it is defined by multiple vulnerabilities, Indigeneity and migration, and the multifaceted components of cultural safety.


[Application of new techniques for locating the underlying molecular defects in patients with disorders of oxidative phosphorylation].
The oxidative phosphorylation (OXPHOS) is a system that generates ATP by the transfer of electrons through the complexes of the respiratory chain. Mitochondria are very abundant in organs with high energy demand, including skeletal muscle, heart muscle and brain. The incidence of OXPOS defects is estimated at 1/10,000. Most frequently, a myopathy, encephalopathy or encephalomyopathy is seen. Mutations in the patients with OXPHOS defects can be located in the nuclear genome as well as in the mitochondrial genome which makes the search for the underlying gene defect very difficult. A diagnostic strategy is developed to make the search for the molecular defect easier. Besides the classical spectrophotometric analysis also Blue Native Polyacrylamide Gel Electrophoresis (BN-PAGE) is used. The latter can be combined with activity staining in the gel, or with immunoblotting of the complexes, or with SDS electrophoresis (2-dimensional electrophoresis). Also immunocytological and immunohistochemical analyses are used, especially for detection of heteroplasmy. Skeletal muscle and cultured skin fibroblasts are the favorite tissues used for the application of BN-PAGE and immunological techniques. BN-PAGE followed by activity staining in the gel is especially suited for detection of a deficiency of complex I or of complex V With the spectrophotometric method is it difficult to detect these deficiencies in cultured skin fibroblasts. With BN-PAGE the presence of subcomplexes of complex V can be visualized, which is an indication of a decreased intramitochondrial translation. The immunological stainings on the other hand are well suited for detection of heteroplasmy. The combined use of all these techniques allows the identification of the underlying gene defect in a significant number of patients.


Effects of feeding graded levels of vitamin D3 on egg shell pimpling in aged hens.
Pimpled egg shells are one of the various types of egg shell problems in the industry today. In this study, graded levels of vitamin D3 (D3) (0, 138, 275, 550, 2200, 22,000, 44,000, and 88,000 ICU of D3/kg of feed) were fed in a corn-soy ration to Single Comb White Leghorn hens (78 weeks of age), randomly assigned to one of the eight treatments. Feed consumption, egg production, egg weight, egg specific gravity, and pimple score were determined at weekly or biweekly intervals for a 10-week period. At termination of the experiment, calcium, sodium, potassium, and ash content of the uterus and serum calcium levels were assayed. Results showed that a significant (P less than .05) linear increase in pimple score, uterine ash, and serum calcium occurred as dietary levels of D3 increased. Egg production and egg specific gravity were correlated to D3 level in a quadratic fashion. Uterine sodium levels declined with increased D3 in the diet, while potassium values showed no differences. Calcium levels of uterine tissue tended to increase with increased D3. The lowest (0 ICU/kg) and highest level of D3 (88,000 ICU/kg) significantly decreased feed consumption. It was concluded that egg shell pimpling is directly related to level of cholecalciferol (D3) in the diet.


Test-Retest Reliability and Translation of the Musculoskeletal Screening Protocol Questionnaire Used in the Swedish Armed Forces.
Musculoskeletal disorders (MSDs) in military personnel are common, and it is important to identify those at risk so that appropriate preventive and rehabilitative strategies can be undertaken. The Musculoskeletal Screening Protocol (MSP) questionnaire is part of the implemented prevention strategy to reduce MSDs in the Swedish Armed Forces. The aims of this study were to evaluate the questionnaire's reliability and to translate it into English. One-week test-retest reliability of the questionnaire was evaluated in a sample of 35 Swedish military personnel. Reliability was evaluated by calculations of Cohen's kappa or quadratic-weighted kappa. Percent agreement was used as a parameter for measurement error. Translation into English included forward and backward translations and expert committee discussions. Kappa values relating to physical complaints/injuries were excellent (>0.75) except for knee and lower leg MSDs and for the intensity ratings, where Kappa values were mostly interpreted as fair-to-good (0.4-0.75). Kappa values of items pertaining physical performance, physical activity and exercise, eating and tobacco habits, sleep, and perceived health ranged between 0.72 and 1. Kappa values for feeling mentally or physical prepared were 0.47 and 0.65, respectively. Most percentage agreement values ranged between 90% and 100%. The English version was found to be satisfactorily equivalent to the Swedish MSP questionnaire. The Swedish MSP questionnaire was found to be highly reliable and was satisfactorily translated into English. This provides support for the questionnaire's ability to trustworthily capture the prevalence of MSDs and perceived health in military personnel. Future research is warranted on the psychometric properties of the English MSP questionnaire.


Dietary supplementation of vitamin D3 and calcium partially recover the compromised time budget and circadian rhythm of lying behavior in lactating cows under heat stress.
Heat stress impedes cattle behavior and performance and is an animal comfort and welfare issue. The objective of this study was to characterize the time budget and circadian rhythm of lying behavior in dairy cows during heat stress and to assess the effect of dietary supplementation of vitamin D3 and Ca. Twelve multiparous Holstein cows (42.2 ± 5.6 kg milk/d; 83 ± 27 d in milk) housed in tie-stalls were used in a split-plot design with the concentration of dietary vitamin E and Se as main plots (LESe: 11.1 IU/kg and 0.55 mg/kg, and HESe: 223 IU/kg and 1.8 mg/kg, respectively). Within each plot cows were randomly assigned to: 1) heat stress with low concentrations of vitamin D3 and Ca (HS, 1012 IU/kg and 0.73%, respectively), 2) heat stress with high concentrations of vitamin D3 and Ca (HS+D3/Ca; 3,764 IU/kg and 0.97%, respectively), or 3) thermoneutral pair-fed (TNPF) with low concentrations of vitamin D3 and Ca (1012 IU/kg and 0.73%, respectively) in a Latin Square design with 14-d periods and 7-d washouts. Lying behavior was measured with HOBO® Loggers in 15-min intervals. Overall, cows in HS spent less time lying per day relative to TNPF from d 7 to 14. Daily lying time was positively correlated with milk yield, energy-corrected milk yield, and feed efficiency, and was negatively correlated with rectal temperature, respiratory rate, fecal calprotectin, tumor necrosis factor-α, and C-reactive protein. A treatment by time interaction was observed for lying behavior: the time spent lying was lesser for cows in HS than in TNPF in the early morning (0000 - 0600 h) and in the night (1800 - 2400 h). The circadian rhythm of lying behavior was characterized by fitting a cosine function of time into linear mixed model. Daily rhythmicity of lying was detected for cows in TNPF and HS+D3/Ca, whereas only a tendency in HS cows was observed. Cows in TNPF had the highest mesor (the average level of diurnal fluctuations; 34.2 min/h) and amplitude (the distance between the peak and mesor; 17.9 min/h). Both the mesor and amplitude were higher in HS+D3/Ca relative to HS (26.6 vs. 25.2 min/h and 3.91 min/h vs. 2.18 min/h, respectively). The acrophase (time of the peak) of lying time in TNPF, HS, and HS+D3/Ca were 0028, 0152, and 0054 h, respectively. Lastly, a continuous increase in daily lying time in TNPF was observed during the first 4 d of the experimental period in which DMI was gradually restricted, suggesting that intake restrictions may shift feeding behavior and introduce biases in the behavior of animals. In conclusion, lying behavior was compromised in dairy cows under heat stress, characterizing reduced daily lying time and disrupted circadian rhythms, and the compromised lying behavior can be partially restored by supplementation of vitamin D3 and Ca. Further research may be required for a more suitable model to study behavior of cows under heat stress.


A gene-specific requirement for FACT during transcription is related to the chromatin organization of the transcribed region.
The FACT complex stimulates transcription elongation on nucleosomal templates. In vivo experiments also involve FACT in the reassembly of nucleosomes traversed by RNA polymerase II. Since several features of chromatin organization vary throughout the genome, we wondered whether FACT is equally required for all genes. We show in this study that the in vivo depletion of Spt16, one of the subunits of Saccharomyces cerevisiae FACT, strongly affects transcription of three genes, GAL1, PHO5, and Kluyveromyces lactis LAC4, which exhibit positioned nucleosomes at their transcribed regions. In contrast, showing a random nucleosome structure, YAT1 and Escherichia coli lacZ are only mildly influenced by Spt16 depletion. We also show that the effect of Spt16 depletion on GAL1 expression is suppressed by a histone mutation and that the insertion of a GAL1 fragment, which allows the positioning of two nucleosomes, at the 5' end of YAT1 makes the resulting transcription unit sensitive to Spt16 depletion. These results indicate that FACT requirement for transcription depends on the chromatin organization of the 5' end of the transcribed region.


