Prevalence and Survival Impact of Self-Reported Symptom and Psychological Distress Among Patients With Multiple Myeloma.
Advances in the management of multiple myeloma (MM) have extended survival and reduced painful skeletal-related events. As MM is evolving toward a chronic disease, we sought to determine the prevalence of self-reported symptom burden and psychological distress, and to determine the association of distress with survival. The CPASS-7 patient-reported outcome instrument was administered to a convenience sample of MM patients at 7 outpatient cancer centers. A total of 239 patients completed the CPASS-7 between September 2015 and October 2016%; 57% of respondents were male, and median age was 67 years. Forty-eight percent were concerned that they could not do the things they wanted to do, with 33% reporting decreased performance status. Financial toxicity concerns were self-reported by 44%, with family burdens noted in 24%. Although depression was reported by only 15%, 41% noted lack of pleasure. Pain was a concern in 36%. With a median follow-up of 316 days since CPASS-7 completion, 13% of patients had died. A high total distress score was noted in 57 (24%) and trended toward an association with a decreased survival rate compared to the 182 patients (76%) with a low total distress score (P = .066). The 6-month survival rates for patients with high and low distress scores were 86% and 96%, respectively, and 12-month survival rates were 76% and 87%, respectively. Despite dramatic improvements in survival among patients with MM, symptom, financial, and psychosocial concerns continue to be major patient concerns. As MM becomes a chronic disease, additional attention to addressing these issues is required.


Severe electrical injury.
From January 1979 to January 1987, 125 patients were treated in our Centre for various electrical injuries. Among them, 85 patients were over 15 years of age (89.4 per cent were males and 10.6 per cent females) and 40 patients were below 15 years of age (92.5 per cent were males and 7.5 per cent females). Electricians were the most frequently injured in the over 15-year-old age-group, whereas most patients under 15 years old were students. We focused our study on five patients with multiple and severe electrical injury. Two of these patients were injured while erecting TV aerials, two were injured at work and the other one was working on a house roof. Despite all our efforts extensive limb amputations were required. Following complete healing, we fitted prostheses to the amputation stumps. All the patients have now returned to society as capable individuals, two of them to their previous occupations and the other three with new occupations. Our experience with five patients showed that patients with severe electrical injury and multiple amputations have a reasonable chance of recovery. Rehabilitation therapy must be given as early as possible after the electrical injury so that the patients may return to their normal place in society.


Improved deinking and biobleaching efficiency of enzyme consortium from Thermomyces lanuginosus VAPS25 using genetic Algorithm-Artificial neural network based tools.
The present study reports the combined enzymatic production efficiency of thermophilic fungus Thermomyces lanuginosus VAPS25 using a combinatory artificial intelligence-based tool, resulting in 2.7 IU/ml, 5.2 IU/ml, and 18.85 U/ml activity of endoglucanase, amylase, and lipase, respectively with good thermostability at 90 °C (pH 8-10). Interestingly, the metal ions viz. Cu2+ and Mg2+ increased the endoglucanase activity to 5 folds, i.e.,5.6 IU/ml compared to control. Further, the amylase and lipase activity was also enhanced by Fe2+ and Co2+ to 5.4 IU/ml and 19.57 U/ml, respectively. Additionally, the deinking efficiency was improved by 68.9%, 42.7%, and 52.8% by endoglucanase, amylase, and lipase, respectively, while the consortium increased the deinking efficiency to 72.7%. The bio-bleached paper strength parameters such as burst index, breaking length, tear index, and tensile index of sheets were significantly improved by 1.38%, 13.54%, 7.54%, and 20.88%, respectively. These enzymes at an industrial scale would help develop an economical paper recycling process.


Microplastics in the sediments of small-scale Japanese rivers: Abundance and distribution, characterization, sources-to-sink, and ecological risks.
Microplastic pollution in small-scale river sediments remains mostly unknown. This study explored microplastics in the sediments of four small-scale Japanese rivers in Yamaguchi Prefecture: the Awano, Ayaragi, Asa, and Majime. Sediment samples (n = 23) were collected from the selected stations. Density separation and wet peroxidation methods were applied to extract microplastics. Polymers were detected through attenuated total reflectance-Fourier transform infrared spectroscopy. Microplastic abundance indicated relatively moderate values in the small-scale Japanese rivers compared to other rivers around the world. Large microplastics (1-5 mm) in size, fragments in shape, and high-density particles of diverse polymers dominated. Polyvinyl chloride, polyethylene, and polypropylene were the major polymers. The polymers-polyvinyl chloride, polymethylmethacrylate, polyurethane, fluorinated ethylene propylene, and polybutylene in sediments were distinct from those detected in surface water, as were the predominance of large-size (1-5 mm) and fragment-shape microplastics. In contrast to surface water, sediments preserved both common and distinctive microplastics. Thus, the riverine sediment compartment acted as microplastic sink. Scanning electron microscopic (SEM) analysis suggested the presence of weathered microplastics in sediments. Energy dispersive X-ray spectroscopic analysis (EDX) revealed metal contaminants on the microplastic surfaces, indicating synergistic hazard potentials in the riverine ecosystems. Ecological risk assessment results suggested low to very high risks of microplastic pollution for the rivers. The higher abundances of microplastics and highly toxic polymers contributed to the elevated ecological risks. Polyvinyl chloride, acrylonitrile butadiene styrene, polyurethane, and polymethylmethacrylate were the detected highly toxic polymers. The urban and residential areas affected stations ranked high to very high ecological risks. The sites posing very high ecological risks were regarded as pollution hotspots. Overall, this study developed new insights into microplastic pollution in the small-scale rivers and ecological risks for riverine environments, as well as providing a baseline for more comprehensive risk assessments and developing pollution control and management strategies.


A Polygenic Score for Higher Educational Attainment is Associated with Larger Brains.
People who score higher on intelligence tests tend to have larger brains. Twin studies suggest the same genetic factors influence both brain size and intelligence. This has led to the hypothesis that genetics influence intelligence partly by contributing to the development of larger brains. We tested this hypothesis using four large imaging genetics studies (combined N = 7965) with polygenic scores derived from a genome-wide association study (GWAS) of educational attainment, a correlate of intelligence. We conducted meta-analysis to test associations among participants' genetics, total brain volume (i.e., brain size), and cognitive test performance. Consistent with previous findings, participants with higher polygenic scores achieved higher scores on cognitive tests, as did participants with larger brains. Participants with higher polygenic scores also had larger brains. We found some evidence that brain size partly mediated associations between participants' education polygenic scores and their cognitive test performance. Effect sizes were larger in the population-based samples than in the convenience-based samples. Recruitment and retention of population-representative samples should be a priority for neuroscience research. Findings suggest promise for studies integrating GWAS discoveries with brain imaging to understand neurobiology linking genetics with cognitive performance.


Utilization of Cladophora glomerata extract nanoparticles as eco-nematicide and enhancing the defense responses of tomato plants infected by Meloidogyne javanica.
Tomato (Solanum Lycopersicum L.) is an important vegetable crop that belongs to the family Solanaceae. Root-knot nematodes reflect the highly critical economically damaging genera of phytoparasitic nematodes on tomato plants. In this study, the eco-nematicide activity of freshwater green macroalga Cladophora glomerata aqueous extract and their synthesized silver nanoparticles (Ag-NPs) against root-knot nematodes Meloidogyne javanica was investigated on tomato plants. The formation and chemical structure of Ag-NPs was examined. The aqueous extract from C. glomerata was applied against the root-knot nematodes besides the biosynthesized green silver nanoparticles with 100, 75, 50, and 25% (S, S/2, S/3, S/4) concentrations. To investigate the plant response toward the Green Synthesized Silver Nanoparticles (GSNPs) treatment, expression profiling of Phenylalanine Ammonia-Lyase (PAL), Poly Phenol Oxidase (PPO), and Peroxidase (POX) in tomato were examined using Quantitative Real-Time PCR (Q-PCR). The results indicated that GSNPs from C. glomerata exhibited the highest eco-nematicide activity in the laboratory bioassay on egg hatchability and juveniles (J2S) mortality of M. javanica compared with the chemical commercial nematicide Rugby 60%. Also, results showed a significant reduction in galls number, egg masses, females per root system/plant, and mortality of juveniles. The results of PAL and PPO enzyme expression for the control plants remained relatively stable, while the plant inoculated with nematode M. javanica as well as the activity of genes in scope was increased from 14 to 28 Days after Nematode Inoculation (DANI). These activities were improved in inoculated plants and treated with C. glomerata extract and their green syntheses of Ag-NPs and the other plants treated with Rugby 60% (4 mL/L). The greatest activities of the three enzymes were evident after 14 days after the nematode inoculation. It can be concluded that the green synthesized nanoparticles using C. glomerata could be used as potent nematicides against M. javanica which induces the immune system to defend against nematode infection.


Pituitary-targeted medical therapy of Cushing's disease.
The goals of ideal medical therapy for Cushing's disease should be to target the aetiology of the disorder, as is the case for surgery, which is the current 'gold standard' treatment. However, no effective drug that directly and reliably targets the adrenocorticotropin-secreting pituitary adenoma has yet been found. To summarise pituitary-targeted medical treatment of Cushing's disease. Compounds with neuromodulatory properties and ligands of different nuclear hormone receptors involved in hypothalamo-pituitary regulation have been investigated. The somatostatin analogue pasireotide and the dopamine agonist cabergoline, as well as their combination, show some therapeutic promise in the medical therapy of Cushing's disease. Other treatments such as retinoic acid analogues look promising and may be a possible option for further investigation. No other medical therapies seem to be reliably effective currently. Since a percentage of patients treated with surgery are not cured, or improve and subsequently relapse, there is an urgent need for effective medical therapies for this disorder. At present, only cabergoline and pasireotide are under active investigation.


Cyclopropene fatty acids of selected seed oils from bombacaceae, malvaceae, and sterculiaceae.
Fatty acid compositions of seed oils from three species of Bombacaceae, eleven from Malvaceae, and six from Sterculiaceae were determined. Each of the seed oils contains varying amounts of both malvalic and sterculic acids accompanied by one or both of the corresponding cyclopropane fatty acids. In addition, the seed oil of Pachira aquatic Aubl. (Bombacaceae) contains 12.8% alpha-hydroxysterculic acid.


