Skeletal Toxicity of Coplanar Polychlorinated Biphenyl Congener 126 in the Rat Is Aryl Hydrocarbon Receptor Dependent.
Epidemiological evidence links polychlorinated biphenyls (PCBs) to skeletal toxicity, however mechanisms whereby PCBs affect bone are poorly studied. In this study, coplanar PCB 126 (5 μmol/kg) or corn oil vehicle was administered to N = 5 and 6 male and female, wild type (WT) or AhR -/- rats via intraperitoneal injection. Animals were sacrificed after 4 weeks. Bone length was measured; bone morphology was assessed by microcomputed tomography and dynamic histomorphometry. Reduced bone length was the only genotype-specific effect and only observed in males (p < .05). WT rats exposed to PCB 126 had reduced serum calcium, and smaller bones with reduced tibial length, cortical area, and medullary area relative to vehicle controls (p < .05). Reduced bone formation rate observed in dynamic histomorphometry was consistent with inhibition of endosteal and periosteal bone growth. The effects of PCB 126 were abolished in AhR -/- rats. Gene expression in bone marrow and shaft were assessed by RNA sequencing. Approximately 75% of the PCB-regulated genes appeared AhR dependent with 89 genes significantly (p < .05) regulated by both PCB 126 and knockout of the AhR gene. Novel targets significantly induced by PCB 126 included Indian hedgehog (Ihh) and connective tissue growth factor (Ctgf/Ccn2), which regulate chondrocyte proliferation and differentiation in the bone growth plate and cell-matrix interactions. These data suggest the toxic effects of PCB 126 on bone are mediated by AhR, which has direct effects on the growth plate and indirect actions related to endocrine disruption. These studies clarify important mechanisms underlying skeletal toxicity of dioxin-like PCBs and highlight potential therapeutic targets.


Molecular characterization of a novel UT-A urea transporter isoform (UT-A5) in testis.
Urea movement across plasma membranes is modulated by specialized transporter proteins that are products of two genes, termed UT-A and UT-B. These proteins play key roles in the urinary concentrating mechanism and fluid homeostasis. We have isolated and characterized a 1.4-kb cDNA from testes encoding a new isoform (UT-A5) belonging to the UT-A transporter family. For comparison, we also isolated a 2. 0-kb cDNA from mouse kidney inner medulla encoding the mouse UT-A3 homologue. The UT-A5 cDNA has a putative open reading frame encoding a 323-amino acid protein, making UT-A5 the smallest UT-A family member in terms of molecular size. Its putative topology is of particular interest, because it calls into question earlier models of UT-A transporter structure. Expression of UT-A5 cRNA in Xenopus oocytes mediates phloretin-inhibitable urea uptake and does not translocate water. The distribution of UT-A5 mRNA is restricted to the peritubular myoid cells forming the outermost layer of the seminiferous tubules within the testes and is not detected in kidney. UT-A5 mRNA levels are coordinated with the stage of testes development and increase 15 days postpartum, commensurate with the start of seminiferous tubule fluid movement.


Patterns of plasma cobalamins in control subjects and in cases of vitamin B12 deficiency.
A method for thin-layer chromatography and bioautography of plasma cobalamins is described. It requires only 5 ml of blood. Results are reported in 35 healthy people and hospital controls, and in 14 cases of untreated pernicious anaemia. In the control group there were two major components, methylcobalamin and a component which is probably a mixture of hydroxocobalamin and deoxyadenosyl cobalamin. Many cases of untreated pernicious anaemia showed a characteristic pattern in which methylcobalamin was reduced in relation to hydroxocobalamin. This pattern was also seen in one vegan who was taking a diet without B(12) supplement. A minority of subjects showed traces of cyanocobalamin; this compound was not confined to smokers. The significance of the results and possible diagnostic utility of the technique are discussed.


Evaluation of a 32-channel versus a 12-channel head coil for high-resolution post-contrast MRI in giant cell arteritis (GCA) at 3T.
The aim of this study was to evaluate the diagnostic value of a 32-channel head coil for the characterization of mural inflammation patterns in the superficial cranial arteries in patients with giant cell arteritis (GCA) compared to a standard 12-channel coil at 3T MRI. 55 patients with suspected GCA underwent high resolution T1-weighted post-contrast MRI at 3T to detect inflammation related vessel wall enhancement using both coils. To account for different time delays between contrast agent injection and sequence acquisition, the patients were divided into two cohorts: 27 patients were examined with the 32-channel coil first and 28 patients with the 12-channel coil first. Images were evaluated by two blinded readers with regard to image quality, artifact level and arteries' inflammation according to a standardized ranking scale; furthermore signal-to-noise ratio (SNR) measurements were performed at three locations. Identification of arteries' inflammation was achieved with both coils with excellent inter-observer agreement (κ=0.89 for 12-channel and κ=0.96 for 32-channel coil). Regarding image grading, the inter-observer variability was moderate for the 12-channel (κ=0.5) and substantial for the 32-channel coil (κ=0.63). Significantly higher SNR and improved image quality (p<0.01) were obtained with the 32-channel coil in either coil order. Image quality for depiction of the superficial cranial arteries was superior for the 32-channel coil. For standardized GCA diagnosis, the 12-channel coil was sufficient.


Health-related quality-of-life and treatment satisfaction of individuals with hemophilia A treated with turoctocog alfa pegol (N8-GP): a new recombinant extended half-life FVIII.
Prophylactic treatment regimens lead to improvements in health-related quality-of-life (HRQoL) among individuals with hemophilia. Turoctocog alfa pegol (N8-GP) provides the benefit of extending the duration of protection from bleeding and reducing the number of injections, which is expected to impact HRQoL and treatment satisfaction (TS). To investigate the HRQoL and TS of patients with severe hemophilia A from two phase III trials evaluating the safety and efficacy of N8-GP. HRQoL was assessed using the Haemo-QoL (reported by children and their parents) and Haem-A-QoL (reported by adults). TS was assessed using Hemo-Sat. Domain and total scores for all questionnaires ranged from 0 to 100, with lower scores indicating a better HRQoL or TS. A negative change in score indicates an improvement in HRQoL/TS. Mean changes in HRQoL scores were reported for 14 children aged 4-7 years, 21 children aged 8-11 years, 10 adolescents aged 13-16 years, and 163 adults (17 years and above). Mean changes in children/adolescents-reported Haemo-QoL total score were -14.0 for ages 4-7 years, -3.6 for ages 8-11 years, and -0.1 for ages 13-16 years. Mean changes in parent-reported Haemo-QoL total scores were -11.5 for 4-7 years, -8.6 for ages 8-11 years, and -4.0 for 13-16 years. Adults' mean change in Haem-A-QoL total score was -3.1 for those receiving on-demand treatment and -2.3 for those receiving prophylaxis treatment. High levels of TS with N8-GP were reported by parents of children/adolescents and the adults at the end of the trial. While most patients reported a relatively good baseline HRQoL when entering the respective trials, the HRQoL of patients was either maintained or further improved when treated with N8-GP. Adults and parents of children and adolescents reported a high level of treatment satisfaction with N8-GP.


Is it possible to use transaminases for deciding on surgical or non-operative treatment for blunt liver trauma?
We aimed to research the relation of transaminase levels in blunt liver trauma (BLT) with the intensity of the trauma and the use of transaminase levels for deciding on surgical or non-operative treatment. In all, 44 patients with BLT diagnosed by computerized tomography (CT) were involved in this retrospective study. By testing the correlation of the transaminase levels and the grade of liver injury with receiver operator characteristics (ROC), area under the curve (AUC) was calculated; besides, the sensitivity, specificity, and cut-off values of transaminases were calculated separately for the grades. Moreover, same method was repeated for the surgically and non-operatively treated patients. Cut-off value was assessed for surgical and non-operative treatments. The efficiency of transaminases in deciding non-operative treatment was compared with that of other methods using ROC test applied on focused abdominal sonography in trauma (FAST), hemodynamic instability, blood replacement rate, aspartate aminotransferase (AST), and alanine aminotransferase (ALT). It was observed that the AUC, sensitivity, and specificity increased correspondingly with the grade rise of transaminase levels in BLT. In the selection of non-operative treatment/surgery, following values have been confirmed: AUC for AST: 0.851 (sensitivity: 86%, specificity: 73%, cut-off value: 498 U/L), AUC for ALT: 0.880 (sensitivity: 86%, specificity: 81%, cut-off value: 498 U/L), AUC for replacement: 0.948 (sensitivity: 86%, specificity: 94%), AUC for hemodynamic instability: 0.902 (sensitivity: 86%, specificity: 94%), and AUC for FAST: 0.642 (sensitivity: 57%, specificity: 75%). It was found that in BLT, transaminases can predict the injury rating with higher accuracy as the grade rises, and they outrival FAST in terms of determining the need for laparotomy.


Paraneoplastic Pemphigus: Autoimmune-Cancer Nexus in the Skin.
Paraneoplastic pemphigus (PNP) is a debilitating and lethal adult and pediatric autoimmune blistering skin disease that occurs in the setting of a known or occult neoplasm. It is characterized by painful mucosal erosions that are often resistant to therapy. These clinical characteristics, in addition to positive immunohistochemistry findings make the diagnosis of PNP. The ability to recognize and diagnose PNP has dramatically improved in the last two and half decades. However, the mortality remains 75-90% with a mean survival of less than 1 year. The disease typically progresses from localized skin manifestations to multiple organ failure despite treatment with high dose corticosteroids and immunosuppressives. Because PNP has a low incidence and prevalence, information on treatment and management strategies has depended on a limited number of case reports and case series. The rarity of the disease hampers the ability to conduct large-scale clinical trials as well as investigations into the pathophysiology of PNP. In this article, we review clinical presentation, diagnosis, management, treatment, and pathophysiology of PNP.