Dietary Fish Oil and Vitamin E Reduce Cryoinjuries and Apoptosis in Vitrified Laying Hens' Ovarian Tissue.
The occurrence of cryoinjuries during ovarian tissue freezing necessitates development of methods that can overcome these challenges in cell and tissue cryopreservation. It has been hypothesized that omega-3 and vitamin E diet supplementation to the animal could be an appropriate strategy to preserve post-thaw ovarian quality. The laying hen is an appropriate animal model that can be used to study the effects of providing dietary supplements on the outcomes of ovary cryopreservation. The purpose of the study was to evaluate the dietary effects of fish oil, sunflower oil, and vitamin E on 68 laying hens according to the following treatments: basal diet + 1.5% sunflower oil (control; C); basal diet + 1.5% sunflower oil + 1.1 IU alpha-tocopherol/hen/day (E); basal diet + 1.5% fish oil + 1.1 IU alphatocopherol/hen/day (n-3+E); and basal diet + 1.5% fish oil (n-3). The effects on ovarian structure and preservation, apoptosis-related gene expression, and the fatty acid profiles in ovarian laying hen (n = 7 in each group) were studied. The number of intact primordial follicles in n-3+E group was significantly higher than other groups (85% vs. 71%, 72%, and 77% for n-3+E, C, E, and n-3, respectively; p < 0.01). There was a significant reduction in expression of Cas3, as well as Cas8, in n-3 and n-3+E than C and E (p ≤ 0.05). A trend to decrease in Bak (p = 0.089) and Bak/Bcl2 ratio (p = 0.095) in the mRNA was observed in n-3+E. Ovarian eicosapentaenoic acid (C20:5n3) concentration in n-3 was the highest among C, E, and n-3+E (p < 0.01). Docosahexaenoic acid (C22:6 n-3) concentrations in ovaries of the n-3 group were elevated five times more than control. The n-3: n-6 ratio in groups receiving omega-3 (n-3+E and n-3) was higher than other groups (p < 0.01). In conclusion, consumption of dietary omega-3 fatty acids with vitamin E improves the results of vitrification of ovarian tissues in laying hens.


[Results of vitrectomy in cystoid diabetic macular edema detected by optical coherence tomography].
To evaluate the surgical results of the pars plana vitrectomy (PPV) with separation of the posterior hyaloid (PH) with the cystoid diabetic macular edema (DME) using optical coherence tomography (OCT). PPV with removing of the PH was performed in 10 eyes of 10 patients with cystoid DME. The macular structure, the vitreoretinal interface and the foveal thickness before and after PPV was evaluated using OCT and was correlated with a slit lamp biomicroscope. All 10 eyes had undergone panretinal and macular photocoagulation. OCT demonstrated postoperatively in all 10 eyes the regression of cystoid DME and the presence of foveal depression. Visual acuity (VA) has improved by 2 and more Snellen lines in 6 eyes with preoperative decrease of VA not longer than 5 months. PPV with separation of PH is efficient method in treatment of cystoid DME. Duration of cystoid DME is a significant factor for determination of functional prognosis. OCT facilitates the follow-up of the dynamics of regression of the structure and thickness of the fovea.


[Prevalence of hepatitis B virus infection in patients suffering from acute and chronic liver disease in three public hospitals in Durango, Mexico].
We carried out an observational, descriptive, and retrospective epidemiological study in order to determine the prevalence of hepatitis B virus infection (HBV) in patients with acute and chronic liver disease in three public hospitals of Durango, Mexico. Sixty five adult patients were included in the study. Fifty eight (89%) were inpatients and 7 were outpatients. Twenty three patients suffered from acute hepatitis, 10 chronic hepatitis, 29 liver cirrhosis, 2 hepatocellular carcinoma, and I fulminant hepatitis. A questionnaire was administered to all participants that included sociodemographic and epidemiological data. In addition, serum samples were analyzed for hepatitis B surface antigen (HBsAg) by an immunoassay (A UZYME Monoclonal), manufactured by ABBOTT Diagnostics (North Chicago, IL, USA). Out of the 65 patients, 2 (3%) were positive for HBsAg. Of the two positive cases, one had chronic hepatitis and other liver cirrhosis. Both positive cases had histories of blood transfusion, surgery, and alcohol abuse. In addition, one of them had a history of acupuncture. Previous traveling (within Mexico, abroad or both) was more frequently observed in HBsAg positive patients than in HBsAg negative patients (p <0.05). We concluded that the prevalence of HBV infection in patients with liver disease in the city of Durango is low. This prevalence is comparable or lower than the one reported in other Mexican cities, and lower than other countries.


Expanding the lens of evidence-based practice in psychotherapy to include a common factors perspective: comment on Laska, Gurman, and Wampold.
Laska, Gurman, and Wampold (2014, pp. 467-481) raise a number of interesting arguments for clinical practice that involves the integration of the Common Factors and Empirically Supported Therapies perspectives. The merits, validity, and weaknesses in these arguments are discussed from a conceptual and empirical viewpoint. While we agree that the division in the field between the 2 approaches is excessive and interferes in the delivery of effective patient care, we highlight the important reasons to use unbiased, replicable assessments of treatment effects and interpretation when choosing a treatment approach. We emphasize the need to conduct empirical comparisons using study designs that allow us to vigorously test the influence of common factors over and beyond specific treatment ingredients, before we can more widely advocate for their necessary inclusion in existing treatments.


Sirt6-mediated Nrf2/HO-1 activation alleviates angiotensin II-induced DNA DSBs and apoptosis in podocytes.
Recent studies suggested that DNA double-strand breaks (DSBs) were associated with the pathogenesis of chronic kidney disease (CKD). The purpose of this investigation was to determine the role of Sirtuin6 (Sirt6), a histone deacetylase related to DNA damage repair, in angiotensin (Ang) II-induced DNA DSBs and the cell injury of podocytes and explore the possible mechanism. Here we showed that an increase of DNA DSBs was accompanied by a reduction in Sirt6 expression in the glomeruli of patients with hypertensive nephropathy (HN). Similar results were found in rat kidneys infused with Ang II and in cultured podocytes stimulated with Ang II. Sirt6 overexpression inhibited Ang II-induced ROS generation and DNA DSBs, and thus served as a protection against Ang II-induced apoptosis in podocytes. Moreover, Sirt6 activation enhanced Nrf2 and HO-1 gene expressions in podocytes after Ang II treatment. Furthermore, Nrf2 knockdown could partly reverse the cytoprotective effects of Sirt6 activation. In conclusion, our observations demonstrated that the Sirt6-Nrf2-HO-1 pathway played a vital role in relieving Ang II-mediated oxidative DNA damage and podocyte injury.


Reproductive morphology of Ornithonyssus sylviarum (Canestrini and Fanzago) (Acari: Macronyssidae).
The male reproductive system consists of paired tests, vasa deferentia and dark-staining lateral accessory glands, single ventromedial spongy accessory gland, seminal vesicle, ejaculatory apparatus, and gonopore. The female system consists of paired rami sacculi, sacculus foemineus, ovary (lyriform and medial portions), oviduct, vagina, and paired vaginal glands.


Wilms' tumor: prognostic factors and survival.
A statistical analysis of 38 cases of Wilms' tumor treated and followed by the Pediatric Oncology Group of Cerrahpaşa Medical Faculty, from 1977 to 1984, is presented. The two-year survival rate was 67% and the five-year survival rate was found to be 63%. There was a strong correlation between the stage and age of the patients and prognosis. The median age was 16 months in stages I and II of the disease and the two-year survival rate was 87%. The median age was found to be 5 years in advanced stages and the survival rate at 2 years was 43%. No correlation was found between survival and initial symptoms of the tumor or its localization. The effects of histological grade on prognosis of disease were also investigated.


On the problem of boundaries and scaling for urban street networks.
Urban morphology has presented significant intellectual challenges to mathematicians and physicists ever since the eighteenth century, when Euler first explored the famous Königsberg bridges problem. Many important regularities and scaling laws have been observed in urban studies, including Zipf's law and Gibrat's law, rendering cities attractive systems for analysis within statistical physics. Nevertheless, a broad consensus on how cities and their boundaries are defined is still lacking. Applying an elementary clustering technique to the street intersection space, we show that growth curves for the maximum cluster size of the largest cities in the UK and in California collapse to a single curve, namely the logistic. Subsequently, by introducing the concept of the condensation threshold, we show that natural boundaries of cities can be well defined in a universal way. This allows us to study and discuss systematically some of the regularities that are present in cities. We show that some scaling laws present consistent behaviour in space and time, thus suggesting the presence of common principles at the basis of the evolution of urban systems.


Molecular Analysis of Congenital Hypothyroidism in Saudi Arabia: SLC26A7 Mutation Is a Novel Defect in Thyroid Dyshormonogenesis.
Congenital hypothyroidism (CH) is the most common neonatal endocrine disorder, affecting one in 3000 to 4000 newborns. Since the introduction of a newborn screening program in 1988, more than 300 cases have been identified. The underlying genetic defects have not been systematically studied. To identify the mutation spectrum of CH-causing genes. Fifty-five patients from 47 families were studied by next-generation exome sequencing. Mutations were identified in 52.7% of patients (29 of 55) in the following 11 genes: TG, TPO, DUOX2, SLC26A4, SLC26A7, TSHB, TSHR, NKX2-1, PAX8, CDCA8, and HOXB3. Among 30 patients with thyroid dyshormonogenesis, biallelic TG mutations were found in 12 patients (40%), followed by biallelic mutations in TPO (6.7%), SLC26A7 (6.7%), and DUOX2 (3.3%). Monoallelic SLC26A4 mutations were found in two patients, one of them coexisting with two tandem biallelic deletions in SLC26A7. In 25 patients with thyroid dysgenesis, biallelic mutations in TSHR were found in six patients (24%). Biallelic mutations in TSHB, PAX 8, NKX2-1, or HOXB3 were found once in four different patients. A monoallelic CDCA8 mutation was found in one patient. Most mutations were novel, including three TG, two TSHR, and one each in DUOX2, TPO, SLC26A7, TSHB, NKX2-1, PAX8, CDCA8, and HOXB3. SLC26A7 and HOXB3 were novel genes associated with thyroid dyshormonogenesis and dysgenesis, respectively. TG and TSHR mutations are the most common genetic defects in Saudi patients with CH. The prevalence of other disease-causing mutations is low, reflecting the consanguineous nature of the population. SLC26A7 mutations appear to be associated with thyroid dyshormonogenesis.