Absence of association between -286C>A>T polymorphism in the CRP gene and metabolic syndrome in Iranian pediatric.
As a common pathophysiological condition worldwide, metabolic syndrome (MetS) is a clustering of multiple risk factors implicating in the development of many chronic disorders. Of note, obesity-induced chronic, low-grade inflammation is a major cause of insulin resistance and MetS. In the present study, we evaluated the association of rs3091244 variant of the C-reactive protein (CRP) gene, a well-recognized systemic inflammatory marker, with MetS in Iranian children and adolescents. Genotyping was performed by mismatched polymerase chain reaction-restriction fragment length polymorphism in 100 MetS and 100 normal individuals aged 9-19 years recruited in the central part of Iran in 2011. A t-test or one-way ANOVA with post-hoc multiple comparisons were used to analyze the differences between groups. Statistical significance was defined as P ≤ 0.05. Logistic regression used to evaluate the association between alleles of the CRP rs3091244 and increased MetS risk. There were no differences in the genotype frequencies or allele distribution for -286C>A>T CRP polymorphism between MetS and control groups. Logistic regression showed that only the T allele of the CRP rs3091244 and not any of the genotypes confers a borderline significant (P = 0.059) increased MetS risk compared to A allele with the odds ratio of 1.70 (0.98-2.96). This study suggests that in Iranian children and adolescents, -286C>A>T CRP polymorphism is not associated with the increased risk for MetS.


Combined implantation of artificial sphincter and penile prosthesis.
Concurrent sphincteric incontinence and organic impotence are not uncommon; they can be caused by many congenital and acquired conditions. In the past simultaneous implantation of the artificial sphincter and penile prosthesis was met with skepticism. Of 65 patients who had concurrent implantation of the artificial sphincter and various categories of penile prosthesis 60 were followed for a mean of 35.74 months (range 8 to 55 months). Continence was graded as good or satisfactory in 95 per cent of the patients and poor in 5 per cent. The penile implants were functional in 98 per cent of the patients. Of the 60 patients 33 required 59 corrections, for an average of 0.98 correction per patient. These results indicate that staged or concurrent implantation of dual prostheses is feasible technically, functionally and cosmetically, and without increased risk for surgical or mechanical problems.


Lipid profile, statin use, and outcome after intravenous thrombolysis for acute ischaemic stroke.
Low cholesterol levels have been associated with an increased risk of haemorrhagic stroke. This study investigated whether lipid levels or prior statin use influence outcome in patients with acute ischaemic stroke treated with IV thrombolysis. The relation between admission lipid levels or statin use and both the development of symptomatic intracerebral haemorrhage (sICH) and 3-months functional outcome was assessed in a prospective hospital-based stroke registry comprising 252 patients treated with IV tissue plasminogen activator (tPA). The fasting status of the patients was unknown. Favourable outcome at 3 months was defined as a modified Rankin scale score <or= 2. Logistic regression analysis was performed with adjustment for possible confounders. Low density lipoprotein (LDL), total cholesterol levels, and statin use were not associated with sICH. Mean triglyceride levels were significantly higher (2.5 mmol/L vs 1.8 mmol/L, p = 0.02) and high density lipoprotein (HDL) was significantly lower (1.0 mmol/L vs 1.2 mmol/L, p = 0.03) in patients with sICH than in patients without sICH. Multivariable analysis showed that higher triglyceride levels were independently associated with sICH (OR 2.16 per mmol/ L increase, 95 % CI 1.20-3.91, p = 0.01). There was no relation between any of the lipid levels or statin use and functional outcome at 3 months. High admission triglyceride levels were independently associated with a higher risk of sICH, but were not associated with a reduced chance of a favourable functional outcome at 3 months. Total cholesterol levels, LDL levels and statin use had no influence on both the occurrence of sICH or functional outcome.


Neuroprotective profile of the multitarget drug rasagiline in Parkinson's disease.
Monoamine oxidase (MAO) inhibitors were reported to have therapeutic value in several common neurodegenerative conditions owed to their diverse pharmacological functions in neuron survival. Rasagiline (N-propargyl-1-(R)-aminoindan) is a novel, highly potent irreversible MAO-B inhibitor in the treatment of Parkinson's disease (PD). It has been demonstrated to be neuroprotective in PD model systems by preventing the formation of reactive oxygen species derived from prevention of derived from oxidation of dopamine by MAO-B and via an antiapoptotic action, which appears to be independent of MAO-B inhibition and related to its embedded N-propargyl moiety. This review reflects on earlier and present evidence supporting a role for rasagiline as a neuroprotective molecule in the treatment of PD.


Radiation enhancement by the combined use of topoisomerase I inhibitors, RFS-2000 or CPT-11, and topoisomerase II inhibitor etoposide in human lung cancer cells.
We have tested the camptothecin analogs, RFS-2000 or CPT-11, in combination with both etoposide and ionizing radiation in vitro to examine the radiation enhancing potential of topoisomerase I plus topoisomerase II (Topo I+Topo II) inhibition in human cancer cells. H460 human lung carcinoma cells were plated and treated with 10nM RFS-2000 or 4.5microM CPT-11 for 4h. Cells were then irradiated with various doses and treated with 1microM etoposide for 1.5h. Cell survival and sublethal damage recovery (SLDR) were determined by clonogenic assay. 7-aminoactinomycin D (7-AAD) staining and flow cytometry were used to analyze cell viability/apoptosis after combined treatment of drugs with radiation. Survival experiments showed radiation dose enhancement ratios (DER) of 1.26, 1.34, and 1.63 for RFS-2000, etoposide, and RFS-2000 plus etoposide, respectively; the corresponding DER values were 1.30, 1.39, and 1.65 for CPT-11, etoposide, and CPT-11 plus etoposide. The analysis of cell viability/apoptosis using 7-AAD staining and flow cytometry showed an additive effect. Greater inhibition of SLDR was observed with RFS-2000 plus etoposide than with either agent separately, but CPT-11 plus etoposide showed a more modest effect upon SLDR. These data show that the combination of Topo I inhibitors, RFS-2000 or CPT-11 plus Topo II inhibitor etoposide, is a more effective radiation enhancer than either agent alone in human lung cancer cells. The mechanism of radiation enhancement may involve inhibition of SLDR with RFS-2000 plus etoposide, but other mechanisms may be involved in the combined treatment including CPT-11.


[Treatment of recurrent neuroblastoma in childhood with whole body thermochemotherapy].
More than 30% of the children suffering from an advanced solid tumour disease or tumour recurrence cannot be cured despite intensive oncological treatment. A new possible therapy is the application of whole-body hyperthermia in childhood in combination with chemotherapy and radiation treatment. The fundamental principles and the method of the whole-body thermochemotherapy are briefly explained. The treatment of one patient with a neuroblastoma recurrence is reported as a clinical example for the effectiveness of whole-body thermochemotherapy in childhood and the course of therapy is discussed.


Results of a cooperative educational program to improve prostate pathology reports among patients undergoing radical prostatectomy.
The information contained in pathology reports of radical prostatectomy specimens is critically important to treating physicians for the selection of adjuvant therapy, the evaluation of therapy, estimating prognosis, and analyzing outcomes. This information is also important to patients and their families. The first phase of this study consisted of a retrospective chart review of 554 cases of radical prostatectomy (ICD-9-CM procedure code of 60.5) in New York State for the second six-month period of 1996. This review focused on ten elements (quality indicators): submission of a frozen section, location of the adenocarcinoma, proportion of specimen involved by adenocarcinoma, perineural involvement, vascular involvement, seminal vesicle status, periprostate fat status, number of nodes submitted, status of nodes, and PIN (prostate intra-epithelial neoplasia). The second phase of this project consisted of an educational feedback program involving the directors of pathology laboratories in all hospitals in New York State. A post-intervention review of the medical charts of all male Medicare patients discharged from New York State acute care hospitals with the ICD-9-CM procedure code of 60.5 (radical prostatectomy) was conducted for the six-month period February 1 through July 31, 1999. A total of 304 charts were reviewed. Performance on the ten indicators in the first phase of the study varied from 14.8% (periprostate fat status) to 85.9% (seminal vesicle involvement). Performance for all hospitals was 50% for four quality indicators and less than 70% for seven. Post-intervention improvements in performance occurred with nine of the ten quality indicators. These improvements ranged from 1.4% (status of lymph nodes submitted) to 23.9% (proportion of specimen involved by adenocarcinoma). The results of this study demonstrate that the issues identified in the baseline with radical prostatectomy pathology reports were amenable to a cooperative educational intervention.


Advanced structural and functional MRI in childhood epilepsies.
New noninvasive MR imaging techniques are currently deeply changing the exploration of epileptic and functional networks in childhood epilepsies, as well as of the normally developing brain. While DTI can be used to look at the anatomical connectivity and at the microstructural changes that reflect the organization of an epileptic network, in addition to other techniques such as SPECT and PET, functional MRI is nowadays used routinely in the presurgical planning of focal epilepsies to assess the cortical organization of motor and language networks, helping to select surgical patients and plan the resection. Precise and robust motor mapping can be obtained in children comparably to adults. The assessment of language dominance by fMRI has reduced the need for invasive techniques such as the Wada test, provided age-related paradigms are being used in cooperating children (from 5 to 6 years of developmental age, with IQs of at least 60, and without behavioral disorders). Recent data indicate that the localizing value of language fMRI might be good when compared to cortical stimulation, and memory fMRI is emerging in children. However, invasive techniques are still necessary in difficult cases with high risk of postoperative deficit.


Antigen-stimulated CD4 T cell expansion can be limited by their grazing of peptide-MHC complexes.
It was recently shown that the expansion of CD4(+) T cells during a primary immune reaction to a peptide from cytochrome c decreases ~0.5 log for every log increase in the number of cognate precursor cells, and that this remains valid over more than four orders of magnitude (Quiel et al. 2011. Proc. Natl. Acad. Sci. USA. 108: 3312-3317). This observed "power law" was explained by a mechanism where nondividing mature T cells inhibit the proliferation of less-differentiated cells of the same specificity. In this article, we interpret the same data by a mechanism where CD4(+) T cells acquire cognate peptide-MHC (pMHC) complexes from the surface of APCs, thereby increasing the loss rate of pMHC. We show that a mathematical model implementing this "T cell grazing" mechanism, and having a T cell proliferation rate that is determined by the concentration of pMHC, explains the data equally well. As a consequence, the data no longer unequivocally support the previous explanation, and the increased loss of pMHC complexes on APCs at high T cell densities is an equally valid interpretation of this striking data.