Metformin therapy decreases hyperandrogenism and ovarian volume in women with polycystic ovary syndrome.
It is well known that there is a close relationship between elevated androgen plasma levels and the ultrasound findings of stromal hypertrophy in polycystic ovary syndrome (PCOS). The objective of this study was to investigate the effects metformin on the hyperandrogenism and ovarian volume in PCOS. The study is an unrandomized clinical trial with before-after design. Twenty eight patients with infertility (male or female factor) meeting the Rotterdam ESHRE/ASRM criteria for PCOS were studied during the 2008-2009. The anthropometric characteristics of the patients, mean bilateral ovarian volume, and morphology by trans vaginal sonography as well as the plasma levels of leutinizing hormone, follicle stimulating hormone, estradiol, testosterone, 17-α-hydroxyprogesterone, and dehydroepianderosterone sulfate were obtained before and after treatment with metformin (500 mg three times a day) for three months. Paired t, Pearson's Correlation Coefficient, or Partial Correlation test was used to analyze the findings. The patients had a mean age of 25.67 years. A significant reduction in mean ovarian volume (11.70±4.31 ml vs 8.27±3.71 ml P=0.001), body mass index (BMI, 28.11±4.55 kg/m(2) vs 26.84±4.55 kg/m(2) P=0.000) and serum androgen levels was seen after three months of treatment with metformin. There was positive correlations between the ovarian volume and serum testosterone level (r=0.589, P=0.001) or BMI (r=0.663, P=0.000). Metformin therapy may lead to a reduction in ovarian volume. It is likely that the reduction of ovarian volume reflect a decrease in the mass of androgen producing tissues. IRCT138903244176N1.


Critical role for cross-linking of trimeric lectin domains of surfactant protein D in antiviral activity against influenza A virus.
Collectins are multimeric host defence lectins with trimeric CRDs (carbohydrate-recognition domains) and collagen and N-terminal domains that form higher-order structures composed of four or more trimers. Recombinant trimers composed of only the CRD and adjacent neck domain (termed NCRD) retain binding activity for some ligands and mediate some functional activities. The lung collectin SP-D (surfactant protein D) has strong neutralizing activity for IAVs (influenza A viruses) in vitro and in vivo, however, the NCRD derived from SP-D has weak viral-binding ability and lacks neutralizing activity. Using a panel of mAbs (monoclonal antibodies) directed against the NCRD in the present study we show that mAbs binding near the lectin site inhibit antiviral activity of full-length SP-D, but mAbs which bind other sites on the CRD do not. Two of the non-blocking mAbs significantly increased binding and antiviral activity of NCRDs as assessed by haemagglutination and neuraminidase inhibition and by viral neutralization. mAb-mediated cross-linking also enabled NCRDs to induce viral aggregation and to increase viral uptake by neutrophils and virus-induced respiratory burst responses by these cells. These results show that antiviral activities of SP-D can be reproduced without the N-terminal and collagen domains and that cross-linking of NCRDs is essential for antiviral activity of SP-D with respect to IAV.


Binding energies of water to lithiated valine: formation of solution-phase structure in vacuo.
Dissociation kinetics for loss of a water molecule from hydrated ions of lithiated valine, alanine ethyl ester and betaine are determined using blackbody infrared radiative dissociation at temperatures between -60 and 110 degrees C. From master equation modeling of these data, values of the threshold dissociation energy are obtained for clusters containing one through three water molecules. By comparing the values for valine with its two isomers, one a model for the nonzwitterion structure, the other a model for the zwitterion structure, information about the structure of valine in these hydrated clusters is inferred. Structures, relative energies, and water binding energies for these ions are also calculated at the B3LYP/6-31++G** level of theory. With one water molecule, both experiment and theory indicate that valine is not a zwitterion and that the lithium ion coordinates with the amino nitrogen and the carbonyl oxygen (NO coordinated) and the water molecule interacts directly with the lithium ion. With two water molecules, the zwitterion and nonzwitterion structures are nearly isoenergetic, but the experiment clearly indicates a NO-coordinated nonzwitterion structure. With three water molecules, both the experimental data and theory indicate that the lithium ion binds to the carboxylate group of valine, i.e., valine is zwitterionic with three water molecules. The agreement between the experimentally determined and calculated binding energies is good for all the clusters, with deviations of <== 0.12 eV.


Increased serum levels of epidermal growth factor in children with autism.
The etiology of autism is unclear, however autism is considered as a multifactorial disorder that is influenced by neurological, environmental, immunological and genetic factors. Growth factors, including epidermal growth factor (EGF), play an important role in the cellular proliferation and the differentiation of the central and peripheral nervous system. In this study we hypothesized that EGF may play a role in the pathophysiology of autism and examined serum EGF levels in children with autism. We measured serum levels of EGF in the 27 autistic children and 28 age- matched normal controls. The serum levels of EGF in the subjects with autism were significantly higher than those of normal control subjects. However, there were no correlations between serum EGF levels and clinical variables in the subjects with autism. This is the first report demonstrating the increased serum levels of EGF in children with autism. This study suggests that increased levels of EGF might have an importance in the pathophysiology of autism.


Waist circumference cutoff points in school-aged Chinese Han and Uygur children.
To examine the distribution of age- and gender-specific waist circumference (WC) and to identify optimal cutoffs for predicting cardiovascular (CV) risk factors in Chinese Han and Uygur children. In total 4,224 Han and Uygur children aged 7-18 were randomly selected from schools in Urumqi city, China. WC, height, and weight were accurately measured in all subjects. Blood pressure, fasting lipids, glucose, and insulin were determined in 258 overweight/obese children and 370 age-, gender-, and ethnicity-matched normal-weight controls selected from the same study sample. LMS (lambda-mu-sigma) method was used to construct WC centile curves. Optimal WC cutoffs were determined by comparing the performance of five sets of WC cutoffs in predicting CV risk factors. Han boys and girls had higher WC at all percentiles and ages except for girls over the age of 16. Uygur girls also showed a greater increase in WC corresponding with age (2.1 cm/year vs. 1.6 cm/year for the median) than Han girls. Compared with the other four sets of cutoffs, the 85th WC percentile showed the best combination of sensitivity (81.0%) and specificity (71.4%). The two sets of WC cutoffs constructed by allowing centile curves passing through the adult cutoffs for central adiposity using the fitted LMS curves provided poor sensitivities in predicting the presence of cluster of CV risk factors. The growth pattern of WC varies with gender and ethnicity. The 85th percentile of WC is an appropriate cutoff for Chinese Han and Uygur children in the prediction of CV risks.


Acute polyarthritis associated with active Epstein-Barr virus infection.
Nine patients with an initial onset of symptoms of acute arthritis within the preceding four weeks were enrolled in a prospective serological study with clinical follow-up for six months to two years. Four adults with chronic rheumatoid arthritis and ten healthy adults were similarly studied. Serial titers measured included antibodies to Epstein-Barr virus (EBV) antigens, group B coxsackieviruses, rubella virus, cytomegalovirus, and herpes simplex virus. Serological evidence of active EBV infection was found in four of the patients with acute arthritis, none of the patients with chronic arthritis, and one of the ten healthy adults. There was no similar correlation between acute disease and presence of antibodies to the other viruses tested. We suggest that EBV may cause acute rheumatic illnesses more commonly than is currently appreciated but is probably not involved in the etiology of typical chronic rheumatoid arthritis.


COVID-19 Outbreak and Physical Activity in the Italian Population: A Cross-Sectional Analysis of the Underlying Psychosocial Mechanisms.
Italy is one of the first European epicenters of the COVID-19 pandemic. In attempts to hinder the spread of the novel coronavirus disease, Italian government hardened protective measures, from quarantine to lockdown, impacting millions of lives dramatically. Amongst the enacted restrictions, all non-essential activities were prohibited as well as all outdoor activities banned. However, at the first spur of the outbreak, for about a dozen of days, physical and sports activities were permitted, while maintaining social distancing. In this timeframe, by administering measures coming from self-determination theory and theory of planned behavior and anxiety state, in an integrated approach, we investigated the prevalence of these activities by testing, via a Structural Equation Model, the influence of such psychosocial variables on the intention to preserve physical fitness during the healthcare emergency. Through an adequate fit of the hypothesized model and a multi-group analysis, we compared the most COVID-19 hit Italian region - Lombardy - to the rest of Italy, finding that anxiety was significantly higher in the Lombardy region than the rest of the country. In addition, anxiety negatively influenced the intention to do physical activity. Giving the potential deleterious effects of physical inactivity due to personal restrictions, these data may increase preparedness of public health measures and attractiveness of recommendations, including on the beneficial effects of exercise, under circumstances of social distancing to control an outbreak of a novel infectious disease.


A reader's guide to surgical decision analysis.
Studies using decision analysis appear increasingly often in the surgical literature. Because readers and reviewers may be unfamiliar with decision analysis, we review the technique and provide guidance on its interpretation. Review article. Decision analysis is a systematic approach to structuring a decision, collecting relevant information about the probability and relative value of outcomes, and making quantitative recommendations. Decision analysis includes the following basic components: (1) the decision model, (2) the probabilities of clinical outcomes in the model, (3) the utilities of clinical outcomes, and (4) the analysis and interpretation. To critically interpret the results of a decision analysis, readers must consider the validity of each component. The model should include all relevant clinical strategies and all important clinical outcomes. Probability estimates, whether derived from published studies or based on "clinical consensus," should be in general agreement with the reader's clinical experience. Utilities (values assigned to outcomes) are often expressed in terms of quality-adjusted life expectancy. Methods used to estimate life expectancy and to adjust for quality of life must be scrutinized carefully. Within the analysis, readers should consider the effect of varying uncertain variables in the model (sensitivity analysis) and, thus, the stability of the results. Finally, readers must assess whether the magnitude of expected benefit from the favored clinical strategy is clinically important. As decision analysis becomes more frequently used to influence clinical policy in surgery, surgeons must learn to examine the technique more critically.


