Cross-sectional study of pulmonary function in cadmium alloy workers.
Two groups of cadmium workers (7 and 9 men) and a group of reference workers (122 men) were studied for the purpose of determining the pulmonary effects of cadmium. Indices of pulmonary function, based on the forced expiratory flow volume curve and respiratory impedance, were measured for all the groups, and indicators of cadmium exposure and effects on renal tubular reabsorption functions were also measured in the two groups of cadmium workers. The mean blood and urinary levels of cadmium were 2.08 microgram/100 ml (185.06 nmol/l) and 32.6 microgram/l (290.04 nmol/l), respectively, and the level of inhalation exposure was estimated at about 1 mg/m3 as the 8-h average concentration for about 5 a in the high exposure group. The percentage of the predicted function values of the highly exposed workers was significantly deteriorated for forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1.0), peak expiratory flow, maximum expiratory flow at 75, 50, and 25% of the FVC, percentage of FEV1.0 to FVC, and respiratory impedance, whereas those of the slightly exposed workers were reduced only for FVC and FEV1.0. A paired comparison between the highly exposed workers and matched referents disclosed the same results. It was concluded that chronic obstructive pulmonary changes had been induced by cadmium in Japanese workers without a history of acute or subacute cadmium pneumonitis.


Developing an analytical framework for assessing progress toward ecosystem-based management.
Ecosystem-based management (EBM) has become a key instrument of contemporary environmental policy and practice. Given the increasingly important role of EBM, there is an urgent need for improved analytical approaches to assess if and to what extent EBM has been accomplished in any given case. Drawing on the vast literature on EBM, we identify five key ecosystem aspects for assessment. By linking these aspects to four phases of management, we develop an interdisciplinary, analytical framework that enables a high-resolution and systematic assessment of the degree of specificity and integration of ecosystem aspects in an EBM. We then apply the framework to evaluate five coastal EBM initiatives in Sweden, four on the Baltic coast and one on the west coast. Our results demonstrate our framework's usefulness for in-depth and continuous assessments of processes aiming for EBM, and also provide an empirical basis for inferences about the key challenges for successful EBM.


Physical child abuse demands increased awareness during health and socioeconomic crises like COVID-19.
Background and purpose - Physical abuse of children, i.e., nonaccidental injury (NAI) including abusive head trauma (AHT) is experienced by up to 20% of children; however, only 0.1% are diagnosed. Healthcare professionals issue less than 20% of all reports suspecting NAI to the responsible authorities. Insufficient knowledge concerning NAI may partly explain this low percentage. The risk of NAI is heightened during health and socioeconomic crises such as COVID-19 and thus demands increased awareness. This review provides an overview and educational material on NAI and its clinical presentation.Methods - We combined a literature review with expert opinions of the senior authors into an educational paper aiming to help clinicians to recognize NAI and act appropriately by referral to multidisciplinary child protection teams and local authorities.Results - Despite the increased risk of NAI during the current COVID-19 crisis, the number of reports suspecting NAI decreased by 42% during the lockdown of the Danish society. Healthcare professionals filed only 17% of all reports of suspected child abuse in 2016.Interpretation - The key to recognizing and suspecting NAI upon clinical presentation is to be aware of inconsistencies in the medical history and suspicious findings on physical and paraclinical examination. During health and socioeconomic crises the incidence of NAI is likely to peak. Recognition of NAI, adequate handling by referral to child protection teams, and reporting to local authorities are of paramount importance to prevent mortality and physical and mental morbidity.


Desalinated underground seawater of Jeju Island (Korea) improves lipid metabolism in mice fed diets containing high fat and increases antioxidant potential in t-BHP treated HepG2 cells.
This study was performed to investigate the effect of desalinated underground seawater (named as 'magma seawater', MSW) of Jeju Island in Korea on lipid metabolism and antioxidant activity. MSW was collected from underground of Han-Dong in Jeju Island, and freely given to high fat diet (HFD)-fed C57BL/6 mice for 10 weeks. Although there were no significant differences in the body weight changes and plasma lipid levels, hepatic triglyceride levels were significantly lower in the MSW group than in the normal tap water (TW)-drunken control group. Furthermore, the activity of fatty acid synthase (FAS) was significantly decreased and carnitine palmitoyltransferase (CPT) activity was increased in MSW group compared to TW group. Similarly, real-time PCR analysis revealed that mRNA expressions of lipogenic genes were lowered in MSW groups compared to the control group. In a morphometric observation on the liver tissue, accumulation of fats was remarkably reduced in MSW group. Meanwhile, in vitro assay, free radical scavenging activity measured by using diphenylpicrylhydrazyl (DPPH) was increased in MSW group. The 2'-7'-dichlorofluorescein diacetate (DCF-DA) staining followed with fluorescent microscopy showed a low intensity of fluorescence in MSW-treated HepG2 cells, compared to TW-treated HepG2 cells, which indicated that the production of reactive oxygen species by tert-butyl hydroperoxide (t-BHP) in HepG2 cells was decreased by MSW treatment. The antioxidant effect of MSW on t-BHP-induced oxidative stress in HepG2 cells was supported by the increased activities of intracellular antioxidant enzymes such as catalase and glutathione reductase. From these results, we speculate that MSW has an inhibitory effect on lipogenesis in liver and might play a protective role against cell damage by t-BHP-induced oxidative stress.