An Update on the Treatment and Follow-up of Patients with Primary Biliary Cholangitis.
Primary biliary cholangitis (PBC) is an autoimmune liver disease characterized by chronic granulomatous lymphocytic cholangitis of the small bile ducts. PBC was a leading indication for liver transplant in the United States; with early diagnosis and treatment, the majority of patients with PBC have a normal life expectancy. Pathogenesis involves inflammatory damage of bile duct epithelium secondary to innate and adaptive immune responses, and toxicity from accumulated bile acids. Cholestasis and disease progression can lead to cirrhosis. Extrahepatic complications include dyslipidemia, metabolic bone disease, and fat-soluble vitamin deficiency. Ursodeoxycholic acid is a well-established therapy. Novel targeted therapeutics are being developed.


Differential responsiveness to a parenting intervention for mothers in substance abuse treatment.
This study examines the relationship between levels of psychological distress in substance-dependent mothers and their differential response to a dyadic parent-child intervention. A sample of 66 mothers who were receiving treatment for substance abuse, as well as a simultaneous parenting intervention, were interviewed pre and post-treatment on measures of psychological distress, adult and child trauma history, parental reflective functioning, and child social-emotional development. Additionally, clinicians provided assessments of the parent-child relationships. As anticipated, trauma histories for mothers and children, children's social emotional development, and parental reflective functioning were associated with aspects of maternal psychological distress. Kruskal-Wallis and subsequent Wilcoxson signed rank tests revealed that women with highest levels of baseline psychological distress showed significant improvements in psychological functioning post-treatment while women with moderately elevated levels of psychological distress did not. Women who were most distressed at baseline showed increased levels of parental reflective functioning post-treatment while women with moderate and lower levels of baseline psychological distress showed improvements on clinician-rated assessments of parent-child relationships. Chi Square analyses showed that parents who endorsed the highest levels of distress at baseline reported that their children's risk status regarding social-emotional development decreased post-treatment. Despite similarities in substance dependence, mothers in this sample had different needs and outcomes in the context of this parenting intervention due to variation in mental health. Given this variation, parenting interventions for substance-dependent mothers need to account for the individual differences in levels of psychological distress.


Smartphone Biosensor With App Meets FDA/ISO Standards for Clinical Pulse Oximetry and Can Be Reliably Used by a Wide Range of Patients.
Millions of smartphones contain a photoplethysmography (PPG) biosensor (Maxim Integrated) that accurately measures pulse oximetry. No clinical use of these embedded sensors is currently being made, despite the relevance of remote clinical pulse oximetry to the management of chronic cardiopulmonary disease, and the triage, initial management, and remote monitoring of people affected by respiratory viral pandemics, such as severe acute respiratory syndrome coronavirus 2 or influenza. To be used for clinical pulse oximetry the embedded PPG system must be paired with an application (app) and meet US Food and Drug Administration (FDA) and International Organization for Standardization (ISO) requirements. Does this smartphone sensor with app meet FDA/ISO requirements? Are measurements obtained using this system comparable to those of hospital reference devices, across a wide range of people? We performed laboratory testing addressing ISO and FDA requirements in 10 participants using the smartphone sensor with app. Subsequently, we performed an open-label clinical study on 320 participants with widely varying characteristics, to compare the accuracy and precision of readings obtained by patients with those of hospital reference devices, using rigorous statistical methodology. "Breathe down" testing in the laboratory showed that the total root-mean-square deviation of oxygen saturation (Spo2) measurement was 2.2%, meeting FDA/ISO standards. Clinical comparison of the smartphone sensor with app vs hospital reference devices determined that Spo2 and heart rate accuracy were 0.48% points (95% CI, 0.38-0.58; P < .001) and 0.73 bpm (95% CI, 0.33-1.14; P < .001), respectively; Spo2 and heart rate precision were 1.25 vs reference 0.95% points (P < .001) and 5.99 vs reference 3.80 bpm (P < .001), respectively. These small differences were similar to the variation found between two FDA-approved reference instruments for Spo2: accuracy, 0.52% points (95% CI, 0.41-0.64; P < .001) and precision, 1.01 vs 0.86% points (P < .001). Our findings support the application for full FDA/ISO approval of the smartphone sensor with app tested for use in clinical pulse oximetry. Given the immense and immediate practical medical importance of remote intermittent clinical pulse oximetry to both chronic disease management and the global ability to respond to respiratory viral pandemics, the smartphone sensor with app should be prioritized and fast-tracked for FDA/ISO approval to allow clinical use. ClinicalTrials.gov; No.: NCT04233827; URL: www.clinicaltrials.gov.


Visceral hypersensitivity in female but not in male serotonin transporter knockout rats.
Visceral hypersensitivity occurs in irritable bowel syndrome (IBS), particularly in women. Serotonin signaling, including reduced serotonin transporter (SERT) expression, may be disrupted in IBS patients. We studied SERT gene knockout (KO) rats to determine if they exhibited sex-related alterations in visceral sensitivity. We measured serotonin in the colonic mucosa using HPLC and amperometric microelectrode techniques. Visceral sensitivity was assessed using the electromyographic visceromotor response (VMR) in response to colorectal balloon distention (CRD). We studied the electrophysiologic properties of colon projecting sensory neurons in vitro using whole-cell recordings. Mucosal serotonin levels were not different among male and female WT and SERT KO rats. Serotonin oxidation currents in vitro were larger (P < 0.05) in tissues from male and female SERT KO compared with WT rats. Oxidation currents in male and female WT, but not SERT KO, rats were increased (P < 0.05) by the SERT inhibitor fluoxetine (1 μmol L(-1) ). The VMR to CRD was increased in female but not in male SERT KO rats (P < 0.05); this response varied with the estrous cycle. Colon projecting sensory neurons from female SERT KO rats fired more action potentials compared with neurons from female WT rats. There were no differences in action potential firing in neurons from male WT and SERT KO rats. Increased colonic extracellular serotonin in female SERT KO rats is associated with visceral hypersensitivity and hyperexcitability of colon projecting sensory neurons. The SERT KO rat is a model for studying interactions between serotonin, sex and visceral sensation.


Interference of salts used on aqueous two-phase systems on the quantification of total proteins.
In this study the interference of potassium phosphate, sodium citrate, sodium chloride and sodium nitrate salts on protein quantification by Bradford's method was assessed. Potassium phosphate and sodium citrate salts are commonly used in aqueous two-phase systems for enzyme purification. Results showed that the presence of potassium phosphate and sodium citrate salts increase the absorbance of the samples, when compared with the samples without any salt. The increase in absorptivity of the solution induces errors on protein quantification, which are propagated to the calculations of specific enzyme activity and consequently on purification factor. The presence of sodium chloride and sodium nitrate practically did not affect the absorbance of inulinase, probably the metals present in the enzyme extract did not interact with the added salts.


Effects of AY 9944 on low density lipoprotein metabolism in cultured human fibroblasts.
Treatment of cultured human fibroblasts with the hypocholesterolemic drug AY 9944 resulted in a marked increase in low density lipoprotein internalization and degradation for concentrations up to 5 X 10(-6)M. Low density lipoprotein binding was less affected. Concentrations above 5 X 10(-6)M resulted in a relative decrease in low density lipoprotein degradation, whereas binding and internalization plateaued. The stimulation of low density lipoprotein internalization took place within the first hours of incubation of cells with the drug, which suggests a direct effect on the cell membrane. Such phenomenon could account at least partially for the hypocholesterolemic effect of the drug, besides its inhibitory effect on 7-dehydrocholesterol reductase.


Enhanced lignin biodegradation by a laccase-overexpressed white-rot fungus Polyporus brumalis in the pretreatment of wood chips.
The laccase gene of Polyporus brumalis was genetically transformed to overexpress its laccase. The transformants exhibited increased laccase activity and effective decolorization of the dye Remazol Brilliant Blue R than the wild type. When the transformants were pretreated with wood chips from a red pine (softwood) and a tulip tree (hardwood) for 15 and 45 days, they showed higher lignin-degradation activity as well as higher wood-chip weight loss than the wild type. When the wood chips treated with the transformant were enzymatically saccharified, the highest sugar yields were found to be 32.5 % for the red pine wood and 29.5 % for the tulip tree wood, on the basis of the dried wood weights, which were 1.6-folds higher than those for the wild type. These results suggested that overexpression of the laccase gene from P. brumalis significantly contributed to the pretreatment of lignocellulose for increasing sugar yields.


Use of recombinant factor VIIa in the management of severe bleeding episodes in patients with Bernard-Soulier syndrome.
Bernard-Soulier syndrome (BSS) is a rare congenital platelet disorder characterized by defective platelet adhesion and manifested by spontaneous and often profuse bleeding. Recombinant factor VIIa (rFVIIa) is a haemostatic agent licensed for the treatment of bleeding episodes in patients with haemophilia and inhibitors, which may represent a low-risk alternative to existing therapies in the management of patients with BSS. Here, we describe the use of rFVIIa for the treatment of three severe bleeding episodes in two patients with BSS. Data were extracted by automated searching of the international, Internet-based registry http://www.haemostasis.com . Patient 1, a 24-year-old woman, was admitted with severe epistaxis and hypotension. The diagnosis of BSS was confirmed by macrothrombocytopenia, absence of ristocetin-induced platelet agglutination (RIPA) and absence of glycoprotein (GP) Ibalpha and IX on the platelet surface. Epsilon aminocaproic acid (EACA; two 50-mg/kg doses), packed red blood cells (PRBCs, 2 U) and platelets (30 U) failed to control the bleeding and, after 13 h, three bolus doses of rFVIIa (90 microg/kg body weight) and a third dose of EACA were administered; bleeding stopped after the third dose of rFVIIa. Patient 2, a 15-year-old girl, initially presented with severe menorrhagia. A lack of RIPA and severe deficiency of GPIbalpha on the platelet surface confirmed the diagnosis of BSS. EACA and fresh-frozen plasma did not control the haemorrhage, but two bolus doses of rFVIIa (98 microg/kg body weight) resulted in a marked decrease in bleeding. On second admission, patient 2 had severe epistaxis and mild menorrhagia. Two rFVIIa doses (98 and 122.5 microg/kg body weight) were given, and the bleeding stopped. No adverse events were reported in these cases. These three admissions highlight the potential of rFVIIa for the treatment of severe bleeds in patients with BSS.


Beyond antibiotics: recent developments in the diagnosis and management of nontuberculous mycobacterial infection.
Nontuberculous mycobacteria (NTM) pulmonary disease represents a significant clinical challenge with suboptimal therapy and increasing prevalence globally. Although clinical practice guidelines seek to standardise the approach to diagnosis and treatment of NTM disease, a lack of robust evidence limits their utility and significant variability exists in clinical practice. Here we walk through some novel approaches in diagnosis and therapy that are under development to tackle a disease where traditional strategies are failing. To recognise the growing prevalence and importance of NTM pulmonary disease globally.To identify shortfalls in current diagnostic and therapeutic strategies, and highlight the challenges that must be addressed in future research and development efforts.To appreciate the role of novel therapeutic approaches such as immunomodulation of host defence, and to explore some examples of burgeoning therapies.


