The Association Between Meningioma and Breast Cancer: A Systematic Review and Meta-analysis.
A potential relationship between meningioma and breast cancer was suggested 70 years ago. However, to date, no conclusive evidence is available on this topic. To provide a comprehensive review of the literature on the association of meningioma with breast cancer, supported by a meta-analysis. A systematic PubMed search was performed up to April 2023 to identify articles on the association of meningioma with breast cancer. The following key words were used strategically: meningioma, breast cancer, breast carcinoma, association, relation. All studies reporting women diagnosed with meningioma and breast cancer were identified. The search strategy was not limited by study design or publication date but only included articles in English. Additional articles were identified via citation searching. Studies reporting a complete population of meningiomas or breast cancer patients throughout a specific study period and a proportion of patients with a second pathology could be used for the meta-analysis. Data extraction was performed by 2 authors in accordance with the Preferred Reporting Items for Systematic Reviews (PRISMA) statement. Meta-analyses regarding both populations were performed using a random-effects model. Risk of bias was assessed. The main measures were whether there was an increased prevalence of breast cancer in female patients with meningioma and whether there was an increased prevalence of meningioma in female patients with breast cancer. A total of 51 retrospective studies (case reports, case series, and cancer registry reports) describing 2238 patients with both diseases were identified; 18 studies qualified for prevalence analyses and meta-analysis. The random-effects meta-analysis (13 studies) revealed a significantly greater prevalence of breast cancer in female patients with meningioma than in the overall population (odds ratio [OR], 9.87; 95% CI, 7.31-13.32). Meningioma incidence in patients with breast cancer (11 studies) was greater than that in the baseline population; however, the difference according to the random-effects model was not statistically significant (OR, 1.41; 95% CI, 0.99-2.02). This large systematic review and the meta-analysis on the association between meningioma and breast cancer found nearly 10-fold higher odds of breast cancer in female patients with meningioma compared with the general female population. These findings suggest that female patients with meningioma should be screened more intensively for breast cancer. Further research is required to identify the factors causing this association.


Labour analgesia: a randomised, controlled trial comparing intravenous remifentanil and epidural analgesia with ropivacaine and fentanyl.
To compare the analgesic efficacy and side-effects of remifentanil intravenous patient-controlled analgesia (IVPCA) with walking epidural analgesia (EDA) during labour. Thirty-nine parturient patients of mixed parity, with normal singleton pregnancies, were randomised to receive either remifentanil IVPCA (RA group) or EDA (EA group). The epidural solution contained ropivacaine 1 mg ml⁻¹ and fentanyl 2 μg ml⁻¹, and the initial dose was 10 ml h⁻¹. Starting bolus of remifentanil was 0.15 μg kg⁻¹, with subsequent steps of 0.15 μg kg⁻¹. Lock-out time was 2 min, bolus infusion speed 2 ml min⁻¹ (100 μg min⁻¹) and there was no background infusion. Visual analogue scale was used for pain assessment. Maternal heart rate, blood pressure, oxygen saturation, respiratory rate, sedation, nausea/vomiting, itching, satisfaction and fetal/neonatal outcome were recorded. Thirty-seven parturient patients were analysed. Both treatments provided good analgesia, but with higher pain scores in the RA group. Pain reduction at the end of first and during second stage and maximum pain reduction were similar (RA/EA group): 27/26 (P = 0.920), 31/29 (P = 0.909) and 61/59 (P = 0.855), respectively. Maternal satisfaction was similar. Two parturients receiving remifentanil (6%) converted to epidural, one because of inadequate analgesia. Remifentanil produced more maternal sedation, desaturation (SaO₂ < 92%) and need for supplemental oxygen. Neonatal outcome was reassuring. Highest mean total dose of remifentanil was 0.70 μg kg⁻¹ (range 0.30-1.05). Remifentanil IVPCA and epidural provided effective analgesia, with high maternal satisfaction scores and reassuring neonatal outcome. Remifentanil produced more maternal sedation and oxygen desaturation. Close monitoring is, therefore, mandatory.


U.S. lung cancer mortality and declining cigarette tobacco consumption.
The usual method for estimating population exposure to cigarette tobacco has been annual per capita consumption of cigarettes, expressed as pack-years or numbers of cigarettes consumed. This technique is shown to result in an inaccurate estimate of exposure. It underestimates by 11 years the latency period from peak exposure to peak mortality. Over the years, cigarettes changed markedly. Filters came into prominence and tobacco was "fluffed". On average, tobacco content of cigarettes decreased 39.1% from 1953 to 1981. National per capita consumption of cigarette tobacco declined by 43%. Total exposure to cigarette tobacco has been declining for males for approximately 35 years; for females for 20 years. As of 1982, the secular trend for lung cancer mortality was declining for women below age 45 and for most age groups of men below 65. We appear to be at the threshold of a reversal in overall lung cancer mortality.


In silico investigation of molecular networks linking gastrointestinal diseases, malnutrition, and sarcopenia.
Malnutrition (MN) is a common primary or secondary complication in gastrointestinal diseases. The patient's nutritional status also influences muscle mass and function, which can be impaired up to the degree of sarcopenia. The molecular interactions in diseases leading to sarcopenia are complex and multifaceted, affecting muscle physiology, the intestine (nutrition), and the liver at different levels. Although extensive knowledge of individual molecular factors is available, their regulatory interplay is not yet fully understood. A comprehensive overall picture of pathological mechanisms and resulting phenotypes is lacking. In silico approaches that convert existing knowledge into computationally readable formats can help unravel mechanisms, underlying such complex molecular processes. From public literature, we manually compiled experimental evidence for molecular interactions involved in the development of sarcopenia into a knowledge base, referred to as the Sarcopenia Map. We integrated two diseases, namely liver cirrhosis (LC), and intestinal dysfunction, by considering their effects on nutrition and blood secretome. We demonstrate the performance of our model by successfully simulating the impact of changing dietary frequency, glycogen storage capacity, and disease severity on the carbohydrate and muscle systems. We present the Sarcopenia Map as a publicly available, open-source, and interactive online resource, that links gastrointestinal diseases, MN, and sarcopenia. The map provides tools that allow users to explore the information on the map and perform in silico simulations.


Transcript profiling of the phytotoxic response of wheat to the Fusarium mycotoxin deoxynivalenol.
Deoxynivalenol (DON) is a trichothecene mycotoxin commonly produced by Fusarium graminearum and F. culmorum during infection of cereal plants, such as wheat and barley. This toxin is a fungal virulence factor that facilitates the development of Fusarium head blight (FHB) disease. Wheat cultivar (cv.) Remus is susceptible to DON; the toxin causes premature bleaching of spikelets and inhibits root growth. This study used custom-made wheat cDNA arrays to analyse the effect of DON on the transcriptome of heads of the toxin-sensitive wheat cv. Remus at both 4 and 24 h post-toxin treatment. DON-induced transcripts encoded an array of proteins collectively associated with a range of cellular functions, such as metabolite transformation and detoxification, the ubiquitin-proteasome proteolytic pathway, jasmonate biosynthesis and signalling, carbohydrate metabolism, and phenylpropanoid biosynthesis. This study is the first to demonstrate that the fungal virulence factor DON modulates jasmonate biosynthesis and signalling. It also highlights the fact that the toxin-mediated accumulation of transcripts associated with metabolite transformation and detoxification, proteolysis and phenylpropanoid accumulation is not unique to DON-resistant wheat genotypes. Therefore, the respective encoded proteins are likely part of the general wheat defence against DON. Comparative analysis of the results of this and other studies suggests that it is likely to be the rapidity and magnitude rather than the components of the response that are critical in determining resistance to DON and thus the spread of FHB disease in wheat heads.


[Intensive care management of hematological and oncological patients].
Management of critically ill cancer patients warrants stringent admission criteria and clear concepts concerning duration and limits of intensive care. Recent developments in mechanical ventilation and sepsis therapy can easily be used to improve the outcome of critically ill cancer patients. The incidence and overall prognosis of cancer is constantly growing and, thus, the number of critically ill cancer patients is increasing. Furthermore, novel oncology drugs-in particular immune modulators-produce unexpected and substantial side effects. Therefore, the development of an interdisciplinary algorithm by oncologists and intensivists remains an important and dynamic challenge.


Potentially toxic elements contamination and its removal by aquatic weeds in the riverine system: A comparative approach.
Thamirabarani river acquires large untreated sewage effluents from the Tirunelveli and Thoothukudi districts of South Tamil Nadu. This study examined the concentration of trace elements in water, sediment, and phytoaccumulation potential of aquatic weeds viz., A. cristata, E. crassipes, S. natans, and P. stratiotes, growing along Srivaikundam dam of Thamirabarani river. The Pb, As, Hg, Cd, and Ni concentrations in water were slightly higher than the US Food and Drug Administration (USFDA) drinking water guidelines; however, their accumulation in sediment was below WHO's sediment quality guideline. This study concludes that the phytoaccumulation factor (PAF) and translocation factor (TF) was >1 in E. crassipes and A. cristata, representing them as hyperaccumulators, suitable for phytoremediation in polluted localities. E. crassipes, A. cristata, and S. natans accumulated (100-500 fold) higher trace elements concentrations than that present in the water. Also, the concentrations of trace elements found in the aquatic weeds were below the recommended levels for the critical plant range (CRP). These selected aquatic weeds are more suitable for plant hybridization to be modified as superbug plants.


Hydrophobic surfactant effects on aortic cholesterol accumulation and atherosclerosis in hypercholesterolemic rabbits.
Studies were performed in hypercholesterolemic rabbits to determine whether the hydrophobic surfactant, Poloxalene 2930 (Pol), is of benefit under these conditions. Lipoprotein analyses plus chemical and morphologic studies of the aorta were performed to evaluate the results. In one study, rabbits were made hypercholesterolemic by dietary means and then divided into two groups and given a cholesterol-free diet with one group additionally given Pol with treatment continued for 10 weeks. Pol treatment resulted in less atherosclerosis but the mechanism for this effect was not apparent from lipoprotein analysis. In the other study 3 groups of rabbits were given a cholesterol-rich diet for 16 weeks. Two groups received Pol supplement with one of these groups receiving a dose that was too small to prevent hypercholesterolemia. In this group plus the group on diet alone comparable degrees of hypercholesterolemia were maintained throughout the study. Lipoprotein abnormalities were similar in these two groups except that those on Pol had a more normal cholesterol to apolipoprotein B ratio. The amount of atherosclerosis in both groups was mild but aortic cholesterol content was much less for the Pol group. It is concluded that Pol limits cholesterol accumulation in the aortic wall of hypercholesterolemic rabbits and can retard the development of atherosclerosis.


