Recurrence in Patients Achieving Pathological Complete Response After Neoadjuvant Treatment for Advanced Pancreatic Cancer.
The aim of this study was to characterize the patterns and treatment of disease recurrence in patients achieving a pathological complete response (pCR) following neoadjuvant chemoradiation for advanced pancreatic ductal adenocarcinoma (PDAC). A pCR is an independent predictor for improved survival in PDAC. However, disease recurrence is still observed in these patients. Patients with advanced PDAC who were treated with neoadjuvant therapy and had a pCR were identified between 2009 and 2017. Overall survival (OS) was determined from the initiation of neoadjuvant, disease-free survival (DFS) from the date of surgery, and post-recurrence survival (PRS) from the date of recurrence. Factors associated with recurrence were analyzed using a Cox-regression model. Of 331 patients with borderline resectable or locally advanced PDAC, 30 achieved a pCR following neoadjuvant treatment and pancreatectomy. The median DFS for pCR patients was 29 months and OS 76 months. Recurrence was observed in 14 patients. No clinicopathologic or treatment characteristics were associated with survival. The median PRS following recurrence was 25 months. Treatment following recurrence included chemotherapy, radiation or ablation, and surgical resection. Hepatectomy or completion pancreatectomy was accomplished in 2 patients that remain alive 13 and 62 months, respectively, following metastasectomy. A pCR following neoadjuvant therapy in patients with advanced PDAC is associated with remarkable survival, although recurrence occurs in about half of patients. Nevertheless, patients with pCR and recurrence respond well to treatment and survival remains encouraging. Advanced molecular characterization and longitudinal liquid biopsy may offer additional assistance with understanding tumor biologic behavior after achieving a pCR.


Dropout associated with osteopathic manual treatment for chronic noncancerous pain in randomized controlled trials.
Reviews exploring harm outcomes such as adverse effects (AE), all cause dropouts (ACD), dropouts due to inefficacy, and dropouts due to AE associated with osteopathic manipulative treatment (OMT) or osteopathic manual therapy (OMTh) are scant. To explore the overall AE, ACD, dropouts due to inefficacy, and AE in chronic noncancerous pain (CNCP) patients receiving OMTh through a systematic review of previous literature. For this systematic review and meta-analysis, the authors searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Physiotherapy Evidence Database (PEDro), EMCare, and Allied and Complementary Medicine Database (AMED), and Ostmed.Dr, as well as the bibliographical references of previous systematic reviews evaluating OMTh for pain severity, disability, quality of life, and return to work outcomes. Randomized controlled trials with CNCP patients 18 years or older with OMTh as an active or combination intervention and the presence of a control or combination group were eligible for inclusion. In this sub-study of a previous, larger systematic review, 11 studies (n=1,015) reported data that allowed the authors to perform meta-analyses on ACD and dropouts due to AE. The risk of bias (ROB) was assessed with the Cochrane ROB tool and the quality of evidence was determined with the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The pooled analysis showed that ACD was not significantly different for visceral OMTh (vOMTh) vs. OMTh control (odds ratio [OR]=2.66 [95% confidence interval [[CI]], 0.28, 24.93]) or for OMTh vs. standard care (OR=1.26 [95% CI, 0.84, 1.89]; I2=0%). Single study analysis showed that OMTh results were nonsignificant in comparison with chemonucleolysis, gabapentin, and exercise. OMTh in combination with gabapentin (vs. gabapentin alone) and OMTh in combination with exercise (vs. exercise alone) showed nonsignificant ACD. Dropouts due to AE were not significantly different, but the results could not be pooled due to an insufficient number of studies. Most articles did not explicitly report AEs, ACD rates, or dropouts due to AEs and inefficacy. The limited data available on dropouts showed that OMTh was well tolerated compared with control interventions, and that the ACD and dropouts due to AEs were not significantly different than comparators. Future trials should focus on explicit reporting of dropouts along with beneficial outcomes to provide a better understanding of OMTh efficacy.


Rem sleep, early experience, and the development of reproductive strategies.
We hypothesize that rapid eye movement or REM sleep evolved, in part, to mediate sexual/reproductive behaviors and strategies. Because development of sexual and mating strategies depends crucially on early attachment experiences, we further hypothesize that REM functions to mediate attachment processes early in life. Evidence for these hypotheses comes from (1) the correlation of REM variables with both attachment and sexual/reproductive variables; (2) attachment-related and sex-related hormonal release during REM; (3) selective activation during REM of brain sites implicated in attachment and sexual processes; (4) effects of maternal deprivation on REM; (5) effects of REM deprivation on sexual behaviors; and (6) the REM-associated sexual excitation. To explain why we find associations among REM sleep, attachment, and adult reproductive strategies, we rely on recent extensions of parent-offspring conflict theory. Using data from recent findings on genomic imprinting, Haig (2000) and others suggest that paternally expressed genes are selected to promote growth of the developing fetus/child at the expense of the mother, while maternally expressed genes counter these effects. Because developmental REM facilitates attachment-related outcomes in the child, developmental REM may be regulated by paternally expressed genes. In that case, REM may have evolved to support the "aims" of paternal genes at the expense of maternal genes.


The C282Y mutation of the HFE gene is not found in Chinese haemochromatotic patients: multicentre retrospective study.
To detect two novel mutations (C282Y and H63D) of the HFE gene in Chinese patients with hepatic iron overload. Multicentre retrospective study. Four public hospitals, Hong Kong. Fifty Chinese patients who presented from January 1987 through December 1999 with hepatic iron overload from various causes. The DNA from liver biopsy samples was tested for HFE mutations by restriction fragment length polymorphism analysis. The sample DNA quality was unsatisfactory for analysis of the C282Y mutation in one case and the H63D mutation in nine cases. The C282Y mutation was not detected in any of the 49 satisfactory samples. Three of the 41 samples were heterozygous for the H63D mutation and only one was homozygous, giving an allele frequency of 6.1%. Of the three H63D-heterozygotes, one had beta-thalassaemia major, one had beta-thalassaemia minor, and one had hereditary spherocytosis. None of the 12 patients who were presumed to have primary haemochromatosis were positive for either mutation. The classical form of human leukocyte antigen-linked hereditary haemochromatosis appears to be absent form this locality. The H63D mutation is found in a minority (9.8%) of the patients, in whom it may act synergistically with an erythropoietic factor.


FGF signaling facilitates postinjury recovery of mouse hematopoietic system.
Previous studies have shown that fibroblast growth factor (FGF) signaling promotes hematopoietic stem and progenitor cell (HSPC) expansion in vitro. However, it is unknown whether FGF promotes HSPC expansion in vivo. Here we examined FGF receptor 1 (FGFR1) expression and investigated its in vivo function in HSPCs. Conditional knockout (CKO) of Fgfr1 did not affect phenotypical number of HSPCs and homeostatic hematopoiesis, but led to a reduced engraftment only in the secondary transplantation. When treated with 5-fluorouracil (5FU), the Fgfr1 CKO mice showed defects in both proliferation and subsequent mobilization of HSPCs. We identified megakaryocytes (Mks) as a major resource for FGF production, and further discovered a novel mechanism by which Mks underwent FGF-FGFR signaling dependent expansion to accelerate rapid FGF production under stress. Within HSPCs, we observed an up-regulation of nuclear factor κB and CXCR4, a receptor for the chemoattractant SDF-1, in response to bone marrow damage only in control but not in Fgfr1 CKO model, accounting for the corresponding defects in proliferation and migration of HSPCs. This study provides the first in vivo evidence that FGF signaling facilitates postinjury recovery of the mouse hematopoietic system by promoting proliferation and facilitating mobilization of HSPCs.


Unification of regression-based methods for the analysis of natural selection.
Regression analyses are central to characterization of the form and strength of natural selection in nature. Two common analyses that are currently used to characterize selection are (1) least squares-based approximation of the individual relative fitness surface for the purpose of obtaining quantitatively useful selection gradients, and (2) spline-based estimation of (absolute) fitness functions to obtain flexible inference of the shape of functions by which fitness and phenotype are related. These two sets of methodologies are often implemented in parallel to provide complementary inferences of the form of natural selection. We unify these two analyses, providing a method whereby selection gradients can be obtained for a given observed distribution of phenotype and characterization of a function relating phenotype to fitness. The method allows quantitatively useful selection gradients to be obtained from analyses of selection that adequately model nonnormal distributions of fitness, and provides unification of the two previously separate regression-based fitness analyses. We demonstrate the method by calculating directional and quadratic selection gradients associated with a smooth regression-based generalized additive model of the relationship between neonatal survival and the phenotypic traits of gestation length and birth mass in humans.


Identification of 3 alpha, 6 alpha, 7 alpha, 12 alpha-tetrahydroxy-5 beta-cholestanoic acid in Zellweger's syndrome.
In order to confirm the occurrence of 3 alpha, 6 alpha, 7 alpha, 12 alpha-tetrahydroxy-5 beta-cholestanoic acid in Zellweger's syndrome, the nature of tetrahydroxycholestanoic acids present in a patient with this disease was studied. Urinary bile acids were extracted with a Sep-pak C18 cartridge and methylated after alkaline hydrolysis. The methyl esters were purified by silica gel column chromatography, and the methyl tetrahydroxycholestanoate fraction was analyzed by gas liquid chromatography-mass spectrometry. Along with already known side chain hydroxylated derivatives of 3 alpha, 7 alpha, 12 alpha-trihydroxy-5 beta-cholestanoic acid, 3 alpha, 7 alpha, 12 alpha, 24- and 3 alpha, 7 alpha, 12 alpha, 26-tetrahydroxy-5 beta-cholestanoic acids, three nuclear hydroxylated derivatives of 3 alpha, 7 alpha, 12 alpha-trihydroxy-5 beta-cholestanoic acid were found. One of them was identified as 3 alpha, 6 alpha, 7 alpha, 12 alpha-tetrahydroxy-5 beta-cholestanoic acid by direct comparison with the authentic standard which was chemically synthesized from 3 alpha, 6 alpha, 7 alpha, 12 alpha-tetrahydroxy-5 beta-cholanoic acid by side chain elongation.