Real impact of oxaliplatin in adjuvant chemotherapy for patients with stage III colon cancer based on the Multi-Institutional Registry of Large Bowel Cancer in Japan.
Although fluoropyrimidine plus oxaliplatin is the standard of care for stage III colon cancer, fluoropyrimidine alone is also recommended for stage III patients in Japanese and other practice guidelines. We assessed efficacy of adjuvant fluoropyrimidine with or without oxaliplatin across a population of patients with stage III colon cancer in the Multi-Institutional Registry of Large Bowel Cancer in Japan. From the registry, we analyzed 6,834 stage III colorectal cancer patients. Approximately 70% of colorectal cancer patients received some form of chemotherapy. Of these, we analyzed those who received adjuvant chemotherapy between 2008 and 2011. Based on the TNM classification, the 5-year overall survival rates of colon and rectal cancer after the covariate adjustment by regimens of adjuvant chemotherapy were 95.7% with fluoropyrimidines and 90.6% with oxaliplatin-combined therapy at stage IIIA (Stratified log-rank P < 0.001), 86.5% and 80.8% at stage IIIB (P < 0.001), and 72.1% and 70.7% at stage IIIC (P < 0.001), respectively. Oxaliplatin did not enhance efficacy with regard to relapse-free survival as well as overall survival. Adjuvant fluoropyrimidine monotherapy and fluoropyrimidine plus oxaliplatin show comparable efficacy benefits for the treatment of stage III of Japanese colon cancer patients. This supports the use of fluoropyrimidine alone as a standard option for this patient group in Japan.


The Mason Brown Lecture. Scots and paediatric surgery.
Scotland and Scots paediatric surgeons have been in the forefront of the development of surgical services for children. Development has occurred at different rates in sections of society. Progress or obstruction has seldom been for 'scientific' reasons but much more according to the personal interests or drive of individuals. The Scots can justifiably claim some influence in the overall evolution of paediatric surgery. It is no wonder that Henley wrote after his visit to Walter Scott in Edinburgh, "The conceit of these bloody Scotsmen is atrocious".


A new framework for reverse cholesterol transport: non-biliary contributions to reverse cholesterol transport.
Reduction of low-density lipoprotein-cholesterol through statin therapy has only modestly decreased coronary heart disease (CHD)-associated mortality in developed countries, which has prompted the search for alternative therapeutic strategies for CHD. Major efforts are now focused on therapies that augment high-density lipoprotein (HDL)-mediated reverse cholesterol transport (RCT), and ultimately increase the fecal disposal of cholesterol. The process of RCT has long been thought to simply involve HDL-mediated delivery of peripheral cholesterol to the liver for biliary excretion out of the body. However, recent studies have revealed a novel pathway for RCT that does not rely on biliary secretion. This non-biliary pathway rather involves the direct excretion of cholesterol by the proximal small intestine. Compared to RCT therapies that augment biliary sterol loss, modulation of non-biliary fecal sterol loss through the intestine is a much more attractive therapeutic strategy, given that excessive biliary cholesterol secretion can promote gallstone formation. However, we are at an early stage in understanding the molecular mechanisms regulating the non-biliary pathway for RCT, and much additional work is required in order to effectively target this pathway for CHD prevention. The purpose of this review is to discuss our current understanding of biliary and non-biliary contributions to RCT with particular emphasis on the possibility of targeting the intestine as an inducible cholesterol secretory organ.


Femur Fractures in 5 Individuals With Pantothenate Kinase-associated Neurodegeneration: The Role of Dystonia and Suggested Management.
Pantothenate kinase-associated neurodegeneration (PKAN) is a rare, neurodegenerative disorder that manifests with progressive loss of ambulation and refractory dystonia, especially in the early-onset classic form. This leads to osteopenia and stress on long bones, which pose an increased risk of atraumatic femur fractures. The purpose of this study is to describe the unique challenges in managing femur fractures in PKAN and the effect of disease manifestations on surgical outcomes. A retrospective case review was conducted on 5 patients (ages 10 to 20 y) with PKAN with a femur fracture requiring surgical intervention. Data regarding initial presentation, surgical treatment, complications, and outcomes were obtained. All patients were non-ambulatory, with 4 of 5 patients sustaining an atraumatic femur fracture in the setting of dystonia episode. One patient had an additional contralateral acetabular fracture. Postoperatively, 4 of the 5 patients sustained orthopaedic complications requiring surgical revision, with 3 of these secondary to dystonia. Overall, 4 required prolonged hospitalization in the setting of refractory dystonia. Femur fractures in PKAN present distinct challenges for successful outcomes. A rigid intramedullary rod with proximal and distal interlocking screws is most protective against surgical complications associated with refractory dystonia occurring during the postoperative period. Multidisciplinary planning for postoperative care is essential and may include aggressive sedation and pain management to decrease the risk of subsequent injuries or complications. Level IV.


Consequences, conditions and caveats: a qualitative exploration of the influence of undergraduate health professions students at distributed clinical training sites.
Traditionally, the clinical training of health professionals has been located in central academic hospitals. This is changing. As academic institutions explore ways to produce a health workforce that meets the needs of both the health system and the communities it serves, the placement of students in these communities is becoming increasingly common. While there is a growing literature on the student experience at such distributed sites, we know less about how the presence of students influences the site itself. We therefore set out to elicit insights from key role-players at a number of distributed health service-based training sites about the contribution that students make and the influence their presence has on that site. This interpretivist study analysed qualitative data generated during twenty-four semi-structured interviews with facility managers, clinical supervisors and other clinicians working at eight distributed sites. A sampling grid was used to select sites that proportionally represented location, level of care and mix of health professions students. Transcribed data were subjected to thematic analysis. Following an iterative process, initial analyses and code lists were discussed and compared between team members after which the data were coded systematically across the entire data set. The clustering and categorising of codes led to the generation of three over-arching themes: influence on the facility (culturally and materially); on patient care and community (contribution to service; improved patient outcomes); and on supervisors (enriched work experience, attitude towards teaching role). A subsequent stratified analysis of emergent events identified some consequences of taking clinical training to distributed sites. These consequences occurred when certain conditions were present. Further critical reflection pointed to a set of caveats that modulated the nature of these conditions, emphasising the complexity inherent in this context. The move towards training health professions students at distributed sites potentially offers many affordances for the facilities where the training takes places, for those responsible for student supervision, and for the patients and communities that these facilities serve. In establishing and maintaining relationships with the facilities, academic institutions will need to be mindful of the conditions and caveats that can influence these affordances.


Neuroimaging in acute ischaemic stroke: insights into unanswered questions of pathophysiology.
The treatment of acute ischaemic stroke is based on the principle that there is ischaemic but still potentially salvageable tissue that could be rescued if blood flow could be restored quickly. It is assumed that salvage might only be possible in the first few hours, and that infarct expansion is a direct result of failed recanalization of the main artery. This concept arose from experimental work in the 1970s, supported more recently by studies using imaging to identify penumbral tissue. However, although magnetic resonance diffusion and perfusion imaging is a way of imaging penumbral tissue and has been around for over a decade, it is not an easy technique to apply in practice and its use has produced conflicting results. Computed tomography perfusion, and any other tissue perfusion imaging technique, is likely to encounter the same difficulties. Indeed many factors, other than the presence of a diffusion-perfusion mismatch acutely, may determine or influence ultimate tissue fate even days after the stroke, and in turn, clinical outcome. Many of these potential influences are beginning to emerge from studies using different forms of imaging at later times after stroke. This review will explore the information now emerging from imaging studies in large artery ischaemic stroke to summarize knowledge to date and indicate unresolved issues for the future.


[Application of V.A.C.-therapy during plastic surgical treatment of a bifocal Marjolin ulcer].
Marjolin ulcers are scar carcinomas most often found in old instable burn scars, the majority histopathologically characterized as squamous cell carcinomas. Surgical therapy includes radical excision and subsequent defect closure. We report about a 69 year old patient suffering from two scar carcinomas on the right cheek and right chest and abdomen due to an extensive infant burn injury. During a 2 stage procedure, both ulcers were initially excised and resulting soft tissue defects were closed temporarily by applying V.A.C. therapy. During a second procedure defect closure on the right cheek was achieved by using a free radial forearm flap following neck dissection. Additionally, the extensive defect including chest and abdominal wall as well as the flap donor site on the left forearm were covered with split thickness skin grafts and subsequently secured by applying V.A.C. therapy for 5 days. 13 days later, the patient was discharged from our clinic. All skin grafted areas as well as the free flap were stably healed. Our report demonstrates that the application of vacuum therapy is not only useful during temporary closure of large wound sites but also secures healing of large and critical areas grafted with split thickness skin grafts in tumour patients.


[Prediction of seizures in sleep based on power spectrum].
Seizures during sleep increase the probability of complication and sudden death. Effective prediction of seizures in sleep allows doctors and patients to take timely treatments to reduce the aforementioned probability. Most of the existing methods make use of electroencephalogram (EEG) to predict seizures, which are not specific developed for the sleep. However, EEG during sleep has its characteristics compared with EEG during other states. Therefore, in order to improve the sensitivity and reduce the false alarm rate, this paper utilized the characteristics of EEG to predict seizures during sleep. We firstly constructed the feature vector including the absolute power spectrum, the relative power spectrum and the power spectrum ratio in different frequencies. Secondly, the separation criterion and branch-and-bound method were applied to select features. Finally, support vector machine classifier were trained, which is then employed for online prediction. Compared with the existing method that do not consider the characteristics of sleeping EEG (sensitivity 91.67%, false alarm rate 9.19%), the proposed method was superior in terms of sensitivity (100%) and false alarm rate (2.11%). This method can improve the existing epilepsy prediction methods and has important clinical value.


Permeability of rapid prototyped artificial bone scaffold structures.
In this work, various three-dimensional (3D) scaffolds were produced via micro-stereolithography (µ-SLA) and 3D printing (3DP) techniques. This work demonstrates the advantages and disadvantages of these two different rapid prototyping methods for production of bone scaffolds. Compared to 3DP, SLA provides for smaller feature production with better dimensional resolution and accuracy. The permeability of these structures was evaluated experimentally and via numerical simulation utilizing a newly derived Kozeny-Carman based equation for intrinsic permeability. Both experimental and simulation studies took account of porosity percentage, pore size, and pore geometry. Porosity content was varied from 30% to 70%, pore size from 0.34 mm to 3 mm, and pore geometries of cubic and hexagonal closed packed were examined. Two different fluid viscosity levels of 1 mPa · s and 3.6 mPa · s were used. The experimental and theoretical results indicated that permeability increased when larger pore size, increased fluid viscosity, and higher percentage porosity were utilized, with highest to lowest degree of significance following the same order. Higher viscosity was found to result in permeabilities 2.2 to 3.3 times higher than for water. This latter result was found to be independent of pore morphology type. As well as demonstrating method for determining design parameters most beneficial for scaffold structure design, the results also illustrate how the variations in patient's blood viscosity can be extremely important in allowing for permeability through the bone and scaffold structures.