Validation of the EQ-5D in Patients with Traumatic Limb Injury.
The measurement properties of the EQ-5D have not been explored for patients with traumatic limb injuries. The purpose of this study was to examine the construct validity, predictive validity, and responsiveness of the EQ-5D in patients with traumatic limb injuries. A consecutive cohort of 1,167 patients was assessed with the EQ-5D and the World Health Organization Quality of Life instrument (WHOQOL-BREF) at baseline while the patients were hospitalized because of the injury, and the patients were followed up at 3 months (1,003 patients), 6 months (1,010 patients), and 12 months (987 patients) after injury via telephone interview. The utility and visual analogue scale (VAS) scores of the EQ-5D had moderate to high association with the physical and psychological domains and the two general questions (overall QOL and overall health) of the WHOQOL-BREF at all time points except baseline (Pearson's correlation coefficient >0.3), but the EQ-5D profiles were weakly associated with the social and environment domains of the WHOQOL-BREF (absolute value of Spearman's correlation coefficient <0.3). These results indicate that the EQ-5D has satisfactory construct validity. The utility and VAS scores of the EQ-5D at 3 and 6 months after injury can predict (with moderate to large relationships) the four domains and two general questions of the WHOQOL-BREF administered at 12 months after injury. The responsiveness of the utility and VAS of the EQ-5D were high (effect sizes >0.9) at 0-3, 0-6, and 0-12 months after injury. The EQ-5D has sufficient construct validity, predictive validity, and responsiveness, and also provides evidence for using the utility of the EQ-5D for cost-utility analyses of patients with traumatic limb injuries in the future.


Applying medicinal chemistry strategies to understand odorant discrimination.
Associating an odorant's chemical structure with its percept is a long-standing challenge. One hindrance may come from the adoption of the organic chemistry scheme of molecular description and classification. Chemists classify molecules according to characteristics that are useful in synthesis or isolation, but which may be of little importance to a biological sensory system. Accordingly, we look to medicinal chemistry, which emphasizes biological function over chemical form, in an attempt to discern which among the many molecular features are most important for odour discrimination. Here we use medicinal chemistry concepts to assemble a panel of molecules to test how heteroaromatic ring substitution of the benzene ring will change the odour percept of acetophenone. This work allows us to describe an extensive rule in odorant detection by mammalian olfactory receptors. Whereas organic chemistry would have predicted the ring size and composition to be key features, our work reveals that the topological polar surface area is the key feature for the discrimination of these odorants.


Biomedicine in the environment: cyclotides constitute potent natural toxins in plants and soil bacteria.
Bioactive compounds produced by plants are easily transferred to soil and water and may cause adverse ecosystem effects. Cyclotides are gene-encoded, circular, cystine-rich mini-proteins produced in Violaceae and Rubiaceae in high amounts. Based on their biological activity and stability, cyclotides have promising pharmaceutical and agricultural applications. We report the toxicity of the cyclotides: kalata B1, kalata B2, and cycloviolacin O2 extracted from plants to green algae (Pseudokirchneriella subcapitata), duckweed (Lemna minor L.), lettuce (Lactuca sativa L.), and bacteria extracted from soil measured as [³H]leucine incorporation. Quantification by liquid chromatography-mass spectrometry demonstrated up to 98% loss of cyclotides from aqueous solutions because of sorption to test vials. Sorption was prevented by adding bovine serum albumin (BSA) to the aqueous media. Cyclotides were toxic to all test organisms with EC50 values of 12 through 140 µM (algae), 9 through 40 µM (duckweed), 4 through 54 µM (lettuce), and 7 through 26 µM (bacteria). Cycloviolacin O2 was the most potent cyclotide in all assays examined. This report is the first to document toxic effects of cyclotides in plants and soil bacteria and to demonstrate that cyclotides are as toxic as commonly used herbicides and biocides. Hence, cyclotides may adversely affect soil and aquatic environments, which needs to be taken into account in future risk assessment of cropping systems for production of these highly bioactive compounds.


Upregulation of miR-130b Contributes to Risk of Poor Prognosis and Racial Disparity in African-American Prostate Cancer.
Prostate cancer incidence and mortality rates are higher in African-American (AA) than in European-American (EA) men. The main objective of this study was to elucidate the role of miR-130b as a contributor to prostate cancer health disparity in AA patients. We also determined whether miR-130b is a prognostic biomarker and a new therapeutic candidate for AA prostate cancer. A comprehensive approach of using cell lines, tissue samples, and the TCGA database was employed. We performed a series of functional assays such as cell proliferation, migration, invasion, RT2-PCR array, qRT-PCR, cell cycle, luciferase reporter, immunoblot, and IHC. Various statistical approaches such as Kaplan-Meier, uni-, and multivariate analyses were utilized to determine the clinical significance of miR-130b. Our results showed that elevated levels of miR-130b correlated with race disparity and PSA levels/failure and acted as an independent prognostic biomarker for AA patients. Two tumor suppressor genes, CDKN1B and FHIT, were validated as direct functional targets of miR-130b. We also found race-specific cell-cycle pathway activation in AA patients with prostate cancer. Functionally, miR-130b inhibition reduced cell proliferation, colony formation, migration/invasion, and induced cell-cycle arrest. Inhibition of miR-130b modulated critical prostate cancer-related biological pathways in AA compared with EA prostate cancer patients. In conclusion, attenuation of miR-130b expression has tumor suppressor effects in AA prostate cancer. miR-130b is a significant contributor to prostate cancer racial disparity as its overexpression is a risk factor for poor prognosis in AA patients with prostate cancer. Thus, regulation of miR-130b may provide a novel therapeutic approach for the management of prostate cancer in AA patients.