Short-term toxicity of 1-methylnaphthalene to Americamysis bahia and 5 deep-sea crustaceans.
There are few studies that have evaluated hydrocarbon toxicity to vertically migrating deep-sea micronekton. Crustaceans were collected alive using a 9-m2 Tucker trawl with a thermally insulated cod end and returned to the laboratory in 10 °C seawater. Toxicity of the polycyclic aromatic hydrocarbon 1-methylnaphthalene to Americamysis bahia, Janicella spinacauda, Systellaspis debilis, Sergestes sp., Sergia sp., and a euphausiid species was assessed in a constant exposure toxicity test utilizing a novel passive dosing toxicity testing protocol. The endpoint of the median lethal concentration tests was mortality, and the results revealed high sensitivity of the deep-sea micronekton compared with other species for which these data are available. Threshold concentrations were also used to calculate critical target lipid body burdens using the target lipid model. Environ Toxicol Chem 2017;36:3415-3423. © 2017 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC.


The power of place: space and time in women's and community health centres in South Australia.
This paper focuses on the importance of time and space in an Australian medical setting. It draws on research findings from a one year project that aimed to explore community perspectives of, and experiences of medical services in three South Australian women's and community health centres. Both qualitative and quantitative methods of data collection and analysis were used in order to address these objectives. A significant finding was the way in which participants described the organisation and experience of time and space in these centres and how this impacted on their health and well being and that of the community. In analysing these spatio-temporal dimensions and the underlying philosophical structures of women's and community health centres, this paper argues that experiences associated with space and time have a positive effect on health status by: diminishing barriers to health services, improving quality of care, increasing community participation, providing safe places for social interaction and strengthening people's sense of belonging or attachment to a particular community and place. Based on these findings, the authors conclude that the spatio-temporal dimensions of health care provision have empowering and positive impacts on a community's health, a significant finding that has implications for the maintenance and future funding of this style of health service.


Cost-benefit analysis of the recovery of carbon disulfide in the manufacturing of viscose rayon.
Constraints in the management of occupational hazards include problems with technical feasibility and costs of control measures. A pilot investigation of the effectiveness of a carbon disulfide (CS2) recovery system in the manufacturing of viscose rayon by means of cost-benefit analysis was conducted at a Shanghai viscose rayon factory. The annual amount of carbon disulfide recovered with the new system reached approximately 1 500 t in 1982. It is estimated that the company has made a net profit of 1 million yuan (about USD 500 000 at the time of the study) per year from this system (almost equal to 10% of the production value of the factory). This study documented a control measure that was both effective in reducing a hazard for workers and economically beneficial to the company.


Usefulness of Extended-FAST (EFAST-Extended Focused Assessment with Sonography for Trauma) in critical care setting.
Trauma is the leading cause of death in people below 45 years-old in Brazil, and responsible for one third of all intensive care unit admissions. The increasing knowledge on ultrasound diagnosis methods and its availability for life-threatening injuries (such as cardiac tamponade and abdominal cavity solid organs rupture leading to hemorrhagic shock) diagnosis and monitoring, lead to the development o the FAST (Focused Assessment with Sonography for Trauma) protocol, aimed to be used both in the emergency and intensive care unit settings. Due to its reproducibility, lack of radiation exposure, and bedside feasibility, this technology is being increasingly accepted. A new protocol extension, the Extended-FAST, provides valuable information for improved patients' management, extending its availability from the abdominal conditions to other diagnosis such as hemothorax, pleural effusion and pneumothorax. We must underline that this technique is able to replace computed tomography and diagnostic peritoneal wash, and do not delay surgical procedure instead of perform this exam . Thus, its careful appraisal in connection with the clinical information should guide the therapeutic approaches, specially in inhospitable sites such as intensive care units in war zones, rural or distant places, were other imagery methods are not available.


Comparison of Clinical Efficacy of Cytarabine with Different Regimens in Postremission Consolidation Therapy for Adult t(8;21) AML Patients: A Multicenter Retrospective Study in China.
The survival of patients with acute myeloid leukemia (AML) with t(8;21) was reported to be shorter in China than in other countries. We analyzed the correlation between different cytarabine (Ara-c) regimens and outcome in 255 t(8;21) AML patients in China who received postremission consolidation chemotherapy only. The 5-year overall survival (OS) of the high-dose Ara-c group (HDAC; 2≤ Ara-c ≤3 g/m2), intermediate-dose Ara-c group (MDAC; 1.0≤ Ara-c <2.0 g/m2), low-dose Ara-c group (LDAC; 0.2< Ara-c <1.0 g/m2) and standard-dose Ara-c group (SDAC; 0.1≤ Ara-c ≤0.2 g/m2) were 65.3, 39.4, 25.2 and 27.9%, respectively (p = 0.003). In the HDAC group, but not in the MDAC group, the 5-year OS of patients who achieved 3-4 cycles of chemotherapy was superior to those who underwent 1-2 cycles (84.4 vs. 43.6%, p < 0.05), and the 3-year OS of patients who achieved an accumulated 36 g/m2 of Ara-c was significantly higher compared to those who did not (85.3 vs. 39.2%, p < 0.05). Multivariate analysis indicated that factors such as WBC >3.5 × 109/l, PLT ≤30 × 109/l, and extramedullary infiltration were associated with a poor prognosis. The survival of t(8;21) AML patients treated with high-dose Ara-c (≥2 g/m2) was superior to other dose levels in postremission consolidation chemotherapy. Patient survival was improved by 3-4 cycles of chemotherapy with an accumulated concentration of 36 g/m2 of Ara-c. WBC >3.5 × 109/l, PLT ≤30 × 109/l and extramedullary infiltration could be indicative of a poor clinical prognosis.


Our failures and ways to decrease hospital mortality in surgical management of thoracoabdominal aortic aneurysms.
The present study was undertaken to investigate the structure of hospital mortality associated with surgical treatment of 166 patients presenting with thoracoabdominal aortic aneurysms. According to the findings obtained, haemorrhagic, renal, and pulmonary complications turned out to predominate in the structure of an unfavourable postoperative outcome, accounting for 54%, 25% and 17%, respectively. Also determined and outlined herein are promising trends aimed at decreasing the hospital lethality rate related to the pathology involved. These include but are not limited to the following measures to be taken: making an early and accurate diagnosis of the nosological entity concerned, maximally diminishing the operative wound and reducing blood loss to a minimum, as well as using the state-of-the-art "sparing" methods of protecting the patient.


Endobronchial tuberculosis with expectoration of tracheal cartilages.
A case of endotracheal tuberculosis with expectorations of the lateral one-third of the multiple tracheal cartilages is reported. Fibreoptic bronchoscopy revealed caseous materials and loosening of the tracheal cartilages. The patient expectorated cartilaginous material several times before and after fibreoptic bronchoscopy. In spite of the loss of tracheal cartilages, tracheal lumen was maintained with a mild airflow limitation. The remaining two-thirds of the tracheal cartilage rings seemed to be strong enough to support the tracheal lumen opening during the respiratory cycle. Although rare, expectoration of bronchial cartilage can be one of the clinical features of endobronchial tuberculosis.


Phase IB study of gene-mediated cytotoxic immunotherapy adjuvant to up-front surgery and intensive timing radiation for malignant glioma.
Despite aggressive therapies, median survival for malignant gliomas is less than 15 months. Patients with unmethylated O(6)-methylguanine-DNA methyltransferase (MGMT) fare worse, presumably because of temozolomide resistance. AdV-tk, an adenoviral vector containing the herpes simplex virus thymidine kinase gene, plus prodrug synergizes with surgery and chemoradiotherapy, kills tumor cells, has not shown MGMT dependency, and elicits an antitumor vaccine effect. Patients with newly diagnosed malignant glioma received AdV-tk at 3 × 10(10), 1 × 10(11), or 3 × 10(11) vector particles (vp) via tumor bed injection at time of surgery followed by 14 days of valacyclovir. Radiation was initiated within 9 days after AdV-tk injection to overlap with AdV-tk activity. Temozolomide was administered after completing valacyclovir treatment. Accrual began December 2005 and was completed in 13 months. Thirteen patients were enrolled and 12 completed therapy, three at dose levels 1 and 2 and six at dose level 3. There were no dose-limiting or significant added toxicities. One patient withdrew before completing prodrug because of an unrelated surgical complication. Survival at 2 years was 33% and at 3 years was 25%. Patient-reported quality of life assessed with the Functional Assessment of Cancer Therapy-Brain (FACT-Br) was stable or improved after treatment. A significant CD3(+) T-cell infiltrate was found in four of four tumors analyzed after treatment. Three patients with MGMT unmethylated glioblastoma multiforme survived 6.5, 8.7, and 46.4 months. AdV-tk plus valacyclovir can be safely delivered with surgery and accelerated radiation in newly diagnosed malignant gliomas. Temozolomide did not prevent immune responses. Although not powered for efficacy, the survival and MGMT independence trends are encouraging. A phase II trial is ongoing.


[The prohibition of lithotomy within the Hippocratic Oath: historical and ethical considerations on the history of surgery].
A passage with one of the most contradictory interpretations of the so-called Hippocratic Oath, which was presumably created between 500 and 300 before Christ, is the prohibition of lithotomy. The oldest handwritten traditions of the Hippocratic Oath are dating back to the 11th-12th century. However the section of the prohibition of lithotomy is missing in the oldest preserved tradition (Codex Urbinas gr. 64), which led to some authors interpretation of being added later on. Beyond all doubt the analysis of the texture of the Hippocratic Oath leads to the conclusion that the prohibition of bladder stone lithotomy must have been an integrative part of the oath from the very first beginning. The author could have been inspired by the following reasons to have a non oath related doctor let done the medical operation: the removal of a bladder stone by an operation, which was outfitted with many complications, was one of the most difficult surgical interventions in the antique. Celsus (1st century A. D.) mentioned "severe fever, urine fistula and deadly inflammations" after lithotomy. Since the operation was done perineally, presumably a negative sexual potency was feared. No doctor engaged to help and not to harm his patients was allowed to make this kind of operation, which was often followed by many complications. Nevertheless sometimes patients were "tantalised to death by suffering dreadful pain" through those bladder stone diseases. Consequently "practising men" (the term "surgeon" was created at a later date), those who had been specialised in that operation and had not been linked to the oath, were allowed to make this kind of dangerous operation. Due to a greater experience of those specialists (named as "Lithotomos" by Celsus ih the 1st century A. D.) the danger of this kind of operation was reduced. The prohibition of lithotomy could be interpreted as a commitment to realize the limits of ones own medical actions.