[Changes in erythrocyte ATP after the oral administration of buflomedil hydrochloride].
Variations in erythrocyte ATP content were studied after the oral administration of 600 mg Buflomedil a day for seven days in ten vasculopathy patients. In all patients the drug increased erythrocyte ATP.


Targeting adipose tissue in the treatment of obesity-associated diabetes.
Adipose tissue regulates numerous physiological processes, and its dysfunction in obese humans is associated with disrupted metabolic homeostasis, insulin resistance and type 2 diabetes mellitus (T2DM). Although several US-approved treatments for obesity and T2DM exist, these are limited by adverse effects and a lack of effective long-term glucose control. In this Review, we provide an overview of the role of adipose tissue in metabolic homeostasis and assess emerging novel therapeutic strategies targeting adipose tissue, including adipokine-based strategies, promotion of white adipose tissue beiging as well as reduction of inflammation and fibrosis.


Polysaccharides and glycosides from Aralia echinocaulis protect rats from arthritis by modulating the gut microbiota composition.
Aralia echinocaulis has been used in traditional medicines in China and exhibits good effects on rheumatoid arthritis (RA). Aralia echinocaulis is rich in polysaccharides and glycosides. This study aims to explore the effect of total polysaccharide and glycoside (TPG) from A. echinocaulis on an RA rat model and the role of alterations in gut microbes mediated by TPG. In this study, a collagen-induced arthritis (CIA) rat model was constructed and used to evaluate the effects of TPG in vivo. 16S rRNA sequencing was used to detect the changes in the gut microbiota. A cooccurrence analysis was conducted by calculating Spearman's rank correlations. Microbial functions were predicted using PICRUSt with the KEGG and COG databases. The results showed that TPG from A. echinocaulis could inhibit arthritis, reduce serum IL-1β and TNF-α levels, and improve synovial pathology in the RA rat model but failed to produce the same results in a pseudoaseptic RA rat model. 16S rRNA sequencing verified that TPG could modulate the gut microbiota community structure of RA rats. The cooccurrence analysis found 19 out of the 50 most abundant genera in a cooccurrence network, of which 16 showed a positive correlation and 3 showed a negative correlation. KEGG pathway and COG function analyses found that TPG-induced alterations in the gut microbiota might be correlated with the circulatory system, excretory system, metabolic diseases, signaling molecules and interactions, coenzyme transport and metabolism, and nucleotide transport and metabolism. TPG from A. echinocaulis had significant effects on the RA rat model, which are related to the modulation of the gut microbiota. These results are useful to better understanding the mechanisms of TPG in RA.


Polarized microtubule dynamics directs cell mechanics and coordinates forces during epithelial morphogenesis.
Coordinated rearrangements of cytoskeletal structures are the principal source of forces that govern cell and tissue morphogenesis1,2. However, unlike for actin-based mechanical forces, our knowledge about the contribution of forces originating from other cytoskeletal components remains scarce. Here, we establish microtubules as central components of cell mechanics during tissue morphogenesis. We find that individual cells are mechanically autonomous during early Drosophila wing epithelium development. Each cell contains a polarized apical non-centrosomal microtubule cytoskeleton that bears compressive forces, whereby acute elimination of microtubule-based forces leads to cell shortening. We further establish that the Fat planar cell polarity (Ft-PCP) signalling pathway3,4 couples microtubules at adherens junctions (AJs) and patterns microtubule-based forces across a tissue via polarized transcellular stability, thus revealing a molecular mechanism bridging single cell and tissue mechanics. Together, these results provide a physical basis to explain how global patterning of microtubules controls cell mechanics to coordinate collective cell behaviour during tissue remodelling. These results also offer alternative paradigms towards the interplay of contractile and protrusive cytoskeletal forces at the single cell and tissue levels.


Screening study of blood-supplementing active components in water decoction of Angelica sinensis processed with yellow rice wine based on response surface methodology.
Angelica sinensis (Oliv.) Diels (Apiaceae) (syn. Angelica polymorpha Maxim var. sinensis Oliver) processed with yellow rice wine (WAS) has a blood-supplementing effect. To establish an optimal technology for preparing water decoction of WAS (WASD), and screen blood-supplementing fractions. Ferulic acid and crude polysaccharide were used in optimizing the preparation technology for WASD through response surface methodology. The independent variables were liquid-solid ratio, soaking time, and extraction time. Eighty Kunming mice were randomly divided into normal control, model, and six intervention groups (n = 10). The intervention groups were given different WASD fractions by gavage (5 or 10 g/kg). The model intervention groups received acetylphenyl hydrazine (subcutaneous injection) and cyclophosphamide (intraperitoneal injection). Duration of study, 9 days. The components of blood-supplementing fractions were analyzed. The optimum extraction parameters were liquid-solid ratio, 7.69:1 mL/g; soaking time, 119.78 min; and extraction time, 143.35 min. The optimal OD value was 0.8437. RBC, WBC, and Hb in the water fraction (5, 10 g/kg) and n-butanol fraction (10 g/kg) intervention groups increased significantly compared with the model group (p < 0.05). Polysaccharide and caffeic acid contents of water fraction were 252.565 and 0.346 μg/mg, respectively; ferulic acid was not detected. Caffeic acid and ferulic acid contents of n-butanol fraction were 1.187 and 0.806 μg/mg, respectively, polysaccharide was not detected. The optimum preparation technology of WASD was obtained, and the water, n-butanol fractions were blood-supplementing fractions. This study provides a theoretical foundation for further application of WAS in the pharmaceutical industry.


Effect of bisphenol A on maturation and quality of semen and eggs in the brown trout, Salmo trutta f. fario.
In the present study male and female brown trout (Salmo trutta f. fario) were exposed to environmentally relevant concentrations of bisphenol A (1.75, 2.40, 5.00 microg l(-1)) during the late prespawning and spawning period and the effect of this contaminant on maturation, quantity and quality of semen and eggs was investigated. In males exposed to estimated BPA concentrations of 1.75 and 2.40 microg l(-1) semen quality was lower than in the control in the beginning of spawning (reduced sperm density, motility rate, and swimming velocity) and in the middle of spawning (reduced swimming velocity, at 2.40 microg l(-1) BPA also reduced sperm motility rate). Therefore, production of high quality semen was restricted to the end of the spawning season and delayed for approximately 4 weeks in comparison to the control. At BPA exposure levels of 5.00 microg l(-1) only one of eight males gave semen of low quality (reduced semen mass, motility rate, and swimming velocity). The percentage of ovulated females was similar for the control group and the groups exposed to estimated BPA concentrations of 1.75 and 2.40 microg l(-1), whereas at 5.00 microg l(-1) BPA females did not ovulate during the investigation. While brown trout of the control group ovulated between the 28 October and 12 November, brown trout exposed to estimated BPA concentrations of 1.75 microg l(-1) BPA ovulated approximately 2 weeks later and brown trout exposed to 2.40 microg l(-1) BPA approximately 3 weeks later. Therefore, the tested BPA concentrations affected the percentage of ovulated females and the time point of ovulation. No effect was observed on the quality of eggs (egg mass, percentile mass increase during hardening, egg fertility).


Mobilization of the interdisciplinary critical care team at home and abroad.
Already it is clear that managed care organizations seek delivery innovations that can move homecare beyond being a posthospitalization add-on to becoming a true alternative to hospitalization. Throughout its history, home health care nurses have epitomized Florence Nightingale's philosophy that nurses are "messengers of health as well as ministers of disease." With the development of more sophisticated models of interdisciplinary practice in high-tech homecare, nurses are in a position to help create a health care delivery system that in a sense brings people back to the future. The natural setting of the home is the best place to provide holistic care, it is where patients overwhelmingly prefer to be cared for, and it is affordable. Indeed, affordability has become the operant word, worldwide, for a health care delivery system that can continue to meet the growing demands of the future.


The interaction of cationic antimicrobial peptides with vesicles containing synthetic glycolipids as models of the outer membrane of gram-negative bacteria.
Two simple lipid A analogues methyl 2,3-di-O-tetradecanoyl-alpha-D-glucopyranoside (GL1) and methyl 2,3-di-O-tetradecanoyl-alpha-D-glucopyranoside 4-O-phosphate (GL2) were synthesized and used for preparing mixed phosphocholine vesicles as models of the outer membrane of gram-negative bacteria. The interaction of these model membranes with magainin 2, a representative of the alpha-helical membrane active peptides, and apidaecin Ib and drosocin, two insect Pro-rich peptides which do not act at the level of the cellular membrane, were studied by CD and dye-releasing experiments. The CD spectra of apidaecin Ib and drosocin in the presence of GL1- or GL2-containing vesicles were consistent with largely unordered structures, whereas, according to the CD spectra, magainin 2 adopted an amphipathic alpha-helical conformation, particularly in the presence of negatively charged bilayers. The ability of the peptides to fold into amphipathic conformations was strictly correlated to their ability to bind and to permeabilize phospholipid as well as glycolipid membranes. Apidaecin Ib and drosocin, which are unable to adopt an amphipathic structure, showed negligible dye-leakage activity even in the presence of GL2-containing vesicles. It is reasonable to suppose that, as for the killing mechanism, the two classes of antimicrobial peptides follow different patterns to cross the bacterial outer membrane.


Vibrational spectra of the hydrated carbonate minerals ikaite, monohydrocalcite, lansfordite and nesquehonite.
The Raman (200-4000 cm(-1)) and infrared (600-4000 cm(-1)) spectra of four rare carbonate hydrate minerals are reported. These are naturally occurring and synthetic ikaite CaCO3.6H2O, and nesquehonite MgCO3.3H2O; natural monohydrocalcite CaCO3.H2O, and synthetic lansfordite MgCO3.5H2O. The spectra of synthetic ikaite partially substituted with 2H2O and also with 13C were measured, as were those of synthetic deuteriated nesquehonite. Spectra of ikaite and lansfordite, both of which decompose at room temperatures, were measured below 0 degrees C. Assignments of fundamental modes are proposed.