Use of profound hypothermia and circulatory arrest for the calcified aorta.
This case report discusses one method of dealing with the extensively calcified aorta in patients undergoing open heart surgery. Profound hypothermia and circulatory arrest was used in a patient undergoing aortic valve replacement with severe calcification of the ascending aorta and transverse arch. This patient recovered from surgery and was discharged from the hospital with no neurologic deficits.


EIT based pulsatile impedance monitoring during spontaneous breathing in cystic fibrosis.
Evaluating the lung function in patients with obstructive lung disease by electrical impedance tomography (EIT) usually requires breathing maneuvers containing deep inspirations and forced expirations. Since these maneuvers strongly depend on the patient's co-operation and health status, normal tidal breathing was investigated in an attempt to develop continuous maneuver-free measurements. Ventilation related and pulsatile impedance changes were systematically analyzed during normal tidal breathing in 12 cystic fibrosis (CF) patients and 12 lung-healthy controls (HL). Tidal breaths were subdivided into three inspiratory (In1, In2, In3) and three expiratory (Ex1, Ex2, Ex3) sections of the same amplitude of global impedance change. Maximal changes of the ventilation and the pulsatile impedance signal occurring during these sections were determined (▵I V and ▵I P). Differences in ▵I V and ▵I P among sections were ascertained in relation to the first inspiratory section. In addition, ▵I V/▵I P was calculated for each section. Medians of changes in ▵I V were <0.05% in all sections for both subject groups. Both groups showed a similar pattern of ▵I P changes during tidal breathing. Changes in ▵I P first decreased during inspiration (In2), then increased towards the end of inspiration (In3) and reached a maximum at the beginning of expiration (Ex1). During the last two sections of expiration (Ex2, Ex3) ▵I P changes decreased. The CF patients showed higher variations in ▵I P changes compared to the controls (CF: -426.5%, HL: -158.1%, coefficient of variation). Furthermore, ▵I V/▵I P significantly differed between expiratory sections for the CF patients (Ex1-Ex2, p < 0.01; Ex1-Ex3, p < 0.001; Ex2-Ex3, p < 0.05), but not for the controls. No significant differences in ▵I V/▵I P between inspiratory sections were determined for both groups. Differences in ▵I P changes and in ▵I V/▵I P between both subject groups were speculated to be caused by higher breathing efforts of the CF patients due to airway obstruction leading to higher intrathoracic pressures, and thus to greater changes in lung perfusion.


PROX1 gene is differentially expressed in oral cancer and reduces cellular proliferation.
Homeobox genes are a family of transcription factors that play a pivotal role in embryogenesis. Prospero homeobox 1 (PROX1) has been shown to function as a tumor suppressor gene or oncogene in various types of cancer, including oral squamous cell carcinoma (OSCC). We have previously identified PROX1 as a downregulated gene in OSCC. The aim of this study is to clarify the underlying mechanism by which PROX1 regulates tumorigenicity of OSCC cells. PROX1 mRNA and protein expression levels were first investigated in 40 samples of OSCC and in nontumor margins. Methylation and amplification analysis was also performed to assess the epigenetic and genetic mechanisms involved in controlling PROX1 expression. OSCC cell line SCC9 was also transfected to stably express the PROX1 gene. Next, SCC9-PROX1-overexpressing cells and controls were subjected to proliferation, differentiation, apoptosis, migration, and invasion assays in vitro. OSCC samples showed reduced PROX1 expression levels compared with nontumor margins. PROX1 amplification was associated with better overall survival. PROX1 overexpression reduces cell proliferation and downregulates cyclin D1. PROX1-overexpressing cells also exhibited reduced CK18 and CK19 expression and transcriptionally altered the expression of WISP3, GATA3, NOTCH1, and E2F1. Our results suggest that PROX1 functions as a tumor suppressor gene in oral carcinogenesis.


[Treament of morphine-induced constipation with oral naloxone].
Almost all patients treated with opioids suffer from constipation. Numerous laxatives are used to overcome the problem, but none has yet been found to yield favourable results in all patients. Several studies have attempted to reverse opioid-induced constipation by the use of oral naloxone. Experiments carried out in rats showed that morphine-induced constipation is reduced by oral naloxone without impairment of antinociception [4]. However, evaluation of clinical studies reveals that there is uncertainty about the dosage regimen (the daily dose of naloxone ranged from 0.5% to about 60% that of morphine) and a lack of larger numbers of patients studied. Fifteen patients suffering from opioid-induced constipation participated in the present study. Constipation had been present for 5 to 14 days despite the use of laxatives. According to the results obtained in the animal experiments [4], it was originally planned to administer oral naloxone at a dose ratio of 1:1 with respect to morphine on day 1 and 2; reducing it on day 3 and 4 to one-half and then to one-fourth of the initial dose on day 5 and 6. Twelve patients experienced a strong laxative effect with spontaneous bowel evacuation 1 to 4 h after the first intake of oral naloxone. Three patients had no laxative effects even after repeated doses. Eleven of the 15 patients reported an average loss of 10%-15% of analgesia after oral naloxone as measured by visual analogue scales. Increasing the morphine dose by about 15% restored the previous level of analgesia without reappearance of constipation. Eight of the 12 patients having a laxative effect experienced abdominal cramps, and therefore, the total dose of naloxone was reduced on day 2 to 2%-15% of that originally planned; this dose still produced a laxative effect. Four of the 15 patients had a withdrawal syndrome. A single dose of morphine equivalent to their daily morphine intake abolished the symptoms. The medical history of the 3 patients in whom naloxone failed to abolish constipation revealed neurological disturbances. Treatment of these patients included the use of neuroleptics, antiemetics, and other drugs. In this context, it should be noted that oral naloxone can be expected to abolish only opioid-induced constipation. In conclusion, it was found that the treatment of opioid-induced constipation by administration of oral naloxone produced positive results. A controlled study will show, whether the side effects can be minimized by reducing the naloxone dose.


Spontaneous white matter damage, cognitive decline and neuroinflammation in middle-aged hypertensive rats: an animal model of early-stage cerebral small vessel disease.
Cerebral small vessel disease (cSVD) is one of the most prevalent neurological disorders. The progressive remodeling of brain microvessels due to arterial hypertension or other vascular risk factors causes subtle, but constant cognitive decline through to manifest dementia and substantially increases the risk for stroke. Preliminary evidence suggests the contribution of the immune system to disease initiation and progression, but a more detailed understanding is impaired by the unavailability of appropriate animal models. Here, we introduce the spontaneously hypertensive rat (SHR) as a model for early onset cSVD and unveiled substantial immune changes in conjunction with brain abnormalities that resemble clinical findings. In contrast to age-matched normotensive Wistar Kyoto (WKY) rats, male SHR exhibited non-spatial memory deficits. Magnetic resonance imaging showed brain atrophy and a reduction of white matter volumes in SHR. Histological analyses confirmed white matter demyelination and unveiled a circumscribed blood brain barrier dysfunction in conjunction with micro- and macrogliosis in deep cortical regions. Flow cytometry and histological analyses further revealed substantial disparities in cerebral CD45high leukocyte counts and distribution patterns between SHR and WKY. SHR showed lower counts of T cells in the choroid plexus and meningeal spaces as well as decreased interleukin-10 levels in the cerebrospinal fluid. On the other hand, both T and NK cells were significantly augmented in the SHR brain microvasculature. Our results indicate that SHR share behavioral and neuropathological characteristics with human cSVD patients and further undergird the relevance of immune responses for the initiation and progression of cSVD.


Induction of biologically active IL-1 beta-converting enzyme and mature IL-1 beta in human keratinocytes by inflammatory and immunologic stimuli.
IL-1beta, a major mediator of inflammatory and immunologic skin disease, undergoes post-translational site-specific cleavage by a novel cysteine protease termed IL-1beta-converting enzyme (ICE). Although in human skin keratinocytes produce significant amounts of the 31-kDa IL-1beta precursor protein, they fail under nonpathologic conditions to convert it to the 17.5-kDa bioactive form. In this study, we examined whether haptens and inflammatory agents might serve as stimuli for ICE activity in human keratinocytes, and, if so, whether ICE activity might precipitate enzymatic processing of IL-1beta to its 17.5-kDa form. Baseline levels of ICE mRNA were detected in keratinocyte cultures devoid of Langerhans cells and were up-regulated by nontoxic concentrations of the reactive hapten urushiol and by the irritant chemicals sodium lauryl sulfate and PMA. Although untreated keratinocytes expressed the 31-kDa form of the protein, 17.5-kDa IL-1beta was easily detected in keratinocytes and keratinocyte supernatants treated with either urushiol or the irritant chemicals. Enzymatic conversion from the 31-kDa to the 17.5-kDa form of IL-1beta was blocked by addition of a highly specific aldehyde inhibitor that contained a tetrapeptide recognition sequence specific for ICE, but not by an aldehyde inhibitor of a related ICE-like cysteine protease. Induction of IL-1beta-converting enzyme by immunologic and inflammatory stimuli may be one of the key regulatory elements in the pathogenesis of allergic and irritant contact hypersensitivity.