Isolation and Quantification of Bacterial Membrane Vesicles for Quantitative Metabolic Studies Using Mammalian Cell Cultures.
Bacterial membrane vesicles (BMVs) are produced by most bacteria and participate in various cellular processes, such as intercellular communication, nutrient exchange, and pathogenesis. Notably, these vesicles can contain virulence factors, including toxic proteins, DNA, and RNA. Such factors can contribute to the harmful effects of bacterial pathogens on host cells and tissues. Although the general effects of BMVs on host cellular physiology are well known, the underlying molecular mechanisms are less understood. In this study, we introduce a vesicle quantification method, leveraging the membrane dye FM4-64. We utilize a linear regression model to analyze the fluorescence emitted by stained vesicle membranes to ensure consistent and reproducible vesicle-host interaction studies using cultured cells. This method is particularly valuable for identifying host cellular processes impacted by vesicles and their specific cargo. Moreover, it outcompetes unreliable protein concentration-based methods. We (1) show a linear correlation between the number of vesicles and the fluorescence signal emitted from the FM4-64 dye; (2) introduce the "vesicle load" as a new semi-quantitative unit, facilitating more reproducible vesicle-cell culture interaction experiments; (3) show that a stable vesicle load yields consistent host responses when studying vesicles from Pseudomonas aeruginosa mutants; (4) demonstrate that typical vesicle isolation contaminants, such as flagella, do not significantly skew the metabolic response of lung epithelial cells to P. aeruginosa vesicles; and (5) identify inositol monophosphatase 1 (SuhB) as a pivotal regulator in the vesicle-mediated pathogenesis of P. aeruginosa.


A novel head-neck cooling device for concussion injury in contact sports.
Emerging research on the long-term impact of concussions on athletes has allowed public recognition of the potentially devastating effects of these and other mild head injuries. Mild traumatic brain injury (mTBI) is a multifaceted disease for which management remains a clinical challenge. Recent pre-clinical and clinical data strongly suggest a destructive synergism between brain temperature elevation and mTBI; conversely, brain hypothermia, with its broader, pleiotropic effects, represents the most potent neuro-protectant in laboratory studies to date. Although well-established in selected clinical conditions, a systemic approach to accomplish regional hypothermia has failed to yield an effective treatment strategy in traumatic brain injury (TBI). Furthermore, although systemic hypothermia remains a potentially valid treatment strategy for moderate to severe TBIs, it is neither practical nor safe for mTBIs. Therefore, selective head-neck cooling may represent an ideal strategy to provide therapeutic benefits to the brain. Optimizing brain temperature management using a National Aeronautics and Space Administration (NASA) spacesuit spinoff head-neck cooling technology before and/or after mTBI in contact sports may represent a sensible, practical, and effective method to potentially enhance recover and minimize post-injury deficits. In this paper, we discuss and summarize the anatomical, physiological, preclinical, and clinical data concerning NASA spinoff head-neck cooling technology as a potential treatment for mTBIs, particularly in the context of contact sports.


Erythropoietin promotes erection recovery after nerve-sparing radical retropubic prostatectomy: a retrospective analysis.
Erectile dysfunction persists as a major functional complication of nerve-sparing radical prostatectomy. To evaluate retrospectively the potential benefit of erythropoietin administration to improve erectile function recovery following radical prostatectomy. Preoperatively potent patients who underwent nerve-sparing radical retropubic prostatectomy between March 2005 and February 2006 elected to receive erythropoietin treatment (40,000 IU subcutaneously, single injection on their preoperative day; treatment group, N = 15). A contemporaneous clinically matched cohort comprising patients who elected postoperative standard surveillance only served for comparison (control group, N = 21). Phosphodiesterase type 5 (PDE5) inhibitor "on-demand" use was applied. Potency evaluations were monitored by International Index of Erectile Function-5 questionnaires administered preoperatively and at 3, 6, and 12 months postoperatively. Erection recovery. Health comorbidities as well as erectile function status were demonstrated to be no different between groups at baseline. Erythropoietin-treated patients demonstrated significantly higher postoperative International Index of Erectile Function-5 questionnaire scores than control group patients at 3, 6, and 12 months postoperatively with or without use of PDE5 inhibitors (P < 0.05). At 12 months postoperatively, the percentages of patients performing sexual activity were 87% and 68% of erythropoietin-treated and control patients, respectively (P = 0.213), although the erythropoietin-treated patients had a significantly greater ability to perform sexual intercourse with minimal or no difficulty (P < 0.05). Erythropoietin administration on the preoperative day before undergoing nerve-sparing radical prostatectomy in men reporting normal erectile function preoperatively may confer improved erectile function recovery postoperatively.


Prehospital Double Sequential Defibrillation: A Matched Case-Control Study.
The goal of our study was to determine whether prehospital double sequential defibrillation (DSD) is associated with improved survival to hospital admission in the setting of refractory ventricular fibrillation/pulseless ventricular tachycardia (VF/pVT). This project is a matched case-control study derived from prospectively collected quality assurance/quality improvement data obtained from the San Antonio Fire Department out-of-hospital cardiac arrest (OHCA) database between January 2013 and December 2015. The cases were defined as OHCA patients with refractory VF/pVT who survived to hospital admission. The control group was defined as OHCA patients with refractory VF/pVT who did not survive to hospital admission. The primary variable in our study was prehospital DSD. The primary outcome of our study was survival to hospital admission. Of 3,469 consecutive OHCA patients during the study period, 205 OHCA patients met the inclusion criterion of refractory VF/pVT. Using a predefined algorithm, two blinded researchers identified 64 unique cases and matched them with 64 unique controls. Survival to hospital admission occurred in 48.0% of DSD patients and 50.5% of the conventional therapy patients (p > 0.99; odds ratio = 0.91, 95% confidence interval = 0.40-2.1). Our matched case-control study on the prehospital use of DSD for refractory VF/pVT found no evidence of associated improvement in survival to hospital admission. Our current protocol of considering prehospital DSD after the third conventional defibrillation in OHCA is ineffective.


HGH20k species and variability of GH responses to long-duration exercise in male cyclists fed different food supplements.
Exercise studies dealing with hGH have always considered this hormone as a unique molecular entity. We postulated that the well-known variability in blood total hGH response could possibly be explained, at least in part, by concomitant changes in blood hGH20k levels, variant form possibly expressing some of the hGH anti-insulinic properties. Six male trained cyclists were imposed a 2-hr long ergocycle exercise. Food supplements were given prior to and/or during exertion to exacerbate a possible contribution from hGH20k to total hGH variability by modification of substrate availability. Both blood total hGH and hGH20k levels increased with exercise, the largest increases being observed in absence of supplementation. Large variability of responses were observed in both blood total hGH and hGH20k levels, the latter variant contributing minimally to total blood hGH response (4.3 +/- 0.8%), and being closely associated with the main species (r = 0.90; p less than 0.001). It was concluded that variations associated with hGH20k increases observed in response to prolonged exercise cannot explain the large intra-and inter-individual variability measured in blood total hGH response.


Lentivirus display: stable expression of human antibodies on the surface of human cells and virus particles.
Isolation of human antibodies using current display technologies can be limited by constraints on protein expression, folding and post-translational modifications. Here we describe a discovery platform that utilizes self-inactivating (SIN) lentiviral vectors for the surface display of high-affinity single-chain variable region (scFv) antibody fragments on human cells and lentivirus particles. Bivalent scFvFc human antibodies were fused in frame with different transmembrane (TM) anchoring moieties to allow efficient high-level expression on human cells and the optimal TM was identified. The addition of an eight amino acid HIV-1 gp41 envelope incorporation motif further increased scFvFc expression on human cells and incorporation into lentiviral particles. Both antibody-displaying human cells and virus particles bound antigen specifically. Sulfation of CDR tyrosine residues, a property recently shown to broaden antibody binding affinity and antigen recognition was also demonstrated. High level scFvFc expression and stable integration was achieved in human cells following transduction with IRES containing bicistronic SIN lentivectors encoding ZsGreen when scFvFc fusion proteins were expressed from the first cassette. Up to 10(6)-fold enrichment of antibody expressing cells was achieved with one round of antigen coupled magnetic bead pre-selection followed by FACS sorting. Finally, the scFvFc displaying human cells could be used directly in functional biological screens with remarkable sensitivity. This antibody display platform will complement existing technologies by virtue of providing properties unique to lentiviruses and antibody expression in human cells, which, in turn, may aid the discovery of novel therapeutic human mAbs.


Development and Characterisation of a Whole Hybrid Sol-Gel Optofluidic Platform for Biosensing Applications.
This work outlines, for the first time, the fabrication of a whole hybrid sol-gel optofluidic platform by integrating a microfluidic biosensor platform with optical waveguides employing a standard photolithography process. To demonstrate the suitability of this new hybrid sol-gel optofluidic platform, optical and bio-sensing proof-of-concepts are proposed. A photoreactive hybrid sol-gel material composed of a photopolymerisable organically modified silicon alkoxide and a transition metal complex was prepared and used as the fabrication material for the entire optofluidic platform, including the optical waveguides, the sensing areas, and the microfluidic device. The most suitable sol-gel materials chosen for the fabrication of the cladding and core of the waveguides showed a RIC of 3.5 × 10-3 and gave thicknesses between 5.5 and 7 μm. The material was optimised to simultaneously meet the photoreactive properties required for the photolithography fabrication process and the optical properties needed for the effective optical operability of the microstructured waveguides at 532 and 633 nm with an integrated microfluidic device. The optical proof-of-concept was performed using a fluorescent dye (Atto 633) and recording its optical responses while irradiated with a suitable optical excitation. The biosensing capability of the platform was assessed using a polyclonal primary IgG mouse antibody and a fluorescent labelled secondary IgG anti-mouse antibody. A limit of detection (LOD) of 50 ug/mL was achieved. A correlation between the concentration of the dye and the emission fluorescence was evidenced, thus clearly demonstrating the feasibility of the proposed hybrid sol-gel optofluidic platform concept. The successful integration and operability of optical and microfluidic components in the same optofluidic platform is a novel concept, particularly where the sol-gel fabrication material is concerned.