Body mass index influences the outcome of acute pancreatitis: an analysis based on the Japanese administrative database.
This study aimed to investigate the relationship between body mass index (BMI) and risk of death in patients with acute pancreatitis (AP) using a Japanese national administrative database. We analyzed a total of 6002 patients with AP. We collected patient information, including sex, age, BMI, severity of AP based on the Japan Pancreas Society scoring system, and prognosis. We classified BMI into 5 categories (underweight [BMI, <18.5], normal range [18.5-24.9], preobese [25-29.9], obese class I [30-34.9], and obese class II/III [>35]) and investigated the relationship between each category and risk of death in AP. There was a good correlation between the Japanese AP severity score and in-hospital mortality. Overall mortality of severe pancreatitis was 7.0% (n = 2245). Mortality in each BMI category was as follows: underweight, 6.4%; normal range, 3.6%; preobese, 2.4%; obese class I, 3.2%; and obese class II/III, 5.7%. Underweight and obese class II/III patients had significantly higher relative risk (RR) of death in AP compared with preobese patients after adjusting for sex, age, and severity of AP (RR, 2.7; 95% confidence interval, 1.6-4.5; and RR, 6.4; 95% confidence interval, 1.9-20.9, respectively). Underweight or overweight was the independent risk factor for mortality in AP.


Engineering yeast for the production of plant terpenoids using synthetic biology approaches.
Covering: 2011-2022The low amounts of terpenoids produced in plants and the difficulty in synthesizing these complex structures have stimulated the production of terpenoid compounds in microbial hosts by metabolic engineering and synthetic biology approaches. Advances in engineering yeast for terpenoid production will be covered in this review focusing on four directions: (1) manipulation of host metabolism, (2) rewiring and reconstructing metabolic pathways, (3) engineering the catalytic activity, substrate selectivity and product specificity of biosynthetic enzymes, and (4) localizing terpenoid production via enzymatic fusions and scaffolds, or subcellular compartmentalization.


Pulmonary vasculopathy in idiopathic spontaneous pneumothorax in young subjects.
We have encountered instances where young subjects with idiopathic spontaneous pneumothorax have been needlessly referred for investigation of pulmonary hypertension because surgical pathologists have misinterpreted the significance of medial hypertrophy and intimal fibrosis of muscular pulmonary arteries in lung resection specimens. We reviewed 20 cases of idiopathic spontaneous pneumothorax and determined the prevalence and severity of medial and intimal lesions in the pulmonary arteries and pulmonary veins. We correlated the vascular changes with inflammation and fibrosis in the lung. Pulmonary artery medial hypertrophy was seen in 15% of cases, pulmonary artery intimal fibrosis in 90% of cases, and pulmonary vein intimal fibrosis in 80% of cases. In 95% of cases, the lung showed some fibrosis and chronic inflammation. There was a significant positive correlation between pulmonary artery medial thickness and lung fibrosis and inflammation scores. Pulmonary artery medial hypertrophy and intimal fibrosis of pulmonary arteries and pulmonary veins are commonly seen in resected lung tissue from patients with idiopathic spontaneous pneumothorax. The vascular lesions are probably secondary to chronic inflammation and fibrosis in the adjacent lung. They are not clinically significant and do not represent hypertensive pulmonary vascular disease.


Sport Preparticipation Screening for Asymptomatic Atlantoaxial Instability in Patients With Down Syndrome.
Down syndrome (DS) is a clinical syndrome comprising typical facial features and various physical and intellectual disabilities due to extra genetic material on chromosome 21, with one in every 1000 babies born in the United Kingdom affected. Patients with Down syndrome are at risk of atlantoaxial instability (AAI). Although AAI can occur in other conditions, such as rheumatoid arthritis, this position statement deals specifically with patients with DS and asymptomatic AAI. Atlantoaxial instability, also referred to as atlantoaxial subluxation, is defined as increased movement between the first (atlas) and second (axial) cervical vertebra joint articulation, the atlantoaxial joint. Atlantoaxial instability is reported to occur in 6.8% to 27% of the DS population, although this varies depending on the age of the patients whom you are screening. Less than 1% to 2% of these patients are then thought to later develop symptomatic AAI, although the natural history and progression of AAI is not well understood. The risks associated with AAI are neurological injury from excessive movement of the cervical vertebra impinging on and then damaging the spinal cord, although the risk of this during sporting activities is extremely rare. Clearly, physical activity and sports participation for patients with DS has many biological, psychological, and social benefits, and the Faculty of Sport and Exercise Medicine (FSEM), United Kingdom, wishes to promote safe physical activity and sport for all. The FSEM, United Kingdom, has therefore produced a statement regarding sport preparticipation screening for asymptomatic AAI in patients with DS.


Molecular basis for globotriaosylceramide regulation and enzyme uptake in immortalized aortic endothelial cells from Fabry mice.
Fabry disease is caused by deficient activity of α-galactosidase A and subsequent intracellular accumulation of glycosphingolipids, mainly globotriaosylceramide (Gb3). Vascular endothelial cells may play important roles in disease pathogenesis, and are one of the main target cell types in therapeutic interventions. In this study, we generated immortalized aortic endothelial cell lines from a mouse model of Fabry disease. These cells retained endothelial cell-specific markers and functions. Gb3 expression level in one of these clones (referred to as FMEC2) was highly susceptible to culture media, and appeared to be regulated by glucosylceramide synthase. Results also showed that Gb3 could be upregulated by hydrocortisone. FMEC2 express the mannose 6-phosphate receptor and sortilin but not the mannose receptor. Uptake studies suggested that sortilin plays a role in the binding and internalization of mammalian cell-produced α-galactosidase A. Moss-aGal (a plant-made enzyme) was endocytosed by FMEC2 via a receptor other than the aforementioned receptors. In conclusion, this study suggests that glucosylceramide synthase and hydrocortisone may play important roles in modulating Gb3 levels in Fabry mouse aortic endothelial cells, and that endocytosis of recombinant α-galactosidase A involves a combination of multiple receptors depending on the properties of the enzyme.


Efficient Tm:YAG and Tm:LuAG lasers pumped by 681 nm tapered diodes.
In this paper, we present highly efficient continuous-wave (cw) laser operation of Tm:YAG and Tm:LuAG lasers pumped by high-brightness red tapered diodes. The single-emitter tapered diode lasers (TDLs) provide up to 1 W of pump power around 680 nm. By adjusting the operation temperature of the TDL, the pump central wavelength could be matched to the strong absorption peak of Tm3+ ions in this region (H63→F33 excitation). This absorption peak is around threefold stronger than the usually employed 785 nm transition (H63→H34). In the cw laser experiments, we have achieved slope efficiencies exceeding 55% at room temperature, which is far above the Stokes limited slope efficiency (34%), indicating presence of a strong two-for-one cross-relaxation process. Pumping with high-brightness tapered diode lasers further facilitated usage of smaller pump spots (enabling quite low lasing thresholds) and generation of near-diffraction limited output beam profiles from standard z-type cavities. To the best of our knowledge, this is the first report of diode pumping of Tm-doped solid-state lasers around 680 nm as well as the first usage of TDLs as pump sources in Tm-doped laser systems.


Role of T lymphocytes in the development of rheumatoid arthritis. Implications for treatment.
T cells play a role in the initiation and perpetuation of tissue inflammation that can lead to tissue destruction. With the discovery of a number of T helper subsets and their potential plasticity during disease it became clear that the T cell behaviour in autoimmune diseases is much more complex than the first Th1/Th2 concept. From experimental autoimmune arthritis models it became clear that the IL-23/IL-17 immune pathway is critical in the development of autoimmune arthritis and IL-17A has been recognized to be a key cytokine involved in initiation and perpetuation of chronic destructive arthritis. Functional studies using T cells and stromal cells from patients with RA revealed improvement of anti-TNF effects when combined with agents neutralizing IL-17A or agents suppressing Th17 cytokines production. Clinic trials will be needed to test whether these data from experimental settings can be translated to human arthritis. Different approaches are available or under investigation to target: (1) pathogenic T cell activity by inhibiting RORc or STAT3 or the costimulator pathway by CTLA4-Ig; (2) Th17 cytokine production by anti-IL-17A, anti-IL-22, or combination of anti-IL-17A/anti-TNF approaches; (3) Th17 polarization by neutralizing IL-23 using an anti-IL-23 specific antibody, IL-12/IL-23 by an anti-p40 antibody, or the IL-6 signaling pathway; (4) Th17 migration by interfering the CCR6-CCL20 interaction. The challenge is to bring the best to the clinic to further improve current therapy for patients with RA and to reach stable remission or even prevent the development of this disabling disease.


Out of the desert: Paleoclimatic changes drove the diversification of arid-adapted Ocymyrmex ants in southern Africa.
A highly endemic ant fauna is found in the arid regions of southern Africa, including species in the genus Ocymyrmex. This genus of ants has higher species richness in the western arid regions of southern Africa compared to tropical and subtropical parts of the continent. The processes that have produced these patterns of diversity and distribution of arid adapted ants in southern Africa have never been investigated. The diversification of many other taxa in the region has been associated with past climate fluctuations that occurred during the Miocene epoch. In this study, the nature and timing of historical processes that may have led to the diversification within Ocymyrmex were assessed. We hypothesized that past climate oscillations, characterized by long periods of aridification, have driven the current distribution of Ocymyrmex species that resulted in the highest species richness of the genus in the Deserts & xeric shrublands biome in southern Africa. Ninety-four Ocymyrmex worker specimens from Botswana, Kenya, Namibia, South Africa, Tanzania and Zimbabwe, representing 21 currently described species and six morphospecies, were included in a phylogenomic analysis. Phylogenies for the genus, based on next generation sequencing data from ultraconserved elements, were inferred using Maximum Likelihood, and a dating analysis was performed using secondary age estimates as calibration points. A distribution database of Ocymyrmex records was used to assign species ranges, which were then coded according to major biomes in southern Africa and used as input for biogeographical analysis. We explored the phylogenomic relationships of Ocymyrmex and analysed these within a biogeographical and paleoclimatic framework to disentangle the potential processes responsible for diversification in this group. Dating analyses estimated that the crown age of Ocymyrmex dates to the Oligocene, around 32 Ma. Diversification within this group occurred between the mid-Miocene (∼12.5 Ma) and Pleistocene (∼2 Ma). Our biogeographic analyses suggest that Ocymyrmex species originated in the south-western region of southern Africa, which is now part of the Deserts & xeric shrublands biome and diversified into eastern subtropical areas during the Pliocene. Paleoclimatic changes resulting in increased aridity during the Miocene likely drove the diversification of the genus Ocymyrmex. It is most likely that the diversification of grasslands, because of historical climate change, facilitated the diversification of these ants to the eastern parts of southern Africa when open grasslands replaced forests during the early Miocene.