The ANZROD model: better benchmarking of ICU outcomes and detection of outliers.
To compare the impact of the 2013 Australian and New Zealand Risk of Death (ANZROD) model and the 2002 Acute Physiology and Chronic Health Evaluation (APACHE) III-j model as risk-adjustment tools for benchmarking performance and detecting outliers in Australian and New Zealand intensive care units. Data were extracted from the Australian and New Zealand Intensive Care Society Adult Patient Database for all ICUs that contributed data between 1 January 2010 and 31 December 2013. Annual standardised mortality ratios (SMRs) were calculated for ICUs using the ANZROD and APACHE III-j models. They were plotted on funnel plots separately for each hospital type, with ICUs above the upper 99.8% control limit considered as potential outliers with worse performance than their peer group. Overdispersion parameters were estimated for both models. Overall fit was assessed using the Akaike information criterion (AIC) and Bayesian information criterion (BIC). Outlier association with mortality was assessed using a logistic regression model. The ANZROD model identified more outliers than the APACHE III-j model during the study period. The numbers of outliers in rural, metropolitan, tertiary and private hospitals identified by the ANZROD model were 3, 2, 6 and 6, respectively; and those identified by the APACHE III-j model were 2, 0, 1 and 1, respectively. The degree of overdispersion was less for the ANZROD model compared with the APACHE III-j model in each year. The ANZROD model showed better overall fit to the data, with smaller AIC and BIC values than the APACHE III-j model. Outlier ICUs identified using the ANZROD model were more strongly associated with increased mortality. The ANZROD model reduces variability in SMRs due to casemix, as measured by overdispersion, and facilitates more consistent identification of true outlier ICUs, compared with the APACHE III-j model.


Increased self-administration of d-amphetamine by rats pretreated with metergoline.
Rats trained to self-administer d-amphetamine were pretreated with metergoline, a long-acting 5-hydroxytryptaminergic antagonist, and immediately placed in self-administration cages for 8 hours. During the first 3 hours after metergoline the normal pattern of d-amphetamine self-administration was unaltered, but thereafter the rate of self-injections was increased. Between 4 and 6 hr the self-injections in metergoline-treated rats were increased in a regular fashion and subsequently (7-8 hr) in a stereotyped manner, i.e., rapid bursts of lever presses with little space between injections. In amphetamine-naive rats the levels of striatal and nucleus accumbens dopamine metabolites, dihydroxyphenylacetic acid and homovanillic acid, rose with time after metergoline injection. Levels of 5-hydroxyindoleacetic acid remained unchanged in these brain areas. The neurochemical results suggest a correlation between the dopaminergic actions of metergoline and d-amphetamine self-administration.


Computerized tomography and nuclear imaging of the liver: a comparative study in 83 cases.
This study was performed to comparatively assess the diagnostic accuracy of computerized tomography (CT) and nuclear liver-scanning in detecting and defining circumscript and diffuse liver diseases in 83 patients. Presence or absence of liver diseases was assessed based on the results of invasive diagnostic procedures such as biopsy, laparoscopy, laparotomy, and/or autopsy. The percentage of true negative diagnoses was 94% for CT and 91% for static gamma-imaging (n = 33). With a rate of 94% true positive diagnoses, CT proved to be superior to gamma imaging with radiocolloids (81% true positives) in diagnosing circumscript liver diseases (n = 31). In addition. CT was superior to nuclear imaging regarding discrimination of number and size of space-occupying lesions within the liver. In contrast to nuclear screening, CT scans were pathognomonic to some circumscript liver diseases such as cysts, metastases, and perhaps echinococciasis. This was also true for obstructive jaundice. Nuclear imaging, because it reflects a sort of liver function, was superior with cirrhosis, whereas CT showed only alterations in the size and shape of the liver and spleen.


Enhanced risk assessment for primary coronary heart disease events by maximal exercise testing: 10 years' experience of Seattle Heart Watch.
A 10 year prospective community practice study in Seattle of risk of primary morbidity (defined by hospital admission) and mortality due to coronary heart disease in 3,611 men and 547 women initially free of clinical manifestations of this disease revealed a crude incidence of 202 coronary heart disease events, or 4.9% in 6.1 +/- 2.6 years of follow-up. The case fatality rate was 16.8%. Stratification by clinical classification of asymptomatic healthy persons versus patients with atypical chest pain syndrome (not angina pectoris) and hypertension (as classified by physicians) showed an incidence rate of primary events due to coronary heart disease of 2.9, 5.5 (not significant) and 10.0% (p less than 0.001), respectively. Identification of conventional risk factors is known to be important for risk assessment. However, the presence of any conventional risk factor, in conjunction with two or more selected maximal exercise predictors (which vary with the clinical classification) at enrollment, substantially increased the cumulative 6 year incidence rate to 24.3, 15.5 and 33.3% in asymptomatic healthy men, patients with atypical chest pain syndrome and hypertensive patients, respectively. Observation of the exercise predictors in the absence of conventional risk factors increased the risk much less, suggesting that the use of maximal exercise testing for risk assessment in those with no clinical manifestations of disease might be limited to persons with one or more conventional risk factors.


Exploration of wellbeing in entering first year doctor of pharmacy students.
The purpose of this study was to assess wellbeing in entering first-year student pharmacists beginning their doctor of pharmacy degree program. This was a mixed-methods study conducted in entering first-year student pharmacists during their pharmacy school orientation. After their wellbeing orientation session, students were asked to complete a voluntary survey that asked students to rate their current level of wellbeing according to the Warwick-Edinburgh Mental Wellbeing Scale (WEMWBS). Students also wrote a reflection related to their wellbeing and perceptions. Qualitative analysis was completed for student responses to reflection questions to identify recurring themes. One hundred thirty-one students attended the wellbeing orientation session and completed the reflection assignment. Of those, 87 (66.4%) completed the voluntary quantitative survey. On average, first-year student pharmacists indicated having a moderate level of wellbeing based on WEMWBS scores. Major themes that emerged as most influential on student pharmacist wellbeing included sense of optimism/self-care, social isolation and emotional connectedness, and uncertainty/worry/anxiety. Entering student pharmacists had slightly lower than average levels of wellbeing based on WEMWBS scores. Pharmacy programs should continue to consider the importance of variables that impact student wellbeing (e.g., promotion of self-care, mental health, social and emotional connectedness).


Application of polysaccharides for the encapsulation of beneficial microorganisms for agricultural purposes: A review.
Intensive farming practices have increased the consumption of chemical-based pesticides and fertilizers thereby creating health issues for humans and animals and also causing a deterioration in the natural ecosystem. The promotion of biomaterials synthesis could potentially lead to the replacement of synthetic products and improve soil fertility, protect plants from pathogen attacks, and enhance the productivity of the agricultural sector resulting in less environmental pollution. Microbial bioengineering involving the use and improvement of encapsulation using polysaccharides has the required potential to address environmental issues and promote green chemistry. This article describes various encapsulation techniques and polysaccharides which have an immense applicable capability to encapsulate microbial cells. The review elucidates the factors that may result in a reduced viable cell count during encapsulation, particularly using the spray drying method, where a high temperature is required to dry the suspension, this may damage the microbial cells. The environmental advantage of the application of polysaccharides as carriers of beneficial microorganisms, which do not pose a risk for soil due to their full biodegradability, was also shown. The encapsulated microbial cells may assist in addressing certain environmental problems such as ameliorating the unfavourable effects of plant pests and pathogens, and promoting agricultural sustainability.


Notchplasty alters knee biomechanics after anatomic ACL reconstruction.
The aims of this study were (1) to study the biomechanics of single-bundle anatomic ACL reconstructed knees with and without notchplasty using a robotic testing system and (2) to determine if there would be a difference between performing a small or large notchplasty. Fifteen fresh-frozen specimens were used in this study. The ACL reconstruction (ACL-R) was performed using an anatomic single-bundle technique with the 8 mm soft tissue graft fixed at 30° with suspensory fixation on the femoral side and a screw and washer on the tibial side. The notchplasty was then created with a burr. The following knee states were compared: (1) ACL-R, (2) ACL-R with a small (3 mm) notchplasty, and (3) ACL-R with a large (6 mm) notchplasty. Four loading conditions were applied: (1) an anterior drawer with an 89 N anterior tibial load, (2) simulated pivot-shift loading, (3) a 5 Nm internal rotational moment, and (4) a 5 Nm external rotational moment. Under anterior tibial loading, anterior tibial translation increased, and graft force decreased significantly after ACL-R + 3 mm notchplasty and ACLR + 6 mm notchplasty compared to ACL-R alone at FE, 15° and 30° of knee flexion. There were no changes in either anterior tibial translation or graft force under simulated pivot-shift loading, internal rotational moment, or external rotational moment. When added to anatomic ACL reconstruction, notchplasty increased anterior tibial translation and decreased graft forces during low knee flexion angles. There was no difference between a small and large notchplasty. The findings of this study are clinically relevant as the purpose of anatomic ACL reconstruction is to restore normal knee laxity, and while notchplasty may be helpful in avoiding graft impingement and improving visualization, removing even 3 mm of bone leads to biomechanical changes.


SARS-CoV-2 Vaccination IgG Antibody Responses in Patients with Hematologic Malignancies in a Myeloid Enriched Cohort: A Single Center Observation.
Patients diagnosed with hematologic malignancies are at increased risk for severe SARS-CoV-2 infection. We evaluated the serological IgG response following two doses of the SARS-CoV-2 vaccine in patients with hematologic malignancies. Patients treated at UT Southwestern Medical Center with a diagnosis of a myeloid or lymphoid neoplasm were included. SARS-CoV-2 vaccination response was defined as a positive quantifiable spike IgG antibody titer. Sixty patients were included in the study and 60% were diagnosed with a myeloid neoplasm. The majority (85%) of the patients with a myeloid malignancy and 50% of the patients with a lymphoid malignancy mounted a serological response after receiving two doses of the vaccine. Vaccination should be offered irrespective of ongoing treatment or active disease. Findings require validation in a larger cohort of patients.