Specific increase in potency via structure-based design of a TCR.
Adoptive immunotherapy with Ag-specific T lymphocytes is a powerful strategy for cancer treatment. However, most tumor Ags are nonreactive "self" proteins, which presents an immunotherapy design challenge. Recent studies have shown that tumor-specific TCRs can be transduced into normal PBLs, which persist after transfer in ∼30% of patients and effectively destroy tumor cells in vivo. Although encouraging, the limited clinical responses underscore the need for enrichment of T cells with desirable antitumor capabilities prior to patient transfer. In this study, we used structure-based design to predict point mutations of a TCR (DMF5) that enhance its binding affinity for an agonist tumor Ag-MHC (peptide-MHC [pMHC]), Mart-1 (27L)-HLA-A2, which elicits full T cell activation to trigger immune responses. We analyzed the effects of selected TCR point mutations on T cell activation potency and analyzed cross-reactivity with related Ags. Our results showed that the mutated TCRs had improved T cell activation potency while retaining a high degree of specificity. Such affinity-optimized TCRs have demonstrated to be very specific for Mart-1 (27L), the epitope for which they were structurally designed. Although of somewhat limited clinical relevance, these studies open the possibility for future structural-based studies that could potentially be used in adoptive immunotherapy to treat melanoma while avoiding adverse autoimmunity-derived effects.


[Hypothermal perfusion: protection or damage?].
Ninety six patients were examined during operations on the open heart and great vessels: 25 perfusions were performed at a temperature of 30-32 degrees C; 41 perfusions at 26-29 degrees C; 10 at 23-26 degrees C; 20 at 12-14 degrees C. It was found that with superficial hypothermia and moderate PaO2, blood myoglobin (MG) release was minimal and the count and activity of platelets were optimal. The degree of myoglobinemia increased as PaO2 rose. As the body's temperature lowered, the blood concentrations of MG, its differences smoothed in the subgroups with different PaO2 values. Critical myoglobinemia (over 30 times higher than the baseline values) was noted in a group with superdeep cooling to a temperature of 14 degrees C. By taking into account the fact that the myocardium contains large quantities of MG, loss of this heme-containing protein involves myocardial blood supply disorders and hence decreased myocardial contractility. A considerable platelet loss entails higher postoperative hemorrhagic diathesis and requires efforts in correcting coagulopathies.


Mechanisms and Impact of Aminoglycoside-Induced Vestibular Deficits.
Acquired vestibulotoxicity from hospital-prescribed medications such as aminoglycoside antibiotics affects as many as 40,000 people each year in North America. However, there are no current federally approved drugs to prevent or treat the debilitating and permanent loss of vestibular function caused by bactericidal aminoglycoside antibiotics. This review will cover our current understanding of the impact of, and mechanisms underlying, aminoglycoside-induced vestibulotoxicity and highlight the gaps in our knowledge that remain. Aminoglycoside-induced vestibular deficits have long-term impacts on patients across the lifespan. Additionally, the prevalence of aminoglycoside-induced vestibulotoxicity appears to be greater than cochleotoxicity. Thus, monitoring for vestibulotoxicity should be independent of auditory monitoring and encompass patients of all ages from young children to older adults before, during, and after aminoglycoside therapy.


Caplacizumab: an anti-von Willebrand factor antibody for the treatment of thrombotic thrombocytopenic purpura.
The pharmacology, pharmacokinetics, efficacy, safety, dosing and administration, and place in therapy of caplacizumab, a novel antibody fragment that inhibits von Willebrand factor, for the treatment of acquired thrombotic thrombocytopenic purpura (TTP) are summarized. Caplacizumab is a humanized anti-von Willebrand factor monoclonal antibody fragment that inhibits the interaction between ultralarge von Willebrand factor multimers and platelets. Caplacizumab is indicated for use in combination with standard-of-care modalities such as plasma exchange and immunosuppressive therapy for the treatment of adults with acquired TTP. By inhibiting von Willebrand factor, caplacizumab offers a new approach to the management of TTP by preventing the development of potentially life-threatening microvascular thrombosis that can occur in the disease process. In a randomized, placebo-controlled phase 3 trial, patients with acquired TTP treated with caplacizumab had more rapid platelet level normalization than placebo users; caplacizumab use also resulted in lower rates of disease recurrence and TTP-related death. The most common adverse events associated with caplacizumab use are bleeding-related events. In a phase 3 trial, serious bleeding-related adverse events were reported in 8 patients (11%) in the caplacizumab group and 1 patient (1%) in the placebo group. Caplacizumab is administered as an 11-mg intravenous loading dose 15 minutes prior to plasma exchange, followed by administration of 11 mg subcutaneously daily after plasma exchange. Once-daily caplacizumab administration can be continued for 30 days after the last plasma exchange. The medication and supplies for administration are provided as a single-use kit; patients should be trained on proper reconstitution and self-administration technique prior to the use of caplacizumab in the ambulatory setting. Caplacizumab is a first-in-class von Willebrand factor inhibitor approved for the treatment of adults with acquired TTP.


Comparison of some selected methods for accident investigation.
Even if the focus on risk management is increasing in our society, major accidents resulting in several fatalities seem to be unavoidable in some industries. Since the consequences of such major accidents are unacceptable, a thorough investigation of the accidents should be performed in order to learn from what has happened, and prevent future accidents. During the last decades, a number of methods for accident investigation have been developed. Each of these methods has different areas of application and different qualities and deficiencies. A combination of several methods ought to be used in a comprehensive investigation of a complex accident. This paper gives a brief description of a selection of some important, recognised, and commonly used methods for investigation of accidents. Further, the selected methods are compared according to important characteristics.


Long-term response in biochemical markers of bone turnover during enzyme replacement therapy in a case-series of patients with Gaucher disease type I from Northern Greece.
Gaucher disease (GD) is a lysosomal storage disorder characterized by severe skeletal complications. Bone complications are an important cause of morbidity of GD and are thought to result from imbalance in bone remodeling. The objective of this case series was to analyze the long-term effect of enzyme replacement therapy on chemokines MIP-1a and MIP-1b, cytokines IL-3, IL-6, IL-10, and IL-12, osteoprotegerin (OPG) and osteocalcin (BGP), chitotriosidase, quantitative ultrasound sonography (QUS), bone magnetic resonance imaging (MRI) and dual-energy X-ray absorptiometry (DXA) in patients with GD in Northern Greece. In addition, the study aimed in investigating possible relationship between the above mentioned parameters. Seven patients with GD type I (three males and four females) were included in the study. Mean age was 26.29 ± 15.34 years (range 7-47 years). Six patients were receiving enzyme replacement therapy (ERT), with 40-60 IU/kg of imiglucerase weekly, for a mean period of 36 months prior to study initiation. One patient started ERT after his inclusion in the study. The levels of MIP-1a, MIP-1b, IL-3, IL-6, IL-10, IL-12, OPG, BGP, chitotriosidase, bone imaging parameters assessed with two different techniques (QUS and DXA) and MRI data were estimated at baseline (T0) and after two years on ERT. Chitotriosidase, MIP-1a, and IL-6 levels decreased in all patients after two years of ERT (p =0.05). In contrast, OPG and BGP levels increased (p =0.04 and p =0.02, respectively). Bone mineral density (BMD) demonstrated a progressive improvement with regards to the Z-score in all patients (p =0.05). The decrease in the plasma levels of MIP-1a strongly correlated with a decrease in the plasma levels of chitotriosidase. Additionally, decreased plasma levels of IL-6 were correlated with increased Z-score both at baseline (T0) as well as two years later, in all patients. There was no correlation between MRI findings and any inflammatory biomarker. Measurement of serum markers in patients with GD under ERT could be used as an auxiliary tool in the monitoring of bone involvement, in combination with MRI imaging and BMD. However, larger studies involving higher numbers of GD patients are needed to confirm these conclusions. Hippokratia 2016, 20(2): 153-159.


Mounting evidence for vitamin D as an environmental factor affecting autoimmune disease prevalence.
Low vitamin D status has been implicated in the etiology of autoimmune diseases such as multiple sclerosis, rheumatoid arthritis, insulin-dependent diabetes mellitus, and inflammatory bowel disease. The optimal level of vitamin D intake required to support optimal immune function is not known but is likely to be at least that required for healthy bones. Experimentally, vitamin D deficiency results in the increased incidence of autoimmune disease. Mechanistically, the data point to a role for vitamin D in the development of self-tolerance. The vitamin D hormone (1,25-dihydroxy vitamin D(3)) regulates T helper cell (Th1) and dendritic cell function while inducing regulatory T-cell function. The net result is a decrease in the Th1-driven autoimmune response and decreased severity of symptoms. This review discusses the accumulating evidence pointing to a link between vitamin D and autoimmunity. Increased vitamin D intakes might decrease the incidence and severity of autoimmune diseases and the rate of bone fracture.


A novel genetic engineering platform for the effective management of biological contaminants for the production of microalgae.
Microalgal cultivation that takes advantage of solar energy is one of the most cost-effective systems for the biotechnological production of biofuels, and a range of high value products, including pharmaceuticals, fertilizers and feed. However, one of the main constraints for the cultivation of microalgae is the potential contamination with biological pollutants, such as bacteria, fungi, zooplankton or other undesirable microalgae. In closed bioreactors, the control of contamination requires the sterilization of the media, containers and all materials, which increases the cost of production, whereas open pond systems severely limits the number of species that can be cultivated under extreme environmental conditions to prevent contaminations. Here, we report the metabolic engineering of Chlamydomonas reinhardtii to use phosphite as its sole phosphorus source by expressing the ptxD gene from Pseudomonas stutzeri WM88, which encodes a phosphite oxidoreductase able to oxidize phosphite into phosphate using NAD as a cofactor. Engineered C. reinhardtii lines are capable of becoming the dominant species in a mixed culture when fertilized with phosphite as a sole phosphorus source. Our results represent a new platform for the production of microalgae, potentially useful for both closed photobioreactors and open pond systems without the need for using sterile conditions nor antibiotics or herbicides to prevent contamination with biological pollutants.