Design, synthesis and in vitro biological studies of novel triazoles with potent and broad-spectrum antifungal activity.
A series of novel triazole derivatives containing aryl-propanamide side chains was designed and synthesised. In vitro antifungal activity studies demonstrated that most of the compounds inhibited the growth of six human pathogenic fungi. In particular, parts of phenyl-propionamide-containing compounds had excellent, broad-spectrum antifungal activity against Candida albicans SC5314, Cryptococcus neoformans 22-21, Candida glabrata 537 and Candida parapsilosis 22-20 with MIC values in the range of ≤0.125 µg/mL-4.0 µg/mL. In addition, compounds A1, A2, A6, A12 and A15 showed inhibitory activities against fluconazole-resistant Candida albicans and Candida auris. Preliminary structure-activity relationships (SARs) are also summarised. Moreover, GC-MS analysis demonstrated that A1, A3, and A9 interfered with the C. albicans ergosterol biosynthesis pathway by inhibiting Cyp51. Molecular docking studies elucidated the binding modes of A3 and A9 with Cyp51. These compounds with low haemolytic activity and favourable ADME/T properties are promising for the development of novel antifungal agents.


Aflatoxin B1 degradation during co-cultivation of Aspergillus flavus and Pleurotus ostreatus strains on rice straw.
Aflatoxin B1 (AFB1) produced by Aspergillus flavus is known to have carcinogenic and teratogenic effects on animal health. Accidental feeding of AFB1-contaminated rice straw may be detrimental to dairy cattle. White-rot basidiomycetous fungus Pleurotus ostreatus can grow on different agronomic wastes by synthesizing different ligninolytic enzymes. These extracellular enzymes are capable of degrading many environmentally hazardous compounds including AFB1. The present study examines the ability of different strains of P. ostreatus to degrade AFB1 in contaminated rice straw. Different strains of A. flavus were inoculated on rice straw for AFB1 production. The moldy straw was then subjected to co-cultivation by different strains of P. ostreatus. The extent of AFB1 degradation was determined by high performance liquid chromatography. Results indicated the presence of AFB1 in the moldy straw samples at levels of 27.95 ± 0.23 and 21.26 ± 0.55 µg/g of dry substrate for A. flavus MTCC 2798 and A. flavus GHBF09, respectively. Co-cultivation of P. ostreatus strains on AFB1-contaminated rice straw revealed their ability to rapidly colonize the substrate by profuse hyphal ramification. Highest degradation of AFB1 (89.41 %) was recorded in the straw containing co-cultures of A. flavus MTCC 2798 and P. ostreatus GHBBF10. Natural isolate P. ostreatus GHBBF10 demonstrated higher AFB1-degradation potential than P.ostreatus MTCC 142. This basidiomycete strain can be further exploited to effectively degrade moderate concentrations of AFB1 in contaminated moldy rice straw.


A review of the international early recommendations for departments organization and cancer management priorities during the global COVID-19 pandemic: applicability in low- and middle-income countries.
Coronavirus disease 2019 (COVID-19) is an infectious disease caused by a new virus that has never been identified in humans before. COVID-19 caused at the time of writing of this article, 2.5 million cases of infections in 193 countries with 165,000 deaths, including two-third in Europe. In this context, Oncology Departments of the affected countries had to adapt quickly their health system care and establish new organizations and priorities. Thus, numerous recommendations and therapeutic options have been reported to optimize therapy delivery to patients with chronic disease and cancer. Obviously, while these cancer care recommendations are immediately applicable in Europe, they may not be applicable in certain emerging and low- and middle-income countries (LMICs). In this review, we aimed to summarize these international guidelines in accordance with cancer types, making a synthesis for daily practice to protect patients, staff and tailor anti-cancer therapy delivery taking into account patients/tumour criteria and tools availability. Thus, we will discuss their applicability in the LMICs with different organizations, limited means and different constraints.


Uremic serum damages endothelium by provoking excessive neutrophil extracellular trap formation.
Cardiovascular disease (CVD) is the leading cause of death in patients with chronic kidney disease (CKD). Endothelial cell (EC) dysfunction is a key CKD-specific risk factor; however, the mechanisms by which uremia harms the endothelium are still unclear. We report a role for excessive neutrophil extracellular trap (NET) formation induced by uremic serum on EC injury. Level of plasma nucleosome and myeloperoxidase-DNA, established in vivo markers of NETs, as well as intracellular adhesion molecule (ICAM)-1 were measured in hemodialysis (HD) patients and healthy volunteers (HV) and their prognostic role evaluated. For in vitro studies, HV-derived neutrophils and differentiated HL-60 cells by retinoic acid were used to determine the effect of uremic serum-induced NETs on human umbilical vein EC (HUVEC). The level of in vivo NETs was significantly higher in incident HD patients compared to HV, and these markers were strongly associated with ICAM-1. Specifically, nucleosome and ICAM-1 levels were independent predictors of a composite endpoint, all-cause mortality, or vascular access failure. In vitro, HD-derived uremic serum significantly increased NET formation both in dHL-60 and isolated neutrophils compared to control serum, and these NETs decreased EC viability and induced their apoptosis. In addition, the level of ICAM-1, E-selectin and von Willebrand factor in HUVEC supernatant was significantly increased by uremic serum-induced NETs compared to control serum-induced NETs. Dysregulated neutrophil activities in the uremic milieu may play a key role in vascular inflammatory responses. The high mortality and CVD rates in ESRD may be explained in part by excessive NET formation leading to EC damage and dysfunction.


Fecal biomarkers of environmental enteric dysfunction and associated factors among children aged 24-59 months in east Dembiya district, northwest Ethiopia.
Environmental enteric dysfunction is a subclinical intestinal disorder characterized by gut inflammation accompanied by morphological changes, such as blunted villi and crypt hyperplasia. This is a common illness in low and middle-income countries. However, environmental enteric dysfunction evidence is limited in Ethiopia. Accordingly, this study was conducted to measure fecal biomarkers of environmental enteric dysfunction and associated factors among children aged 24-59 months in rural northwest Ethiopia. A community-based cross-sectional study was employed among 235 randomly selected children in a rural setting of the east Dembiya district. Stool samples were collected without fixative and analyzed for fecal biomarkers of environmental enteric dysfunction (Alpha-1-antitrypsin, neopterin, and myeloperoxidase) using commercial enzyme-linked immunosorbent assay kits and analyzed for intestinal parasites using wet mount and Kato-Katz techniques. Child behaviors related with exposure to enteropathogens, condition of the living environment and socio-demographic information were collected using interviewer-administered questionnaire and structure observation. We fitted multivariable linear regression model to assess the association between environmental factors and concentration of fecal biomarkers of environmental enteric dysfunction in the stool. Statistically significant associations were declared based on adjusted betas with the corresponding 95% confidence interval and p-value < 0.05. The median concentration of fecal markers of environmental enteric dysfunction was 350 μg/ml for Alpha-1-antitrypsin, 3320.2 ng/ml for myeloperoxidase, and 1562 nmol/l for neopterin. The median concentration of Alpha-1-antitrypsin among 161 (68.5%), myeloperoxidase among 168 (71.5%), and neopterin among 188 (80%) of the stool samples were above the normal values in non-tropical settings. Moreover, 100 (42.6%) of the children had high EED disease activity score (above the median score). The elevated concentrations of fecal biomarkers of gut inflammation and the high EED disease activity score were significantly associated with open defecation practice, mouthing of soil contaminated materials, Escherichia coli (E. coli) contamination of drinking water, E. coli contamination of foods, E. coli contamination of soil, and intestinal parasites. Overall, Alpha-1-antitrypsin, myeloperoxidase, and neopterin levels among the children in the studied region were highly elevated in comparison to populations in high-income countries. Moreover, the EED disease activity score in significant proportion of children was high, suggesting widespread intestinal inflammation and increased intestinal permeability. Extensive E. coli contamination of the living environment (drinking water, ready-to-eat foods, and courtyard soil), hygiene and sanitation behaviors (such as open defecation and mouthing of soil contaminated materials), and a high burden of intestinal parasites were identified as factors associated with the elevated concentration of fecal biomarkers of environmental enteric dysfunction. Parental care to children to avoid mouthing of soil contaminated materials and other risky behaviors that increase exposure enteric infections, and protecting the living environment (water, food and soil) from fecal contamination are important.


Elevating athletic performance: Maximizing strength and power in long jumpers through combined low-intensity blood flow restriction and high-intensity resistance training.
This study aimed to evaluate the effects of low-intensity blood flow restriction (BFR) training and high-intensity resistance training (HI-RT) on the leaping performance of long-jumpers. Long jump players were divided into two groups; one group (group A) receiving HI-RT (n = 8) and the other group (group B) receiving combined low-intensity BFR training plus HI-RT (n = 8). Muscle power and knee muscle strength was assessed at baseline, 3 weeks and 6 weeks of intervention. 1-RM was found to be significantly different between Group A and Group B at 3 and 6 weeks. Further, IKDQR, IKDHR and IKDQL was significantly improved in group B as compared to group A both at 3 and 6 weeks. There was significant time effect, group effect and time-group interaction in the strength of quadriceps and hamstring of both left and right leg measured through isokinetic device. Post-hoc analysis for 1-RM in group B showed a significant improvement at baseline and 6 weeks and the broad jump was significant at baseline and 3 weeks and at baseline and 6 weeks. The combined effects of low-intensity BFR training and HI-RT is effective in improving the muscle strength and power of lower limbs in long jumpers.


The association between hypertension and glucose tolerance among adults with prediabetes in Hail City, Saudi Arabia.
As a worldwide epidemic, the frequency of prediabetes is rapidly increasing. As a result, the present study investigated pre-diabetes synergistic factors in the Saudi population. This descriptive study used samples from 31 Hail-area primary health clinics (PHCs). Participants were chosen at random from December 2021 to June 2022. There were 164 participants in this study, of which 86 males (52.4%) and 78 females (47.6%). The GTT revealed that none of the study participants had diabetes, but an A1C test revealed that all of them had A1C levels above 6.5%. Approximately 16/86 (18.6%) of the 86 men were overweight, whereas 53/86 (61.6%) were obese. Saudi Arabia's prediabetes rate has increased due to obesity/overweight, family history of diabetes, heart rate variability, and poor sleep quality. HbA1c screening should replace GTT to prevent progression to T2DM.


Development of photocrosslinked polyacrylic acid hydrogel as an adhesive for dermatological patches: involvement of formulation factors in physical properties and pharmacological effects.
Photocrosslinked polyacrylic acid hydrogel is a promising candidate adhesive for dermatological patches. In this study, we investigated the effects of the composition and molecular weight of the polymer on the characteristics of the hydrogel. Several photocrosslinkable polymers with different photocrosslinkable moieties or molecular weights were prepared, and various physical properties were measured. Differences in photocrosslinkable modifications markedly affected the swelling behavior of the hydrogel. The molecular weight of the polymer had a significant effect on various physical properties, such as the viscosity of the polymer solution, gel formation, and the swelling behavior of the prepared hydrogels. The pharmacological effects of the hydrogel were also evaluated using carrageenan-induced edema in rats. Application of the hydrogels maintained the skin surface at a reduced temperature throughout the experimental period, and the cooling effect was accompanied by an anti-inflammatory response. Because we can freely control the physical properties of the hydrogel and anticipate the significant pharmacological effects, photocrosslinked polyacrylic acid hydrogel is an attractive candidate adhesive for dermatological patches.