A quality improvement project to decrease emergency department and medical intensive care unit transfer times.
To reduce transfer time of critically ill patients from the emergency department (ED) to the medical intensive care unit (MICU). A prospective, observational study assessing preimplementation and postimplementation of quality improvement interventions in a tertiary academic medical center. A team of frontline health care professional including ED, MICU, and supporting services using the clinical microsystems approach mapped out existing practice patterns, determined causes for delays, and used the Plan-Do-Study-Act to test changes. Measurements and Main Results The team identified multiple issues that contributed to delays. These included poor coordination between transport services, respiratory therapy, and nursing in transferring patients from the ED as well delays in identification and transfer of stable MICU patients. These interventions reduced transfer time from 4.2 (3.4-5.7) hours to 2.2 (1.4-3.1) hours (median [interquartile range]; P<.001). Hospital length of stay decreased from 9.9±9 to 8.3±7 days (P<.03). A team made up of frontline health care professionals using a structured quality improvement process and implementing multifaceted, multistage interventions, reduced transfer delays, and length of stay. Added benefits included engagement among members of the 2 microsystems and a more cohesive approach to patient care.


Often forgotten manifestations of systemic sclerosis.
Many clinical manifestations of systemic sclerosis (scleroderma) often go unrecognized; yet they can cause significant morbidity and are challenging to manage. This article discusses osteolysis, avascular necrosis of the wrist, oral manifestations, erectile dysfunction, pharyngeal weakness, fecal incontinence, nonscleroderma renal disease, liver disease, thyroid disease, and neurological disease in the scleroderma patient.


[Demands for preserved blood and blood transfusions in planned operations].
An analysis is described which deals with the relation existing between those amounts of stored blood which are demanded and used in serological cross tests on the one hand and that transfused stored blood used in operations which can be planned in selected clinics on the other hand by accounting for the demanding parameters of 3 stored blood items and less and 4 stored blood items and more.


Dual-color click beetle luciferase heteroprotein fragment complementation assays.
Understanding the functional complexity of protein interactions requires mapping biomolecular complexes within the cellular environment over biologically relevant time scales. Herein, we describe a set of reversible multicolored heteroprotein complementation fragments based on various firefly and click beetle luciferases that utilize the same substrate, D-luciferin. Luciferase heteroprotein fragment complementation systems enabled dual-color quantification of two discrete pairs of interacting proteins simultaneously or two distinct proteins interacting with a third shared protein in live cells. Using real-time analysis of click beetle green and click beetle red luciferase heteroprotein fragment complementation applied to β-TrCP, an E3-ligase common to the regulation of both β-catenin and IκBα, GSK3β was identified as a candidate kinase regulating IκBα processing. These dual-color protein interaction switches may enable directed dynamic analysis of a variety of protein interactions in living cells.


Glacial lake inventory and lake outburst potential in Uzbekistan.
Climate change has been shown to increase the number of mountain lakes across various mountain ranges in the World. In Central Asia, and in particular on the territory of Uzbekistan, a detailed assessment of glacier lakes and their evolution over time is, however lacking. For this reason we created the first detailed inventory of mountain lakes of Uzbekistan based on recent (2002-2014) satellite observations using WorldView-2, SPOT5, and IKONOS imagery with a spatial resolution from 2 to 10m. This record was complemented with data from field studies of the last 50years. The previous data were mostly in the form of inventories of lakes, available in Soviet archives, and primarily included localized in-situ data. The inventory of mountain lakes presented here, by contrast, includes an overview of all lakes of the territory of Uzbekistan. Lakes were considered if they were located at altitudes above 1500m and if lakes had an area exceeding 100m2. As in other mountain regions of the World, the ongoing increase of air temperatures has led to an increase in lake number and area. Moreover, the frequency and overall number of lake outburst events have been on the rise as well. Therefore, we also present the first outburst assessment with an updated version of well-known approaches considering local climate features and event histories. As a result, out of the 242 lakes identified on the territory of Uzbekistan, 15% are considered prone to outburst, 10% of these lakes have been assigned low outburst potential and the remainder of the lakes have an average level of outburst potential. We conclude that the distribution of lakes by elevation shows a significant influence on lake area and hazard potential. No significant differences, by contrast, exist between the distribution of lake area, outburst potential, and lake location with respect to glaciers by regions.


Cardiovascular disease and its management in children and adults undergoing hematopoietic stem cell transplantation.
Hematopoietic stem cell transplantation (HSCT) is a potentially curative treatment for many malignancies, hemoglobinopathies, metabolic diseases, bone marrow failure syndromes, and primary immune deficiencies. Despite the significant improvement in survival afforded by HSCT, the therapy is associated with major short and long-term morbidity and mortality. Cardiovascular complications such as cardiomyopathy, arrhythmias, pulmonary hypertension, and pericardial effusions are increasingly recognized as potential outcomes following HSCT. The incidence of cardiac complications is related to various factors such as age, co-morbid medical conditions, whether patients received cardiotoxic chemotherapy prior to HSCT, the type of HSCT (autologous versus allogeneic), and the specific conditioning regimen. Thus, the cardiovascular evaluation has become a core component of the pre-transplant assessment, however, the practice differs from center to center as national guidelines and contemporary high-quality studies are lacking. We review the incidence of cardiotoxicity in pediatric and adult HSCT, potential mechanisms of injury, and effects on long-term outcomes. We also discuss the possible therapeutic approaches when disease arises, as well as the indications and need for surveillance before, during, and after transplantation.


Self-assembled micellar nanoparticles of a novel star copolymer for thermo and pH dual-responsive drug release.
An amphiphilic star block copolymer comprised of a hydrophobic PMMA block and a hydrophilic tri-arm poly(NIPAAm-co-DMAEMA) block was synthesized by copolymerization of NIPAAm and DMAEMA, with Ce(4+) ions and tris(hydroxymethyl)methylamine as a redox initiatory system. The star copolymer undergoes self-assembly to the micellar nanoparticles with a core-shell structure and the thermo/pH dual-response, originated from the thermo-sensitivity of PNIPAAm and the pH-sensitivity of PDMAEMA. A fluorescence probe study showed the pH-dependent low CMCs (7.5 to 11.2 mg/L) of the micelles, confirming the formation of stable micelles. Morphological investigations showed that the blank and drug-loaded micelles both had spherical and uniform shapes. The sizes of the blank and drug-loaded nanoparticles were between 80 and 120 nm, depending on the given pH. The LCSTs of the star copolymer were determined to be 32 degrees C, 36.6 degrees C and 39.5 degrees C, corresponding to pH 5, pH 7.4 and pH 9, respectively, demonstrating a pH-dependent thermo-response. As a drug delivery, the micellar nanoparticles showed the dual-responsive release profiles in vitro, which were confirmed by the drug release studies. The obtained results showed the thermo-triggered accelerated release at pH 7.4, and the pH-triggered accelerated release at 37 degrees C, indicating the micelles nanoparticles would be a promising site-specific drug delivery for enhancing the accumulation of drug in targeting pathological areas.


Antimicrobial resistance of Klebsiella pneumoniae in a Saudi Arabian hospital: results of a 6-year surveillance study, 1998-2003.
There are few data regarding the prevalence and trends of antibiotic resistance to Klebsiella pneumoniae in Saudi Arabia over time. Thus, we evaluated the prevalence and the trends in antibiotic resistance of K. pneumoniae at the Saudi Aramco Medical Services Organization over a 6-year period. This was a retrospective study of the in vitro pattern and trends of antibiotic resistance of K. pneumoniae from 1998 to 2003. A total of 3070 distinct isolates of K. pneumoniae were analyzed. Hospital-acquired isolates were more resistant to the tested antibiotics than the outpatient isolates. The resistance rates to cefazolin, trimethoprim-sulfamethoxazole, and ciprofloxacin were 10.8% (n = 79/730), 5% (n = 103/2093), and 15.8% (n = 93/586) for hospital-acquired isolates; and 11% (n = 216/1964), 9.6% (n = 60/624), and 4.4% (n = 68/1526) for outpatient isolates. Resistance to ceftriaxone and ceftazidime was detected in 5.6% (n = 37/659) and 13.8% (n = 24/174) of hospital-acquired isolates and in 1% (n = 17/1713) and 2.7% (n = 6/219) of outpatient isolates, respectively. All tested isolates were susceptible to imipenem. Resistance to three or more classes of antibiotics was present in 1.7% (n = 8/468) of the hospital-acquired isolates and in 0.6% (n = 9/1389) of the outpatient isolates. The data showed increased resistance rates of hospital-acquired isolates of K. pneumoniae to ceftriaxone, gentamicin, and ciprofloxacin; the data also showed that hospital-acquired, rather than outpatient isolates, were more likely to be resistant to multiple antibiotics.


Weight gain-based targeted selective treatments (TST) of gastrointestinal nematodes in first-season grazing cattle.
A three-year trial was performed in south-western Sweden to compare animal performance and levels of parasite control in three grazing groups, each with 18-24 first-season grazing (FSG) calves in similar set-stocked pasture enclosures. These groups were subjected to: (1) no parasite control (NT), (2) monthly repeated doramectin (Dectomax(®)) injections (SP), or (3) targeted selective weight gain-based anthelmintic treatments (TST) but only when individual calf performance was inferior to the average of the poorer 50% of those calves in group SP. In each year, weight and parasitological variables were measured at turn-out and then at predetermined intervals for 22-24 weeks during the grazing season. The dewormed calves in group SP had a higher average weight gain at housing (range 0.39-0.61 kg/day) than those in TST (0.36-0.50 kg/day), which in turn always exceeded the NT group (0.23-0.42 kg/day). This indicates that the parasite challenge in the NT group was sufficiently high to result in production loss. However, the average cumulative faecal egg counts (FEC) at housing in NT were in the range 1271-1953 eggs per gram faeces (epg) and in TST 1221-1968 epg. In contrast, parasite eggs were rarely recorded in group SP and then only during the first two years (on average 12 and 38 epg). There were also no significant differences in FEC or serum pepsinogen levels between FSG in groups NT and TST. The animals in SP received 7 doses of doramectin each year, whereas those in TST received an average of 0.5 doses. Thus, the TST approach represented a 92% reduction in anthelmintic use. The average weight gain in animals subjected to TST was always significantly lower than in animals dewormed regularly. In addition, there were no signs of short-term selection for anthelmintic resistance in the group SP animals, despite the fairly intensive use of injectable doramectin.