Osteoporosis Canada 2010 guidelines for the assessment of fracture risk.
Osteoporosis Canada's 2010 Clinical Practice Guidelines for the Diagnosis and Management of Osteoporosis in Canada focus on the clinical impact of fragility fractures, and on the assessment and management of women and men at high risk for fragility fracture. These guidelines now integrate a 10-year absolute fracture risk prediction into an overall management approach by using validated risk assessment tools. There currently is a large gap between optimal practices and those that are now being provided to Canadians with osteoporosis. These guidelines are part of a concerted effort to close this gap. Key changes from the 2002 guidelines of interest and relevance to radiologists are highlighted in this report.


Venom from Bothrops lanceolatus, a Snake Species Native to Martinique, Potently Activates the Complement System.
Bothrops lanceolatus snake venom causes systemic thrombotic syndrome but also local inflammation involving extensive oedema, pain, and haemorrhage. Systemic thrombotic syndrome may lead to fatal pulmonary embolism and myocardial and cerebral infarction. Here, we investigated the ability of B. lanceolatus venom to activate the Complement system (C) in order to improve the understanding of venom-induced local inflammation. Data presented show that B. lanceolatus venom is able to activate all C-pathways. In human serum, the venom strongly induced the generation of anaphylatoxins, such as C5a and C4a, and the Terminal Complement complex. The venom also induced cleavage of purified human components C3, C4, and C5, with the production of biologically active C5a. Furthermore, the venom enzymatically inactivated the soluble C-regulator and the C1-inhibitor (C1-INH), and significantly increased the expression of bound C-regulators, such as MCP and CD59, on the endothelial cell membrane. Our observations that B. lanceolatus venom activates the three Complement activation pathways, resulting in anaphylatoxins generation, may suggest that this could play an important role in local inflammatory reaction and systemic thrombosis caused by the venom. Inactivation of C1-INH, which is also an important inhibitor of several coagulation proteins, may also contribute to inflammation and thrombosis. Thus, further in vivo studies may support the idea that therapeutic management of systemic B. lanceolatus envenomation could include the use of Complement inhibitors as adjunct therapy.


The endogenous cannabinoid system in the gut of patients with inflammatory bowel disease.
Activation of cannabinoid receptors (CBs) by endocannabinoids impacts on a number of gastrointestinal functions. Recent data indicate that CB1 agonists improve 2,4-dinitrobenzene sulfonic acid-induced colitis in mice, thus suggesting a role for the endocannabinoid agonist anandamide (AEA) in protecting the gut against inflammation. We here examined the gut endocannabinoid system in inflammatory bowel disease (IBD) patients, and investigated the ex vivo and in vitro effects of the non-hydrolysable AEA analog methanandamide (MAEA) on the mucosal proinflammatory response. The content of AEA, but not of 2-arachidonoyl-glycerol and N-palmitoylethanolamine, was significantly lower in inflamed than uninflamed IBD mucosa, and this was paralleled by lower activity of the AEA-synthesizing enzyme N-acyl-phosphatidylethanolamine-specific phospholipase D and higher activity of the AEA-degrading enzyme fatty acid amide hydrolase. MAEA significantly downregulated interferon-γ and tumor necrosis factor-α secretion by both organ culture biopsies and lamina propria mononuclear cells. Although these results are promising, further studies are needed to determine the role of cannabinoid pathways in gut inflammation.


From Osler to Olafson. The evolution of veterinary pathology in North America.
Most branches of biological science in North America developed first in the United States, and later were taught and practiced in Canada. An exception was veterinary pathology, which as a discipline taught in veterinary colleges and as a field of research, developed first in Canada, and from there crossed the border to the United States. Pathology was first taught at the Montreal Veterinary College, founded in 1866 by Duncan McEachran, a graduate of the Edinburgh Veterinary College. From the outset, he formed a close association with the medical faculty of McGill University, permitting his students to attend the same classes in the basic subjects with the medical students. Eventually, the Montreal Veterinary College became formally affiliated with McGill University, as the Faculty of Comparative Medicine and Veterinary Science. The McGill veterinary faculty was forced to close for economic reasons in 1903, but it left an enduring legacy, particularly in the field of veterinary pathology. The legacy, a novel concept in the 1870's, was that pathology was the cornerstone of a veterinary education; the place where anatomy, physiology, chemistry and botany met with the clinical subjects, and gave the latter meaning. This tradition was formed at the Montreal Veterinary College by the world renowned physician William Osler, North America's leading medical teacher, whom McEachran had invited to teach at the College in 1876 in addition to his duties in the faculty of medicine. Osler had studied with Virchow in Berlin and applied his methods of autopsy technique and of scientific inquiry to his teaching of both human and veterinary pathology at McGill. Osler also undertook investigations into various diseases of domestic animals, at the request of McEachran, who doubled as Chief Veterinary Inspector for the Dominion Department of Agriculture. Osler left McGill University in 1884. Only after that year did other North American veterinary schools adopt pathology as a discipline of instruction. However, by 1884, Osler had already left his indelible imprint on the students (both medical and veterinary) he had taught in Montreal, one of whom took over the teaching of pathology in the veterinary college. Another, who followed Osler's example and also studied in Berlin with Virchow, wrote the first book in the English language on veterinary post mortem technique in 1889.(ABSTRACT TRUNCATED AT 400 WORDS)


Random-effects meta-analyses are not always conservative.
It is widely held that random-effects summary effect estimates are more conservative than fixed-effects summaries in epidemiologic meta-analysis. This view is based on the fact that random-effects summaries have higher estimated variances and, consequently, wider confidence intervals than fixed-effects summaries when there is evidence of appreciable heterogeneity among the results from the individual studies. In such instances, however, the random-effects point estimates are not invariably closer to the null value nor are their p values invariably larger than those of fixed-effects summaries. Thus, random-effects summaries are not predictably conservative according to either of these two connotations of the term. The authors give an example from a meta-analysis of water chlorination and cancer in which the random-effects summaries are less conservative in both of these alternative senses and possibly more biased than the fixed-effects summaries. The discussion of when to use random effects and when to use fixed effects in computing summary estimates should be replaced by a discussion of whether summary estimates should be computed at all when the studies are not methodologically comparable, when their results are discernibly heterogeneous, or when there is evidence of publication bias.


Climate drives adaptive genetic responses associated with survival in big sagebrush (Artemisia tridentata).
A genecological approach was used to explore genetic variation for survival in Artemisia tridentata (big sagebrush). Artemisia tridentata is a widespread and foundational shrub species in western North America. This species has become extremely fragmented, to the detriment of dependent wildlife, and efforts to restore it are now a land management priority. Common-garden experiments were established at three sites with seedlings from 55 source-populations. Populations included each of the three predominant subspecies, and cytotype variations. Survival was monitored for 5 years to assess differences in survival between gardens and populations. We found evidence of adaptive genetic variation for survival. Survival within gardens differed by source-population and a substantial proportion of this variation was explained by seed climate of origin. Plants from areas with the coldest winters had the highest levels of survival, while populations from warmer and drier sites had the lowest levels of survival. Survival was lowest, 36%, in the garden that was prone to the lowest minimum temperatures. These results suggest the importance of climatic driven genetic differences and their effect on survival. Understanding how genetic variation is arrayed across the landscape, and its association with climate can greatly enhance the success of restoration and conservation.


Ultrastructural and microbial analyses of cellulose degradation in leaf-cutter ant colonies.
Leaf-cutter ants (Atta and Acromyrmex) use fresh leaves to cultivate a mutualistic fungus (Leucoagaricus gongylophorus) for food in underground gardens. A new ant queen propagates the cultivar by taking a small fragment of fungus from her parent colony on her nuptial flight and uses it to begin her own colony. Recent research has shown that the ants' fungus gardens are colonized by symbiotic bacteria that perform important functions related to nitrogen fixation and have been implicated in contributing to plant biomass degradation. Here, we combine bacterial culturing in several media for counts and identification using the 16S rRNA gene with electron microscopy to investigate the process of cellulose degradation in the fungus garden and refuse dumps, and to assess the potential role of symbiotic bacteria. We show through electron microscopy that plant cell walls are visibly degraded in the bottom section of fungus gardens and refuse dumps, and that bacteria are more abundant in these sections. We also consistently isolated cellulolytic bacteria from all sections of fungus gardens. Finally, we show by culture-dependent and electron microscopy analysis that the fungus garden pellets carried by recently mated queens are colonized by fungus garden-associated bacteria. Taken together, our results indicate that cellulose is degraded in fungus gardens, and that fungus garden bacteria that may contribute to this deconstruction are vertically transmitted by new queens.


Interpretation of Nasal Swab Measurements Following Suspected Releases of Actinide Aerosols.
For radionuclides such as plutonium and americium, detection of removable activity in the nose (i.e., nasal swab measurements) are frequently used to determine whether follow-up bioassay measurements are warranted following a potential intake. For this paper, the authors analyzed 429 nasal swab measurements taken following incidents or suspicious circumstances (such as an air monitor alarming) at Los Alamos National Laboratory (LANL) for which the dose was later evaluated using in vitro bioassay. Nasal swab measurements were found to be very poor predictors of dose and should not be used as such in the field. However, nasal swab measurements can be indicative of whether a reliably detectable committed effective dose (CED) occurred. About 14% of nasal swab measurements between 1.25 and 16.7 Bq corresponded to CEDs greater than 1 mSv, so in general, positive nasal swabs always indicate that follow-up bioassay should be performed (positive nasal swabs less than 1.25 Bq are considered separately). This probability increased significantly for nasal swabs greater than 16.7 Bq. Only about 3% of nasal swabs with no detectable activity (NDA) corresponded to reliably detectable CEDs. A nasal swab with NDA is therefore necessary, but not sufficient, to negate the need for a follow-up bioassay if it was collected following other workplace indicators of a potential intake.


Carbohydrate and fatty acid metabolism of cultured adult cardiac myocytes.
The energy metabolism of exogenous and endogenous substrates was investigated in Ca-tolerant adult ventricular myocytes in short-term culture. CO2 production from exogenous glucose (5 mM), lactate (5 mM), and palmitate (100 microM) were 8, 20, and 29 mumol X h-1 X g wet wt-1. Endogenous lipolysis shared in energy production by 78, 61, and 31%, respectively. Fatty acids represented the main respiratory fuel even when 10(-7) M insulin, 5 mM lactate, or 5 mM dichloroacetate were supplied in addition to glucose. With palmitate, triglyceride contents were doubled within 3 h of cell incubation. With 5 mM glucose as sole exogenous substrate the energy turnover in these resting cells resembled that of arrested hearts, corresponding to 2 ml O2 X min-1 X 100 g wet wt-1. It is concluded that the basic features of substrate metabolism resemble those of the intact myocardium in that fatty acids represent the major fuel, but the contribution of endogenous lipolysis is greater than in the beating heart.