Evaluation of clustering algorithms for protein-protein interaction networks.
Protein interactions are crucial components of all cellular processes. Recently, high-throughput methods have been developed to obtain a global description of the interactome (the whole network of protein interactions for a given organism). In 2002, the yeast interactome was estimated to contain up to 80,000 potential interactions. This estimate is based on the integration of data sets obtained by various methods (mass spectrometry, two-hybrid methods, genetic studies). High-throughput methods are known, however, to yield a non-negligible rate of false positives, and to miss a fraction of existing interactions. The interactome can be represented as a graph where nodes correspond with proteins and edges with pairwise interactions. In recent years clustering methods have been developed and applied in order to extract relevant modules from such graphs. These algorithms require the specification of parameters that may drastically affect the results. In this paper we present a comparative assessment of four algorithms: Markov Clustering (MCL), Restricted Neighborhood Search Clustering (RNSC), Super Paramagnetic Clustering (SPC), and Molecular Complex Detection (MCODE). A test graph was built on the basis of 220 complexes annotated in the MIPS database. To evaluate the robustness to false positives and false negatives, we derived 41 altered graphs by randomly removing edges from or adding edges to the test graph in various proportions. Each clustering algorithm was applied to these graphs with various parameter settings, and the clusters were compared with the annotated complexes. We analyzed the sensitivity of the algorithms to the parameters and determined their optimal parameter values. We also evaluated their robustness to alterations of the test graph. We then applied the four algorithms to six graphs obtained from high-throughput experiments and compared the resulting clusters with the annotated complexes. This analysis shows that MCL is remarkably robust to graph alterations. In the tests of robustness, RNSC is more sensitive to edge deletion but less sensitive to the use of suboptimal parameter values. The other two algorithms are clearly weaker under most conditions. The analysis of high-throughput data supports the superiority of MCL for the extraction of complexes from interaction networks.


Spatiotemporal feature attribution for the perception of visual size.
This study examined the role of spatiotemporal feature attribution in the perception of the visual size of objects. A small or a large leading disk, a test disk of variable size, and a probe disk of a fixed size were sequentially presented at the same position for durations of 16.7 ms with interstimulus intervals of 117 ms. Observers compared the visual size of the test with the probe disk. The size of the test disk was underestimated and overestimated when the test followed small and large leading disks, respectively (Experiment 1). These modulations of visual size occurred even when disks were sequentially presented so as to invoke apparent motion (Experiment 2). Furthermore, when two streams of apparent motion consisting of the three types of disk were diagonally overlapped, modulation of visual size occurred in accordance with the size of the attended leading disk (Experiment 3). Retinotopic and non-retinotopic feature attribution and the related attentional mechanisms are discussed.


Liver disease in cystic fibrosis.
This review highlights recent developments in liver disease associated with cystic fibrosis. The broad spectrum of hepatobiliary problems in cystic fibrosis includes specific alterations ascribable to the underlying defect as well as lesions of iatrogenic origin or that reflect the effects of a disease process occurring outside the liver. Focal biliary cirrhosis, resulting from biliary obstruction and progressive periportal fibrosis, is the most clinically relevant problem, because extension of the initially focal fibrogenic process may lead to multilobular biliary cirrhosis, portal hypertension and eventually liver failure. Cystic fibrosis associated liver disease is presently classified among genetic cholangiopathies and results from lack or dysfunction of the cystic fibrosis transmembrane regulator at the apical membrane of bile duct cells. Major advances have been achieved regarding characterization of natural history, risk factors, diagnostic modalities and treatment options. Liver disease is a relatively frequent and early complication of cystic fibrosis. The pathogenesis is apparently multifactorial, with contributions from environmental and genetic determinants. Its impact on quality of life and survival will increase in future years, and its early detection and treatment will become increasingly important issues. Ursodeoxycholic acid is the only treatment currently available, but novel therapeutic options are being evaluated.


Autoinflammatory skin disorders in inflammatory bowel diseases, pyoderma gangrenosum and Sweet's syndrome: a comprehensive review and disease classification criteria.
Pyoderma gangrenosum (PG) and Sweet's syndrome (SS) are skin diseases usually presenting with recurrent ulcers and erythematous plaques, respectively. The accumulation of neutrophils in the skin, characteristic of these conditions, led to coin the term of neutrophilic dermatoses to define them. Recently, neutrophilic dermatoses have been included in the group of autoinflammatory diseases, which classically comprises genetically determined forms due to mutations of genes regulating the innate immune response. Both PG and SS are frequently associated with inflammatory bowel diseases (IBDs); however, IBD patients develop PG in 1-3 % of cases, whereas SS is rarer. Clinically, PG presents with deep erythematous-to-violaceous painful ulcers with well-defined borders; bullous, pustular, and vegetative variants can also occur. SS is characterized by the abrupt onset of fever, peripheral neutrophilia, tender erythematous skin lesions, and a diffuse neutrophilic dermal infiltrate. It is also known as acute febrile neutrophilic dermatosis. Treatment of PG involves a combination of wound care, topical medications, antibiotics for secondary infections, and treatment of the underlying IBD. Topical therapies include corticosteroids and the calcineurin inhibitor tacrolimus. The most frequently used systemic medications are corticosteroids and cyclosporine, in monotherapy or in combination. Dapsone, azathioprine, cyclophosphamide, methotrexate, intravenous immunoglobulins, mycophenolate mofetil, and plasmapheresis are considered second-line agents. Hyperbaric oxygen, as supportive therapy, can be added. Anti-TNF-α agents such as etanercept, infliximab, and adalimumab are used in refractory cases. SS is usually responsive to oral corticosteroids, and the above-mentioned immunosuppressants should be considered in resistant or highly relapsing cases.