Utility of viscoelastic coagulation testing in liver surgery: a systematic review.
The objective of the current study was to summarize and evaluate all published evidence regarding viscoelastic testing in the field of liver surgery. A systematic search of the literature was performed using Medline/PubMed, Scopus, Cochrane Library Central, Google Scholar, and clinicaltrials.gov databases. The following keywords were used:"Thromboelastography", "Thromboelastometry", "Viscoelastic tests OR testing", "Sonoclot Devices", "Point-of-care tests OR testing", "Coagulation OR Haemostasis OR Hemostasis", "Liver OR Hepatic Surgery", "Cirrhosis." A total of 12 studies analyzing 348 patients who underwent viscoelastic testing of coagulation during liver surgery for benign or malignant diseases were included; 7 (58.3%) studies reported on the use of thromboelastography (TEG), and 5 (41.7%) reported on rotational thromboelastometry (ROTEM). Viscoelastic testing (TEG and ROTEM) identified normo-, hyper- and hypo-coagulable status in 77% (n = 268/348), 18.4% (n = 64/348), and 4.6% (n = 16/348) of patients, respectively. In contrast, conventional coagulation tests indicated normo-coagulability in 111 patients (34.2% out of 325) and hypo-coagulability in 214 (65.8% out of 325) patients following liver resection. No patient (0% out of 291) experienced postoperative hemorrhage, whereas 5.8% (n = 17/291) experienced postoperative thromboembolic events. Global viscoelastic testing may be a reasonable adjunct to conventional coagulation testing to provide a more robust assessment of the coagulation status of patients undergoing liver surgery.


A functionally defined high-density NRF2 interactome reveals new conditional regulators of ARE transactivation.
NRF2 (NFE2L2) is a cytoprotective transcription factor associated with >60 human diseases, adverse drug reactions and therapeutic resistance. To provide insight into the complex regulation of NRF2 responses, 1962 predicted NRF2-partner interactions were systematically tested to generate an experimentally defined high-density human NRF2 interactome. Verification and conditional stratification of 46 new NRF2 partners was achieved by co-immunoprecipitation and the novel integration of quantitative data from dual luminescence-based co-immunoprecipitation (DULIP) assays and live-cell fluorescence cross-correlation spectroscopy (FCCS). The functional impact of new partners was then assessed in genetically edited loss-of-function (NRF2-/-) and disease-related gain-of-function (NRF2T80K and KEAP1-/-) cell-lines. Of the new partners investigated >77% (17/22) modified NRF2 responses, including partners that only exhibited effects under disease-related conditions. This experimentally defined binary NRF2 interactome provides a new vision of the complex molecular networks that govern the modulation and consequence of NRF2 activity in health and disease.


Immediate application of negative pressure wound therapy following lower extremity flap reconstruction in sixteen patients.
Negative pressure wound therapy (NPWT) is usually applied in wound management and soft-tissue salvage after the development of complications. However, immediate postoperative application of NPWT over the flap coverage is seldom reported. We evaluate the effectiveness of immediate postoperative application of NPWT following fasciocutaneous or muscle flap coverage for lower leg reconstruction. A retrospective review of patients who underwent either fasciocutaneous or muscle flap coverage of lower leg soft-tissue defects applied with NPWT immediately after surgery was conducted in a level I trauma center. Sixteen patients, with an average age of 51.2 years, were included in the study. Nine patients had trauma-related soft-tissue loss, six had subsequent soft-tissue defects after debridement, and one had burn injury. Two patients had been treated with free anterolateral thigh flaps, 11 with pedicle flaps, and three with muscle flaps. All flaps survived except for those in two patients with venous congestion on postoperative day 1, which needed further debridement and skin grafting. Therefore, the use of immediate incisional NPWT is an alternative for wound care following flap coverage. The U-shaped design allows easy flap observation and temperature check. Furthermore, this method eliminates any concerns of vascular pedicle compression under negative pressure.


Continuous subcutaneous insulin infusion does not correspond with pregnancy outcomes despite better glycemic control as compared to multiple daily injections in type 1 diabetes - Significance of pregnancy planning and prepregnancy HbA1c.
The aim of the study was to compare pregnancy outcomes with glycemic control, total increase in insulin requirement, and body weight gain in the women with Type 1 Diabetes Mellitus (T1DM) using continuous subcutaneous insulin infusion (CSII) or multiple daily injections (MDI). This was a single center retrospective observational study involving 209 pregnant Caucasian women. Among the study participants, 95 subjects were treated with MDI and 114 patients were using CSII therapy. The primary outcomes were pregnancy results, while secondary ones were HbA1c, increase in daily dose of insulin (DDI), and body weight gain. At baseline, the CSII users were older (P = 0.0373), they were diagnosed with T1DM at a younger age (P = 0.047), and more often planned pregnancy (P = 0.032). A majority of the women were classified as class D, according to the White classification. Among the CSII users, a significantly higher proportion of the subjects in class B was noted than in the MDI users, with no differences in the proportion of the remaining White classes. Prepregnancy HbA1c was insignificantly lower in the CSII group, however, a significantly higher proportion of the CSII users reached the target value of HbA1c (P = 0.008). A prepregnancy daily dose of insulin (both total and per kg of body weight), body weight, and body mass index (BMI) did not differ between the groups. The 1st and 2nd trimester HbA1c was lower among the CSII users (6.83 ± 1.38 vs 7.52 ± 2.11%, P = 0.01 and 6.17 ± 0.9 vs 6.57 ± 1.12%, P = 0.009, respectively), while the 3rd trimester HbA1c as well as the total change in HbA1c were comparable. Neither DDI and body weight in concecutive trimesters, nor their total gestational increase, differed between the groups. The rate of pregnancy loss, such as abortions, fetal and neonatal death did not differ between the groups. As regards composite pregnancy loss, prepregnancy HbA1c was 8.41%±2.81% among the MDI cohort vs 7.22%±1.31% in the CSII users (P = 0.517). No differences were found in the gestational age at delivery, the mode of delivery, neonatal birth weight, the rate of macrosomy, LGA or SGA. A higher Apgar score was noted among the CSII users (8.63 ± 1.63 vs 8.03 ± 2.49%, P = 0.047), however, the proportion of neonates with an Apgar score lower than 7 points was similar. In the women planning pregnancy, as compared to the subjects who did not, HbA1c was significantly lower in the 1st trimester, together with a significantly higher rate of the women achieving the target HbA1c value during planning as well as in the 1st trimester. In the group of women planning pregnancy, significantly lower 1st trimester HbA1c and composite outcome of pregnancy loss were observed in the CSII users vs the MDI treated women. Lack of pregnancy planning and a high HbA1c level in the 1st trimester were independent predictors of both LGA (OR = 4.99 [95%CI 1.12-21.0], P = 0.033 and OR = 3.02 [95%CI 1.19-7.65], P = 0.019, respectively) and macrosomia (OR = 8.43 [95%CI 1.36-51.93], P = 0.021 and OR = 5.47 [95%CI 1.77-16.87], P = 0.003, respectively). The course of pregnancy and obstetric outcomes were not dependent on the mode of insulin delivery, but only on pregnancy planning and HbA1c in early pregnancy. Further studies are needed to explore more precise parameters describing both glycemic control in pregnant women as well as perinatal infant well-being.


Comparative analysis for the production of fatty acid alkyl esterase using whole cell biocatalyst and purified enzyme from Rhizopus oryzae on waste cooking oil (sunflower oil).
The petroleum fuel is nearing the line of extinction. Recent research and technology have provided promising outcomes to rely on biodiesel as the alternative and conventional source of fuel. The use of renewable source - vegetable oil constitutes the main stream of research. In this preliminary study, Waste Cooking Oil (WCO) was used as the substrate for biodiesel production. Lipase enzyme producing fungi Rhizopus oryzae 262 and commercially available pure lipase enzyme were used for comparative study in the production of Fatty Acid Alkyl Esters (FAAE). The whole cell (RO 262) and pure lipase enzyme (PE) were immobilized using calcium alginate beads. Calcium alginate was prepared by optimizing with different molar ratios of calcium chloride and different per cent sodium alginate. Entrapment immobilization was done for whole cell biocatalyst (WCB). PE was also immobilized by entrapment for the transesterification reaction. Seven different solvents - methanol, ethanol, n-propanol, n-butanol, iso-propanol, iso-butanol and iso-amyl alcohol were used as the acyl acceptors. The reaction parameters like temperature (30°C), molar ratio (1:3 - oil:solvent), reaction time (24 h), and amount of enzyme (10% mass ratio to oil) were also optimized for methanol alone. The same parameters were adopted for the other acyl acceptors too. Among the different acyl acceptors - methanol, whose reaction parameters were optimized showed maximum conversion of triglycerides to FAAE-94% with PE and 84% with WCB. On the whole, PE showed better catalytic converting ability with all the acyl acceptor compared to WCB. Gas chromatography analysis (GC) was done to determine the fatty acid composition of WCO (sunflower oil) and FAAE production with different acyl acceptors.


A clinical prototype for auditory memory span.
An initial examination of an experimental test for auditory memory span was administered to 12 children (ages 5,6 to 7,0) with moderate to severe functional articulation problems. The experimental retention test (ERT), based on a minimal-pairs, distinctive feature paradigm, correlated significantly with three indices of articulatory performance: consonantal intelligibility, total sounds in error, and total number of misarticulations. Descriptive data are presented for clinical evaluation and further test development.


[Establishing the cause of death in pneumopathies].
The article deals with determination and differential diagnosis of the cause of death in different forms of pneumopathy and mechanical asphyxia on the basis of developed morphometric method for separate evaluation of the volume of lung tissue per se, the air and pathologic contents of airways.


Uptake of 17β-estradiol and biomarker responses in brown trout (Salmo trutta) exposed to pulses.
In streams, chemicals such as 17β-estradiol (E2) are likely to occur in pulses. We investigated uptake and biomarker responses in juvenile brown trout (Salmo trutta) of 3- or 6-h pulses of concentrations up to 370 ng E2 L(-1). Uptake by the fish was estimated from disappearance of E2 from tank water. A single 6-h pulse of 370 ng E2 L(-1) increased the plasma vitellogenin concentration, liver Erα- and vitellogenin-mRNA. Exposure to 150-160 ng E2 L(-1) for 6 h increased vitellogenin in one experiment but not in another. Two 6-h pulses had a larger effect one pulse. Brown trout in the size range 24-74 g took up E2 linearly with time and exposure concentration with a concentration ratio rate of 20.2 h(-1). In conclusion, the threshold for induction of estrogenic effects in juvenile brown trout at short term pulse exposure appears to be in the range 150-200 ng E2 L(-1).