Central nervous system toxoplasmosis in acquired immunodeficiency syndrome: An emerging disease in India.
With the incidence of patients infected with human immuno-deficiency virus (HIV) increasing in India, the central nervous system (CNS) manifestations of the disease will be seen more frequently. The CNS may be primarily afflicted by the virus or by opportunistic infections and neoplasms secondary to the immune suppression caused by the virus. In India, although mycobacterium tuberculosis has been reported to be the most common opportunistic infection, toxoplasmosis may become as common owing to the ubiquitous nature of the protozoan. Since an empirical trial of medical therapy without histopathological diagnosis is recommended, the true incidence of this condition may remain under estimated. The role of ancillary tests such as radiology and serology in the initial diagnosis of this condition remain crucial. This report highlights two patients who were diagnosed to have acquired immuno-deficiency syndrome (AIDS) only after the biopsy of the intracranial lesion was reported as toxoplasmosis. Presently all patients for elective neurosurgery are tested for HIV antigen. The management protocol to be followed in a known patient with AIDS presenting with CNS symptoms is discussed in detail. The value of ancillary tests is also reviewed.


Nature and Nurture in Early Feeding Behavior.
Obesity has reached epidemic proportions and research into its prevention is increasingly focusing on the earliest stages of life. Avidity of appetite has been linked to a higher risk of obesity, but studies in infancy were scarce. The Gemini twin cohort was established to investigate genetic and environmental determinants of weight trajectories in early childhood with a focus on appetite and the home environment. Gemini families have been supplying questionnaire data at regular intervals, starting when the twins were 8 months old. Analyses of data on infant appetite and weight have provided a number of important findings. Firstly, a prospective study found that appetite in infancy drives weight gain more strongly than weight drives appetite, although the two processes do coexist. A further study using a subsample of twins discordant for appetite ruled out the possibility of familial confounding, suggesting a causal role for appetite in weight. Heritability estimates for appetitive traits were moderate to high (53-84%). Finally, multivariate analyses indicated that roughly one third of the genes related to weight are also related to appetite and vice versa. Environmental factors affecting appetite in infancy are understudied, but some potential strategies for minimizing over- or underconsumption by at-risk individuals are suggested.


Production of xylanolytic enzymes by Penicillium janczewskii.
The production of extracellular xylanase, beta-xylosidase and alpha-l-arabinofuranosidase by the mesophilic fungus Penicillium janczewskii under submerged cultivation was investigated with different carbon sources. Optimization steps included studies of carbon source concentration, temperature of cultivation and initial pH of culture medium. The production of these enzymes was increased two times when cultures were supplemented with brewer's spent grain at 2% concentration, pH 6.0 and carried out at 25 degrees C. Under these optimized conditions were obtained xylanase activity of 15.19UmL(-1) and 23.54Umgprot(-1), beta-xylosidase activity of 0.16UmL(-1) and 0.25Umgprot(-1) and alpha-l-arabinofuranosidase activity of 0.67UmL(-1) and 1.04Umgprot(-1). Brewer's spent grain is a promising substrate for P. janczewskii growth and xylanolytic enzyme production, since it is the main by-product from the brewing industry, available in large amounts and at low-cost in many countries.


Fatigue in MS is associated with specific clinical features.
fatigue is a common and disabling symptom in multiple sclerosis (MS). In this study we evaluated if fatigue is associated with different demographic and clinical features of MS. A survey was performed on 507 consecutive patients affected by clinically definite MS referred to our centre between January 1 and December 31, 1993. During the examination patients were asked to answer a brief fatigue questionnaire. To evaluate the probability of the occurrence of fatigue in association with several covariant factors (age, sex, duration, disease form, disease severity, month of examination, functional sub-systems on the expanded disability status scale (EDSS), a logistic regression analysis was performed. we confirmed that fatigue is common in MS, recorded in 53% of patients. Patients affected by a more severe disability, by progressive MS, both primary and secondary, with an older age at examination, and assessed during spring, had a significantly higher risk of fatigue. Sex was not associated with the occurrence of fatigue. When the single items of EDSS were considered, we found that fatigue is also associated with the occurrence of cerebellar, sphincteric, pyramidal and sensitive signs, but not with brain stem, visual and cognitive impairment. fatigue in MS is more frequent in association with specific clinical features.


Gastrin 17 and gastrin 34, before and after a meal, in newborn infants.
In 89 healthy full-term newborn infants, we studied the different contribution of gastrin 17 (G17) and gastrin 34 (G34) to neonatal hypergastrinemia and the G17 and G34 response to a meal in the first days of life. Serum concentrations of G17 and G34 were measured by radioimmunoassay specific for the NH2-terminus of G17 and G34 in 23 newborn infants in the cord blood and in 66 newborn infants before or 20 min after bottle-feeding. Basal serum G17 and G34 values were also obtained in 38 healthy fasting adults. Mean (+/- SEM) G17 levels in the cord blood were not different from those of the adult controls (29.28 +/- 4.16 versus 31.00 +/- 2.62 pg/ml) and increased significantly either at 12 h (48.06 +/- 7.32 pg/ml, p less than 0.025) or on the 4th day of life (80.56 +/- 9.99 pg/ml, p less than 0.01). Serum G34 levels in the cord blood were significantly higher than in adult controls (163.22 +/- 11.19 versus 126.68 +/- 5.57 pg/ml, p less than 0.005) and increased at 12 h of life (225.22 +/- 25.95 pg/ml, p less than 0.02), but no increase was found on the 4th day of life (204.87 +/- 18.08 pg/ml). Neither postprandial G17 nor G34 increases were found on the 1st or on the 4th day of postnatal life. The study supports the following conclusions: (a) neonatal hypergastrinemia is mainly due to G34 fraction; (b) the increased levels of gastrin on the 4th day of life are due to G17 fraction; (c) bottle-feeding does not stimulate either G17 or G34 release in the first 4 days of life.


Tracking in a ground-to-satellite optical link: effects due to lead-ahead and aperture mismatch, including temporal tracking response.
Establishing a link between a ground station and a geosynchronous orbiting satellite can be aided greatly with the use of a beacon on the satellite. A tracker, or even an adaptive optics system, can use the beacon during communication or tracking activities to correct beam pointing for atmospheric turbulence and mount jitter effects. However, the pointing lead-ahead required to illuminate the moving object and an aperture mismatch between the tracking and the pointing apertures can limit the effectiveness of the correction, as the sensed tilt will not be the same as the tilt required for optimal transmission to the satellite. We have developed an analytical model that addresses the combined impact of these tracking issues in a ground-to-satellite optical link. We present these results for different tracker/pointer configurations. By setting the low-pass cutoff frequency of the tracking servo properly, the tracking errors can be minimized. The analysis considers geosynchronous Earth orbit satellites as well as low Earth orbit satellites.


[False-positive results obtained on examining slaughtered animals for the presence of antibiotic residues (author's transl)].
As part of the examination of emergency-slaughtered animals for the presence of antibiotic residues, studies were done to see whether false-positive results would be obtained when the Sarcina lutea kidney test and Bacillus subtilis BGA test were performed. When the S. lutea kidney test was positive in cattle, calves and swine, penicillin was invariably found to be present in those animals, the histories of which showed that they had not been given antibiotics. A syringe and an injected fluid containing penicillin residues are regarded as possible causes of these positive results. When the S. lutea kidney test was performed in horses which had been in a state of stress prior to slaughter, false-positive results were occasionally observed. When the German B. subtilis BGA test was used, a large number of false-positive results were recorded, among others in equine kidneys. This shows that the use of this test in examining the kidney is a highly controversial matter. A number of drugs used in veterinary medicine may have an inhibitory effect on the growth of S. lutea and B. subtilis BGA test organisms in vitro. When these drugs were used therapeutically (in vivo), the result of the S. lutea kidney test was not positive in any of the cases studied. On the other hand, false-positive results were obtained when the B. subtilis BGA renal medullary test was performed in those animals in which lidocaine and calcium borogluconate had also been injected.


[On the "receptor" mechanism of the effect of biologically active substances in ultra low concentrations].
On the basis of antioxidant (alpha-tocopherol and phenosan potassium salt) and peptide (thyroliberin) effects on the lipid peroxide oxidation (LPO) and lipid structural parameters of the endoplasmic reticulum membranes in wide concentration range (10(-20)-10(-4) mol/l) in vitro the possibility concerning a proposed role of "super-affine" receptors in the mechanism of biologically active substances (BAS) action in ultra low doses (ULD) is discussed. Because these substances modulate investigated processes in the membranes which have not ordinarily receptors the conclusion about availability of non-receptor component in the mechanism of BAS effect in ULD and a low probability of "super-affine" receptor existence has been done.


Mismatch in Spouses' Anger-Coping Response Styles and Risk of Early Mortality: A 32-Year Follow-Up Study.
Research in psychosomatic medicine includes a long history of studying how responses to anger-provoking situations are associated with health. In the context of a marriage, spouses may differ in their anger-coping response style. Where one person may express anger in response to unfair, aggressive interpersonal interactions, his/her partner may instead suppress anger. Discordant response styles within couples may lead to increased relational conflict, which, in turn, may undermine long-term health. The current study sought to examine the association between spouses' anger-coping response styles and mortality status 32 years later. The present study used data from a subsample of married couples (N = 192) drawn from the Life Change Event Study to create an actor-partner interdependence model. Neither husbands' nor wives' response styles predicted their own or their partners' mortality. Wives' anger-coping response style, however, significantly moderated the association of husbands' response style on mortality risk 32 years later, β = -0.18, -0.35 to -0.01, p = .039. Similarly, husbands' response style significantly moderated the association of wives' response style and their later mortality, β = -0.24, -0.38 to -0.10, p < .001. These effects were such that the greater the mismatch between spouses' anger-coping response style, the greater the risk of early death. For a three-decade follow-up, husbands and wives were at greater risk of early death when their anger-coping response styles differed. Degree of mismatch between spouses' response styles may be an important long-term predictor of spouses' early mortality risk.