Synergistically enhanced anticancer effect of codelivered curcumin and siPlk1 by stimuli-responsive α-lactalbumin nanospheres.
To achieve enhanced anticancer efficacy by combined siPlk1 and curcumin (cur) therapy using α-lactalbumin (α-lac) nanocarrier delivery. α-Lac was partially hydrolyzed into amphiphilic peptides, and then self-assembled into nanospheres (NS). Cur was loaded into their hydrophobic core during the self-assembly process. siPlk1-SH was cross-linked with the endogenous cysteines on the NS. CRGDK peptide was conjugated on NS to target integrins overexpressed in HeLa cells. The Cur and siPlk1 coloaded NS formulations possessed an enhanced tumor targeting and antitumor properties. Drugs were responsively released from disulfide bonds cross-linked RGD-NS/Cur/siPlk1 corresponding to the high intracellular glutathione concentrations of cancer cells. Both in vitro cell viability experiments and in vivo antitumor evaluations demonstrated that the codelivered nanosphere platform exhibited excellent tumor targeting and synergistic antitumor efficacy.


Modifiable and emerging risk factors for type 2 diabetes in Africa: a systematic review and meta-analysis protocol.
Type 2 diabetes mellitus (T2DM) remains a public health problem in low-income countries, including African countries. Risk factors of this disease in Africa are still unclear. This study will examine the modifiable and emerging risk factors associated with T2DM in Africa. The study will include a systematic review and meta-analysis of published and unpublished empirical studies, reporting quantitative data only. We will conduct a search on scientific databases (e.g. Global Health), general online search engines (e.g. Google Scholar) and key websites for grey literature using a combination of key countries/geographic terms, risk factors (e.g. overweight/obesity) and T2DM (including a manual search of the included reference lists). We will use the Comprehensive Meta-Analysis Software (CMA) version 2.0 for data management and analysis. This protocol follows the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P). The systematic review and meta-analysis will provide a robust and reliable evidence base for policy makers and future research. This may help with identifying and implementing more cost-effective diabetes prevention strategies and improved resource allocation. This protocol has been registered with the PROSPERO international prospective register of systematic reviews. The reference number is CRD42016043027 .


Feasibility studies. The use of NMR spectrometry as a possible substitute of or complement to several analytical tests in pharmacopoeia monographs.
NMR spectrometry has many analytical applications; for instance, the identification of known substances; the structure elucidation of unknown ones; the quantification of APIs, impurities, solvent and water; kinetic studies, stereochemistry determinations, and the analyses of complex mixtures as in metabonomics. NMR spectrometry has the potential to substitute or complement existing analyses that are performed on APIs. In this work, 4 different NMR analyses were done on 2 APIs: fluvastatin sodium and benzalkonium chloride with good results.


The automation of the acquisition and evaluation of pyrolysis-gas chromatography-mass spectrometry data for paint samples.
The evaluation is described of an automated pyrolysis-gas chromatography-mass spectrometry system combined with a software package to convert total ion current chromatograms into forms that resemble a conventional mass spectra called "spectragrams". The spectragram for a single paint sample can be "closest fit" matched to a previously created paint pyrogram library via pre-determined target compounds in a handling list. Up to 45 paint samples can be dealt with in an overnight unattended run.


Vulvar hidradenoma papilliferum (HP) is located on the sites of mammary-like anogenital glands (MLAGs): Analysis of the photographs of 52 tumors.
Hidradenoma papilliferum (HP) is a benign tumor that primarily affects the anogenital area of adult women. Previously considered apocrine tumors, anogenital HP tumors are now interpreted as adenomas of mammary-like anogenital glands based on their histologic features. This clinical study was undertaken to determine whether vulvar HP is located on mammary-like anogenital gland sites and to describe its morphologic features. The clinical photographs of 52 histologically confirmed vulvar HP provided by 7 vulva specialists were analyzed. In all, 90.4% of the HP were located on the interlabial sulcus, adjacent zone, or the perineum. These tumors were polymorphous in terms of number (1 or multiple), size (<1-4.5 cm), color (pink, red, blue), surface (ulcerated or not), and architecture (unilobular or multilobular). Eight histologic reports could not be reviewed by the authors but the contributors confirmed that the photographs sent were only those of histologically confirmed HPs. Vulvar HP is mainly located on mammary-like anogenital gland sites, thereby providing further evidence to their histogenesis. Although a nonulcerated or ulcerated tumor of the interlabial sulcus should evoke a HP diagnosis, the latter must be confirmed histologically.


Magnetic resonance T1w/T2w ratio in the middle cerebellar peduncle might be a sensitive biomarker for multiple system atrophy.
We aimed to investigate the use of a myelin-sensitive MRI contrast, the standardized T1-weighted/T2-weighted (sT1w/T2w) ratio, for detecting early changes in the middle cerebellar peduncle (MCP) in cerebellar subtype multiple system atrophy (MSA-C) patients. We included 28 MSA-C patients, including a subset of 17 MSA-C patients within 2 years of disease onset (early MSA-C), and 28 matched healthy controls. T1w and T2w scans were acquired using a 3-T MR system. The sT1w/T2w ratio in MCP was analyzed using SPM12 by utilizing a region-of-interest approach in normalized space. The diagnostic performance of the MCP sT1w/T2w ratio in discriminating MSA-C and the subgroup of early MSA-C from the matched controls was assessed. Correlation analyses were performed to evaluate the relationship between the MCP sT1w/T2w ratio and other clinical parameters including the International Cooperative Ataxia Scale (ICARS) score for quantifying cerebellar ataxia. Compared to controls, the sT1w/T2w ratio in the MCP was markedly lower in all (p < 0.001) MSA-C patients and 17 early (p < 0.001) MSA-C patients. The MCP sT1w/T2w ratio had high sensitivity (96%) and specificity (100%) to distinguish MSA-C from controls (area under the curve = 0.99), even for the early MSA-C group (area under the curve = 0.99; sensitivity = 94%, specificity = 100%). The MCP sT1w/T2w ratio correlated with the ICARS score in early MSA-C. The sT1w/T2w ratio can detect MSA-C-related changes in the MCP, even in the early stages of the disorder, and could be a sensitive biomarker for MSA-C. • The sT1w/T2w ratio can detect MSA-C-related changes in the middle cerebellar peduncle, even in the early stages of the disorder. • The middle cerebellar peduncle sT1w/T2w ratio correlated with a cerebellar ataxia score in early MSA-C patients.


Association of serum uric acid with hepatic steatosis detected by controlled attenuation parameter in the United States population.
The relationship between serum uric acid (SUA) and nonalcoholic fatty liver disease (NAFLD) has been previously reported. Controlled attenuation parameter (CAP) has better diagnostic performance than ultrasonography for assessing hepatic steatosis. The association of SUA with hepatic steatosis detected by CAP is worth further study. The US population aged 20 years or older from the National Health and Nutrition Examination Survey (NHANES) was assessed. Hepatic steatosis was evaluated by the controlled attenuation parameter (CAP). NAFLD status was defined as CAP values of 268 dB/m without hepatitis B or C virus infection or considerable alcohol consumption. Multiple imputations were performed to fill in the missing covariate values. Linear regression, logistic regression, and smooth curve fitting were used to examine the association. In total, 3919 individuals participated in this study. There was a positive association between SUA (µmol/L) and CAP (β = 0.14, 95% CI: 0.12-0.17, P < 0.01). After stratification by sex, a significant relationship between SUA and CAP existed in both males (β = 0.12, 95% CI: 0.09-0.16, P < 0.01) and females (β = 0.17, 95% CI: 0.14-0.20, P < 0.01) after multiple imputation. The inflection points of the threshold effect of SUA on CAP were 487.7 µmol/L in males and 386.6 µmol/L in females. There was a positive association between SUA (mg/dL) and NAFLD (OR = 1.30, 95% CI: 1.23-1.37, P < 0.01). After stratification by race, positive relationships were also observed. Meanwhile, a positive relationship existed between hyperuricemia and NAFLD (OR = 1.94, 95% CI: 1.64-2.30, P < 0.01). The positive relationship was more significant in females than in males (P for interaction < 0.01). There was a positive association between SUA and CAP, as well as between SUA and NAFLD. Subgroup studies stratified by sex and ethnicity demonstrated that the effects were consistent.


Highly enantioselective organocatalysis of the Hajos-Parrish-Eder-Sauer-Wiechert reaction by the beta-amino acid cispentacin.
The beta-amino acid cispentacin promotes the Hajos-Parrish-Eder-Sauer-Wiechert reaction with levels of enantioselectivity comparable to or higher than proline.


Decision-making framework for a resilient sustainable production system during COVID-19: An evidence-based research.
This work presents a decision-making framework for integrating resilience and sustainability in managing production systems during COVID-19. An operationalization scheme manifested via a case study at a manufacturer in the food production sector supports the proposed framework. The focus is laid on the tactical and operational decisions within the production system. Through the discussion of the introduced changes to mitigate risks emanating from COVID-19, a set of findings related to the deployment of digital solutions, new dimensions of sustainability and resilience, the introduction of new workforce scheduling rules, the importance of alignment and coordination across supply chain members, and the approach of risk management are identified. This work contributes to a better understanding of the decision-making process during the pandemic and to building up knowledge for the management of resilient and sustainable production systems.


Access to information about donors by donor-conceived individuals: a human rights analysis.
While assisted reproductive treatment using donated gametes is widespread, and in many places, widely accepted, it has historically been shrouded in secrecy. Over time, however, there has been an increasing call from donor-conceived people, recipient parents and some donors to end the secrecy, and to release identifying information about donors to donor-conceived people. "Rights-based" arguments have at times been used to justify this call. This article examines whether a human rights framework supports the release of information and how such a framework might be applied when there are competing rights. It argues that the current balancing approach used to resolve such issues weighs in favour of release. Legal action has the potential to be legitimate and justifiable. A measure such as a contact veto system, which would serve to prevent unwanted contact with the person lodging the veto (either the donor or the donor-conceived person), would ensure proportionality. In this way, both donor-conceived people's rights to private life, identity and family, and donors' rights to privacy may be recognised and balanced.


Sarcoidosis and selective IgA deficiency.
Two patients are described in whom selective deficiency of IgA coexisted with a clinical condition compatible with a diagnosis of sarcoidosis. The literature on the rare association of the two conditions is reviewed. Any such association is probably coincidental.