Mouse tumor-associated macrophages do not generate procoagulant activity in response to different stimuli.
Mononuclear phagocytes, an integral part of the lymphoreticular infiltrate of human and experimental tumors, might contribute to fibrin deposition within malignant tissues through the production of procoagulant activity (PCA). We have studied the PCA of tumor-associated macrophages (TAM) in 2 poorly immunogenic, metastatic murine sarcomas (mFS6 and MN/MCA1); peritoneal macrophages (PM) from tumor-bearing and control animals were also studied, as reference cell populations. PCA was evaluated by a one-stage clotting assay immediately after isolation (basal PCA) and following in vitro stimulation. Basal PCA was very low (less than 1 U/10(4) macrophages) in all cell preparations. Exposure of PM from both normal and tumor-bearing animals to bacterial endotoxin (lipopolysaccharide, LPS), phorbol myristate acetate (PMA) or the chemotactic peptide formyl-methionyl-leucyl-phenylalanine (FMLP) resulted in 10-, 7- and 3-fold increases in PCA, respectively. In contrast, TAM from mFS6 and MN/MCA1 consistently failed to generate PCA in response to different concentrations of the same stimuli. Treatment of TAM with aspirin did not affect cell unresponsiveness. Fluorescence microscopy showed that almost all PM were stained with fluorescein isothiocyanate (FITC)-LPS, while less than 10% of the TAM were stained. These data, coupled with previous evidence that TAM have a lower number of specific binding sites for phorbol esters than PM, suggest that the defective responsiveness of TAM to endotoxin, PMA and, possibly, FMLP, is due to the lack, or very low expression, of binding sites for these agents on the cell surface. The tumor environment may orient the functional status of in situ macrophages in a direction less favorable to the host.


Intraspecific variation in production of astringent phenolics over a vegetation-resource availability gradient.
The chemical constituency of flowering dogwood (Cornus florida L.) and red maple (Acer rubrum L.) foliage was analyzed over a species compositional gradient to test the hypothesis that over subtle gradients of moisture and nutrient availability production of phenolic compounds will be increased on sites of greatest stress. Calcium and nitrogen concentrations declined along the gradient in both species, while phosphorus showed a significant decline only in red maple. Lignin concentrations in both species were unrelated to the vegetation gradient, but astringent phenolics increased by 156% and 159% in dogwood and red maple, respectively. The correlation between production of polyphenolds and site quality supports previous observations that under conditions of environmental stress production of many secondary compounds is increased, and suggests that this relationship is significant over subtle environmental gradients.


The inhibitory effects of a dermal extract upon granulation tissue.
Injection of a water-soluble dermal extract into adult rats resulted in depression of DNA synthesis in granulation tissue at 3 different sites of injury, but not in epithelium. This suggests that connective tissue proliferation may be controlled in part by a chalone-like mechanism.


Quorum quenching by a type IVA secretion system effector.
Proteobacteria primarily utilize acyl-homoserine lactones (AHLs) as quorum-sensing signals for intra-/interspecies communication to control pathogen infections. Enzymatic degradation of AHL represents the major quorum-quenching mechanism that has been developed as a promising approach to prevent bacterial infections. Here we identified a novel quorum-quenching mechanism revealed by an effector of the type IVA secretion system (T4ASS) in bacterial interspecies competition. We found that the soil antifungal bacterium Lysobacter enzymogenes OH11 (OH11) could use T4ASS to deliver the effector protein Le1288 into the cytoplasm of another soil microbiome bacterium Pseudomonas fluorescens 2P24 (2P24). Le1288 did not degrade AHL, whereas its delivery to strain 2P24 significantly impaired AHL production through binding to the AHL synthase PcoI. Therefore, we defined Le1288 as LqqE1 (Lysobacter quorum-quenching effector 1). Formation of the LqqE1-PcoI complex enabled LqqE1 to block the ability of PcoI to recognize/bind S-adenosy-L-methionine, a substrate required for AHL synthesis. This LqqE1-triggered interspecies quorum-quenching in bacteria seemed to be of key ecological significance, as it conferred strain OH11 a better competitive advantage in killing strain 2P24 via cell-to-cell contact. This novel quorum-quenching also appeared to be adopted by other T4ASS-production bacteria. Our findings suggest a novel quorum-quenching that occurred naturally in bacterial interspecies interactions within the soil microbiome by effector translocation. Finally, we presented two case studies showing the application potential of LqqE1 to block AHL signaling in the human pathogen Pseudomonas aeruginosa and the plant pathogen Ralstonia solanacearum.


[Mechanisms of involvement of Na+(Li+) in the process of intracellular transmission of the trigger signal in skeletal muscles].
The data obtained suggest that Li+ can replace Na+ in transmission of triggering signal from excited surface membrane of muscle fibers onto intracellular effector systems. The participation of extracellular calcium in transmission of activation into the cell being excluded, the Ca2+-activation of the contractile apparatus and kinase-phosphorylase system in electrically stimulated muscles presumably proceeds from the induction of Ca2+ release from sarcoplasmic reticulum (SR) by transmembrane Na+- or Li+-current. The chemical specific features of Na+ and Li+ displayed at that, corroborate the hypothesis of Na+-trigger mechanism of Ca2+ release from the SR in skeletal muscle fibers of vertebrates.


Serotonin (5-HT) uptake by blood platelets in anorexia nervosa.
Platelet serotonin (5-HT) uptake was determined in 15 underweight anorexia nervosa patients and a control group of 15 healthy individuals. The Vmax (picomoles/10(8) platelets/5 min) was 424 +/- 103 in patients and 424 +/- 69 in controls. The Km was 1.19 +/- 0.2 microM in patients and 1.08 +/- 0.17 microM in controls. The differences between the groups were not significant. These findings do not support the hypothesis that serotonin metabolism is disturbed in anorexia nervosa.


The road less traveled: regulation of leukocyte migration across vascular and lymphatic endothelium by galectins.
Leukocyte entry from the blood into inflamed tissues, exit into the lymphatics, and migration to regional lymph nodes are all crucial processes for mounting an effective adaptive immune response. Leukocytes must cross two endothelial cell layers, the vascular and the lymphatic endothelial cell layers, during the journey from the blood to the lymph node. The proteins and cellular interactions which regulate leukocyte migration across the vascular endothelium are well studied; however, little is known about the factors that regulate leukocyte migration across the lymphatic endothelium. Here, we will summarize evidence for a role for galectins, a family of carbohydrate-binding proteins, in regulating leukocyte migration across the vascular endothelium and propose that galectins are also involved in leukocyte migration across the lymphatic endothelium.


Cranial fracture patterns and estimate of direction from low velocity gunshot wounds.
Cranial trauma produced by low velocity gunshot wounds is investigated in an autopsy series. In skeletonized remains with postmortem damage, or after surgical debridement, the primary internal or external beveling may become obscured, causing difficulty with the identification of entrance and exit wounds. The morphology of associated secondary and tertiary fractures based upon the mechanics of their production is discussed as a means of establishing bullet entrance and exit sites.


Paragonimus westermani infection manifesting as a pulmonary cavity and adrenal gland mass: A case report.
We report a case of Paragonimus westermani infection simultaneously affecting two separate organs that presented as both a pulmonary cavity and adrenal mass in an immunocompromised host. A 65-year-old male with a previous kidney transplant visited our clinic because of hemoptysis. Chest computed tomography (CT) showed a pulmonary cavity and right adrenal gland mass. The Aspergillus antigen titer in bronchial lavage fluid was elevated and showed positive conversion. It was necessary to differentiate lung cancer with adrenal gland metastasis from a fungal infection with an adrenal gland adenoma. Positron emission tomography CT suggested benign disease, and it was misdiagnosed as pulmonary aspergillosis based on the elevated Aspergillus antigen titer in the bronchial lavage fluid. Owing to the adverse effects of anti-fungal treatment, the patient underwent wedge resection of the lung and P. westermani was confirmed. A careful history revealed that the patient had eaten raw freshwater crabs 3 years earlier, and a test for serum antibodies to P. westermani was positive. Despite treatment with praziquantel, the adrenal mass persisted on 3-month follow-up CT. A right adrenalectomy was performed and a P. westermani infection was confirmed.


Residual biogas potential from the storage tanks of non-separated digestate and digested liquid fraction.
Biogas plants daily produce enormous volumes of digestate that can be handled in its raw form or after mechanical separation. In Italy, effluents are usually stored within aboveground, uncovered tanks, which make them potential emitters of biogas into the atmosphere. The purpose of this study was to estimate the amount of biogas emitted to the atmosphere during the storage phase of non-separated digestate and digested liquid fraction. The trials were performed at two northwest Italy 1 MWel. biogas plants. A floating system for the residual biogas recovery, and a set of three wind tunnels for NH3 emission measurement were used. The experiment demonstrated significant loss to the atmosphere for each of the gases; specifically, on average, 19.5 and 7.90 N m3 biogas MWhel.(-1) were emitted daily from the storage tanks of non-separated digestate and digested liquid fraction, respectively.


Iodine-125 brachytherapy alone for advanced primary parotid gland carcinoma.
This study aimed to evaluate the efficacy of iodine-125 (125I) brachytherapy alone for the treatment of advanced parotid gland carcinoma and to identify predictors of tumour control and patient survival. Primary parotid gland carcinoma patients (n=23) treated with 125I brachytherapy alone between 1 October 2005 and 31 July 2013 at Peking University Stomatology Hospital were enrolled in this retrospective study. All had clinical stage IV disease. The prescribed dose was 60-160Gy. The local control rate, survival rate, and predictors of the prognosis were evaluated. Adverse events related to treatment were also noted. The average follow-up time was 29 months (range 9-74 months). Among the 23 patients, six had local failure and 11 died during the follow-up period. The 1-, 3-, and 5-year overall survival rates were 87.0%, 55.4%, and 47.5%, respectively. The 1-, 3-, and 5-year progression-free survival rates were 73.9%, 47.0%, and 39.2%, respectively. The 1-, 3-, and 5-year local control rates were 82.1%, 73.9%, and 73.9%, respectively. Age and distant metastasis were independent predictors of survival, while the preoperative duration of the disease was an independent predictor of local control. The use of 125I seed brachytherapy alone for the treatment of primary parotid gland carcinoma can provide good short-term results without causing any severe side effects.


Simultaneous determination of fat-soluble vitamins A, D and E and pro-vitamin D2 in animal feeds by one-step extraction and high-performance liquid chromatography analysis.
Traditionally, alkaline saponification for the extraction of vitamins and step-wise HPLC analyses have been widely used for analysis of fat-soluble vitamins in animal feeds. The objective of present study was to develop an analytical method using one-step extraction and simultaneous determination of the vitamins A, D and E and pro-vitamin D2 in animals feeds b HPLC. Various analytical conditions were tested which included sample particle size extraction solvents, the ratio of solvent to sample, extraction approach, extraction time, N2 protection, prepurification with Sep-Pak cartridge and detection wavelength. The accuracy of the developed method has been proven by comparison with the AOAC method. The reproducibility of the developed method has been substantiated by repeated recovery experiments. The detection limit for the four vitamins was 10 ng/g of feed sample. One of the important properties of the present method is rapidity and ease of use.