Does laminar flow ventilation reduce the rate of infection? an observational study of trauma in England.
To determine whether there is any difference in infection rate at 90 days between trauma operations performed in laminar flow and plenum ventilation, and whether infection risk is altered following the installation of laminar flow (LF). We assessed the impact of plenum ventilation (PV) and LF on the rate of infection for patients undergoing orthopaedic trauma operations. All NHS hospitals in England with a trauma theatre(s) were contacted to identify the ventilation system which was used between April 2008 and March 2013 in the following categories: always LF, never LF, installed LF during study period (subdivided: before, during and after installation) and unknown. For each operation, age, gender, comorbidity, socio-economic deprivation, number of previous trauma operations and surgical site infection within 90 days (SSI90) were extracted from England's national hospital administrative Hospital Episode Statistics database. Crude and adjusted odds ratios (OR) were used to compare ventilation groups using hierarchical logistic regression. Subanalysis was performed for hip hemiarthroplasties. A total of 803 065 trauma operations were performed during this time; 19 hospitals installed LF, 124 already had LF, 13 had PV and the type of ventilation was unknown in 28. Patient characteristics were similar between the groups. The rate of SSI90 was similar for always LF and PV (2.7% and 2.4%). For hemiarthroplasties of the hip, the rates of SSI90 were significantly higher for LF compared with PV (3.8% and 2.6%, OR 1.45, p = 0·001). Hospitals installing LF did not see any statistically significant change in the rate of SSI90. The results of this observational study imply that infection rate is similar when orthopaedic trauma surgery is performed in LF and PV, and is unchanged by installing LF in a previously PV theatre. Cite this article: Bone Joint J 2016;98-B:1262-9.


Survival of children with malignant germ cell, trophoblastic and other gonadal tumours in Europe.
Collaborators of the EUROCARE study had provided records on 1263 cases of germ cell, trophoblastic and other gonadal neoplasms, registered in 34 cancer registries in 16 European countries over the period 1978--1992 and followed-up until the end of 1994. Observed 5-year actuarial survival for 490 cases diagnosed in 1985-1989 was 80% (95% confidence interval (CI)=(76, 83)). The corresponding figures were calculated for the intracranial and intraspinal germ cell tumours (68%, 95% CI=(57, 76)), other non-gonadal germ cell tumours (76%, 95% CI=(68, 82)), gonadal germ-cell tumours (89%, 95% CI=(85, 93)) and gonadal carcinomas (50%, CI=(24, 76)). Relatively large differences in survival were observed between age-sex subgroups, which also differed with histology, with extremely poor survival of young children with intracranial and intraspinal germ cell tumours. Lower survival was observed in the countries with formerly socialist economies. Time trends in survival were examined for the entire study period, including only the cases registered in the large contributing registries. For all germ cell tumours, the risk ratios calculated in the Cox regression analysis were markedly lowered for the years after the reference period of 1978--1981. The improved outcome is attributed to treatment advances.


[Metastatic neck adenopathies without known primary tumor. Incidence study 1996-2001].
We made a retrospective descriptive study reviewing 92 patients with cervical lymph node metastases from unknown primary tumour. The study was accomplished during 6 years. (January 1996 to December 2001) in the Department of Otorhinolaryngology of the Hospital Reina Sofia, Córdoba. The median age was 61.7 years old, male 96.7% and heavy smoker (89.1%) and drinkers most of them. According to TNM categories, 72.2% patients were in phase N2a and half of them were localized Level II. Squamous cell carcinoma was the predominant histologic type. The patients were treated with surgery in 70.6% of the cases with or without radiation therapy and/or chemotherapy.


Use of touch preps for diagnosis and evaluation of surgical margins in breast cancer.
The best cosmetic results with conservative breast surgery are obtained at the time of initial excisional biopsy. The usefulness of the touch prep (TP) technique was evaluated for accuracy in diagnosis as well as in evaluation of margins at the time of original breast biopsy. Four hundred twenty-eight consecutive patients with breast masses seen from January 1993 to December 1994 were evaluated prospectively using TP. Three hundred forty-five benign and 83 malignant tumors were evaluated. Tumors ranged in size from microscopic to 8 cm. Pathologic diagnosis was correct as compared to permanent section in 99.3%. The three carcinomas missed on TP were focal and in situ. Sensitivity was 96.39%, and specificity was 100%. Positive predictive value was 100%, and negative predictive value was 99.3%. For margin evaluation, the sensitivity and specificity were both estimated to be 100%. TP has the advantage of being a simple, quick (2 to 3 minutes), safe (no loss of diagnostic material), and accurate method for diagnosis and estimation of tumor margins at the time of the original surgery.


Adult attachment: what are the underlying dimensions?
Using a community sample of 115 young adults, this study applied a range of statistical techniques to five measures of adult attachment to gain a better understanding of what they assess. First, we determined comparability of measures, using both categorical and dimensional approaches to model the association. Agreement among classifications was modest. Next, we examined the relation of attachment classifications and attachment measure subscale scores to criterion variables (i.e. dyadic adjustment, interpersonal sensitivity and severity of psychiatric symptoms). Classification predicted severity of psychological symptoms better than it predicted other measures of adjustment. Finally, using a principal components analysis, we mapped the relationship among underlying constructs, the subscales of the five measures and three criterion measures of psychological adjustment. We discuss our findings from the perspective of underlying constructs of attachment insecurity and strategy for coping with insecurity in relationships, noting implications for further research.


Autonomous learning based on cost assumptions: theoretical studies and experiments in robot control.
Autonomous learning techniques are based on experience acquisition. In most realistic applications, experience is time-consuming: it implies sensor reading, actuator control and algorithmic update, constrained by the learning system dynamics. The information crudeness upon which classical learning algorithms operate make such problems too difficult and unrealistic. Nonetheless, additional information for facilitating the learning process ideally should be embedded in such a way that the structural, well-studied characteristics of these fundamental algorithms are maintained. We investigate in this article a more general formulation of the Q-learning method that allows for a spreading of information derived from single updates towards a neighbourhood of the instantly visited state and converges to optimality. We show how this new formulation can be used as a mechanism to safely embed prior knowledge about the structure of the state space, and demonstrate it in a modified implementation of a reinforcement learning algorithm in a real robot navigation task.


Osimertinib-Induced Unilateral Diffuse Alveolar Hemorrhage in a Patient With Pulmonary Adenocarcinoma.
A 70-year-old man with lung adenocarcinoma was admitted to our hospital due to progressive dyspnea, 4 months after osimertinib initiation. His chest radiograph and computed tomography revealed ground-glass opacities and consolidations dominantly in the upper left lung. He took neither antiplatelet nor anticoagulation agent. No abnormality in coagulation was detected. Bronchoalveolar lavage fluid (BALF) became serially and increasingly hemorrhagic, and confirmed the diagnosis of alveolar hemorrhage. After steroid pulse therapy and withdrawal of osimertinib, his condition gradually improved, accompanied by regression of ground-glass opacities and consolidations. Osimertinib causes not only interstitial pneumonia but also alveolar hemorrhage. The consolidations may spread not bilaterally, but be localized unilaterally. We have to keep this rare adverse event in mind, and consider immediate withdrawal of osimertinib and treatment with steroid. Increased lymphocytes in the BALF may be a potential indicator of sensitivity to steroid and favorable prognosis in diffuse alveolar hemorrhage.


Does organismal pedigree impact the magnitude of topological congruence among gene trees for unlinked loci?
One of the fundamental assumptions in the multi-locus approach to phylogeographic studies is that unlinked loci have independent genealogies. For this reason, congruence among gene trees from unlinked loci is normally interpreted as support for the existence of external forces that may have concordantly shaped the topology of multiple gene trees. However, it is also important to address and quantify the possibility that gene trees within a given species are all inherently constrained to some degree by their shared organismal pedigree, and thus in this strict sense are not entirely independent. Here we demonstrate by computer simulations that gene trees from a shared pedigree tend to display higher topological concordance than do gene trees from independent pedigrees with the same demographic parameters, but we also show that these constraining effects are normally minor in comparison to the much higher degree of topological concordance that can routinely emerge from external phylogeographic shaping forces. The topology-constraining effect of a shared pedigree decreases as effective population size increases, and becomes almost negligible in a random mating population of more than 1,000 individuals. Moreover, statistical detection of the pedigree effect requires a relatively large number of unlinked loci that far exceed what is typically used in current phylogeographic studies. Thus, with the possible exception of extremely small populations, multiple unlinked genes within a pedigree can indeed be assumed, for most practical purposes, to have independent genealogical histories.


Splenectomy for agnogenic myeloid metaplasia.
Only a fraction of the patients with myeloid metaplasia have indications for splenectomy develop. Palliation for symptomatic splenomegaly is highly successful. Significant relief from hypersplenism, anemia or thrombocytopenia was achieved, however, in less than half of the patients. Since patients with severe thrombocytopenia are at continuing risk of spontaneous hemorrhage and of bleeding after minor trauma, splenectomy appears to be justified in these patients, provided that studies of peripheral blood and bone marrow have excluded those with leukemic conversion. The benefit obtained from splenectomy in patients with chronic anemia requiring frequent transfusions in less certain, particularly in men and in patients converting to myeloid metaplasia from polycythemia vera. In some instances, the continuation of transfusions may result in less morbidity and better palliation than operation. Although the course of this myeloproliferative disorder from first symptoms to death frequently extends for more than a decade, the manifestations which may provide an indication for splenectomy usually occur late in the course of the disease. The element as well as the morbidity of the operation makes a thorough evaluation of each patients essential before splenectomy is considered.