Mapping Mind-Brain Development: Towards a Comprehensive Theory.
The relations between the developing mind and developing brain are explored. We outline a theory of intellectual development postulating that the mind comprises four systems of processes (domain-specific, attention and working memory, reasoning, and cognizance) developing in four cycles (episodic, realistic, rule-based, and principle-based representations, emerging at birth, 2, 6, and 11 years, respectively), with two phases in each. Changes in reasoning relate to processing efficiency in the first phase and working memory in the second phase. Awareness of mental processes is recycled with the changes in each cycle and drives their integration into the representational unit of the next cycle. Brain research shows that each type of processes is served by specialized brain networks. Domain-specific processes are rooted in sensory cortices; working memory processes are mainly rooted in hippocampal, parietal, and prefrontal cortices; abstraction and alignment processes are rooted in parietal, frontal, and prefrontal and medial cortices. Information entering these networks is available to awareness processes. Brain networks change along the four cycles, in precision, connectivity, and brain rhythms. Principles of mind-brain interaction are discussed.


Getting quality in qualitative research: a short introduction to feminist methodology and methods.
The present paper reflects a practical activity undertaken by the Nutrition Society's qualitative research network in October 2005. It reflects the structure of that exercise. First, there is an introduction to feminist methodology and methods. The informing premise is that feminist methodology is of particular interest to practitioners (professional and/or academic) engaged in occupations numerically dominated by women, such as nutritionists. A critical argument is made for a place for feminist methodology in related areas of social research. The discussion points to the differences that exist between various feminist commentators, although the central aims of feminist research are broadly shared. The paper comprises an overview of organizing concepts, discussion and questions posed to stimulate discussion on the design and process of research informed by feminist methodology. Issues arising from that discussion are summarized.


Rapid leaf xylem acclimation diminishes the chances of embolism in grapevines.
Under most conditions tight stomatal regulation in grapevines (Vitis vinifera) avoids xylem embolism. The current study evaluated grapevine responses to challenging scenarios that might lead to leaf embolism and consequential leaf damage. We hypothesized that embolism would occur if the vines experienced low xylem water potential (Ψx) shortly after bud break or later in the season under a combination of extreme drought and heat. We subjected vines to two potentially dangerous environments: (i) withholding irrigation from a vineyard grown in a heatwave-prone environment, and (ii) subjecting potted vines to terminal drought 1 month after bud break. In the field experiment, a heatwave at the beginning of August resulted in leaf temperatures over 45 °C. However, effective stomatal response maintained the xylem water potential (Ψx) well above the embolism threshold, and no leaf desiccation was observed. In the pot experiment, leaves of well-watered vines in May were relatively vulnerable to embolism with 50% embolism (P50) at -1.8 MPa. However, when exposed to drought, these leaves acclimated their leaf P50 by 0.65 MPa in less than a week and before reaching embolism values. When dried to embolizing Ψx, the leaf damage proportion matched (percentage-wise) the leaf embolism level. Our findings indicate that embolism and leaf damage are usually avoided by the grapevines' efficient stomatal regulation and rapid acclimation of their xylem vulnerability.


Oligometastatic non-small cell lung cancer: Current management.
In the past decade, major developments have improved the survival of patients with oligometastatic non-small cell lung cancer (NSCLC). About 20% - 50% of patients with NSCLC present with oligometastases at diagnosis. For this group of patients, it seems that an increase in survival would justify aggressive local therapies. The development of minimally invasive surgery and advanced radiotherapy techniques like stereotactic body radiation therapy (SBRT) makes local control possible for selected patients with metastatic NSCLC. The advantage of SBRT over surgery is that it is a non-invasive technique, with minimum side effects, and is more suitable for fragile and elderly patients, non-candidates for surgery, or patients who refuse surgery. The purpose of this review is to summarize the latest scientific evidence on the management of oligometastatic NSCLC, focusing on the role of radiotherapy. The initial treatment recommended for patients with oligometastatic NSCLC is systemic therapy. Patients should be considered for radical treatment to both the primary tumor and oligometastases. Aggressive local therapy comprises surgery and/or definitive radiotherapy such as SRS or SBRT, and may be preceded or followed by systemic treatment. Recent clinical evidence from Phase II trials reports benefits in terms of PFS in patients with good performance status and long disease-free periods, with good response to systemic therapy, especially in EGFR wild-type tumors. Phase I and II trials have shown that radiotherapy combined with immunotherapy can improve tumor response rate and possibly overall survival. The recommendation is also to include OM patients in ongoing clinical trials.


Assessment of Sea Sickness in Naval Personnel: Incidence and Management.
Strategic, operational and tactical superiority of Navy hinges on extremely efficient warships which in turn depend on professionally competent sailors ready to undertake tasks to deliver timely, structured and metered response. Ships and their potentialities are tools to achieve the required strategic advantage which is dependent on the proficiency of sailors. Sailors who are fit ashore may be debilitated on board because of sea sickness. To study the incidence and severity of sea sickness among 500 naval personnel from various ships. Setting and design: An observational study conducted from May 2019 to March 2020 among 500 naval personnel from various ships of the fleet. Motion Sickness Assessment Questionnaire (MSAQ) was used to collect data from personnel of different departments working in different part of ship aged between 20 to 50 years. The majority suffered mild symptoms (78.78%) and did not require any medication. Their symptoms were selflimiting and settled on rest within 24 hours. Moderately severe symptoms were observed among 19.31 % personnel and had to be administered medication and rest for 24 hours. Only 1.91% had severe symptoms and had to be excused from duties along with medication and rest. Sea sickness is unpleasant and has an adverse effect on employability of the sailors. It is mild and self limiting in majority of the personnel not requiring active intervention. Some personnel may require desensitisation along with pharmacotherapy.


Impact of deep-water fish farms on benthic macrofauna communities under different hydrodynamic conditions.
In this study the environmental impacts of two fish farms located over deep water (180-190 m) were compared. MC-Farm was located at a site with slightly higher water currents (mean current speed 3-5 cms(-1)) than LC-farm (<2 cms(-1)). Macrofauna composition, bioirrigation and benthic fluxes (CO2 and NH4(+)) were quantified at different stages of the production cycle, revealing very different impact of the two farms. Macrofauna abundance and bioirrigation were stimulated compared to a non-impacted reference site at MC-farm, while macrofauna diversity was only moderately reduced. In contrast, macrofauna communities and related parameters were severely impoverished at LC-Farm. This study suggests that deep-water fish farms should not be sited in low current areas (<2 cms(-1)), since this will hamper waste dispersal and aggravate environmental impacts. On the other hand, fish farming at slightly more dynamic sites can lead to stimulated benthic macrofauna communities and only moderate environmental impacts.


Determination of the solution structure of the peptide hormone guanylin: observation of a novel form of topological stereoisomerism.
Guanylin is a 15 amino acid mammalian hormone containing two disulfide bonds. Guanylin shares sequence similarity with the bacterial heat-stable enterotoxin (STa) and is capable of binding to and stimulating the STa guanylyl cyclase receptor. Biologically active peptides have been prepared by two methods: (1) enzymatic treatment of a 99 residue proprotein (denoted proguanylin) expressed in Escherichia coli and (2) solid-phase chemical synthesis. Although both sources yield material that is pure by high-performance liquid chromatography and mass spectrometry, analysis by nuclear magnetic resonance (NMR) indicates that peptides from both sources contain two conformationally distinct species present in a 1:1 ratio. The chemical shift differences between the two species are large, allowing unambiguous sequential NMR assignments to be made for both sets of resonances. Exchange between the two forms was not observed even at 70 degrees C. Structural restraints have been generated from nuclear Overhauser effects and scalar coupling constants and used to calculate structures for both forms using distance geometry and restrained energy minimization. The resulting structures for the first isoform are well defined (root-mean-square deviation from the average structure for backbone atoms of 0.47 A) and adopt a right-handed spiral conformation, similar to that observed for heat stable enterotoxin. The second isoform is less well defined (root-mean-square deviation from the average structure for backbone atoms of 1.07 A) but clearly adopts a very different fold consisting of a left-hand spiral. The differences in structure suggest that the two forms may have very different affinities toward the STa receptor. The observation of such isomerism has important implications for the common practice of introducing multiple disulfide bonds into small peptides to limit conformational flexibility and enhance bioactivity.


Microbial community succession of submerged bones in an aquatic habitat.
After death, microbes (including bacteria and fungi) colonize carrion from a variety of sources during the decomposition process. The predictable succession of microbes could be useful for forensics, such as postmortem submersion interval estimation (PMSI) for aquatic deaths. However, gaps exist in our understanding of microbial succession on submerged bone, particularly regarding longer-term decomposition (>1 year), fungal composition, and differences between internal and external microbial communities. To further explore this potential forensic tool, we described the postmortem microbial communities (bacteria and fungi) on and within submerged bones using targeted amplicon sequencing. We hypothesized predictable successional patterns of microbial colonization would be detected on the surface and within submerged bones, which would eventually converge to a similar microbial community. To best replicate forensic contexts, we sampled bones from replicate swine (Sus scrofa domesticus) carcasses submerged in a freshwater pond, every three months for nearly two years. Microbial bone (internal vs. external) community structure (taxa abundance and diversity) of bones differed for both bacteria and fungi, but internal and external communities did not converge to a similar structure. PMSI estimation models built with random forest regression of postmortem microbiomes were highly accurate (>80% variation explained in PMSI) and showed promise for forensic purposes. Overall, we provide further evidence that internal and external bone microbial communities submerged in an aquatic habitat are distinct and each community undergoes predictable succession, demonstrating potential utility in forensics for modeling PMSI in unattended deaths and/or cold cases.