Monitoring of Air-Dispersed Formaldehyde and Carbonyl Compounds as Vapors and Adsorbed on Particulate Matter by Denuder-Filter Sampling and Gas Chromatographic Analysis.
Carbonyl compounds (CCs) are products present both as vapors and as condensed species adsorbed on the carbonaceous particle matter dispersed in the air of urban areas, due to vehicular traffic and human activities. Chronic exposure to CCs is a potential health risk given the toxicity of these chemicals. The present study reports on the measurement of the concentrations of 14 CCs in air as vapors and 2.5 µm fraction PM by the ENVINT GAS08/16 gas/aerosol sampler, a serial sampler that uses annular denuder, as sampling device. The 14 CCs were derivatized during sampling prior to gas-chromatographic separation and multiple detection by mass spectrometry, nitrogen-phosphorus thermionic, electron capture detection. Outdoor air multiple samples were collected in four locations in the urban area of Florence. The results evidenced that formaldehyde, acetaldehyde, and acetone were the more abundant CCs in the studied areas. The data collected was discussed considering the particle to vapor ratio of each CC found. The CCs pollution picture obtained was tentatively related to the nature and intensity of the traffic transiting by the sampling sites. This approach allowed to determine 14 CCs in both concentrated and diluted samples and is proposed as a tool for investigating outdoor and indoor pollution.


Practice parameter: the diagnostic evaluation and treatment of trigeminal neuralgia (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology and the European Federation of Neurological Societies.
Trigeminal neuralgia (TN) is a common cause of facial pain. To answer the following questions: 1) In patients with TN, how often does routine neuroimaging (CT, MRI) identify a cause? 2) Which features identify patients at increased risk for symptomatic TN (STN; i.e., a structural cause such as a tumor)? 3) Does high-resolution MRI accurately identify patients with neurovascular compression? 4) Which drugs effectively treat classic and symptomatic trigeminal neuralgia? 5) When should surgery be offered? 6) Which surgical technique gives the longest pain-free period with the fewest complications and good quality of life? Systematic review of the literature by a panel of experts. In patients with trigeminal neuralgia (TN), routine head imaging identifies structural causes in up to 15% of patients and may be considered useful (Level C). Trigeminal sensory deficits, bilateral involvement of the trigeminal nerve, and abnormal trigeminal reflexes are associated with an increased risk of symptomatic TN (STN) and should be considered useful in distinguishing STN from classic trigeminal neuralgia (Level B). There is insufficient evidence to support or refute the usefulness of MRI to identify neurovascular compression of the trigeminal nerve (Level U). Carbamazepine (Level A) or oxcarbazepine (Level B) should be offered for pain control while baclofen and lamotrigine (Level C) may be considered useful. For patients with TN refractory to medical therapy, Gasserian ganglion percutaneous techniques, gamma knife, and microvascular decompression may be considered (Level C). The role of surgery vs pharmacotherapy in the management of TN in patients with MS remains uncertain.


Correlation of in vivo imaging to morphomolecular pathology in translational research: challenge accepted.
Correlation of in vivo imaging to histomorphological pathology in animal models requires comparative interdisciplinary expertise of different fields of medicine. From the morphological point of view, there is an urgent need to improve histopathological evaluation in animal model-based research to expedite translation into clinical applications. While different other fields of translational science were standardized over the last years, little was done to improve the pipeline of experimental pathology to ensure reproducibility based on pathological expertise in experimental animal models with respect to defined guidelines and classifications. Additionally, longitudinal analyses of preclinical models often use a variety of imaging methods and much more attention should be drawn to enable for proper co-registration of in vivo imaging methods with the ex vivo morphological read-outs. Here we present the development of the Comparative Experimental Pathology (CEP) unit embedded in the Institute of Pathology of the Technical University of Munich during the Collaborative Research Center 824 (CRC824) funding period together with selected approaches of histomorphological techniques for correlation of in vivo imaging to morphomolecular pathology.


Absolute configuration of dolichol.
A derivative of dolichol was formed and then chemically degraded to a small fragment containing the sole centre of asymmetry of the original molecule. Polarimetric comparison of this derivative with a standard prepared from (R)-citronellol showed dolichol to have an S-configuration at C-3. To determine the optical purity of dolichol a diastereoisomeric derivative was prepared and compared with standard diastereoisomers, which could be resolved by high-pressure liquid chromatography. Dolichols from pig liver, human liver and hen oviduct were analysed by this procedure and were all found to be greater than 95% S-configuration.


Crossed cerebral lateralization for verbal and visuo-spatial function in a pair of handedness discordant monozygotic twins: MRI and fMRI brain imaging.
To examine the nature of hemispheric lateralization for neural processes underlying verbal fluency and visuo-spatial attention, we investigated a single pair of handedness discordant monozygotic (MzHd) twins. Imaging of the brain was undertaken using magnetic resonance imaging (MRI) and functional magnetic resonance imaging (fMRI) in combination with manual performance tasks. The twins were discordant for MRI anatomical asymmetries of the pars triangularis and planum temporale, whose asymmetry was consistent with verbal laterality on fMRI. Thus, the right-handed twin had left lateralized verbal with right lateralized visuo-spatial attention, while the left-handed twin had right lateralized verbal with left lateralized visuo-spatial activation; these data lend further support for to the conclusions of Sommer et al.


Comparison of some quality properties of soils around land-mined areas and adjacent agricultural fields.
When agricultural lands are no longer used for agriculture and allowed to recover its natural vegetation, soil organic carbon can accumulate in the soil. Measurements of soil organic carbon and aggregate stability changes under various forms of land use are needed for the development of sustainable systems. Therefore, comparison of soil samples taken from both agricultural and nearby area close to land-mined fields where no agricultural practices have been done since 1956 can be a good approach to evaluate the effects of tillage and agriculture on soil quality. The objective of this study was to compare tillage, cropping and no tillage effects on some soil-quality parameters. Four different locations along the Turkey-Syria border were selected to determine effects of tillage and cropping on soil quality. Each location was evaluated separately because of different soil type and treatments. Comparisons were made between non-tilled and non-cropped fallow since 1956 and adjacent restricted lands that were tilled about every 2 years but not planted (T) or adjacent lands tilled and planted with wheat and lentil (P). Three samples were taken from the depths of 0-20 and 20-40 cm each site. Soil organic carbon (SOC), pH ,electrical conductivity, water soluble Ca(++), Mg(++), CO₃⁻² and HCO₃⁻, extractable potassium (K(+)) and sodium (Na(+)), soil texture, ammonium (NH₄⁺-N) and nitrate (NO(3)-N), extractable phosphorous and soil aggregate stability were determined. While the SOC contents of continuous tillage without cropping and continuous tillage and cropping were 2.2 and 11.6 g kg(-1), respectively, it was 30 g kg(-1) in non-tilled and non-planted site. Tillage of soil without the input of any plant material resulted in loss of carbon from the soil in all sites. Soil extractable NO(3)-N contents of non-tilled and non-cropped sites were greatest among all treatments. Agricultural practices increased phosphorus and potassium contents in the soil profile. P(2)O(5) contents of planted soils were approximately 20 to 39 times greater than those of non-tilled and non-cropped soils at different sites. FTIR spectra showed that never tilled sites had greater phenol, carboxylic acid, amide, aromatic compounds, polysaccharide and carbohydrates than other treatments.


Metrics for assessing cytoskeletal orientational correlations and consistency.
In biology, organization at multiple scales potentiates biological function. Current advances in staining and imaging of biological tissues provide a wealth of data, but there are few metrics to quantitatively describe these findings. In particular there is a need for a metric that would characterize the correlation and consistency of orientation of different biological constructs within a tissue. We aimed to create such a metric and to demonstrate its use with images of cardiac tissues. The co-orientational order parameter (COOP) was based on the mathematical framework of a classical parameter, the orientational order parameter (OOP). Theorems were proven to illustrate the properties and boundaries of the COOP, which was then applied to both synthetic and experimental data. We showed the COOP to be useful for quantifying the correlation of orientation of constructs such as actin filaments and sarcomeric Z-lines. As expected, cardiac tissues showed perfect correlation between actin filaments and Z-lines. We also demonstrated the use of COOP to quantify the consistency of construct orientation within cells of the same shape. The COOP provides a quantitative tool to characterize tissues beyond co-localization or single construct orientation distribution. In the future, this new parameter could be used to represent the quantitative changes during maturation of cardiac tissue, pathological malformation, and other processes.


Genetic and environmental factors associated with incidence of infectious bovine keratoconjunctivitis in preweaned beef calves.
Infectious bovine keratoconjunctivitis (IBK) is one of the most economically important diseases in preweaned calves. This study examined the health records of 45,497 calves over a 20-yr period to determine environmental and genetic factors influencing the incidence of IBK. Three data sets were analyzed with an animal model. The first data set (n = 41,986) evaluated environmental factors and genetic differences among nine purebred (Angus, Braunvieh, Charolais, Gelbvieh, Hereford, Limousin, Pinzgauer, Red Poll, and Simmental) and three composite breeds (MARC I, MARC II, and MARC III). Weaning weights of calves diagnosed with IBK were 8.9 kg lighter (P < 0.05) than weights of healthy calves. Incidence of IBK was related to age of the calf and the seasonal life cycle of the face fly (Musca autumnalis). Incidence of IBK increased in the spring (June), peaked during the summer months (July to September), and then decreased in the fall. Herefords were the most susceptible breed (P < 0.05) compared with all other purebreds and composites. Estimates of direct heritability for the incidence of IBK were generally low and ranged from 0.00 to 0.28 by breed. The maternal permanent environmental and genetic effects of the dam on the incidence of IBK were not significant for most breeds. The second data set (n = 9,606) was used to estimate heterosis for the incidence of IBK from a Hereford and Angus diallel design. The heterosis effect for the incidence of IBK in reciprocal Hereford/Angus crossbred calves was slightly negative (P = 0.12) but not large. The higher incidence of IBK in Angus x Hereford calves compared with Hereford x Angus calves (13.3 vs. 8.9%) suggests a maternal effect related to the incidence of IBK. Incidence of IBK in crossbred calves sired by tropically adapted breeds (Brahma, Boran, Tuli) compared with purebred and crossbred Bos taurus types was investigated in the third data set (n = 2,622). Crossbred calves sired by tropically adapted breeds had a lower incidence of IBK than most Bos taurus types (P < 0.05), but they were not different than either reciprocal crosses of Hereford and Angus or purebred Angus calves. Response to selection for decreasing the incidence of IBK is likely to be slow because of low heritability and low incidence in most breeds. Significant breed differences for incidence of IBK may be important to some producers and management systems.