Cerebral cysticercosis with reference to the natural history of parenchymal lesions.
The cerebral parenchymal response to degeneration of cysticerci was studied in 83 consecutive patients investigated over 5 1/2 years. Virtually all came from an endemic region of South Africa and 67% were children. Occasionally, computed tomography (CT) delineated an inert shower of cysticerci. The humoral and tissue reactions resulting from larval death cause intense cerebral edema and granulomata, which manifest particularly in the pediatric age group. Local and diffuse cerebral edema has not been stressed before nor has its incidence been evaluated. The shortest interval between cysticercal degeneration and its granulomatous response to the final radiographic calcification was found to be 25 months.


Quorum Sensing Determines the Choice of Antiphage Defense Strategy in Vibrio anguillarum.
Selection for phage resistance is a key driver of bacterial diversity and evolution, and phage-host interactions may therefore have strong influence on the genetic and functional dynamics of bacterial communities. In this study, we found that an important, but so far largely overlooked, determinant of the outcome of phage-bacterial encounters in the fish pathogen Vibrio anguillarum is bacterial cell-cell communication, known as quorum sensing. Specifically, V. anguillarum PF430-3 cells locked in the low-cell-density state (ΔvanT mutant) express high levels of the phage receptor OmpK, resulting in a high susceptibility to phage KVP40, but achieve protection from infection by enhanced biofilm formation. By contrast, cells locked in the high-cell-density state (ΔvanΟ mutant) are almost completely unsusceptible due to quorum-sensing-mediated downregulation of OmpK expression. The phenotypes of the two quorum-sensing mutant strains are accurately reflected in the behavior of wild-type V. anguillarum, which (i) displays increased OmpK expression in aggregated cells compared to free-living variants in the same culture, (ii) displays a clear inverse correlation between ompK mRNA levels and the concentration of N-acylhomoserine lactone quorum-sensing signals in the culture medium, and (iii) survives mainly by one of these two defense mechanisms, rather than by genetic mutation to phage resistance. Taken together, our results demonstrate that V. anguillarum employs quorum-sensing information to choose between two complementary antiphage defense strategies. Further, the prevalence of nonmutational defense mechanisms in strain PF430-3 suggests highly flexible adaptations to KVP40 phage infection pressure, possibly allowing the long-term coexistence of phage and host. Comprehensive knowledge on bacterial antiphage strategies and their regulation is essential for understanding the role of phages as drivers of bacterial evolution and diversity. In an applied context, development of successful phage-based control of bacterial pathogens also requires detailed understanding of the mechanisms of phage protection in pathogenic bacteria. Here, we demonstrate for the first time the presence of quorum-sensing-regulated phage defense mechanisms in the fish pathogen Vibrio anguillarum and provide evidence that quorum-sensing regulation allows V. anguillarum to alternate between different phage protection mechanisms depending on population cell density. Further, our results demonstrate the prevalence of nonmutational defense mechanisms in the investigated V. anguillarum strain, which allow flexible adaptations to a dynamic phage infection pressure.


[Screening of the candidate proteins interacting with TaFRA].
F-box protein is an important subunit of SCF complex, an E3 ligase in ubiquitin system, and its function is determined through mediating the specific recognition and combining with substrate protein. TaFRA (F-box protein related to abiotic stress) was identified by RACE based on the fragments diferently expressing in wheat seedling exposed to salt stress and encodes an F-box protein. In this study, pBD-TaFRA bait expression vector was constructed, and cDNA+pGAD+pBD was directly co-transformed into yeast hybrid system to screen condidate proteins interacting with TaFRA. Fourty-four candidate proteins were obtained, in which 32 were known proteins and transcript factors related to stress tolerance such as thioredoxin, metallothinein, ATP synthase, and serine/threonine protein kinase etc. This indicates that TaFRA participates in stress response through regulating above condidate genes, which will provide basis for revealing the mechanism of TaFRA reaction to abiotic stress.


Metastasis to lymph nodes around the vascular tie worsens long-term oncological outcomes following complete mesocolic excision and conventional colectomy for right-sided colon cancer.
Oncologic outcomes after complete mesocolic excision (CME) in colon cancer are under investigation. The aim of our study was to compare CME and conventional colectomy (CC) in terms of pathological and oncological outcomes for right colon cancer and to evaluate the impact of lymph node metastasis around the vascular tie on survival. Consecutive patients with right colon cancer who had CME or CC between January 2011 and August 2018 at two specialized centers in Turkey were included. Statistical analyses were performed with respect to demographic characteristics, operative and pathologic outcomes, harvested and metastatic lymph nodes around the vascular tie (LNVT), recurrences, and survival. There were 91 patients in the CME group (58 males, mean age 64 ± 16 years) and 192 patients in the CC group (96 males, mean age 66 ± 14 years). The mean number of harvested lymph nodes (CME: 42 ± 15 vs CC: 34 ± 13, p = 0.01) and LNVT were higher in the CME group (CME: 3.2 ± 2.2 vs CC: 2.4 ± 1.6, p = 0.001). LNVT metastases were 7.7% and 8.3% in the CME and CC groups, respectively (p = 0.85). Three-year overall and disease-free survival rates were 96.4% and 90.9% in the CME group and 90.4% and 87.6% in the CC group in stage I-III patients (p > 0.05). In stage III patients, the 3-year overall survival (92.5% vs 63.5%, p = 0.03) and disease-free survival (85.6% vs 52.1%, p = 0.008) were significantly better in LNVT-negative patients than in LNVT-positive patients. LNVT metastasis seems to be the key factor associated with poor disease-free and overall survival in right colon cancer regardless of the radicality of surgery.


Changes in pupil size, ocular wavefront aberrations, and accommodation in healthcare workers using FFP3 masks.
To evaluate changes in pupil size, ocular wavefront aberrations (WA), and accommodation in healthcare workers after 4-h usage of Filtering Facepiece class 3 (FFP3) masks. This prospective study included 22 healthy healthcare workers. Pupil size, ocular WA, and accommodation changes before and after FFP3 mask usage were evaluated using a Hartmann Schack aberrometer. Accommodative responses to stimulus ranging from 0 to 5 diopters (D) in increments of 0.5 D were assessed. Ocular high-order aberrations (HOAs) were recorded at baseline and at every accommodative stimulus. Oxygen saturation (SpO2) was measured by pulse oximetry before and after the mask usage. The mean age was 36.6 ± 8.5 years. The SpO2 significantly decreased from 98.95 to 97.95% after usage of the FFP3 mask (p < 0.001). The mean pupil size did not significantly differ before (6.22 ± 0.75 mm) and after (6.38 ± 0.83 mm) the 4-h mask usage (p = 0.093). The mean total RMS of the total HOAs was 0.36 ± 0.17 before and 0.39 ± 0.15 after the mask usage (p = 0.071). Post-mask accommodation showed a significant decrease at the 2 D (p = 0.041), 2.5D (p = 0.022), and 3 D (p = 0.025) stimuli. The present study shows that after 4 h-usage of FFP3 mask, both SpO2 and accommodative response to increasing stimuli might be significantly decreased.


Characterization of Phn15.1, a Newly Identified Phytophthora nicotianae Resistance QTL in Nicotiana tabacum.
Phytophthora nicotianae is an oomycete that causes black shank, one of the most economically important diseases affecting tobacco production worldwide. Identification and introgression of novel genetic variability affecting partial genetic resistance to this pathogen is important because of the increased durability of partial resistance over time as compared with genes conferring immunity. A previous mapping study identified a quantitative trait locus (QTL), hereafter designated as Phn15.1, with a major effect on P. nicotianae resistance in tobacco. In this research, we describe significantly improved resistance of nearly isogenic lines (NILs) of flue-cured tobacco carrying the introgressed Phn15.1 region derived from highly resistant cigar tobacco cultivar Beinhart 1000. The Phn15.1 region appeared to act in an additive or partially dominant manner to positively affect resistance. To more finely resolve the position of the gene or genes underlying the Phn15.1 effect, the QTL was mapped with an increased number of molecular markers (single-nucleotide polymorphisms) identified to reside within the region. Development and evaluation of subNILs containing varying amounts of Beinhart 1000-derived Phn15.1-associated genetic material permitted the localization of the QTL to a genetic interval of approximately 2.7 centimorgans. Importantly, we were able to disassociate the Beinhart 1000 Phn15.1 resistance alleles from a functional NtCPS2 allele(s) which contributes to the accumulation of a diterpene leaf surface exudate considered undesirable for flue-cured and burley tobacco. Information from this research should be of value for marker-assisted introgression of Beinhart 1000-derived partial black shank resistance into flue-cured and burley tobacco breeding programs.


Auditory adaptation: notes on power and parabolic curve fitting across intensity: II.
The classic Simultaneous Dichotic Loudness Balance (SDLB) procedure for the study of auditory adaptation was used by Weiler and Hood (1977) in a successful test of a model for predicting adaptation in db at intensities above the initial baseline values, using a linear approximation across levels. When Balzer et al (Brit. J. Audiol., 1984, 18, 49-50) fitted curves for simple baseline adaptation data from four studies based on SDLB data, they reported good fits for the Gompertz technique and for a parabolic formula, but did not test the relative goodness of fit for the linear formula, nor for power approximations as Stevens (1975) might have proposed. The present study makes use of the data used by Balzer et al but examines a linear fit as well as two approximations to Stevens' power law. The present finding that the linear approximation is the least efficient examined would suggest that the Weiler and Hood model should be re-examined to determine the degree to which the model can be improved by use of a curvilinear baseline fit. In addition, it might be noted that the curvilinear formulae, of necessity, involve two or more stages. It is the the current effort of this laboratory to determine whether this reflects a multifactor basis to the classic SDLB adaptation, as well as results from other adaptation techniques.


[The system for Mendelian analysis of alternative traits (MAH-A1)].
The principle means of the system of applied programs are described. The system is assigned for checking up monogenic diallele hypotheses of inheritance of an alternative trait, on the basis of a population sample of free structured and sized pedigrees, through probands.