Evidence for glucokinase translocation by glucose in rat hepatocytes.
By an immunohistochemical technique, we examined changes in the subcellular distribution of rat liver glucokinase in response to external stimuli. Glucokinase immunoreactivity was found predominantly in the nucleus of hepatocytes. In situ perfusion of the liver with 20 mM glucose for 10 min caused a marked decrease in nuclear immunoreactivity and an increase in cytoplasmic immunoreactivity. Insulin (10 nmol/l) potentiated this glucose effect. However, no change took place when 5 mM glucose was perfused. These results indicate that glucokinase is translocated from the nucleus to the cytoplasm in response to a high concentration of glucose.


Insight into vibrational circular dichroism of proteins by density functional modeling.
Vibrational circular dichroism (VCD) spectroscopy is an excellent method to determine the secondary structure of proteins in solution. Comparison of experimental spectra with quantum-chemical simulations represents a convenient and objective way to extract information on the structure. This has been difficult for such large molecules where approximate theoretical models have to be used. In the present study we applied the Cartesian-coordinate based tensor transfer (CCT) making it possible to extend the density functional theory (DFT) and model spectral intensities of large globular proteins nearly at quantum-chemical precision. Indeed, comparison with experiment provided a better understanding of the dependence of VCD spectral shapes on the geometry, their sensitivity to fine structural details and interactions with the environment. On a model set of globular proteins the simulated spectra correlated well with experimental data and revealed which structural information can (and cannot) be obtained from this kind of spectroscopy. Although the VCD technique has been regarded as being rather insensitive to side-chain variations, we found that the spectra of human and hen lysozyme differing by a few amino acids only are quite distinct. This has been explained by long-distance coupling of the amide vibrations. Likewise, the modeling reproduced some spectral changes caused by protein deuteration even when the protein structure was conserved.


Research Review for Broad Learning System: Algorithms, Theory, and Applications.
In recent years, the appearance of the broad learning system (BLS) is poised to revolutionize conventional artificial intelligence methods. It represents a step toward building more efficient and effective machine-learning methods that can be extended to a broader range of necessary research fields. In this survey, we provide a comprehensive overview of the BLS in data mining and neural networks for the first time, focusing on summarizing various BLS methods from the aspects of its algorithms, theories, applications, and future open research questions. First, we introduce the basic pattern of BLS manifestation, the universal approximation capability, and essence from the theoretical perspective. Furthermore, we focus on BLS's various improvements based on the current state of the theoretical research, which further improves its flexibility, stability, and accuracy under general or specific conditions, including classification, regression, semisupervised, and unsupervised tasks. Due to its remarkable efficiency, impressive generalization performance, and easy extendibility, BLS has been applied in different domains. Next, we illustrate BLS's practical advances, such as computer vision, biomedical engineering, control, and natural language processing. Finally, the future open research problems and promising directions for BLSs are pointed out.


Suppressive effect of α-mangostin for cancer stem cells in colorectal cancer via the Notch pathway.
Since colon cancer stem cells (CSCs) play an important role in chemoresistance and in tumor recurrence and metastasis, targeting of CSCs has emerged as a sophisticated strategy for cancer therapy. α-mangostin (αM) has been confirmed to have antiproliferative and apoptotic effects on cancer cells. This study aimed to evaluate the selective inhibition of αM on CSCs in colorectal cancer (CRC) and the suppressive effect on 5-fluorouracil (5-FU)-induced CSCs. The cell viability assay was performed to determine the optimal concentration of αM. A sphere forming assay and flow cytometry with CSC markers were carried out to evaluate the αM-mediated inhibition of CSCs. Western blot analysis and quantitative real-time PCR were performed to investigate the effects of αM on the Notch signaling pathway and colon CSCs. The in vivo anticancer efficacy of αM in combination with 5-FU was investigated using a xenograft mouse model. αM inhibited the cell viability and reduced the number of spheres in HT29 and SW620 cells. αM treatment decreased CSCs and suppressed the 5-FU-induced an increase in CSCs on flow cytometry. αM markedly suppressed Notch1, NICD1, and Hes1 in the Notch signaling pathway in a time- and dose-dependent manner. Moreover, αM attenuated CSC markers CD44 and CD133, in a manner similar to that upon DAPT treatment, in HT29 cells. In xenograft mice, the tumor and CSC makers were suppressed in the αM group and in the αM group with 5-FU treatment. This study shows that low-dose αM inhibits CSCs in CRC and suppresses 5-FU-induced augmentation of CSCs via the Notch signaling pathway.


A Mannose Receptor from Litopenaeus vannamei Involved in Innate Immunity by Pathogen Recognition and Inflammation Regulation.
Mannose receptor, as a member of the C-type lectin superfamily, is a non-canonical pattern recognition receptor that can internalize pathogen-associated ligands and activate intracellular signaling. Here, a mannose receptor gene, LvMR, was identified from the Pacific white shrimp Litopenaeus vannamei. LvMR encoded a signal peptide, a fibronectin type II (FN II) domain, and two carbohydrate-recognition domains (CRDs) with special EPS and FND motifs. LvMR transcripts were mainly detected in the hepatopancreas, and presented a time-dependent response after pathogen challenge. The recombinant LvMR (rLvMR) could bind to various PAMPs and agglutinate microorganisms in a Ca2+-dependent manner with strong binding ability to D-mannose and N-acetyl sugars. The knockdown of LvMR enhanced the expression of most NF-κB pathway genes, inflammation and redox genes, while it had no obvious effect on the transcription of most phagocytosis genes. Moreover, the knockdown of LvMR caused an increase in reactive oxygen species (ROS) content and inducible nitric oxide synthase (iNOS) activity in the hepatopancreas after Vibrio parahaemolyticus infection. All these results indicate that LvMR might perform as a PRR in immune recognition and a negative regulator of inflammation during bacterial infection.


Evaluation of children with juvenile idiopathic arthritis in southeastern Turkey: a single center experience.
The aim of this study was to investigate the disease characteristics of children with juvenile idiopathic arthritis (JIA) in southeast Turkey. The International League of Associations for Rheumatology (ILAR) criteria were used to diagnose JIA. Hospital records of the Pediatric Rheumatology Unit, of the Dicle University Hospital, were reviewed retrospectively and demographic, clinical and laboratory data were recorded. Totally 213 children (103 boys, 110 girls), with an age range of 1.6-18 years were enrolled. The mean age of the disease onset was 8.1 years. Polyarticular type was the most common (42.3%) presentation. The frequencies of other JIA subtypes were as follows: oligoarticular 37.1%, systemic 8.9%, enthesitis-related arthritis (ERA) 10.8% and psoriatic arthritis 0.9%. The knees (74.2%) and ankles (54.0%) were the most commonly affected joints. Uveitis was found in 4.2% of patients. Anti-nuclear antibodies were positive in 11.7% and HLA-B27 in 2.8% of patients. Active disease was seen in 57 (26.7%) patients at the last visit. In the present study, polyarticular JIA was the predominant subtype and there were fewer patients with positive ANA or uveitis compared to previous studies. Hippokratia 2015, 19 (1): 63-68.


The essential role of exercise in the management of type 2 diabetes.
Exercise is typically one of the first management strategies advised for patients newly diagnosed with type 2 diabetes. Together with diet and behavior modification, exercise is an essential component of all diabetes and obesity prevention and lifestyle intervention programs. Exercise training, whether aerobic or resistance training or a combination, facilitates improved glucose regulation. High-intensity interval training is also effective and has the added benefit of being very time-efficient. While the efficacy, scalability, and affordability of exercise for the prevention and management of type 2 diabetes are well established, sustainability of exercise recommendations for patients remains elusive.


Multiple large infected scrotal sebaceous cysts masking Fournier's gangrene in a 32-year-old man.
Extensive large sebaceous cysts on the scotum are rare and present a problem only when infected or when cosmesis is deemed unacceptable by the patient. Fournier's gangrene is an infective condition with a high death rate. We describe a case of Fournier's gangrene in a patient masked by multiple large infected scrotal sebaceous cysts. A 32-year-old man with a history of alcohol dependency, cirrhosis and multiple scrotal sebaceous cysts presented with acute scrotal pain and erythema. Necrosis of the area became evident within 12 h of his admission and an emergency surgical debridement was performed. The wound was left open to heal via secondary intention over 4 weeks without complication. Fournier's gangrene is a rapidly progressive condition and early surgical debridement is crucial to achieve satisfactory outcomes. In this case, prompt intervention allowed a large scrotal defect to heal without the need for skin grafting.