[Ilha Grande Lazaretto: isolation, imprisonment, and surveillance in the fields of health care and politics (1884-1942)].
The Ilha Grande pest house, located on the coast of Rio de Janeiro state, was built in 1884 to control the spread of epidemics via Brazilian ports. Separated from the continent, the buildings that housed patients could be kept under constant surveillance. Isolation regimens differed in accordance with the class on which passengers had traveled. The complex was used at different times as a military prison and eventually deactivated. In 1942, it was restored and became the Cândido Mendes Penal Colony.


Opting off the New South Wales Pap Test Register in a sexual health setting.
To determine the proportion of women having a Pap smear at Sydney Sexual Health Centre (SSHC) who opted off the NSW Pap Test Register (PTR) and to establish the characteristics of these women. Retrospective cross sectional study involving three time periods during 1996 and 1997. A public sexual health centre in Sydney. 985 women who had a Pap smear at SSHC. The participant's decision to opt on or off, and the demographic and behavioural characteristics associated with opting off the PTR. 590 (59.9%) women opted off the PTR. Using logistic regression, young age (p=0.005), birth outside Australia and New Zealand (p=0.0001), not speaking English at home (p=0.005) and being a commercial sex worker (CSW) (p=0.0001) were variables associated with opting off the PTR. Women from countries outside of Australia and New Zealand were more likely to opt off, whether or not they were a CSW and CSWs were more likely to opt off the PTR irrespective of their country of birth (p=0.013). The majority of women (60%) attending the SSHC opted off the PTR. Studies to evaluate culturally appropriate health promotion material particularly for CSWs and women with poor English skills living in Australia are needed and if successful may improve uptake on the PTR.


Functional tumor cell-intrinsic STING, not host STING, drives local and systemic antitumor immunity and therapy efficacy following cryoablation.
Despite its potential utility in delivering direct tumor killing and in situ whole-cell tumor vaccination, tumor cryoablation produces highly variable and unpredictable clinical response, limiting its clinical utility. The mechanism(s) driving cryoablation-induced local antitumor immunity and the associated abscopal effect is not well understood. The aim of this study was to identify and explore a mechanism of action by which cryoablation enhances the therapeutic efficacy in metastatic tumor models. We used the subcutaneous mouse model of the rhabdomyosarcoma (RMS) cell lines RMS 76-9STINGwt or RMS 76-9STING-/-, along with other murine tumor models, in C57BL/6 or STING-/- (TMEM173-/- ) mice to evaluate local tumor changes, lung metastasis, abscopal effect on distant tumors, and immune cell dynamics in the tumor microenvironment (TME). The results show that cryoablation efficacy is dependent on both adaptive immunity and the STING signaling pathway. Contrary to current literature dictating an essential role of host-derived STING activation as a driver of antitumor immunity in vivo, we show that local tumor control, lung metastasis, and the abscopal effect on distant tumor are all critically dependent on a functioning tumor cell-intrinsic STING signaling pathway, which induces inflammatory chemokine and cytokine responses in the cryoablated TME. This reliance extends beyond cryoablation to include intratumoral STING agonist therapy. Additionally, surveys of gene expression databases and tissue microarrays of clinical tumor samples revealed a wide spectrum of expressions among STING-related signaling components. Tumor cell-intrinsic STING pathway is a critical component underlying the effectiveness of cryoablation and suggests that expression of STING-related signaling components may serve as a potential therapy response biomarker. Our data also highlight an urgent need to further characterize tumor cell-intrinsic STING pathways and the associated downstream inflammatory response evoked by cryoablation and other STING-dependent therapy approaches.


Three-body wear of 3D printed temporary materials.
The aim of this study was to investigate the three-body wear of different additively manufactured temporary materials, one temporary PMMA material for CAD/CAM milling and one resin-based composite for direct restorations as a control group by using an ACTA machine. Specimens (n=8) of the 3D printing materials 3Delta temp, NextDent C&B, Freeprint temp were additively manufactured by DLP 3D printer. Postprocessing was carried out according to the manufacturer's specifications. Telio CAD were cut out of blocks, Tetric EvoCeram was applied directly and light cured. Three-body wear was simulated with an ACTA machine. Data were statistically analysed (ANOVA, post hoc test: Tukey, p<0.05). The worn surfaces of the specimens were examined with a FE-SEM. The average mean wear was 50±15μm for Tetric EvoCeram<62±4μm for 3Delta temp<236±31μm for Telio CAD<255±13μm for NextDent C&B<257±24μm for Freeprint temp. After 200,000 cycles, the wear and wear rates for Tetric EvoCeram and 3Delta temp were significantly lower than those for the other materials. SEM revealed that 3Delta temp has a higher filler proportion than the other 3D printing materials but less than Tetric EvoCeram. The filler content influences the wear behaviour of additively manufactured materials as well as dental restorative composite materials. While most 3D printing materials have a low inorganic filler load, which qualifies the materials for temporary use only, one 3D printing material has an optimized composition that would qualify the material for longer clinical service time if wear is considered as the outcome variable.


Optimization of water distribution of network systems using the Harris Hawks optimization algorithm (Case study: Homashahr city).
In this article applies the Harris Hawks Optimization Algorithm for optimization of the water distribution network of the Homashahr located in Iran for a period of one month (from 30 September 2018 to 30 October 2019). The utilized time-series data included water demand, reservoir storage. In this article, a model based on the Harris Hawks Optimization Algorithm (HHO) was developed for the optimization of the water distribution network. The analysis showed that the best solutions achieved by the Harris Hawks Optimization Algorithm (HHO) were 35,508 $. The results revealed that the HHO algorithm was well in the optimal design of water supply networks problem. At the end, about 12% of the optimization was done by this algorithm.•In this article applied the Harris Hawks Optimization Algorithm for optimization of the water distribution network of the Homashahr located in Iran.•The method presented in this article can be useful for managers of water and wastewater companies, water resource facilities and water distribution system managing director for optimal network design to reduce costs.•The present algorithm performs better than the other algorithms in the discussion of the optimization of water distribution networks.


Rupture of the subscapularis tendon after shoulder arthroplasty: diagnosis, treatment, and outcome.
The purpose of this study was to document the diagnosis, surgical treatment, and functional outcome in patients with subscapularis ruptures after shoulder arthroplasty. Prospective objective and subjective data were collected on 7 patients with symptomatic rupture of the subscapularis tendon after shoulder arthroplasty. Presenting signs and symptoms included pain, weakness in internal rotation, increased external rotation, and anterior instability. All patients were treated with surgical repair of the ruptured tendon. Four required repair augmentation with a transfer of the pectoralis major tendon. After subscapularis repair and pectoralis transfer, 2 patients continued to have anterior instability and required an additional operation to address the instability. At a mean follow-up of 2.3 years (range, 18-55 months), the mean American Shoulder and Elbow Surgeons shoulder score in this study group was 63.2. The mean patient satisfaction rating, on a 10-point scale, was 6.2. Factors associated with post-arthroplasty subscapularis ruptures included subscapularis lengthening techniques used to address internal rotation contracture and previous surgery that violated the subscapularis tendon. Symptomatic subscapularis rupture after shoulder arthroplasty introduces the need for additional surgery and a period of protected or delayed rehabilitation after arthroplasty. Although symptoms were adequately addressed with appropriate surgical treatment, decreased functional outcomes were observed.


Role of Physical Therapists in the Management of Individuals at Risk for or Diagnosed With Venous Thromboembolism: Evidence-Based Clinical Practice Guideline 2022.
No matter the practice setting, physical therapists work with patients who are at risk for or who have a history of venous thromboembolism (VTE). In 2016, the first clinical practice guideline (CPG) addressing the physical therapist management of VTE was published with support by the American Physical Therapy Association's Academy of Cardiovascular and Pulmonary Physical Therapy and Academy of Acute Care, with a primary focus on lower extremity deep vein thrombosis (DVT). This CPG is an update of the 2016 CPG and contains the most current evidence available for the management of patients with lower extremity DVT and new key action statements (KAS), including guidance on upper extremity DVT, pulmonary embolism, and special populations. This document will guide physical therapist practice in the prevention of and screening for VTE and in the management of patients who are at risk for or who have been diagnosed with VTE. Through a systematic review of published studies and a structured appraisal process, KAS were written to guide the physical therapist. The evidence supporting each action was rated, and the strength of statement was determined. Clinical practice algorithms based on the KAS were developed that can assist with clinical decision-making. Physical therapists, along with other members of the health care team, should implement these KAS to decrease the incidence of VTE, improve the diagnosis and acute management of VTE, and reduce the long-term complications of VTE.


Do skeletal muscle properties recover following repeat onabotulinum toxin A injections?
Onabotulinum toxin A (BTX-A) is a frequently used treatment modality to relax spastic muscles by preventing acetylcholine release at the motor nerve endings. Although considered safe, previous studies have shown that BTX-A injections cause muscle atrophy and deterioration in target and non-target muscles. Ideally, muscles should fully recover following BTX-A treatments, so that muscle strength and performance are not affected in the long-term. However, systematic, long-term data on the recovery of muscles exposed to BTX-A treatments are not available, thus practice guidelines on the frequency and duration of BTX-A injections, and associated recovery protocols, are based on clinical experience with little evidence-based information. Therefore, the purpose of this study was to investigate muscle recovery following a six months, monthly BTX-A injection (3.5 U/kg) protocol. Twenty seven skeletally mature NZW rabbits were divided into 5 groups: Control (n=5), zero month recovery - BTX-A+0M (n=5), one month recovery - BTX-A+1M (n=5), three months recovery - BTX-A+3M (n=5), and six months recovery - BTX-A+6M (n=7). Knee extensor strength, muscle mass and percent contractile material in injected and contralateral non-injected muscles was measured at each point of recovery. Strength and muscle mass were partially and completely recovered in injected and contralateral non-injected muscles for BTX-A+6M group animals, respectively. The percent of contractile material partially recovered in the injected, but did not recover in the contralateral non-injected muscles. We conclude from these results that neither target nor non-target muscles fully recover within six months of a BTX-A treatment protocol and that clinical studies on muscle recovery should be pursued.