Maternal obesity support services: a qualitative study of the perspectives of women and midwives.
Twenty percent of pregnant women in the UK are obese (BMI ≥ 30 kg/m2), reflecting the growing public health challenge of obesity in the 21st century. Obesity increases the risk of adverse outcomes during pregnancy and birth and has significant cost implications for maternity services. Gestational weight management strategies are a high priority; however the evidence for effective, feasible and acceptable weight control interventions is limited and inconclusive. This qualitative study explored the experiences and perceptions of pregnant women and midwives regarding existing support for weight management in pregnancy and their ideas for service development. A purposive sample of 6 women and 7 midwives from Doncaster, UK, participated in two separate focus groups. Transcripts were analysed thematically. Two overarching themes were identified, 'Explanations for obesity and weight management' and 'Best care for pregnant women'. 'Explanations' included a lack of knowledge about weight, diet and exercise during pregnancy; self-talk messages which excused overeating; difficulties maintaining motivation for a healthy lifestyle; the importance of social support; stigmatisation; and sensitivity surrounding communication about obesity between midwives and their clients. 'Best care' suggested that weight management required care which was consistent and continuous, supportive and non-judgemental, and which created opportunities for interaction and mutual support between obese pregnant women. Women need unambiguous advice regarding healthy lifestyles, diet and exercise in pregnancy to address a lack of knowledge and a tendency towards unhelpful self-talk messages. Midwives expressed difficulties in communicating with their clients about their weight, given awareness that obesity is a sensitive and potentially stigmatising issue. This indicates more could be done to educate and support them in their work with obese pregnant women. Motivation and social support were strong explanatory themes for obesity and weight management, suggesting that interventions should focus on motivational strategies and social support facilitation.


Dynamic consent: a patient interface for twenty-first century research networks.
Biomedical research is being transformed through the application of information technologies that allow ever greater amounts of data to be shared on an unprecedented scale. However, the methods for involving participants have not kept pace with changes in research capability. In an era when information is shared digitally at the global level, mechanisms of informed consent remain static, paper-based and organised around national boundaries and legal frameworks. Dynamic consent (DC) is both a specific project and a wider concept that offers a new approach to consent; one designed to meet the needs of the twenty-first century research landscape. At the heart of DC is a personalised, digital communication interface that connects researchers and participants, placing participants at the heart of decision making. The interface facilitates two-way communication to stimulate a more engaged, informed and scientifically literate participant population where individuals can tailor and manage their own consent preferences. The technical architecture of DC includes components that can securely encrypt sensitive data and allow participant consent preferences to travel with their data and samples when they are shared with third parties. In addition to improving transparency and public trust, this system benefits researchers by streamlining recruitment and enabling more efficient participant recontact. DC has mainly been developed in biobanking contexts, but it also has potential application in other domains for a variety of purposes.


Composition of the sand fly fauna in Khash County, Southeast Iran.
Sand flies (Diptera: Psychodidae: Phlebotominae) are the biological vectors of leishmaniasis all around the world. In 1997, sand flies were collected in 14 cities and villages of Khash County in southeastern Iran, using 848 sticky traps (castor oil-coated white papers 20 × 30 cm). In this study, a total of 4673 sand flies, with 25.23% females and 74.77% males, were collected and identified to species mainly from mountainous areas. The 21 species of sand flies belonged to the genus Phlebotomus (nine species) and the genus Sergentomyia (12 species). The following 14 species were reported for the first time in Khash County: P. papatasi, P. bergeroti, P. eleanorae, P. halepensis, P. major, P. mesghali, S. hodgsoni, S. mervynae, S. dreyfussi, S. iranica, S. theodori, S. africana, S. clydei, and S. christophersi. The composition of species in Khash County is similar to other parts of Iran. However, the dominance of P. kazeruni in Khash County may suggest that this species should be considered as a potential vector in the region of Khash.


[Necrolytic migratory erythema in Waldmann's disease].
We report a case of necrolytic migratory erythema in a patient with Waldmann's disease. A 55-year-old male patient with a history of Waldmann's disease was hospitalized for a rash on the trunk and limbs comprising annular polycyclic lesions with peripheral scaling evocative of necrolytic migratory erythema. High-protein and fatty-acid-supplemented parenteral feeding led to rapid improvement of the patient's cutaneous lesions. Waldmann's disease is characterized by intestinal lymphatic abnormalities leading to exudative intestinal disease causing protein loss in the bowel lumen and deficient fatty acid absorption. The pathogenesis of necrolytic migratory erythema is not fully understood. Increased serum glucagon does not appear to be the only mechanism involved. The occurrence of necrolytic migratory erythema in a patient with Waldmann's disease supports the current physiopathological hypothesis of the role of decreased plasma protein and amino acid levels in necrolytic migratory erythema.