Outcomes of physical therapy, speech pathology, and occupational therapy for people with motor neuron disease: a systematic review.
This article describes a systematic review and critical evaluation of the international literature on the effects of physical therapy, speech pathology, and occupational therapy for people with motor neuron disease (PwMND). The results were interpreted using the framework of the International Classification of Functioning, Disability and Health. This enabled us to summarize therapy outcomes at the level of body structure and function, activity limitations, participation restrictions, and quality of life. Databases searched included MEDLINE, PUBMED, CINAHL, PSYCInfo, Data base of Abstracts of Reviews of Effectiveness (DARE), The Physiotherapy Evidence data base (PEDro), Evidence Based Medicine Reviews (EMBASE), the Cochrane database of systematic reviews, and the Cochrane Controlled Trials Register. Evidence was graded according to the Harbour and Miller classification. Most of the evidence was found to be at the level of "clinical opinion" rather than of controlled clinical trials. Several nonrandomized small group and "observational studies" provided low-level evidence to support physical therapy for improving muscle strength and pulmonary function. There was also some evidence to support the effectiveness of speech pathology interventions for dysarthria. The search identified a small number of studies on occupational therapy for PwMND, which were small, noncontrolled pre-post-designs or clinical reports.


Cognitive and Neural State Dynamics of Narrative Comprehension.
Narrative comprehension involves a constant interplay of the accumulation of incoming events and their integration into a coherent structure. This study characterizes cognitive states during narrative comprehension and the network-level reconfiguration occurring dynamically in the functional brain. We presented movie clips of temporally scrambled sequences to human participants (male and female), eliciting fluctuations in the subjective feeling of comprehension. Comprehension occurred when processing events that were highly causally related to the previous events, suggesting that comprehension entails the integration of narratives into a causally coherent structure. The functional neuroimaging results demonstrated that the integrated and efficient brain state emerged during the moments of narrative integration with the increased level of activation and across-modular connections in the default mode network. Underlying brain states were synchronized across individuals when comprehending novel narratives, with increased occurrences of the default mode network state, integrated with sensory processing network, during narrative integration. A model based on time-resolved functional brain connectivity predicted changing cognitive states related to comprehension that are general across narratives. Together, these results support adaptive reconfiguration and interaction of the functional brain networks on causal integration of the narratives.SIGNIFICANCE STATEMENT The human brain can integrate temporally disconnected pieces of information into coherent narratives. However, the underlying cognitive and neural mechanisms of how the brain builds a narrative representation remain largely unknown. We showed that comprehension occurs as the causally related events are integrated to form a coherent situational model. Using fMRI, we revealed that the large-scale brain states and interaction between brain regions dynamically reconfigure as comprehension evolves, with the default mode network playing a central role during moments of narrative integration. Overall, the study demonstrates that narrative comprehension occurs through a dynamic process of information accumulation and causal integration, supported by the time-varying reconfiguration and brain network interaction.


Diabetes-associated dysregulation of O-GlcNAcylation in rat cardiac mitochondria.
Elevated mitochondrial O-GlcNAcylation caused by hyperglycemia, as occurs in diabetes, significantly contributes to mitochondrial dysfunction and to diabetic cardiomyopathy. However, little is known about the enzymology of mitochondrial O-GlcNAcylation. Herein, we investigated the enzymes responsible for cycling O-GlcNAc on mitochondrial proteins and studied the mitochondrial transport of UDP-GlcNAc. Analyses of purified rat heart mitochondria from normal and streptozocin-treated diabetic rats show increased mitochondrial O-GlcNAc transferase (OGT) and a concomitant decrease in the mito-specific O-GlcNAcase (OGA). Strikingly, OGT is mislocalized in cardiac mitochondria from diabetic rats. Interaction of OGT and complex IV observed in normal rat heart mitochondria is visibly reduced in diabetic samples, where OGT is mislocalized to the matrix. Live cell OGA activity assays establish the presence of O-GlcNAcase within the mitochondria. Furthermore, we establish that the inner mitochondrial membrane transporter, pyrimidine nucleotide carrier, transports UDP-GlcNAc from the cytosol to the inside of the mitochondria. Knockdown of this transporter substantially lowers mitochondrial O-GlcNAcylation. Inhibition of OGT or OGA activity within neonatal rat cardiomyocytes significantly affects energy production, mitochondrial membrane potential, and mitochondrial oxygen consumption. These data suggest that cardiac mitochondria not only have robust O-GlcNAc cycling, but also that dysregulation of O-GlcNAcylation likely plays a key role in mitochondrial dysfunction associated with diabetes.


BEFRIENding for Depression, Anxiety and Social support in older adults living in Australian residential aged care facilities (BEFRIENDAS): randomised controlled trial protocol.
This protocol describes an ongoing study of the impact of befriending on depression, anxiety and loneliness in older people living in residential aged care facilities in Australia. While systematic reviews of befriending have indicated positive benefits of befriending for people in a range of ages and settings, there have been no randomised controlled trials (RCTs) of befriending for older people living in residential aged care with depression and no studies of the cost effectiveness of befriending in residential aged care facilities (RACFs) in Australia. We are conducting a single blind pragmatic RCT comparing two groups of older people living in RACFs, one receiving an intervention consisting of weekly befriending for 4 months from a trained volunteer and the other receiving treatment as usual. Participants undergo eligibility screening for depression (GDS-15 ≥ 4) and cognitive impairment (GPCog ≥ 4) and assessments at three measurement time points: baseline prior to randomisation, 2 months post-baseline and 4 months post-baseline. The primary outcome measure is depression, and secondary outcome measures are anxiety, loneliness, social isolation and quality of life. The economic evaluation will take the form of a cost-utility analysis based on the outcome of quality of life. The primary and secondary outcomes will be analysed using negative binomial and logistic regressions utilizing the Generalised Estimating Equations approach. To our knowledge, this is the first RCT evaluating the effectiveness of befriending on older people with depression living in residential aged care. It is expected that the befriending intervention will reduce the severity of depression symptoms experienced by older people living in residential aged care. If the intervention proves effective it may be incorporated into volunteer training programs and adopted as a way of supporting older people's mental health. Trial registered with the Australian and New Zealand Clinical Trial Registry (ANZCTR) Number: ACTRN12619000676112 , registered 06/05/2019 - retrospectively registered.


High-resolution calcium mapping of the endoplasmic reticulum-Golgi-exocytic membrane system. Electron energy loss imaging analysis of quick frozen-freeze dried PC12 cells.
The calcium pools segregated within the endoplasmic reticulum, Golgi complex, exocytic, and other organelles are believed to participate in the regulation of a variety of cell functions. Until now, however, the precise intracellular distribution of the element had not been established. Here, we report about the first high-resolution calcium mapping obtained in neurosecretory PC12 cells by the imaging mode of the electron energy loss spectroscopy technique. The preparation procedure used included quick freezing of cell monolayers, followed by freeze-drying, fixation with OSO4 vapors, resin embedding, and cutting of very thin sections. Conventional electron microscopy and high-resolution immunocytochemistry revealed a high degree of structural preservation, a condition in which inorganic elements are expected to maintain their native distribution. Within these cells, calcium signals of nucleus, cytosol, and most mitochondria remained below detection, whereas in other organelles specific patterns were identified. In the endoplasmic reticulum, the distribution was heterogeneous with strongly positive cisternae (more often the nuclear envelope and stacks of parallel elements that are frequent in quick frozen preparations) lying in the proximity of or even in direct continuity with other, apparently negative cisternae. The Golgi complexes were labeled strongly and uniformly in all cisternae and part of their vesicles, with no appreciable differences along the cis-trans axis. Weaker or negative signals were recorded from the trans-Golgi network elements and from scattered vesicles, whereas in contrast secretion granules were strongly positive for calcium. These results are discussed in relation to the existing knowledge about the mechanisms of calcium transport in the variations organelles, and about the processes and functions regulated by organelle lumenal calcium in eukaryotic cells.


Regulation of nitrogen fixation in the phototrophic purple bacterium Rhodobacter capsulatus.
In R. capsulatus synthesis and activity of the molybdenum and the alternative nitrogenase is controlled at three levels by the environmental factors ammonium, molybdenum, light, and oxygen. At the first level, transcription of the nifA1, nifA2, and anfA genes--which encode the transcriptional activators of all other nif and anf genes, respectively--is controlled by the Ntr system in dependence on ammonium availability. Mutations in ginB (coding for the signal transduction protein PII) result in significant expression of nifA and anfA in the presence of ammonium. In contrast to GlnB, the PII-paralogue GlnK is not involved in the Ntr signal transduction mechanism. In addition to ammonium control, transcription of anfA is inhibited by traces of molybdenum via the molybdate-dependent repressor proteins MopA and MopB. At the second level of regulation, activity of NifA1, NifA2, and AnfA is inhibited by ammonium in an NtrC-independent manner. This post-translational ammonium control of NifA activity is partially released in the absence of GlnK, and completely abolished in a glnB/glnK double mutant. In contrast, AnfA activity is still inhibited by ammonium in the glnB/glnK mutant background. At the third level of regulation, both GlnB and GlnK as well as the (methyl)-ammonium transporter AmtB are involved in ammonium control of the DraT/DraG system, which mediates reversible ADP-ribosylation of both nitrogenase reductases (NifH and AnfH) in response to changes in ammonium availability or light intensity. Most remarkably, in a glnB/glnK double mutant ammonium control of the molybdenum (but not of the alternative) nitrogenase is completely relieved, leading to synthesis of active nitrogenase in the presence of high concentrations of ammonium.


Measuring the CP violating phase gamma using B+/- --> pi(+/-)pi(+)pi(-) and B+/- --> K+/-pi(+)pi(-) decays.
A new and simple procedure to measure the angle gamma from B+/--->pi(+/-)pi(+)pi(-) and B+/--->K+/-pi(+)pi(-) decays using SU(3) symmetry is presented. It is based on a full Dalitz plot analysis of these decays. All diagrams, including strong and electroweak penguins, are considered in the procedure. The method is also free from final state interaction problems. The theoretical error in the extraction of gamma within the method should be of the order of 10(0) or even less. Taking into account the B-meson production in the first generation of B factories and recent measurements from CLEO, this method could bring the best measurement of gamma in the next years.


[Serotonin metabolism in acute renal ischemia in rabbits].
In tissue of ischemic kidney of rabbits a 5-hydroxytryptophan decarboxylase activity was decreased at first 15 min of ischemia; in contralateral kidney it was slightly increased. Then, within all the studied periods (24 hrs), activity of the enzyme was gradually decreased in both kidneys. The monoamine oxidase activity (substrates serotonin and p-nitrophenyl ethylamine) changed alternatively in early periods of ischemia; it tended to increase, especially in contralateral kidney, within 3 hrs after constriction of kidney artery.