Engaging hospitalized patients with personalized health information: a randomized trial of an inpatient portal.
To determine the effects of an inpatient portal intervention on patient activation, patient satisfaction, patient engagement with health information, and 30-day hospital readmissions. From March 2014 to May 2017, we enrolled 426 English- or Spanish-speaking patients from 2 cardiac medical-surgical units at an urban academic medical center. Patients were randomized to 1 of 3 groups: 1) usual care, 2) tablet with general Internet access (tablet-only), and 3) tablet with an inpatient portal. The primary study outcome was patient activation (Patient Activation Measure-13). Secondary outcomes included all-cause readmission within 30 days, patient satisfaction, and patient engagement with health information. There was no evidence of a difference in patient activation among patients assigned to the inpatient portal intervention compared to usual care or the tablet-only group. Patients in the inpatient portal group had lower 30-day hospital readmissions (5.5% vs. 12.9% tablet-only and 13.5% usual care; P = 0.044). There was evidence of a difference in patient engagement with health information between the inpatient portal and tablet-only group, including looking up health information online (89.6% vs. 51.8%; P < 0.001). Healthcare providers reported that patients found the portal useful and that the portal did not negatively impact healthcare delivery. Access to an inpatient portal did not significantly improve patient activation, but it was associated with looking up health information online and with a lower 30-day hospital readmission rate. These results illustrate benefit of providing hospitalized patients with real-time access to their electronic health record data while in the hospital. ClinicalTrials.gov Identifier: NCT01970852.


Mutagenic/carcinogenic potential of DEHP and MEHP.
The mutagenic/carcinogenic activities of DEHP and MEHP were studied in bacteria and mammalian cells. MEHP but not DEHP exerted a dose-dependent DNA damaging effect to B. subtilis in Rec-assay. DEHP and MEHP showed mutagenic activities to S. typhimurium TA-100, with and without S-9 mix, respectively. MEHP produced not only the mutation in E. coli WP2B/r but also sister chromatid exchanges (SCE) in Chinese hamster V79 cells. It also induced 8AG/6TG-resistant gene mutations and chromosomal aberrations in the V79 cells. Transplacental administration of DEHP or MEHP to the Syrian golden hamster embryos was carried out by administering DEHP or MEHP to gravid animals on day 11 of gestation, followed by the cultivation of embryonic cells for 15-20 days. Both DEHP and MEHP induced 8AG/6TG-resistant mutation, chromosomal aberrations and morphological transformation in the embryonic cells of the Syrian golden hamster.


Interdisciplinary Screening, Diagnosis, Therapy and Follow-up of Breast Cancer. Guideline of the DGGG and the DKG (S3-Level, AWMF Registry Number 032/045OL, December 2017) - Part 2 with Recommendations for the Therapy of Primary, Recurrent and Advanced Breast Cancer.
Purpose The aim of this official guideline coordinated and published by the German Society for Gynecology and Obstetrics (DGGG) and the German Cancer Society (DKG) was to optimize the screening, diagnosis, therapy and follow-up care of breast cancer. Method The process of updating the S3 guideline published in 2012 was based on the adaptation of identified source guidelines. They were combined with reviews of evidence compiled using PICO (Patients/Interventions/Control/Outcome) questions and with the results of a systematic search of literature databases followed by the selection and evaluation of the identified literature. The interdisciplinary working groups took the identified materials as their starting point and used them to develop suggestions for recommendations and statements, which were then modified and graded in a structured consensus process procedure. Recommendations Part 2 of this short version of the guideline presents recommendations for the therapy of primary, recurrent and metastatic breast cancer. Loco-regional therapies are de-escalated in the current guideline. In addition to reducing the safety margins for surgical procedures, the guideline also recommends reducing the radicality of axillary surgery. The choice and extent of systemic therapy depends on the respective tumor biology. New substances are becoming available, particularly to treat metastatic breast cancer.


PGC-1β regulates angiogenesis in skeletal muscle.
Aerobic metabolism requires oxygen and carbon sources brought to tissues via the vasculature. Metabolically active tissues such as skeletal muscle can regulate blood vessel density to match metabolic needs; however, the molecular cues that coordinate these processes remain poorly understood. Here we report that the transcriptional coactivator peroxisome proliferator-activated receptor-γ coactivator-1β (PGC-1β), a potent regulator of mitochondrial biology, induces angiogenesis in skeletal muscle. PGC-1β induces the expression of vascular endothelial growth factor (VEGF) in cell culture and in vivo. The induction of VEGF by PGC-1β requires coactivation of the orphan nuclear receptor estrogen-related receptor-α (ERRα) and is independent of the hypoxia-inducible factor (HIF) pathway. In coculture experiments, overexpression of PGC-1β in skeletal myotubes increases the migration of adjacent endothelial cells, and this depends on VEGF signaling. Transgenic expression of PGC-1β in skeletal myocytes dramatically increases muscular vessel density. Taken together, these data indicate that PGC-1β is a potent regulator of angiogenesis, thus providing a novel link between the regulations of oxidative metabolism and vascular density.


Polymorphisms in metabolizing enzymes and the risk of head and neck squamous cell carcinoma in the Slavic population of the central Europe.
The question of susceptibility to squamous cell carcinoma of head and neck (SCCHN) in the environmental context was addressed by analysis of functional polymorphisms in enzymes metabolizing smoke constituents and/or alcohol (CYP2A13, CYP1B1, EPHX1, NQO1, GSTM1, GSTP1, GSTT1, ADH1B and ADH1C). Case-control study of 122 age- and sex-matched pairs of subjects was performed using so far unexplored Central European Slavic population with high level of tobacco and alcohol abuse. Age-, gender-, smoking- and alcohol-adjusted logistic regression failed to demonstrate any significant association of the analyzed polymorphisms with the SCCHN risk. When interactions between potential modifiers of effect, i.e. smoking and alcohol were tested, drinkers seemed to be at lower risk than nondrinkers when carrying the heterozygous genotype Ile/Val in codon 432 of CYP1B1 (OR=0.42; 95% CI=0.21-0.83; p=0.013 vs. OR=1.02; 95% CI=0.34-2.94; p=0.977). Similarly, drinkers were at lower risk than nondrinkers when carrying the heterozygous genotype Pro/Ser in codon 187 of NQO1 (OR=0.41; 95% CI=0.19-0.88; p=0.022 vs. OR=0.96; 95% CI=0.29-3.12; p=0.948). More interestingly, drinkers carrying the rare homozygous genotype Val/Val in codon 350 of ADH1C were at significantly higher risk than nondrinkers carrying this genotype (OR=4.01; 95% CI=1.61-10.01; p=0.003 vs. OR=0.93; 95% CI=0.25-3.57; p=0.919). This result confirmed findings of previously published studies. Smoking did not significantly modify the effect of genotypes. Our data thus demonstrate that genetic susceptibility to SCCHN shall be further followed on populations with different genetic background and lifestyle.


Anxiolytic potential of resveratrol and rufinamide combination by modulating GABA-ergic transmission: insights from experiments, molecular docking and dynamics simulations.
Resveratrol is a polyphenolic phytocompound known to possess anxiolytic-like effects but its impact on central gammaaminobutyric acid (GABA) modulation has never been explored. The purpose of this study was to analyze the anxiolytic-like effects of resveratrol alone and in combination with rufinamide, an antiepileptic drug which has never been studied for its anxiolytic potential. The BALB/c mice were tested in a battery of behavior testing after administration of resveratrol (50 mg/kg) and rufinamide (50 mg/kg) alone and in combination. Moreover, molecular docking studies were also carried out to understand the interaction of resveratrol and rufinamide with GABA aminotransferase, GABA receptor and GABA-A transporter type 1. Resveratrol alone exerted notable anxiolytic-like effects and improved outcomes in few experiments but rufinamide alone did not yield any beneficial outcomes. However, the animal co-administered with resveratrol and rufinamide behaved exceptionally well (p<0.05) and preferred open, illuminated and exposed areas of open field, light/dark and elevated plus maze. Further, these animals showed reduced anxiety towards anxiogenic stimuli i.e. holes and marbles in hole board and marble bury tests, respectively. Resveratrol and rufinamide showed moderate to strong binding affinities with GABA proteins, indicating the potential to treat anxiety-like neurological disorders. Moreover, resveratrol and rufinamide were analyzed using molecular docking to determine their interaction with GABA receptors, transporters, and transaminase. The results suggest that their anxiolytic-like effects may be due to inhibiting GABA reuptake transporter 1 protein, leading to increased synaptic levels of GABA neurotransmitter, as seen in stable molecular dynamics results with the 7SK2 GABA transporter protein.