Cortical evolution and human behaviour.
All mammals have complex behaviours but these are generally stereotyped in nature and lack the flexibility of human behaviour. Can the flexibility of human behaviour be understood as an evolutionary extension of previous behaviours or is it a departure? Theories pertaining to this question have a long history including, now refuted, theories on neoteny. This paper, using an evolutionary developmental biology approach, outlines some existing theories and suggests some novel ideas. Previous trends during brain evolution are determined by outlining the phylogeny and ontogeny of the six layered mammalian isocortex with particular reference to the primate lineage. These evolutionary trends are extrapolated to hominids to postulate the effect of increasingly large brains. The palaeoanthropological literature is cited to debate the nature and time course of behavioural change during hominid evolution. In particular, when was truly flexible behaviour first evident, and did it occur gradually or suddenly? The proposed isocortical and behavioural changes during hominid evolution are then equated to determine if modern human behaviour can be seen as part of a continuum. It is concluded that a continuation of previous trends in isocortical evolution maybe inadequate to explain human behavioural flexibility. Several possible departures from previous trends that would be compatible with increased behavioural flexibility are suggested. These mainly relate to evolutionary changes in the later stages of isocortical development and in particular during the activity-dependant phase when cortico-cortical connections are refined.


Effect of influenza A virus on leukocyte histamine release.
Viral respiratory infections provoke asthma in many patients. In the following study we examined the effect of an in vitro incubation of influenza A on leukocyte histamine release. After incubation with a live influenza A (H3N2) virus, calcium ionophore A23187 (0.5, 1.0, and 1.5 microgram/ml)-induced leukocyte histamine release (HR) was enhanced (p less than 0.05). This effect was also found with heat- or ether-inactivated virus. Similarly, influenza A-exposed leukocytes had augmented leukocyte HR during subsequent incubation with ragweed AgE. Incubation of the leukocyte suspension with interferon (800 IU/ml) for 24 hr was also associated with enhanced HR to ragweed AgE. In contrast, interferon did not alter the calcium ionophore A23187 HR. Therefore, although interferon may mediate the enhanced leukocyte HR when ragweed AgE is the inciting stimulus, it does not change HR to the calcium ionophore.


Effects of hypoxia and transferrin on toxicity and DNA binding of ruthenium antitumor agents in hela cells.
Nuclear DNA binding and inhibition of growth of HeLa cells in culture were determined after 24 h incubation with the ruthenium anticancer agents cis-[Cl(2)(NH(3))(4)Ru]Cl (CCR) and (ImH)trans-[(Im)(2)Cl(4)Ru] (ICR) as a function of [Ru], Po(2), and added transferrin. Consistent with the "activation-by-reduction" hypothesis, cytotoxicity and DNA binding for both complexes increased under reduced oxygen conditions. Consistent with the "transferrin- transport" hypothesis, inhibition of cell growth also increased with added transferrin for both complexes. Despite their differences in charge, reduction potentials and substitution rates, both complexes behaved remarkably similarly indicating a common mechanism of action for both. Under atmospheric Conditions (Po(2) = 159 torr), CCR inhibited HeLa cell growth with IC(50) = 3.5 muM, while that for ICR was 2.0 muM. The binding of both complexes to DNA (Ru(DNA)/P(DNA)) correlated with toxicity and was approximately linear in the concentration of the ruthenium complex in the culture medium, [Ru]. For both complexes, IC(50) values decrease and DNA binding increases with decreasing log(Po(2)). In general, DNA binding at all oxygen pressures for both complexes is in the range of one Ru per 1000-2000 DNA base pairs at [Ru] = IC(50).


Histamine release inhibition and prevention of the decrease in membrane fluidity induced by certain anti-allergic drugs: analysis of the inhibitory mechanism of NCO-650.
NCO-650 exerted a dose-dependent inhibition of histamine release from isolated rat mast cells without affecting the Ca-uptake and intracellular cAMP levels. When the membrane stabilizing action of NCO-650 was investigated with the liposomes prepared by various phospholipids with or without cholesterol, it became clear that compound 48/80 decreases the order parameter of liposomes and NCO-650 inhibits the decrease of order parameter. Histamine release from histamine-containing liposomes was brought about by compound 48/80 at concentrations higher than 0.5 micrograms/ml, and pretreatment of the liposomes with NCO-650 inhibited histamine release due to compound 48/80. The incorporation of NCO-650 in the liposomes was effective in abolishing the phase transition of the lipid bilayer membranes from crystalline gel to liquid crystalline phases, and decreased the phase transition temperature. Those changes in the lipid bilayer membranes correspond to those displayed by incorporation of cholesterol in the liposomes. An increase of permeability of lipid membrane by compound 48/80 may be due to partial loosening of the lipid order; NCO-650 rigidified the liposome membrane and as a result of this, it decreased histamine release.


Cloning, expression and characterization of a murine-human chimeric antibody with specificity for pre-S2 surface antigen of hepatitis B virus.
The cloning, expression and characterization of a murine-human chimeric antibody with specificity for the pre-S2 surface antigen (Ag) of hepatitis B virus (HBV) is described. The heavy and light chain variable region (VH and VL) genes encoding the murine monoclonal antibody (mAb) were isolated and combined with human gamma 1 and kappa constant region genes, respectively. The expression vectors containing the chimeric heavy and light chain genes were sequentially electroporated into murine Sp2/0 hybridoma cells and transfectomas secreting chimeric antibody were isolated. The chimeric antibody was purified and characterized by ELISA, Western analysis and competition immunoassay, demonstrating that the transfectoma functionally express and secrete murine-human chimeric antibody which retained the specificity and affinity of the parental murine mAb.


Intestinal anti-inflammatory effects of probiotics in DNBS-colitis via modulation of gut microbiota and microRNAs.
Probiotics have been shown to exert beneficial effects in IBD although their exact mechanisms are not completely understood. The aim of the present study was to assess the intestinal anti-inflammatory activity of different probiotics (Lactobacillus fermentum CECT5716, Lactobacillus salivarius CECT5713, Escherichia coli Nissle 1917, Saccharomyces boulardii CNCMI-745 in the dinitrobenzene sulfonic acid (DNBS) model of mouse colitis and correlate it with the modifications of the gut microbiota and the immune response, focusing on miRNA expression. The probiotics were daily administered orally for 25 days. On day 19 colitis was induced by rectal installation of DNBS. At the end of the treatment, mice were sacrificed and the colonic damage was assessed biochemically by analysing the expression of different markers involved in the immune response, including miRNAs; and the colonic microbiota by pyrosequencing. Probiotics properties were also evaluated in vitro in different immune cell types (CMT-93 intestinal epithelial cells and bone marrow-derived macrophages), where the expression of different mRNAs and miRNAs was examined. All the probiotics displayed intestinal anti-inflammatory effects but slightly different, especially regarding miRNAs expression. Likewise, the probiotics ameliorated the colitis-associated dysbiosis, although showing differences in the main bacterial groups affected. Among the probiotics assayed, Lactobacillus fermentum CECT5716 and Escherichia coli Nissle 1917 appear to present the best intestinal anti-inflammatory effects, being the latter one of the few probiotics with reputed efficacy in human IBD. Therefore, Lactobacillus fermentum CECT5716 could be considered as a complementary nutritional strategy for IBD treatment.


Smoking prevalence, behaviours, and cessation among individuals with COPD or asthma.
Smoking prevalence, behaviours, physician counselling regarding smoking cessation, and smoking cessation medications were evaluated among male and female smokers with COPD and asthma compared to the general smoking population. Data from the large, nationally representative Canadian Community Health Survey (CCHS) was used (for 2003 CCHS, n = 134,072). All data were based on self-report, including the presence of COPD and asthma which were defined by health-professional diagnosis. Nicotine addiction was assessed by the Fagerstrom Test for Nicotine Dependence. In 2003, 32.8% of individuals with COPD, 21.0% with asthma, and 22.1% without COPD or asthma were current smokers. After adjusting for sociodemographic and smoking behaviour confounders, among current smokers, greater odds of high or very high nicotine addiction were observed among women with versus without COPD (OR = 2.49, 95% CI = 1.41-4.39), and among women with versus without asthma (OR = 1.74, 95% CI = 1.01-2.99), but no associations were seen among men. Smokers with COPD and asthma were no more likely to have received physician counselling regarding smoking cessation, nor smoking cessation pharmacotherapy compared to the general smoking population. Gender differences were observed in the association between COPD and asthma and higher nicotine addition levels in current smokers. These findings could in part explain population trends showing that COPD and asthma are increasing more rapidly in women. Physician counselling and pharmacotherapy for smoking cessation do not appear to be received more frequently among individuals with COPD or asthma compared to the general smoking population, despite the greater vulnerability of such patients to smoking effects.


Chemical analysis of a new fucoglucan isolated from an edible mushroom, Termitomyces robustus.
A water-soluble fucoglucan, isolated from alkali-treated edible mushroom, Termitomyces robustus, consists of L-fucose and D-glucose in a molar proportion of 1:4. Structural investigation of the polysaccharide was carried out by using total hydrolysis, methylation analysis, and periodate oxidation followed by GLC-MS, and the final structure was determined using NMR experiments (1H, 13C, DQF-COSY, TOCSY, NOESY, ROESY, HMQC, and HMBC). On the basis of the above experiments it is concluded that the following repeating unit is present in the polysaccharide: [Formula: see text].


Safety evaluation of Nostoc flagelliforme (nostocales, Cyanophyceae) as a potential food.
The safety of the alga genus Nostoc flagelliforme Born. etFlah. as a human food source was evaluated in an oral acute toxicity study and in a 28-day oral subacute toxicity study using rats. In the acute toxicity study, the dried powder of N. flagelliforme was orally administered to male and female rats at a dose of 1250 mg/kg and 2500 mg/kg. Neither mortality nor changes in general condition were observed in either the study groups or the control group over a 14-day observation period. In the subacute toxicity study, N. flagelliforme powder was administered orally to male and female rats at a dose of 500 mg/kg and 1000 mg/kg for a period of 28 days. Neither mortality nor changes in general condition were observed in either the treatment group or the control group throughout the 28-day administration period. No reduction in food consumption or body weight gain was observed in the experimental animals. Ophthalmological tests performed at the end of the administration period revealed no abnormalities within the ophthalmological parameters. In the haematological tests and serum biochemical tests performed at the time of completion of the administration period, no adverse effects of N. flagelliforme were observed. At autopsy, organ weight at the end of the experimental period and histopathological tests of specimens obtained from the autopsied animals revealed no significant influences of N. flagelliforme. In conclusion, considering the absence of adverse effects of N. flagelliforme in this study, findings in the oral acute toxicity study and the 28-day oral subacute toxicity study may indicate the safety of N. flagelliforme for human consumption. This study is in agreement with the novel nutraceutical idea "Phycophagism".