Granulocyte-Colony Stimulating Factor (G-CSF) as an adjunct to antibiotics in the treatment of pneumonia in adults.
Granulocyte colony stimulating factor (G-CSF) is a naturally-occurring cytokine that has been shown to increase neutrophil function and number. Exogenous administration of recombinant G-CSF (filgrastim, pegfilgrastim or lenograstim) has found extensive use in the treatment of febrile neutropaenia, but its role in the treatment of infection in non-neutropaenic hosts is less well defined. We explored the role of G-CSF as an adjunct to antibiotics in the treatment of pneumonia in non-neutropaenic adults. We searched the following electronic databases in 2003 and updated the search in 2004: the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 1, 2004); MEDLINE (January 1966 to March Week 1, 2004); EMBASE (1998 to December 2003); online databases of clinical trials; and reference lists of articles. We also contacted study authors, manufacturers and distributors of G-CSF. We considered randomised controlled trials (RCTs) which included hospitalised adult patients with either community acquired pneumonia or hospital-acquired pneumonia. Two reviewers independently extracted data and assessed trial quality. The primary outcome measure was 28 day mortality. Secondary outcome measures included other markers of mortality as well as markers of adverse events, including organ dysfunction. An assessment of methodological quality was made for each study. Six studies with a total of 1984 people were identified. G-CSF use appeared to be safe with no increase in the incidence of total serious adverse events (pooled odds ratio (OR) 0.91; 95% confidence interval (CI): 0.73 to 1.14) or organ dysfunction. However, the use of G-CSF was not associated with improved 28 day mortality (pooled OR 0.86; 95% CI: 0.56 to 1.31). There is no current evidence supporting the routine use of G-CSF in the treatment of pneumonia. Studies in which G-CSF is administered prophylactically or earlier in therapy may be of interest.


A cryptic rock-paper-scissors game between Drosophila males.
Explaining the maintenance of genetic variation in characters associated with Darwinian fitness is a preoccupation of evolutionary biologists. Spatial or temporal variation in the environment can certainly promote polymorphism, yet even populations of 'model organisms', like fruit flies, kept on invariant protocols for hundreds of generations in the laboratory often show fitness variation that exceeds what would be expected from the input of new mutations alone. Such observations suggest either complexities of selection or of genetic architecture, and offer a powerful tool for the study of mechanisms that promote stable polymorphism. In this issue of Molecular Ecology, Zhang et al. (2013) report examples of nontransitivity in the outcome of postcopulatory sexual selection in the fruit fly, Drosophila, that follow the rules of the popular stalemate-breaking game roshambo - or rock, paper, scissors (RPS). The important feature of RPS is that while each strategy beats one other, it in turn is beaten by the third. Using chromosome extraction lines, the authors confirm earlier findings that the outcome of postcopulatory sexual selection via sperm competition for a male depends, in part, upon the competitor male's genotype. But taking it one step further, they demonstrate the nontransitivities between males required for circular RPS cycles in sperm competition between males, and are able to identify at least four associated loci. Because the postmating phenotype involves hundreds of potentially interacting peptides and receptors, this is an important step to understanding the persistence of variation in a critical component of male fitness.


Adaptive pain inhibition in murine resident-intruder interactions.
In dyadic encounters with aggressive resident conspecifics, male intruder mice display an initial acute nonopioid analgesia followed by a more enduring opioid analgesia. The former reaction occurs in association with active defense (flight or fight) and can be seen in response to the scent of an aggressive conspecific or defeat experience per se. In contrast, the latter (opioid) reaction is associated with passive defense (immobility) and occurs in response to extended conspecific attack. The mechanisms underlying these two ecologically-relevant forms of pain inhibition are contrasted and the phenomena are discussed in relation to the question of adaptive significance.


PHYSIOLOGY OF THE ENTEROCOCCI AS RELATED TO THEIR TAXONOMY.
Deibel, R. H. (American Meat Institute Foundation, Chicago, Ill.), Donald E. Lake, and C. F. Niven, Jr. Physiology of the enterococci as related to their taxonomy. J. Bacteriol. 86:1275-1282. 1963-Studies on a collection of enterococci isolated from diverse sources have confirmed the existence of two distinct species, namely, Streptococcus faecalis and Streptococcus faecium. In contrast with S. faecium, S. faecalis characteristically ferments melezitose, sorbitol, glycerol (anaerobically), citrate, and gluconate; fails to ferment arabinose and melibiose; has strong reducing capacities as demonstrated by prompt reduction of litmus in milk or tetrazolium in an agar medium; initiates growth on an agar medium containing 0.04% potassium tellurite; does not require folic acid for growth; and does not produce strong greening in blood agar. S. liquefaciens and S. zymogenes differ from S. faecalis only in their proteolytic capacities and, therefore, deserve only varietal status. Some S. faecalis and S. faecium strains are proteolytic when tested on agar media. S. durans differs from S. faecium only in its inability to ferment arabinose and mannitol, and the failure of most strains to ferment sucrose. Therefore, it should be considered as a variety of S. faecium. It is recommended that the term "enterococcus" be used only when referring to S. faecalis and S. faecium, and their respective varieties.


[Tuberculosis of the central nervous system: case reports].
Tuberculosis of the central nervous system possess a serious clinical and radiological problem, since early treatment of this condition is crucial for the patient's life, and tuberculous process in the CNS may mimic many other pathologies. In this paper three cases of tuberculous process difficult to diagnose are presented. In all the cases early treatment could be started due to MRI findings suggesting tuberculous etiology. The authors emphasize the importance of presumptive radiological diagnosis in reducing the morbidity and mortality rates due to CNS tuberculosis.


Growth of pulmonary microvasculature in ventilated preterm infants.
Density-based morphometric studies have demonstrated decreased capillary density in infants with bronchopulmonary dysplasia (BPD) and in BPD-like animal models, leading to the prevailing view that microvascular development is disrupted in BPD. To perform a comprehensive analysis of the early and late effects of ventilation on pulmonary microvascular growth in preterm infants. Postmortem lung samples were collected from ventilated preterm infants who died between 23 and 29 wk ("short-term ventilated") or between 36 and 39 wk ("long-term ventilated") corrected postmenstrual age. Results were compared with age-matched infants or stillborn infants ("early" and "late" control subjects). Microvascular growth was studied by anti-platelet endothelial cell adhesion molecule (PECAM)-1 immunohistochemistry, quantitative stereology, analysis of endothelial cell proliferation, and Western blot analysis of pulmonary PECAM-1 protein levels. Measurements were made of capillary density, volume of air-exchanging parenchyma, volume of microvascular endothelial cells, Ki67 labeling index of endothelial cells, and PECAM-1/actin protein levels. Lungs of long-term ventilated infants showed a significant (more than twofold) increase in volume of air-exchanging parenchyma and a 60% increase in total pulmonary microvascular endothelial volume compared with late control subjects, associated with 60% higher pulmonary PECAM-1 protein levels. The marked expansion of the pulmonary microvasculature in ventilated lungs was, at least partly, attributable to brisk endothelial cell proliferation. The microvasculature of ventilated lungs appeared immature, retaining a saccular architectural pattern. The pulmonary microvasculature of ventilated preterm infants displayed marked angiogenesis, nearly proportionate to the growth of the air-exchanging lung parenchyma. These results challenge the paradigm of microvascular growth arrest as a major pathogenic factor in BPD.


Glypican-1 drives unconventional secretion of fibroblast growth factor 2.
Fibroblast growth factor 2 (FGF2) is a tumor cell survival factor that is transported into the extracellular space by an unconventional secretory mechanism. Cell surface heparan sulfate proteoglycans are known to play an essential role in this process. Unexpectedly, we found that among the diverse subclasses consisting of syndecans, perlecans, glypicans, and others, Glypican-1 (GPC1) is the principle and rate-limiting factor that drives unconventional secretion of FGF2. By contrast, we demonstrate GPC1 to be dispensable for FGF2 signaling into cells. We provide first insights into the structural basis for GPC1-dependent FGF2 secretion, identifying disaccharides with N-linked sulfate groups to be enriched in the heparan sulfate chains of GPC1 to which FGF2 binds with high affinity. Our findings have broad implications for the role of GPC1 as a key molecule in tumor progression.


The structural basis of large ribosomal subunit function.
The ribosome crystal structures published in the past two years have revolutionized our understanding of ribonucleoprotein structure, and more specifically, the structural basis of the peptide bonding forming activity of the ribosome. This review concentrates on the crystallographic developments that made it possible to solve these structures. It also discusses the information obtained from these structures about the three-dimensional architecture of the large ribosomal subunit, the mechanism by which it facilitates peptide bond formation, and the way antibiotics inhibit large subunit function. The work reviewed, taken as a whole, proves beyond doubt that the ribosome is an RNA enzyme, as had long been surmised on the basis of less conclusive evidence.