Recording practices and satisfaction of hemophiliac patients using two different data entry systems.
Record keeping is integral to home treatment for hemophilia. Identified problems with paper diaries include suboptimal compliance and questionable data validity and quality. The effects of an electronic data recording system, Advoy, on data quality, patient adherence, and satisfaction were examined. An exploratory approach was used to examine the sequential use of paper diaries and e-diaries by 38 patients. Data were obtained from paper records for the 6 months preceding the introduction of the electronic record and from the first 6 months of use of Advoy. Completion of mandatory and additional treatment details was also compared. More mandatory information (27.57%) was recorded with the e-diary. As well, the amount of completed additional fields nearly doubled (19.9%-36.5%). Patients tended to complete a greater variety of additional fields with the e-diary than with paper records. Finally, a higher percentage of survey respondents (29.4%) indicated that they were "very satisfied" with Advoy compared with paper records (6.7%). Most survey respondents (94.4%) had a previous experience with electronic programs. The use of the e-diary significantly improved patient adherence in recording mandatory treatment information; the increase in additional data provided by the patients was also found to be an added benefit of this technology.


Comparative safety of direct oral anticoagulants and warfarin in venous thromboembolism: multicentre, population based, observational study.
Objective To determine the safety of direct oral anticoagulant (DOAC) use compared with warfarin use for the treatment of venous thromboembolism.Design Retrospective matched cohort study conducted between 1 January 2009 and 31 March 2016.Setting Community based, using healthcare data from six jurisdictions in Canada and the United States.Participants 59 525 adults (12 489 DOAC users; 47 036 warfarin users) with a new diagnosis of venous thromboembolism and a prescription for a DOAC or warfarin within 30 days of diagnosis.Main outcome measures Outcomes included hospital admission or emergency department visit for major bleeding and all cause mortality within 90 days after starting treatment. Propensity score matching and shared frailty models were used to estimate adjusted hazard ratios of the outcomes comparing DOACs with warfarin. Analyses were conducted independently at each site, with meta-analytical methods used to estimate pooled hazard ratios across sites.Results Of the 59 525 participants, 1967 (3.3%) had a major bleed and 1029 (1.7%) died over a mean follow-up of 85.2 days. The risk of major bleeding was similar for DOAC compared with warfarin use (pooled hazard ratio 0.92, 95% confidence interval 0.82 to 1.03), with the overall direction of the association favouring DOAC use. No difference was found in the risk of death (pooled hazard ratio 0.99, 0.84 to 1.16) for DOACs compared with warfarin use. There was no evidence of heterogeneity across centres, between patients with and without chronic kidney disease, across age groups, or between male and female patients.Conclusions In this analysis of adults with incident venous thromboembolism, treatment with DOACs, compared with warfarin, was not associated with an increased risk of major bleeding or all cause mortality in the first 90 days of treatment.Trial registration Clinical trials NCT02833987.


Renal functional response to ischaemic renal failure in chronic hypoxic rats.
1. Chronic hypoxic rats are always polycythaemic. It is possible that an increase in packed cell volume may enhance erythrocyte trapping with a consequent increase in renal damage after renal ischaemia. These experiments were designed to assess renal functional changes after renal arterial occlusion in chronic hypoxic rats. 2. Chronic hypoxic rats were prepared by exposure (15h/day) to an altitude chamber (5486m) for 4 weeks. 3. After 45 min of left renal arterial occlusion, there were significant decreases in the excretion of potassium, p-aminohippurate and inulin and in the p-aminohippurate extraction ratio in 12 sea level ischaemic insulted kidneys. In 12 chronic hypoxic rats, the same parameters were changed after left renal ischaemia but only the p-aminohippurate ratio was significantly altered. 4. Administrations of 1 or 5 mg/kg phosphoramidon did not cause any significant improvement in the measured renal parameters in both kidneys and in both groups of rats after ischaemia. 5. In the second experiment, the rats were challenged by rapid infusion of 10 ml of saline intravenously, and urine was collected for 90 min from each ureter. Four hours after left renal arterial occlusion, the insulted kidney showed increased water and sodium excretion in both sea level and chronic hypoxic rats. However, 24 h after left renal ischaemia, the responses of sea level and chronic hypoxic rats were different. Urinary excretion was significantly reduced in sea level rats, but was almost normal in chronic hypoxic rats. 6. This report suggests that some beneficial factors after chronic hypoxia might play important roles in reducing the damage after renal ischaemia.


A protocol avoiding allogeneic transfusion in joint arthroplasties.
Arthroplasties of hip and knee are associated with blood loss, which may lead to adverse patient outcome. Performing arthroplasties in Jehovah's Witness patients who do not accept transfusion has been a matter of concern. We developed a protocol, which avoids transfusion in arthroplasties of Jehovah's Witness patients, and evaluated the feasibility and safety of the protocol. The target of preoperative hemoglobin was more than 10 g/dL. When preoperative hemoglobin was lower than 10 g/dL, 4000 U erythropoietin (3 times a week) and 100 mg iron supplement (every day) were administered until the hemoglobin reached 10 g/dL. When the preoperative hemoglobin was higher than 10 g/dL, 4000 U erythropoietin and 100 mg iron supplement were administered once, before operation. During the operation, cell saver was used. Postoperatively, erythropoietin and iron supplements were administered until the hemoglobin reached 10 g/dL, similar to the preoperative protocol. We evaluated the feasibility of our protocol, perioperative complications and hematologic changes. From 2002 to 2014, 186 Witness patients visited our department. In 179 patients (96.2 %), 77 total knee arthroplasties, 69 bipolar hemiarthroplasties and 33 total hip arthroplasties were performed. The mean hemoglobin level was 12.3 g/dL preoperatively, 9.4 g/dL on postoperative day 3 and 10.3 g/dL on postoperative day 7. One patient died immediately after the arthroplasty and the remaining 178 patients survived. Total joint arthroplasty could be done without transfusion using this protocol in most of our patients. The rates of infection and mortality were similar with known infection and mortality rates of arthroplasties. In patients who do not want allogeneic transfusions, our protocol is a safe alternative to perform joint arthroplasties.