Antisense Oligonucleotide Inhibition of MicroRNA-494 Halts Atherosclerotic Plaque Progression and Promotes Plaque Stabilization.
We have previously shown that third-generation antisense (3GA) inhibition of 14q32 microRNA (miRNA)-494 reduced early development of atherosclerosis. However, patients at risk of atherosclerotic complications generally present with advanced and unstable lesions. Here, we administered 3GAs against 14q32 miRNA-494 (3GA-494), miRNA-329 (3GA-329), or a control (3GA-ctrl) to mice with advanced atherosclerosis. Atherosclerotic plaque formation in LDLr-/- mice was induced by a 10-week high-fat diet and simultaneous carotid artery collar placement. Parallel to 3GA-treatment, hyperlipidemia was normalized by a diet switch to regular chow for an additional 5 weeks. We show that, even though plasma cholesterol levels were normalized after diet switch, carotid artery plaque progression continued in 3GA-ctrl mice. However, treatment with 3GA-494 and, in part, 3GA-329 halted plaque progression. Furthermore, in the aortic root, intra-plaque collagen content was increased in 3GA-494 mice, accompanied by a reduction in the intra-plaque macrophage content. Pro-atherogenic cells in the circulation, including inflammatory Ly6Chi monocytes, neutrophils, and blood platelets, were decreased upon miRNA-329 and miRNA-494 inhibition. Taken together, treatment with 3GA-494, and in part with 3GA-329, halts atherosclerotic plaque progression and promotes stabilization of advanced lesions, which is highly relevant for human atherosclerosis.


Soft-tissue measurements at the index finger: age and sex characteristics.
Measurements of the soft-tissue width and phalanx width of the index finger were made in 402 normal individuals (270 women and 132 men, age range 20--89 years) in order to establish age-sex characteristics. Men have a significantly larger total finger and phalanx width than women in all age groups. In both sexes a statistically significant increase with age in phalanx width and total finger width is found. The soft-tissue index and soft-tissue thickness is not influenced by age.


Risk associated with bilobectomy after neoadjuvant concurrent chemoradiotherapy for stage IIIA-N2 non-small-cell lung cancer.
The aim of the present study was to evaluate the outcomes of surgical resection, especially bilobectomy, after chemoradiation therapy to treat stage IIIA-N2 non-small-cell lung cancer. Data from all patients who underwent surgical resection after neoadjuvant chemoradiation therapy for stage IIIA-N2 non-small-cell lung cancer between 1998 and 2007 were analyzed retrospectively. The chemotherapy regimen consisted of weekly paclitaxel plus cisplatin or weekly paclitaxel plus carboplatin for 5 weeks. The concurrent thoracic radiotherapy dose was 45 Gy over 5 weeks. Surgical resection was planned at around 4 weeks following the completion of neoadjuvant therapy. Of 186 patients who underwent neoadjuvant therapy, 23 bilobectomies, 28 pneumonectomies, and 135 lobectomies were performed. The early postoperative mortality rate (within 30 days after operation) was 7.1, 8.7, and 1.5% for the pneumonectomy, bilobectomy, and lobectomy groups, respectively. The late postoperative mortality rate (within 90 days) of the lobectomy, bilobectomy, and pneumonectomy groups was 5.9, 13, and 10.7%, respectively. Overall survival was significantly higher among patients treated by lobectomy than among those treated by bilobectomy (p = 0.041) or pneumonectomy (p = 0.010). Recurrence was significantly lower in patients treated by lobectomy than in those treated by pneumonectomy (p = 0.034). Bilobectomy is associated with high operative mortality and poor long-term survival after neoadjuvant concurrent chemoradiotherapy for stage IIIA-N2 non-small-cell lung cancer. The outcomes of bilobectomy were similar to those of pneumonectomy in terms of overall survival, disease-free survival, and postoperative mortality.


Feasibility of Group Cognitive-Behavioral Treatment of Insomnia Delivered by Clinical Video Telehealth.
Clinical video telehealth provides a means for increasing access to psychotherapy. Insomnia is prevalent, is associated with a number of negative sequelae, and can be effectively managed with cognitive behavioral treatment of insomnia (CBT-I). Telehealth technologies can provide a means for increasing access to CBT-I. The Tele-Insomnia program is a Veterans Health Administration (VHA) initiative in which CBT-I is delivered in a group format by telehealth. Veterans received six weekly sessions of group CBT-I, completing the Insomnia Severity Index (ISI) and daily sleep diaries throughout treatment. Paired-samples t-tests were used to examine differences in each measure from the first to the last session of treatment. There were statistically and clinically significant improvements in the ISI and all sleep diary variables with the exception of total sleep time. Video quality was excellent, and there were few connectivity problems. Clinical video telehealth technology can be used to deliver group CBT-I in a manner that produces clinically significant improvement. This model is scalable and has been used to develop a national clinical telehealth program.


Polyploid giant cancer cells, cytokines and cytomegalovirus in breast cancer progression.
Breast cancer is the most common cancer among women. Accumulated evidence over the past decades indicates a very high prevalence of human cytomegalovirus (HCMV) in breast cancer. High-risk HCMV strains possess a direct oncogenic effect displayed by cellular stress, polyploid giant cancer cells (PGCCs) generation, stemness, and epithelial-to-mesenchymal transition (EMT) leading to cancer of aggressive phenotype. Breast cancer development and progression have been regulated by several cytokines where the latter can promote cancer cell survival, help in tumor immune evasion, and initiate the EMT process, thereby resulting in invasion, angiogenesis, and breast cancer metastasis. In the present study, we screened cytokines expression in cytomegalovirus-transformed HMECs (CTH cells) cultures infected with HCMV high-risk strains namely, HCMV-DB and BL, as well as breast cancer biopsies, and analyzed the association between cytokines production, PGCCs count, and HCMV presence in vitro and in vivo. In CTH cultures and breast cancer biopsies, HCMV load was quantified by real-time qPCR. PGCCs count in CTH cultures and breast cancer biopsies was identified based on cell morphology and hematoxylin and eosin staining, respectively. CTH supernatants were evaluated for the production of TGF-β, IL-6, IL1-β, and IL-10 by ELISA assays. The above-mentioned cytokines expression was assessed in breast cancer biopsies using reverse transcription-qPCR. The correlation analyses were performed using Pearson correlation test. The revealed PGCCs/cytokine profile in our in vitro CTH model matched that of the breast cancer biopsies, in vivo. Pronounced cytokine expression and PGCCs count were detected in particularly CTH-DB cultures and basal-like breast cancer biopsies. The analysis of cytokine profiles in PGCCs present mostly in basal-like breast cancer biopsies and derived from CTH cells chronically infected with the high-risk HCMV strains might have the potential to provide novel therapies such as cytokine-based immunotherapy which is a promising field in cancer treatments.


Effects of peptide anabolic hormones on growth of myoblasts in culture.
The roles of growth hormone and somatomedin in stimulating muscle cell proliferation were investigated in a series of experiments on myoblast growth in culture. At levels 100 times normal circulating concentrations, neither growth hormone nor insulin stimulated growth of rat muscle cells in serum-free medium. In contrast, Temin's Multiplication Stimulating Activity (MSA), a close biological and chemical analog which served as a somatomedin surrogate in this study, was active at concentrations corresponding to the reported circulating levels of the somatomedins; MSA gave consistent stimulation of myoblast proliferation, protein accumulation, and [3H]thymidine incorporation by rat myoblasts and by Yaffe's L6 myogenic cell line. (The unreliability of [3H]thymidine in corporation as a quantitative assay for mitogenic activity is illustrated.) Addition of insulin at physiological concentrations and at the very high levels often used to stimulate cell growth did not enhance the effects of MSA on myoblast proliferation; effects were barely additive. We interpret these results to support earlier indications from studies on diaphragm muscle that the somatomedins are physiologically important mediators of the growth-promoting actions of growth hormone in muscle.


Prevalence and characteristics of polycystic ovarian syndrome in patients with bipolar disorder.
Bipolar disorder (BD) is frequently accompanied by endocrine disturbances. We compared the prevalence of polycystic ovary syndrome (PCOS) and related reproductive disorders between drug-naïve BD patients and matched healthy controls (HCs) and between drug-naïve BD patients and BD patients with long-term medication, as well as the clinical metabolic correlates among BD patients. 72 drug-naïve BD patients, 98 HCs, and 72 BD patients with long-term medication were recruited in the study. Menstruation was recorded, reproductive hormone levels and metabolic indicators were measured, and a pelvic ultrasound examination was performed via transvaginal sensor for each participant. PCOS was defined using the Rotterdam criteria. After controlling for demographic variables, drug-naïve BD patients presented higher rates of PCOS than the HCs (OR: 3.02, 95 % CI: 1.09-8.36). Regression analysis showed that long-term treatment with valproate (OR: 3.89, 95 % CI: 1.13-13.37), age (OR: 0.37, 95 % CI: 0.14-0.95), and insulin resistance index (OR: 1.73, 95 % CI: 1.10-12.71) were correlated with PCOS in BD patients. Drug-naïve BD patients are susceptible to developing PCOS, and valproate is correlated with increased occurrence and development of PCOS. Therefore, PCOS in BD patients, especially those who use valproate, needs to be investigated and monitored closely by medical personnel.


Differential estrogenic regulation of small M(r) heat shock protein expression in osteoblasts.
Polymerase chain reaction amplification and sequencing of heat shock protein (HSP) 27-related transcripts present in cDNAs generated from heat-shocked osteoblast RNA revealed the expression of three related open reading frames that encode proteins of 208, 197, or 175 amino acids. Their expression as recombinant proteins in Escherichia coli demonstrated that they encode 27,000, 25,000, or 22,000 M(r) proteins. Northern blot analysis of heat shock protein 27-related transcript expression revealed that, while HSP 27 expression (850-nucleotide transcript) was induced by heat shock alone, the expression of a smaller transcript was facilitated by estrogen treatment prior to heat shock. This corresponded with the co-induction of 18,000 and 22,000 M(r) proteins by estrogen-pretreated, heat-shocked osteoblasts as revealed by fluorography. The identification of these multiple small M(r) heat shock-induced proteins demonstrated that the stress response of mammalian cells is composed of multiple, related proteins whose expression is differentially regulated. The importance of estrogen-regulation of the small M(r) heat shock protein component of the stress response may be of particular significance to osteoblast physiology.