Increasing Incidence and Recurrence Rate of Venous Thromboembolism in Paediatric Oncology Patients in One Single Centre Over 25 Years.
Venous thromboembolism (VTE) is a serious complication in paediatric oncology patients. To identify the incidence, risk factors and recurrence rate of VTE in paediatric oncology patients, an observational, retrospective cohort study of all consecutive children (≤18 years) with malignancies, treated at the Emma Children's Hospital Academic Medical Centre between January 1989 and December 2013, was done. A matched case-control study in children with lymphomas was performed, to identify thrombotic risk factors. Cumulative recurrence-free survival after first VTE was estimated by the Kaplan-Meier method. Of the 2,183 children included (male: female = 1.4:1.0; median age, 6.6 years) with cancer, 78 patients developed VTE (3.6%; 95% confidence interval [CI], 2.8-4.4). The incidence increased from 0.8% (4/478, 95% CI, 0.0-1.6) between 1989 and 1993 to 10.4% (44/423, 95% CI, 7.6-13.4) between 2009 and 2013. Independent risk factors for VTE were age ≥ 12 years, acute lymphoblastic leukaemia (ALL) and lymphoma. The case-control study in lymphoma patients showed a trend for increased VTE incidence in stage IV lymphoma. Twelve (15.4%) patients developed recurrent thrombosis, 7 patients while on therapeutic or prophylactic anticoagulation. The cumulative recurrence-free survival after first VTE was 88.5, 87.1 and 80.6% after 1, 5 and 10 years, respectively. In conclusion, we demonstrated an increasing incidence of VTE in children with malignancies, with age ≥ 12 years, ALL and lymphoma as independent risk factors. The elevated recurrence rate underlines the importance of full anticoagulant therapy and might warrant prophylactic anticoagulation after first VTE during cancer treatment.


Anatomical connectivity between subcortical structures.
Understanding anatomical connectivity is crucial for improving outcomes of deep brain stimulation surgery. Tractography is a promising method for noninvasively investigating anatomical connectivity, but connections between subcortical regions have not been closely examined by this method. As many connections to subcortical regions converge at the internal capsule (IC), we investigate the connectivity through the IC to three subcortical nuclei (caudate, lentiform nucleus, and thalamus) in six macaques. We show that a statistical correction for a known distance-related artifact in tractography results in large changes in connectivity patterns. Our results suggest that care should be taken in using tractography to assess anatomical connectivity between subcortical structures.


Removal of EDTA from low pH printed-circuit board wastewater in a fluidized zero valent iron reactor.
Fluidized zero valent iron (ZVI) process was adopted to reduce ethylenediaminetetraacetic acid (EDTA) from low pH printed-circuit board (PCB) wastewater for two reasons: (1) low pH of the wastewater favoring the ZVI reaction; (2) higher ZVI utilization for fluidized process due to abrasive motion of the ZVI. The results showed that the degradation of EDTA was greatly enhanced under acidic pH, longer hydraulic detention time (HRT) and presence of dissolved oxygen (DO). Without addition of oxygen, 65% of EDTA was removed with capacity of 7.33 mg EDTA/g ZVI at pH 2, ZVI dosage of 424 g/L and HRT 10 min. With 6.8 mg/L of DO, 83% of EDTA was reduced with capacity of 19.01 mg EDTA/g ZVI for the same experimental condition. The presence of oxygen/ZVI initiated a Fenton type reaction to reduce EDTA. The end product after EDTA degradation was analyzed by high performance liquid chromoagraphy (HPLC), where propionic acid (C(2)H(5)COOH) was observed, indicating EDTA (oxidation number for carbon is 2) was oxidized to propionic acid (oxidation number for carbon is 3). Nitrogen species was also measured and the nitrogen in EDTA was converted to ammonium instead of nitrate and nitrite.


[Effect of 7-day immersion hypokinesia on the characteristics of precise movements].
Experiments were carried out to study the effect of 7-day immersion hypokinesia on precision movements that included reproduction of a certain isometric strain of leg muscles (30% from the maximum voluntary level) and angular displacement of the ankle (15 degrees) relative to the 90 degrees position. On the first postimmersion day the precision level deteriorated, i. e., the error and variability of the movements to be reproduced consistently increased. The precision decline was the highest with plantar flexion, when the error of the effort and position reproduction was 24 and 28%, respectively, and the lowest with dorsiflexion, when the error was 17 and 25%, respectively, versus 6-8% in the baseline tests. Precision disorders were seen in the structure of movements which lost their stereotypic pattern and became fragmentary, transforming into slow approximate movements versus the pattern of preimmersion movements that were of a rapid programmed control type. Precision changes during plantar flexion movements were usually excessive, hypermetric and almost twice longer than preimmersion. The origin of the above precision changes seems to be primarily associated with muscle atonia. At the same time data analysis shows that in nearly 50% of cases the values of precision changes in movements of various types (efforts and displacements) and different directions (plantar and dorsiflexion) were correlated. This is suggestive of common central mechanisms underlying their development.


Backbone dynamics of homologous fibronectin type III cell adhesion domains from fibronectin and tenascin.
Fibronectin type III domains are found as autonomously-folded domains in a large variety of multidomain proteins, including extracellular matrix proteins. A subset of these domains employ an Arg-Gly-Asp (RGD) tripeptide motif to mediate contact with cell-surface receptors (integrins). This motif mediates protein-protein interactions in a diverse range of biological processes, such as in tissue development, would healing and metastasis. The molecular basis for affinity and specificity of cell adhesion via type III domains has not been clearly established. The tenth type III domain from fibronectin (FNfn10) and the third type III domain from tenascin-C (TNfn3) have 27% sequence identity and share the same overall protein fold, but present the RGD motifs in different structural contexts. The dynamical properties of the RGD motifs may affect the specificity and affinity of the FNfn10 and TNfn3 domains. Structure-dynamics correlations for these structurally homologous proteins may reveal common molecular features which are important to the dynamical properties of proteins. The intramolecular dynamics of the protein backbones of FNfn10 and TNfn3 have been studied by 15N nuclear spin relaxation. The FG loop in FNfn10, which contains the RGD motif, exhibits extensive flexibility on picosecond to nanosecond timescales, but motions on microsecond to millisecond timescales are not observed. The equivalent region in TNfn3 is as rigid as regular elements of secondary structure. The CC' loop also is more flexible on picosecond-nanosecond timescales in FNfn10 than in TNfn3. Conformational exchange, reflecting flexibility on microsecond-millisecond timescales, is observed in beta strands A and B of both FNfn10 and TNfn3. Comparison of the structures of the FNfn10 and TNfn3 reveals several features related to their different dynamical properties. The larger amplitude motions of loops in FNfn10 are consistent with the hypothesis that flexibility of these regions facilitates induced-fit recognition of fibronectin by multiple receptors. Similarly, the more rigid loops of TNfn3 may reflect greater specificity for particular integrins. The correlations observed between structural features and dynamical properties of the homologous type III domains indicate the influence of hydrogen bonding and hydrophobic packing on dynamical fluctuations in proteins.


High throughput screening of genetic polymorphisms by matrix-assisted laser desorption ionization time-of-flight mass spectrometry.
In the post genomic era, the screening of many different genetic polymorphisms in large populations represents a major goal that will facilitate the understanding of individual genetic variability in the development of multi factor diseases and in drug response and toxicities. The increasing interest in these pathogenetic and pharmacogenomic studies by both academic and pharmaceutical industry researchers has increased the demand for broad genome association studies. This demand has produced a boom in the development of new and robust high throughput screening methods for genotype analysis. Matrix-assisted laser-desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) represents an emerging and powerful technique for DNA analysis because of its high speed, accuracy, no label requirement, and cost-effectiveness. So far, many MALDI-TOF MS approaches have been developed for rapid screening of single nucleotide polymorphisms (SNPs), variable sequences repeat, epigenotype analysis, quantitative allele studies, and for the discovery of new genetic polymorphisms. The more established methods are based on single base primer extension and minisequencing implemented with new chemical features to overcome the limitations associated with DNA analysis using MALDI-TOF MS. These new promising methods of genotyping include both photochemical and other different chemical and enzyme cleavage strategies that facilitate sample automation and MS analysis for both real-time genotyping and resequencing screening. In this review, we analyze and discuss in depth the advantages and the limitations of the more recent developments in MALDI-TOF MS analysis for large-scale genomic studies applications.


[An Experience Applying Life Review and Resilience to a Geriatric Patient With Functional Limitations and Depression].
Negative self-values and attitudes during the process of adapting to disease tend to engender depression in the elderly. This case study describes a nursing experience with an elderly patient with depression related to a decline in activity and family role changes related to unexpected spinal infection. The nursing care in this study was provided between February 28th and April 25th, 2017. A comprehensive geriatric assessment was employed, with results showing that the patient was affected by negative self-identity and attitudes. The geriatric depression scale showed moderate depression. Life review strategy was employed in the interview to impart a positive influence on a different life stage and a resilience model was used to interpret the interview transcript. The protective factors were identified and used to develop an individualized nursing intervention that included promoting the support of the husband in order to enhance positive attitude, promoting interactions with the grandchildren in order to increase feelings of independence. Finally, the patient became cognizant of family support and expressed positive words and self-values, which improved depression symptoms. This case report provides a valuable nursing care experience as a reference for similar cases in the future.


Region of birth, sex, and reproductive health in rural immigrant latino farmworkers: the MICASA study.
Characterize sexual and reproductive health among immigrant Latino farmworkers. We surveyed 806 immigrant Latino farmworkers from Mexico and Central America in a rural agricultural community in California's Central Valley. A total of 556 respondents were born in Mexico (272 men, 284 women) and 250 in Central America (135 men, 115 women). The majority entered the United States as young adults, with median age at immigration ranging from 20 (Mexican-born men) to 24 (Central American-born women). Nearly 95% of respondents were married or cohabiting. Median age for sexual debut was 18 for women and was younger for men (adjusted mean difference: -2.1 years, 95% CI: -2.6 to -1.7). Median number of lifetime sexual partners was 1 for women and greater for men (adjusted mean difference: 2.0 partners, 95% CI: 1.3-2.7). Contraception use was less likely among men and among Central American women compared to Mexico-born women. Among sexually active persons not using contraception, the most common reasons for nonuse were "Don't want to"/"Don't like any" followed by desire to become or being pregnant. Women reported a median of 3 pregnancies; there were no significant differences based on respondents' region of birth. This group of Latino immigrants demonstrated behaviors conducive to reproductive health: late sexual debut, few lifetime sexual partners, and high prevalence of marriage. Preventive education campaigns should focus on maintaining healthy behaviors, especially in men. Identifying groups with common provenance and cultural heritage may aid in maximizing acceptability and effectiveness of prevention programs.


[The problems of premature senescence in occupational lung diseases].
The article presents the results of researches aimed at estimation of the rate of biological aging at dust diseases of lungs. It is proved that influence of fibrogenic aerosols leads to the increase in biological age of patients with the dust diseases of lungs. It is proved that definition of biological age as a criterion of diagnostics is possible at dust diseases of lungs.