Effect of point-of-care computer reminders on physician behaviour: a systematic review.
The opportunity to improve care using computer reminders is one of the main incentives for implementing sophisticated clinical information systems. We conducted a systematic review to quantify the expected magnitude of improvements in processes of care from computer reminders delivered to clinicians during their routine activities. We searched the MEDLINE, Embase and CINAHL databases (to July 2008) and scanned the bibliographies of retrieved articles. We included studies in our review if they used a randomized or quasi-randomized design to evaluate improvements in processes or outcomes of care from computer reminders delivered to physicians during routine electronic ordering or charting activities. Among the 28 trials (reporting 32 comparisons) included in our study, we found that computer reminders improved adherence to processes of care by a median of 4.2% (interquartile range [IQR] 0.8%-18.8%). Using the best outcome from each study, we found that the median improvement was 5.6% (IQR 2.0%-19.2%). A minority of studies reported larger effects; however, no study characteristic or reminder feature significantly predicted the magnitude of effect except in one institution, where a well-developed, "homegrown" clinical information system achieved larger improvements than in all other studies (median 16.8% [IQR 8.7%-26.0%] v. 3.0% [IQR 0.5%-11.5%]; p = 0.04). A trend toward larger improvements was seen for reminders that required users to enter a response (median 12.9% [IQR 2.7%-22.8%] v. 2.7% [IQR 0.6%-5.6%]; p = 0.09). Computer reminders produced much smaller improvements than those generally expected from the implementation of computerized order entry and electronic medical record systems. Further research is required to identify features of reminder systems consistently associated with clinically worthwhile improvements.


The structure of FSTL3.activin A complex. Differential binding of N-terminal domains influences follistatin-type antagonist specificity.
Transforming growth factor beta family ligands are neutralized by a number of structurally divergent antagonists. Follistatin-type antagonists, which include splice variants of follistatin (FS288 and FS315) and follistatin-like 3 (FSTL3), have high affinity for activin A but differ in their affinity for other ligands, particularly bone morphogenetic proteins. To understand the structural basis for ligand specificity within FS-type antagonists, we determined the x-ray structure of activin A in complex with FSTL3 to a resolution of 2.5 A. Similar to the previously resolved FS.activin A structures, the ligand is encircled by two antagonist molecules blocking all ligand receptor-binding sites. Recently, the significance of the FS N-terminal domain interaction at the ligand type I receptor site has been questioned; however, our data show that for FSTL3, the N-terminal domain forms a more intimate contact with activin A, implying that this interaction is stronger than that for FS. Furthermore, binding studies revealed that replacing the FSTL3 N-terminal domain with the corresponding FS domain considerably lowers activin A affinity. Therefore, both structural and biochemical evidence support a significant interaction of the N-terminal domain of FSTL3 with activin A. In addition, structural comparisons with bone morphogenetic proteins suggest that the interface where the N-terminal domain binds may be the key site for determining FS-type antagonist specificity.


Laparoscopic entry techniques.
Laparoscopy is a common procedure in gynaecology. Complications associated with laparoscopy are often related to entry. Life-threatening complications include injury to the bowel, bladder, major abdominal vessels, and an anterior abdominal-wall vessel. Other less serious complications can also occur, such as post-operative infection, subcutaneous emphysema and extraperitoneal insufflation. There is no clear consensus as to the optimal method of entry into the peritoneal cavity. This is an update of a Cochrane review first published in 2008. To evaluate the benefits and risks of different laparoscopic techniques in gynaecological and non-gynaecological surgery. This review has drawn on the search strategy developed by the Cochrane Menstrual Disorders and Subfertility Group. In addition, MEDLINE, EMBASE, CENTRAL and PsycINFO were searched through to February 2011. Randomised controlled trials were included when one laparoscopic entry technique was compared with another. Data were extracted independently by the first three authors. Differences of opinion were registered and resolved by the fourth author. Results for each study were expressed as odds ratio (Peto OR) with 95% confidence interval (CI). The review included 28 randomised controlled trials with 4860 individuals undergoing laparoscopy and evaluated 14 comparisons. Overall there was no evidence of advantage using any single technique in terms of preventing major vascular or visceral complications. Using an open-entry technique compared to a Veress Needle demonstrated a reduction in the incidence of failed entry, Peto OR 0.12 (95% CI 0.02 to 0.92). There were three advantages with direct-trocar entry when compared with Veress Needle entry, in terms of lower rates of failed entry (Peto OR 0.21, 95% Cl 0.14 to 0.31), extraperitoneal insufflation (Peto OR 0.18, 95% Cl 0.13 to 0.26), and omental injury (Peto OR 0.28, 95% CI 0.14 to 0.55).There was also an advantage with radially expanding access system (STEP) trocar entry when compared with standard trocar entry, in terms of trocar site bleeding (Peto OR 0.31, 95% Cl 0.15 to 0.62). Finally, there was an advantage of not lifting the abdominal wall before Veress Needle insertion when compared to lifting in terms of failed entry, without an increase in the complication rate (Peto OR 4.44, 95% CI 2.16 to 9.13). However, studies were limited to small numbers, excluding many patients with previous abdominal surgery and women with a raised body mass index who may have unusually high complication rates. An open-entry technique is associated with a significant reduction in failed entry when compared to a closed-entry technique, with no difference in the incidence of visceral or vascular injury.Significant benefits were noted with the use of a direct-entry technique when compared to the Veress Needle. The use of the Veress Needle was associated with an increased incidence of failed entry, extraperitoneal insufflation and omental injury; direct-trocar entry is therefore a safer closed-entry technique.The low rate of reported complications associated with laparoscopic entry and the small number of participants within the included studies may account for the lack of significant difference in terms of major vascular and visceral injury between entry techniques. Results should be interpreted with caution for outcomes where only single studies were included.