The Relationship Between Body Mass Index and Depression, Anxiety, Body Image, and Eating Attitudes in Adolescents in Iran.
The aim of this study was to investigate the relationship between body mass index (BMI) and depression, anxiety, body image, and eating attitudes in 12- to 16-year-old adolescents. In this descriptive-analytical study on 437 students in Shahrekord, Iran, selected by two-step random sampling (selection of schools and students), participants were divided into normal weight (BMI: 5-85th), overweight (BMI: 85-95th), and obese (BMI >95th) groups and completed the questionnaires and data were analyzed by SPSS version 23. BMI had a positive correlation with anxiety, depression, and dysfunctional eating attitudes, and negative correlation with body image in adolescents. Mean scores of depression and anxiety in both overweight and obese groups were significantly higher than those in normal weight adolescents but scores of body image and eating attitudes were not different between overweight and normal weight groups. Obesity and overweight may have adverse effects on mental health of adolescents and more attention to psychological aspect of obesity can help us to provide better health services to overweight and obese adolescents.


Effect of glucose in dialysis fluid on antibacterial defence in the peritoneal cavity.
To study the effect of glucose concentration and dwell time of dialysis fluid on peritoneal antibacterial defence, an experimental infection with Staphylococcus aureus was induced in rats. For this purpose rats were inoculated intraperitoneally with Staphylococcus aureus at different intervals after the administration of various dialysis fluids. Twenty-four hours later the numbers of bacteria and cells in the peritoneal cavity were determined. The number of bacteria was correlated positively with the glucose concentration. Furthermore, an inverse correlation between dwell time and the number of bacteria was observed. Neither finding could be attributed to a glucose-dependent growth of the bacteria or disruption of the killing capacity of peritoneal cells in vitro. A glucose-dependent increase in the volume of the peritoneal fluid could partially explain the differences found in vivo. It is concluded that the glucose in dialysis fluid impairs antibacterial defence in the peritoneal cavity and that longer dwell times enhance this defence.


Agents of swimmer's itch-dangerous minority in the Digenea invasion of Lymnaeidae in water bodies and the first report of Trichobilharzia regenti in Poland.
Trichobilharzia spp. have been identified as a causative agent of swimmers' itch, a skin disease provoked by contact with these digenean trematodes in water. These parasites have developed a number of strategies to invade vertebrates. Since we have little understanding of the behavior of these parasites inside the human body, the monitoring of their invasion in snail host populations is highly recommended. In our research, lymnaeid snails were collected from several Polish lakes for two vegetation seasons. The prevalence of bird schistosomes in snail host populations was significantly lower than that of other digenean species. We were the first to detect the presence of the snails emitted Trichobilharzia regenti (potentially the most dangerous nasal schistosome) in Poland. In addition, by sequencing partial rDNA genes, we confirmed the presence of the snails positive with Trichobilharzia szidati in Polish water bodies, showing that swimmer's itch is more frequent during summer months and that large snails are more often infected with bird schistosomes than small ones.


Co-transduction for shape retrieval.
In this paper, we propose a new shape/object retrieval algorithm, namely, co-transduction. The performance of a retrieval system is critically decided by the accuracy of adopted similarity measures (distances or metrics). In shape/object retrieval, ideally, intraclass objects should have smaller distances than interclass objects. However, it is a difficult task to design an ideal metric to account for the large intraclass variation. Different types of measures may focus on different aspects of the objects: for example, measures computed based on contours and skeletons are often complementary to each other. Our goal is to develop an algorithm to fuse different similarity measures for robust shape retrieval through a semisupervised learning framework. We name our method co-transduction, which is inspired by the co-training algorithm. Given two similarity measures and a query shape, the algorithm iteratively retrieves the most similar shapes using one measure and assigns them to a pool for the other measure to do a re-ranking, and vice versa. Using co-transduction, we achieved an improved result of 97.72% (bull's-eye measure) on the MPEG-7 data set over the state-of-the-art performance. We also present an algorithm called tri-transduction to fuse multiple-input similarities, and it achieved 99.06% on the MPEG-7 data set. Our algorithm is general, and it can be directly applied on input similarity measures/metrics; it is not limited to object shape retrieval and can be applied to other tasks for ranking/retrieval.


Strategy for the surgical treatment of vestibular schwannomas in patients with neurofibromatosis type 2.
Guidelines for appropriate management of vestibular schwannomas in NF2 patients are controversial. In this paper we reviewed our experience with patients with NF2 for the results of surgical treatment with particular reference to hearing and facial nerve preservation. We included in the study 30 patients (16 women and 14 men) with the diagnosis of NF2 treated in our department between 1998 and 2014 who underwent surgery for vestibular schwannoma removal with a follow-up for at least 1 year. In 3 cases, the vestibular schwannomas were unilateral. Six patients with bilateral vestibular schwannomas underwent unilateral procedure. Therefore, 51 acoustic tumors were studied in 30 patients. No operative death we noted. Significant deterioration to the non-functional level occurred in 19 out of 22 cases with well-preserved preoperative hearing. Only three ears maintained their preoperative good hearing. Hearing was preserved in cases of small schwannoma not exceeding 2 cm. Among 21 patients who underwent bilateral operations hearing was preserved in 3 out of 7 cases when smaller tumor or better hearing level side was attempted at first surgery. In contrary none of the 14 patients retained hearing when the first operation concerned the worse-hearing ear. Among 14 tumors up to 2 cm there was only one case of moderately severe facial nerve dysfunction (House-Brackmann Grade IV) in the long follow-up. Early surgical intervention for vestibular schwannoma in NF2 patient is a viable management strategy to maintain hearing function and preserve facial nerve function.


Endoglin Regulation of Smad2 Function Mediates Beclin1 Expression and Endothelial Autophagy.
Autophagy is the targeted degradation of proteins and organelles critical for homeostasis and cell survival. Transforming growth factor β (TGF-β) differentially regulates autophagy in a context-specific manner, although the precise intracellular mechanisms remain less clear. Importantly, how TGF-β controls autophagic responses in endothelial cells (EC) during angiogenesis is unknown. Here we identified endoglin, an EC-specific TGF-β co-receptor essential for angiogenesis, as a key determinant of autophagy. Among the two opposing TGF-β Smad pathways in the EC system (Smad1/5/8 and Smad2/3), we found Smad2 as the major transcriptional regulator of autophagy that targets beclin1 (BECN1) gene expression. Smad2, but not Smad3, acts as a repressor upstream of the BECN1 promoter region. Overall, endoglin promotes autophagy by impeding Smad2 transcriptional repressor activity. Notably, increased beclin1 levels upon Smad2 knockdown directly correlated with enhanced autophagy during angiogenesis. Taken together, these results establish endoglin as a critical mediator of autophagy and demonstrate a new transcriptional mechanism by which Smad2 inhibits angiogenesis.


Cadmium concentrations in milk and blood of smoking mothers.
Cadmium concentrations were measured by flameless atomic absorption spectrometry in blood and mature milk of 15 nonsmoking and 56 smoking mothers during the nursing period. Both blood and milk concentrations increased with increasing cigarette consumption. The median blood and milk concentrations in nonsmokers were 0.54 and 0.07 microgram/l, respectively; these values rose to 1.54 and 0.16 micrograms/l in blood and milk of mothers smoking more than 20 cigarettes per day. Milk concentrations of cadmium were approximately 10% of corresponding blood concentrations. The cadmium exposure of infants nursed by nonsmoking as well as by smoking mothers was far below the exposure of formula-fed infants or the provisional acceptable weekly intake level set by the WHO.


Ligand-mediated activation of the cAMP-responsive guanine nucleotide exchange factor Epac.
Epac is a cAMP-dependent exchange factor for the small GTP-binding protein Rap. The activity of Epac is inhibited by a direct interaction between the C-terminal helical part of the cAMP-binding domain, called the lid, and the catalytic region, which is released after binding of cAMP. Herein, we show that the activation properties are very sensitive to modifications of the cyclic nucleotide. Some analogues are inhibitory and others are stimulatory; some are characterized by a much higher activation potential than normal cAMP. Mutational analysis of Epac allows insights into a network of interactions between the cyclic nucleotides and Epac. Mutations in the lid region are able to amplify or to attenuate selectively the activation potency of cAMP analogues. The properties of cAMP analogues previously used for the activation of the cAMP responsive protein kinase A and of 8-(4-chlorophenylthio)-2'-O-methyladenosine-3',5'-cyclicmonophosphate, an analogue highly selective for activation of Epac were investigated in detail.


Impact of donor multidrug-resistant organisms on solid organ transplant recipient outcomes.
The impact of donor colonization or infection with multidrug-resistant organisms (MDROs) on solid organ transplant (SOT) recipient outcomes remains uncertain. We thus evaluated the association between donor MDROs and risk of posttransplant infection, graft failure, and mortality. A multicenter retrospective cohort study was performed. All SOT recipients with a local deceased donor were included. The cohort was divided into three exposure groups: recipients whose donors had (1) an MDRO, (2) a non-MDRO bacterial or candidal organism, or (3) no growth on cultures. The primary outcomes were (1) bacterial or invasive candidal infection within 3 months and (2) graft failure or death within 12 months posttransplant. Mixed effect multivariable frailty models were developed to evaluate each association. Of 658 total SOT recipients, 93 (14%) had a donor with an MDRO, 477 (73%) had a donor with a non-MDRO organism, and 88 (13%) had a donor with no organisms on culture. On multivariable analyses, donor MDROs were associated with a significantly increased hazard of infection compared to those with negative donor cultures (adjust hazard ratio [aHR] 1.63, 95% CI 1.01-2.62, p = .04) but were not associated with graft failure or death (aHR 0.45, 95% CI 0.15-1.36, p = .16). MDROs on donor culture increase the risk of early posttransplant infection but do not appear to affect long-term graft or recipient survival, suggesting organ donors with MDROs on culture may be safely utilized. Future studies aimed at reducing early posttransplant infections associated with donor MDROs are needed.


Preparation of Crystalline Samples of Amyloid Fibrils and Oligomers.
The molecular structures of amyloid fibers and oligomers are required in order to understand and control their formation. Yet, their partially disordered and polymorphic nature hinders structural analyses. Fortunately, short segments from amyloid proteins, which exhibit similar biophysical properties to the full-length proteins, also form fibrils and oligomers and their atomic structures can be determined. Here we describe experimental procedures used to assess fiber-forming capabilities of amyloid peptide segments and their crystallization.