Emptying against outflow obstruction--pharmacological aspects.
Outflow obstruction induces changes in muscarinic and adrenergic receptor functions, and in non-adrenergic, non-cholinergic (NANC) mechanisms relevant for detrusor contraction and relaxation. The complexity of the muscarinic regulation of detrusor function makes the relative importance of the different muscarinic receptor subtypes difficult to assess, both in the normal and obstructed detrusor. This means that the optimal profile of subtype selectivity of antimuscarinic drugs meant for treatment of detrusor overactivity still remains to be established. In most animal species, detrusor contraction is mediated by both muscarinic and NANC mechanisms. The most likely transmitter responsible for the NANC-component of contraction is ATP. NANC-components are probably of minor importance in the normal human detrusor. However, if the importance of the ATP-dependent component of contraction increases in the obstructed detrusor, this may have therapeutic implications. In normal human detrusor, alpha-adrenoceptors seem to have no significant role in the contractile activation. However, the effectiveness of alpha-adrenoceptor antagonists on storage symptoms, and, occasionally, on urodynamically proven detrusor instability, in patients with outflow obstruction, suggests an involvement of alpha-adrenoceptors. The functional importance of beta-adrenoceptors for the obstructed detrusor function remains to be settled. In outflow obstruction, changes in the excitability of the detrusor smooth muscle may occur that predisposes for detrusor overactivity. Drugs acting at K+ channels can decrease detrusor excitability, and may, if cardiovascular side effects can be avoided, represent a novel, promising way of treating detrusor overactivity.


Ethnical discrimination in Europe: Field evidence from the finance industry.
The integration of ethnical minorities has been a hotly discussed topic in the political, societal, and economic debate. Persistent discrimination of ethnical minorities can hinder successful integration. Given that unequal access to investment and financing opportunities can cause social and economic disparities due to inferior economic prospects, we conducted a field experiment on ethnical discrimination in the finance sector with 1,218 banks in seven European countries. We contacted banks via e-mail, either with domestic or Arabic sounding names, asking for contact details only. We find pronounced discrimination in terms of a substantially lower response rate to e-mails from Arabic senders. Remarkably, the observed discrimination effect is robust for loan- and investment-related requests, across rural and urban locations of banks, and across countries.


Learning Semantic Part-Based Models from Google Images.
We propose a technique to train semantic part-based models of object classes from Google Images. Our models encompass the appearance of parts and their spatial arrangement on the object, specific to each viewpoint. We learn these rich models by collecting training instances for both parts and objects, and automatically connecting the two levels. Our framework works incrementally, by learning from easy examples first, and then gradually adapting to harder ones. A key benefit of this approach is that it requires no manual part location annotations. We evaluate our models on the challenging PASCAL-Part dataset [1] and show how their performance increases at every step of the learning, with the final models more than doubling the performance of directly training from images retrieved by querying for part names (from 12.9 to 27.2 AP). Moreover, we show that our part models can help object detection performance by enriching the R-CNN detector with parts.


Altered neuronal activity relationships between the pedunculopontine nucleus and motor cortex in a rodent model of Parkinson's disease.
The pedunculopontine nucleus (PPN) is a new deep brain stimulation (DBS) target for Parkinson's disease (PD), but little is known about PPN firing pattern alterations in PD. The anesthetized rat is a useful model for investigating the effects of dopamine loss on the transmission of oscillatory cortical activity through basal ganglia structures. After dopamine loss, synchronous oscillatory activity emerges in the subthalamic nucleus and substantia nigra pars reticulata in phase with cortical slow oscillations. To investigate the impact of dopamine cell lesion-induced changes in basal ganglia output on activity in the PPN, this study examines PPN spike timing with reference to motor cortex (MCx) local field potential (LFP) activity in urethane- or ketamine-anesthetized rats. Seven to ten days after unilateral 6-hydroxydopamine lesion of the medial forebrain bundle, spectral power in PPN spike trains and coherence between PPN spiking and PPN LFP activity increased in the approximately 1 Hz range in urethane-anesthetized rats. PPN spike timing also changed from firing predominantly in phase with MCx slow oscillations in the intact urethane-anesthetized rat to firing predominantly antiphase to MCx oscillations in the hemi-parkinsonian rat. These changes were not observed in the ketamine-anesthetized preparation. These observations suggest that dopamine loss alters PPN spike timing by increasing inhibitory oscillatory input to the PPN from basal ganglia output nuclei, a phenomenon that may be relevant to motor dysfunction and PPN DBS efficacy in PD patients.


Combined psychoeducation and treatment with selective serotonin reuptake inhibitors for youth with generalized social anxiety disorder.
Treatment outcome data for childhood social anxiety are scant. Studies that do exist support the efficacy of both pharmacological and psychotherapeutic interventions. Aside from case reports, studies assessing the efficacy of combined treatment approaches are even more limited. In the current study, we present preliminary findings from a combined psychoeducational and pharmacological treatment program for children and adolescents (ages 8-17 years) with generalized social anxiety disorder. Twelve participants received 12 weeks of citalopram treatment (maximum dose 40 mg/day) and eight brief counseling sessions (15 minutes each). Counseling sessions included education about social anxiety, skills coaching, and behavioral exercises; parents were included in these sessions. Based on clinician global ratings of change, 10 of 12 (83.3%) youths reported improvement: 41.7% (n = 5) of the participants were very much improved, and 41.7% (n = 5) were much improved. Significant changes were also found on self-report ratings of social anxiety, depression, and parents' perceptions of children's social skills during the course of treatment. Findings support the need for double-blind, placebo-controlled studies of combined treatments for youth with generalized social anxiety disorder.


Fisetin inhibits cellular proliferation and induces mitochondria-dependent apoptosis in human gastric cancer cells.
The anticancer effects of fisetin, a dietary agent, are largely unknown against human gastric cancer. Herein, we investigated the mechanisms of fisetin-induced inhibition of growth and survival of human gastric carcinoma AGS and SNU-1 cells. Fisetin (25-100 μM) caused significant decrease in the levels of G1 phase cyclins and CDKs, and increased the levels of p53 and its S15 phosphorylation in gastric cancer cells. We also observed that growth suppression and death of non-neoplastic human intestinal FHs74int cells were minimally affected by fisetin. Fisetin strongly increased apoptotic cells and showed mitochondrial membrane depolarization in gastric cancer cells. DNA damage was observed as early as 3 h after fisetin treatment which was accompanied with gamma-H2A.X(S139) phosphorylation and cleavage of PARP. Fisetin-induced apoptosis was observed to be independent of p53. DCFDA and MitoSOX analyses showed an increase in mitochondrial ROS generation in time- and dose-dependent fashion. It also increased cellular nitrite and superoxide generation. Pre-treatment with N-acetyl cysteine (NAC) inhibited ROS generation and also caused protection from fisetin-induced DNA damage. The formation of comets were observed in only fisetin treated cells which was blocked by NAC pre-treatment. Further investigation of the source of ROS, using mitochondrial respiratory chain (MRC) complex inhibitors, suggested that fisetin caused ROS generation specifically through complex I. Collectively, these results for the first time demonstrated that fisetin possesses anticancer potential through ROS production most likely via MRC complex I leading to apoptosis in human gastric carcinoma cells. © 2016 Wiley Periodicals, Inc.


Efficacy and safety of primary, early and late needle-knife fistulotomy for biliary access.
European Society of Gastrointestinal Endoscopy recommends needle-knife fistulotomy (NKF) as the preferred precut technique. However, there is little information on whether NKF performed at different times is associated with different success and adverse event rates. We compared the outcomes of 3 different timings of NKF. This was an observational study conducted at 4 institutions and this was a retrospective analysis of prospectively collected data. We included 330 consecutive patients submitted to NKF attempt for biliary access. Patients were divided into three groups: NKF as an initial procedure for biliary access (group A, n = 121); early NKF defined as after 5 min, 5 attempts, or 2 pancreatic passages (group B, n = 99); and late NKF: after at least 10 min of unsuccessful standard biliary cannulation (group C, n = 110). We assessed the success rate of biliary cannulation at initial ERCP, time to perform NKF until biliary cannulation, overall biliary cannulation rate (second ERCP when initial failure), adverse event rate, and predictors of post-ERCP pancreatitis (PEP). The initial cannulation rate was 98%, 91% and 94% for groups A, B and C respectively, p = 0.08, whereas overall biliary cannulation rate was 100%, 95% and 98%, p = 0.115. The adverse event rate/PEP was 4.1%/2.5%, 7.1%/4% and 10.9%/8.2%, for groups A, B and C respectively, (p = 0.197 and p = 0.190). Median time for creating the fistula was A = 4.0 min, B = 3.2 min, and C = 5.6 min, p < 000.1. Each additional minute spent attempting cannulation increased the odds ratio (OR) for PEP by 1.072, and patients with 3 or more risk factors for pancreatitis had a higher chance of PEP. In conclusion, the timing of NFK does not appear to influence success rates but late NFK is associated with a higher time to create a fistula and an increased risk of pancreatitis. Primary NFK is associated with a high rate of success and a low rate of PEP and deserves additional investigation.


Ectopic expression of porcine peroxisome proliferator-activated receptor delta regulates adipogenesis in mouse myoblasts.
Peroxisome proliferator-activated receptor gamma (PPARgamma) plays a critical role in regulating adipogenesis. The expression of peroxisome proliferator-activated receptor delta (PPARdelta) precedes that of PPARgamma during adipocyte differentiation in rodents. The current experiment was designed to study the function of porcine PPARdelta and the interaction of PPARdelta and PPARgamma in adipocyte differentiation. Inhibition of myogenesis was observed in mouse myoblasts expressing porcine PPARdelta, similar to myoblasts expressing PPARgamma. Treatment of myoblasts expressing PPARdelta with ligands for both PPARdelta and PPARgamma enhanced lipogenesis and adipogenesis to a greater extent than treatment with a PPARgamma ligand alone, suggesting that both genes were involved in regulating lipogenesis and adipogenesis. The ability to transdifferentiate myoblasts into adipocytes was decreased in myoblasts coexpressing PPARdelta with either wild type or mutated PPARgamma (Ser 112 was mutated to Ala; the mutated PPARgamma is more active than the wild type) compared with myoblasts expressing PPARgamma alone. Adipocyte differentiation in myoblasts coexpressing PPARdelta and mutated PPARgamma was greater than in myoblasts coexpressing PPARdelta and wild type PPARgamma, confirming that Ser 112 is important for the function of PPARgamma. Taken together, our results demonstrate that overexpression of PPARdelta inhibits myotube formation and also enhances adipocyte differentiation. However, the complexity and interaction of PPARdelta and PPARgamma in adipogenesis are not clearly understood.