Emergence of medicine for mass gatherings: lessons from the Hajj.
Although definitions of mass gatherings (MG) vary greatly, they consist of large numbers of people attending an event at a specific site for a finite time. Examples of MGs include World Youth Day, the summer and winter Olympics, rock concerts, and political rallies. Some of the largest MGs are spiritual in nature. Among all MGs, the public health issues, associated with the Hajj (an annual pilgrimage to Mecca, Saudi Arabia) is clearly the best reported-probably because of its international or even intercontinental implications in terms of the spread of infectious disease. Hajj routinely attracts 2·5 million Muslims for worship. WHO's global health initiatives have converged with Saudi Arabia's efforts to ensure the wellbeing of pilgrims, contain infectious diseases, and reinforce global health security through the management of the Hajj. Both initiatives emphasise the importance of MG health policies guided by sound evidence and based on experience and the timeliness of calls for a new academic science-based specialty of MG medicine.


Preventing severe and fatal child maltreatment: making the case for the expanded use and integration of data.
In this article we examine risk factors for severe and fatal child maltreatment. These factors emerge from studies based on different data sources, including official child maltreatment data, emergency department and hospitalization data, death certificates, and data from child death review teams. The empirical literature reflects a growing effort to overcome the measurement uncertainties of any one individual data system. After review and reflection upon what is known, we consider how integrating this information can advance efforts to protect children, providing examples where the use and linkage of multiple sources of data may enhance surveillance, improve front-end decisionmaking, and support cost-effective research and evaluation.


Advanced treatment of biologically pretreated coal chemical industry wastewater using the catalytic ozonation process combined with a gas-liquid-solid internal circulating fluidized bed reactor.
This paper investigated the performance of the combined system of catalytic ozonation and the gas-liquid-solid internal circulating fluidized bed reactor for the advanced treatment of biologically pretreated coal chemical industry wastewater (CCIW). The results indicated that with ozonation alone for 60min, the removal efficiency of chemical oxygen demand (COD) could reach 34%. The introduction of activated carbon, pumice, γ-Al2O3 carriers improved the removal performance of COD, and the removal efficiency was increased by 8.6%, 4.2%, 2%, respectively. Supported with Mn, the catalytic performance of activated carbon and γ-Al2O3 were improved significantly with COD removal efficiencies of 46.5% and 41.3%, respectively; however, the promotion effect of pumice supported with Mn was insignificant. Activated carbon supported with Mn had the best catalytic performance. The catalytic ozonation combined system of MnOX/activated carbon could keep ozone concentration at a lower level in the liquid phase, and promote the transfer of ozone from the gas phase to the liquid phase to improve ozonation efficiency.


Quantitative contributions of TNF receptor superfamily members to CD8+ T-cell responses.
T-cell responses to infections and cancers are regulated by co-signalling receptors grouped into the binary categories of co-stimulation or co-inhibition. The co-stimulation TNF receptor superfamily (TNFRSF) members 4-1BB, CD27, GITR and OX40 have similar signalling mechanisms raising the question of whether they have similar impacts on T-cell responses. Here, we screened for the quantitative impact of these TNFRSFs on primary human CD8+ T-cell cytokine production. Although both 4-1BB and CD27 increased production, only 4-1BB was able to prolong the duration over which cytokine was produced, and both had only modest effects on antigen sensitivity. An operational model explained these different phenotypes using shared signalling based on the surface expression of 4-1BB being regulated through signalling feedback. The model predicted and experiments confirmed that CD27 co-stimulation increases 4-1BB expression and subsequent 4-1BB co-stimulation. GITR and OX40 displayed only minor effects on their own but, like 4-1BB, CD27 could enhance GITR expression and subsequent GITR co-stimulation. Thus, different co-stimulation receptors can have different quantitative effects allowing for synergy and fine-tuning of T-cell responses.