Performance of a bioreactor with submerged membranes for aerobic treatment of municipal waste water.
Aerobic treatment of municipal waste water in a membrane bioreactor was studied for 535 d. Apart from sampling, sludge was retained completely by a submerged hollow fibre membrane with a pore-size of 0.2 microm. The pilot plant comprised an anoxic zone to enable denitrification. The maximum liquid hold-up of the plant was 3.9 m3. In this study the reactor performance and the stability of the process and the membrane capacity were investigated. A stable flux of 181 m(-2)h(-1) could be realised with a mean transmembrane pressure difference of 0.3bar with air-bubbling and backflushing the membrane and cleaning it in place every two months for one or two hours. For about 140d, a flux of 271 m(-2)h(-1) was achieved, but cleaning became necessary more often. The hydraulic retention time (HRT) varied between 10.4 and 15.6h. Accordingly the volumetric loading rate was between 1.1 and 1.7kg CODm(-3)d(-1). No inoculum was used. The mixed liquor suspended solids (MLSS) concentration gradually increased to 18-20g MLSSl(-1). The feed to microorganism (F/M) ratio varied according to the operation conditions but decreased against a value of 0.07 kg COD kg(-1) MLSSd(-1). Treatment performance was very stable and on a high level. The COD was reduced by 95%. Nitrification was complete and up to 82% of the total nitrogen could be denitrified.


Comparison of the effects of biogenic amines on cyclic GMP and cycle AMP levels in mouse cerebellum in vitro.
Norepinephrine (NE) elevates levels of both 3',5'-guanosine monophosphate (cyclic GMP) and 3',5'-adenosine monophosphate (cyclic AMP) in incubated slices of mouse cerebellum. As little as 1 muM NE is capable of increasing the level of either cyclic nucleotide. Maximal elevations of cyclic AMP and cyclic GMP levels produced by NE are 15- to 40-fold and 2- to 4-fold, respectively. Dopamine, serotonin and histamine, other biogenic amines considered to be neurotransmitters in CNS, have no effect on mouse cerebellum cyclic nucleotide levels except at relatively high (1 mM) concentrations. NE-induced accumulation of cyclic GMP, but not cyclic AMP, is blocked by omission of Ca2+ from the incubation media. Theophylline does not alter the effect of this catecholamine on either cyclic nucleotide. In tissue slices incubated in buffered sucrose or in choline-Krebs buffer, NE is still capable of increasing both cyclic GMP and cyclic AMP levels; however, these elevations are less than those observed in brain slices incubated in Krebs-Ringer buffer. NE, in combination with glutamate, produces supra-additive elevations of both cyclic GMP and cyclic AMP levels. However, NE in combination with adenosine or high levels of K+ only has a synergistic effect on cyclic AMP and not on cyclic AMP and not on cyclic GMP combination. The elevation of cyclic AMP levels produced by NE appears to be mediated via both alpha- and beta-adrenergic receptor sites. In contrast, the receptor site(s) mediating cyclic AMP accumulation do not appear to be either typical alpha- or beta-adrenergic receptors.


Proposing a communication module to enhance dental students' attitudes towards people with dementia: Phase 1 of a curriculum revision study.
The number of mentally altered patients a dentist meets in practice is increasing and interaction with them can be very challenging. As a baseline for an interventional study, we want to assess the attitude of dental students and identify areas of improvement in patient communication. This work compares the attitude of dental students towards people suffering from dementia to the attitudes of trained medical caregivers and the general population. Our aim is to use the results to assess the need for training in communicating with mentally altered patients. Fourth-year dental students attended two lectures on dementia given by a psychiatrist as part of the geriatric dentistry lecture and were questioned afterwards using the Dementia Attitude Scale. In 2016 and 2017, 73 students at the University of Greifswald were interviewed. The response rate was 84%. Using a factor analysis, the Dementia Attitude Scale's validated questions were interpreted and compared with data from nursing staff from Switzerland and the USA. The factor analysis of the data showed the same two-factor loadings as the comparative groups, and that dental students' attitude is more comparable to the general population than to medically trained nursing staff. Given the results, we conclude that the implementation of a communication module can serve in improving the attitude of dental students towards patients with dementia.


Downregulation of SEPTIN11 inhibits endometrial epithelial cell adhesive function in patients with elevated peripheral blood natural killer cell counts.
What is the underlying mechanism of IVF and embryo transfer (IVF-ET) failure in patients with elevated peripheral blood natural killer cell (pNK) counts? Patients undergoing IVF-ET cycles for tubal obstruction or pelvic adhesion (n = 486) were assigned to three groups: high (CD56+CD16+pNK >30% [n = 49]); medium (15< CD56+CD16+pNK ≤30% [n = 211]); and normal pNK groups (5≤ CD56+CD16+pNK ≤15% [n = 226]). Their general condition, previous pregnancy history and IVF outcomes were compared. Uterine fluid and endometrial tissue from patients in the high and normal pNK groups were collected during the mid-secretory phase and studied to elucidate the molecular mechanism underlying impaired endometrial receptivity. The highest incidence of IVF-ET cycles (P < 0.0001) and biochemical pregnancy losses (P < 0.0001), and lowest implantation and clinical pregnancy rates (both P < 0.0001), were observed in patients with pNK over 30%. No significant difference was found in the number of previous miscarriages and rate of spontaneous miscarriage in IVF outcomes. Lower Septin11 (SEPT11) expression in the uterine fluid and endometrial epithelial cells (EEC), and higher endometrial IFN-γ, was observed in patients with high pNK. Ishikawa cell and human endometrial epithelial cell (HEEC) adhesion was inhibited after SEPT11 knock-down. Elevated IFN-γ decreased the SEPT11 protein levels in Ishikawa cells and HEECs. CD56+CD16+pNK above 30% may be a threshold for adverse IVF-ET outcomes. Low SEPT11 expression in EEC inhibits cell adhesion, which may cause impaired endometrial receptivity in patients with elevated pNK. The level of SEPT11 in mid-secretory uterine fluid could serve as a non-invasive marker to assess endometrial receptivity in these patients.


Comparison of ethinylestradiol and mestranol in sequential-type oral contraceptives in their effects on blood glucose and serum insulin in oral glucose tolerance tests.
Forty 3-hour oral glucose tolerance tests (OGTTs) were performed in 10 assumedly healthy female volunteers 19 to 30 years old, each serving four times as her own control. Each subject was taking a sequential type oral contraceptive containing either 50 microgram of ethinylestradiol or 80 microgram of mestranol alternatingly in four consecutive treatment cycles. The OGTTs were performed on the 6th day of each cycle, during pure estrogen medication. Blood glucose and serum insulin values did not differ significantly under either estrogen as tested by the t-test for paired observations. Our results do not support the findings of others that mestranol has a more pronounced or even exclusively adverse effect on glucose tolerance as compared with ethinylestradiol.


Characterization and distribution of polybrominated diphenyl ethers in shellfish in Shenzhen coastal waters and assessment of human health risks.
This study aims to investigate the profiles of polybrominated diphenyl ethers (PBDEs) in shellfish obtained from Shenzhen coastal waters and assess the potential health risks. We analyzed 74 shellfish samples from eight different species for PBDEs (BDE-28, -47, -99, -100, -153, -154, -183, -209). The concentrations of total PBDEs in different shellfish species ranged from 2.02 to 360.17 pg g-1 wet weight, with the highest levels found in Pectinidae, Babylonia areolate, Ostreidae, Perna viridis, Haliotis diversicolor, Corbiculidae, Pinctada margaritifera, and Veneridae in descending order. Among the PBDE congeners analyzed, BDE-47 was the most abundant, followed by BDE-154 and BDE-153. Furthermore, the estimated daily intake of PBDEs through shellfish consumption for Shenzhen residents were between 0.11 and 0.19 ng kg-1(bw) day-1. To our knowledge, this is the first study to systematically investigate the profiles of PBDEs in eight different shellfish species from Shenzhen's coastal waters and evaluate the potential human health risks associated with shellfish consumption.


Rapid identification of probiotic lactobacillus biosurfactant proteins by ProteinChip tandem mass spectrometry tryptic peptide sequencing.
A novel ProteinChip-interfaced tandem mass spectrometer was employed to identify collagen binding proteins from biosurfactant produced by Lactobacillus fermentum RC-14. On-chip tryptic digestion of the captured collagen binding proteins resulted in rapid sequence identification of five novel tryptic peptide sequences via collision-induced dissociation tandem mass spectrometry.


Coracobrachialis muscle: morphology, morphometry and gender differences.
Coracobrachialis (CBM) is a complex muscle with a wide range of variations in its morphology and innervation. The goal of this study was to elucidate the morphology, morphometry, gender differences of CBM and precise anatomical position of the musculocutaneous nerve (MCN) with reference to surrounding anatomical landmarks in an adult Sri Lankan population. Cadaveric upper limbs (n = 312) were examined for the proximal and distal attachments, length, width, thickness of CBM and its relationship with the MCN. The CBM originated from the tip of the coracoid process of the scapula and lateral, posterior and medial aspects of the tendon of short head of biceps brachii. Gender differences were observed in all morphometrical parameters of CBM. In 83.33 %, MCN perforated the CBM. In 50 % the MCN pierced the middle one-third of CBM while none pierced the lower one-third. The distance from the coracoid process to the point of entry of MCN into CBM (distance P) was 50.62 mm. A positive correlation was observed between the arm length and distance P indicating that arm length provides an accurate and reliable means of gauging the distance P of an individual. The present study provides new evidence pertaining to the origin of CBM. Further, it was revealed that the predicted distance P of any upper extremity can be calculated by dividing the arm length by 5. Precise anatomical location of MCN in relation to CBM using unequivocal and well-defined anatomical landmarks will be imperative in modern surgical procedures.


RuCl3-catalyzed alkenylation of aromatic C-H bonds with terminal alkynes.
RuCl3-catalyzed regio- and/or stereoselective alkenylation reactions of a variety of arylpyridines proceeded efficiently with terminal alkynes or allylic compounds in the presence of benzoyl peroxide or benzoic acid.


Quality control of Citri reticulatae pericarpium: exploratory analysis and discrimination.
Extracts of Citri reticulatae pericarpium (PCR) are commonly used in the Traditional Chinese Medicine. The quality control of PCR is currently performed by single marker analysis, which can hardly describe the complexity of such natural samples. In this study, a fingerprint methodology for PCR based on high-performance liquid chromatography (HPLC) was developed and validated. A total of 69 fingerprints of authenticated PCR samples, commercial PCR samples, mixed peel samples, and other Citrus peels were recorded. Exploratory data analysis allowed optimizing the extraction procedure and detecting mixed peel samples. Once the optimizations were performed and the method validated, discrimination between the authentic PCR samples and all other samples was performed by p-Discriminant Partial Least Squares. The established model was able to differentiate between classes with a high reliability for each sample. Furthermore, evaluation of the score and loading plots of the model indicated nobiletin, tangeretin, naringin and hesperidin as important markers for the quality control of PCR.