Effect of subminimal inhibitory concentrations of gentamicin, penicillin, trimethoprim-sulfamethoxazole on adherence of uropathogenic Escherichia coli strains.
Evaluating the adherence factor of uropathogenic Escherichia coli is important for assessing the relative efficiency of antimicrobials when used at sub-minimal inhibitory concentration (sub-MICs). The microdilution method was used to determine the MICs of gentamicin, trimethoprim-sulfamethaxozole and penicillin. Then the efficacy of antimicrobial sub-MICs was determined by hemagglutination and adherence assays. Instead of showing nearly the same MICs, gentamicin had nearly twice the activity of trimethoprim-sulfamethaxozole. Gentamicin, as a "long acting" agent, can be accepted as being more effective than trimethoprim-sulfamethaxozole or penicillin, especially at sub-MICs, against adherence factors of uropathogenic E. coli, and can be used as monotherapy for urinary tract infections.


30 Years of Neurosurgical Robots: Review and Trends for Manipulators and Associated Navigational Systems.
This review provides an examination of contemporary neurosurgical robots and the developments that led to them. Improvements in localization, microsurgery and minimally invasive surgery have made robotic neurosurgery viable, as seen by the success of platforms such as the CyberKnife and neuromate. Neurosurgical robots can now perform specific surgical tasks such as skull-base drilling and craniotomies, as well as pedicle screw and cochlear electrode insertions. Growth trends in neurosurgical robotics are likely to continue but may be tempered by concerns over recent surgical robot recalls, commercially-driven surgeon training, and studies that show operational costs for surgical robotic procedures are often higher than traditional surgical methods. We point out that addressing performance issues related to navigation-related registration is an active area of research and will aid in improving overall robot neurosurgery performance and associated costs.


Invasion inhibition effects and immunogenicity after vaccination of SPF chicks with a Salmonella Enteritidis live vaccine.
Meat and eggs from chickens infected with Salmonella Enteritidis, Salmonella Typhimurium and Salmonella Infantis are considered to be an important source of Salmonella infections for humans. In order to control Salmonella infections in chickens, basic biosecurity measures are taken in combination with inactivated or attenuated live vaccines. Apart from an adaptive immune response, some live vaccines also induce innate immune mechanisms that prevent or inhibit systemic invasion with homologous Salmonella serovars. It is unknown whether these invasion inhibition effects are also directed against heterologous Salmonella serovars. Furthermore, it is unclear whether the adaptive immune response after vaccination with a Salmonella Enteritidis phage type 4 live vaccine is also directed against other phage types of Salmonella Enteritidis and Typhimurium. Specific pathogen-free day-old chicks were vaccinated orally with a commercially available Salmonella Enteritidis live vaccine. To test the invasion inhibition effect, the animals were challenged orally with a labelled Salmonella Typhimurium or Salmonella Infantis strain 1 day after vaccination. To demonstrate the adaptive immune response against non-phage type 4 Salmonella Enteritidis strains and a monophasic Salmonella Typhimurium strain, the chickens were challenged with Salmonella Enteritidis strains of phage types 1, 8 and 21 and a monophasic Salmonella Typhimurium strain (Definitive Type 193). After challenge, the abundance of the challenge strain in liver and cecal tissue was enumerated and compared with a corresponding control group. Findings showed that the live Salmonella Enteritidis vaccine inhibits systemic invasion after early infection with Salmonella Typhimurium and Salmonella Infantis. Furthermore, adaptive immunity against the tested non-phage type 4 Salmonella Enteritidis strains and the monophasic Salmonella Typhimurium strain was demonstrated. The results of this study demonstrate that vaccination with the Salmonella Enteritidis phage type 4 live vaccine significantly inhibits the invasion of Salmonella Typhimurium and Infantis. Furthermore, an adaptive immune response was also detected against non-phage type 4 Salmonella Enteritidis strains and a monophasic Salmonella Typhimurium strain.


Changes in prolactin levels caused by luteinizing hormone releasing hormone.
The acute effects of luteinizing hormone releasing hormone (LHRH) on the release of prolactin (PRL) were investigated in 12 normal cycling women and 42 women with various menstrual disorders. LHRH (100 micrograms) was bolusly injected intramuscularly and PRL levels were measured immediately before the injection and at 30 minutes and 60 minutes after the injection. LHRH elicited an increase of more than 25% in PRL levels in 15 cases (27.8%) at both 30 minutes and 60 minutes after the injection, whereas PRL levels were decreased by more than 25% in 7 cases (13.0%). The PRL response to LHRH seemed to be related to basal PRL levels. Especially when the PRL concentration was 20 ng/ml or more, LHRH decreased PRL levels in 7 cases out of 16. On the other hand, LHRH increased PRL levels in the majority of cases with a PRL concentration less than 20 ng/ml. In conclusion, the LHRH injection occasionally alters PRL levels in either a positive or negative manner, depending upon the basal PRL levels.


Mushroom DNA barcoding project: Sequencing a segment of the 28S rRNA gene.
DNA barcoding is an important molecular methodology for species identification that was developed over the last two decades and it should be covered in the biology bachelor curriculum. Here, we present an example of DNA barcoding by sequencing a segment of the 28S nuclear ribosomal large subunit rRNA gene of wild mushrooms and framing the education in a project form for undergraduate students in biology. Students perform this project in 6-8 weeks, which also includes preparing a poster, writing a report and presenting a paper related to the work in a journal club format. First, fieldwork in the Netherlands was carried out, during which students collected mushrooms under supervision of a professional mycologist with the goal to (a) verify morphologically based identifications with a molecular method and (b) assess phylogenetic relationships of the different species collected. Next, DNA extractions and quantitation were performed, PCR amplification was done, and samples were sent out for Sanger sequencing. Students aligned and analyzed the sequences using BLAST and Geneious and subsequently created a phylogenetic tree. In case of collecting DNA barcodes of an earlier sequenced species, students could upload the data to a repository established for facilitation of future research projects. The method described is very robust, reagents and equipment are readily available, and costs are relatively low. In addition, the results can be compared to published fungal phylogenetic trees.


Expert advice about therapeutic exercise during pregnancy reduces the symptoms of sacroiliac dysfunction.
Objectives There are growing evidence that exercise improves sacroiliac dysfunction symptoms in pregnant women; but no data about the effect of expert advice regarding this matter. The aim of this study was to assess the effectiveness of expert advice about therapeutic exercise on sacroiliac dysfunction in pregnancy. Methods A total of 500 women with sacroiliac dysfunction diagnosed in pregnancy were randomized in study and control group. Study group has conducted expert advice on therapeutic exercise; while control group continued with their normal lifestyle. Pain intensity by Visual Analog Scale (VAS) and degree of functional disability by Quebec scale were assessed at enrolment and after 3 and 6 weeks. Results Significantly better reduction in pain intensity assessed by VAS (p=0.001) and degree of functional disability assessed by Quebec scale (p=0.001) was noted in study compared to control group. Better results for both outcome measures were obtained if intervention was implemented earlier i.e., in second (p=0.001; p=0.001) compared to third (p=0.005; p=0.001) trimester. Strong positive correlation was found between pain intensity and degree of functional disability in both groups. Conclusions Expert advice on therapeutic exercise is effective in reduction of sacroiliac dysfunction symptoms during pregnancy. Trial registration ACTRN12617000556347.


Cardio-metabolic responses during horse riding at three different speeds.
The purpose of the present investigation was to study the metabolic demand and cardiovascular response during a typical horse riding session. To this aim, 19 (9 male, 10 female) riders, regularly participating in competitions, were enrolled. They underwent a preliminary, incremental exercise test on a cycle-ergometer to assess their anaerobic threshold (AT) and VO2max. Then, participants underwent a riding training session, which comprised periods of walking, trotting, and cantering for a total of 20 min. Oxygen uptake (VO2), carbon dioxide production (VCO2), and heart rate (HR) were obtained throughout the preliminary and riding test by means of a portable metabolic system. Moreover, excess of CO2 production (CO2excess) and oxygen pulse (OP) were also calculated to obtain an estimate of anaerobic glycolysis and stroke volume. The main result was that all collected parameters remained below the AT level throughout the riding session, with the exception of HR that approached the AT level only during cantering. In detail, during cantering, average VO2, VCO2, HR, CO2excess, and OP values were 1289 ± 331 mL min(-1), 1326 ± 266 mL min(-1), 158 ± 22 bpm, 215 ± 119 mL min(-1), and 7.8 ± 1.6 mL/bpm, respectively. It was concluded that riding imposes only light to moderate stress on the aerobic and anaerobic energy systems. Moreover, cardiovascular reserve is only moderately recruited in terms of inotropism, while chronotropism can be stimulated more.