Access to IUD removal: Data from a mystery-caller study.
This study describes access and barriers to intrauterine device (IUD) removal appointments in 10 mid-sized cities in the United States. This mystery caller study utilized a sampling frame of health centers in 10 mid-sized cities gathered from 3 search engines. We gathered data about the timing of the next available appointment, the requirements for additional appointments prior to IUD removal, and the out-of-pocket cost. We used descriptive statistics to describe the availability and cost of IUD removal visits, and compared results between primary care clinics and family planning or gynecology clinics. Any additional information regarding why a visit was not available or other requirements for IUD removal that was provided to the researcher was also recorded. Of 229 clinics included for analysis, 60.7% could offer an IUD removal appointment to the mystery caller, and the majority of these could provide an initial appointment within 2 weeks (61.2%), with a median of 10 days. Of clinics offering IUD removal, 17.3% required more than one visit before removing the IUD, and 43.2% confirmed that IUD removal would occur at the first visit. Five clinics (5.6%) reported that they would not remove an IUD that was not placed at their clinic. Sliding scale fees were offered at 16.3% of clinics. For the clinics that cited an out-of-pocket cost and did not offer sliding scale fees, the median cost of the IUD removal was $262, with a range of $50 to over $1000. Neither appointment availability nor cost differed between primary care and family planning or gynecology clinics. Overall, timely IUD removal appointments were available at the clinics we sampled, but both financial and clinic policy barriers to IUD removal were documented, including the need for multiple appointments and the total out-of-pocket costs. In our current climate focused on improving access to IUDs, it is essential to address and reduce barriers to IUD removal when desired, in order to preserve reproductive autonomy.


Sri Lanka Pilot Study to Examine Respiratory Health Effects and Personal PM2.5 Exposures from Cooking Indoors.
A pilot study of indoor air pollution produced by biomass cookstoves was conducted in 53 homes in Sri Lanka to assess respiratory conditions associated with stove type ("Anagi" or "Traditional"), kitchen characteristics (e.g., presence of a chimney in the home, indoor cooking area), and concentrations of personal and indoor particulate matter less than 2.5 micrometers in diameter (PM2.5). Each primary cook reported respiratory conditions for herself (cough, phlegm, wheeze, or asthma) and for children (wheeze or asthma) living in her household. For cooks, the presence of at least one respiratory condition was significantly associated with 48-h log-transformed mean personal PM2.5 concentration (PR = 1.35; p < 0.001). The prevalence ratio (PR) was significantly elevated for cooks with one or more respiratory conditions if they cooked without a chimney (PR = 1.51, p = 0.025) and non-significantly elevated if they cooked in a separate but poorly ventilated building (PR = 1.51, p = 0.093). The PRs were significantly elevated for children with wheeze or asthma if a traditional stove was used (PR = 2.08, p = 0.014) or if the cooking area was not partitioned from the rest of the home (PR = 2.46, p = 0.012). For the 13 children for whom the cooking area was not partitioned from the rest of the home, having a respiratory condition was significantly associated with log-transformed indoor PM2.5 concentration (PR = 1.51; p = 0.014).


The B cell-specific transcription factor BSAP regulates B cell proliferation.
The B cell-specific activator protein (BSAP) is a DNA-binding transcription factor expressed in pro-B, pre-B, and mature B cells, but not in plasma cells. In this study, we explored the role of BSAP in B cell function by assessing how the content of this protein varies in cells driven by proliferative stimuli and, conversely, how artificial manipulation of BSAP activity affects cell proliferation. We found that BSAP activity of nuclear extracts increased when B cells were activated by mitogen (lipopolysaccharide [LPS]), antigen receptor-mediated signaling (surface immunoglobulin D [IgD] cross-linking) or T cell-dependent stimulation (CD40 cross-linking). We could suppress BSAP activity by exposure of B cells to phosphorothioate oligonucleotides antisense to the BSAP translation initiation start site, whereas control oligonucleotides were virtually inactive. Antisense-induced BSAP suppression was associated with a striking reduction in LPS-induced proliferation of splenic B cells and in the spontaneous proliferation of B lymphoma cells (CH12.LX), but the antisense oligonucleotide had virtually no effect on proliferation of two cell lines lacking BSAP: the T lymphoma line EL-4 and the plasma cell line MOPC-315. Overexpression of BSAP in splenic B cells or de novo expression in MOPC-315 plasma cells induced by transfection of a BSAP expression plasmid stimulated cell proliferation. Taken together, these results suggest that BSAP activity is a rate-limiting regulator of B cell proliferation. We also found that treatment with the antisense BSAP oligonucleotide downregulated Ig class switching induced by interleukin 4 plus LPS. This effect may be secondary to reduced proliferation or could be mediated through BSAP binding sites in the IgH locus.


Improving pairwise sequence alignment accuracy using near-optimal protein sequence alignments.
While the pairwise alignments produced by sequence similarity searches are a powerful tool for identifying homologous proteins - proteins that share a common ancestor and a similar structure; pairwise sequence alignments often fail to represent accurately the structural alignments inferred from three-dimensional coordinates. Since sequence alignment algorithms produce optimal alignments, the best structural alignments must reflect suboptimal sequence alignment scores. Thus, we have examined a range of suboptimal sequence alignments and a range of scoring parameters to understand better which sequence alignments are likely to be more structurally accurate. We compared near-optimal protein sequence alignments produced by the Zuker algorithm and a set of probabilistic alignments produced by the probA program with structural alignments produced by four different structure alignment algorithms. There is significant overlap between the solution spaces of structural alignments and both the near-optimal sequence alignments produced by commonly used scoring parameters for sequences that share significant sequence similarity (E-values < 10-5) and the ensemble of probA alignments. We constructed a logistic regression model incorporating three input variables derived from sets of near-optimal alignments: robustness, edge frequency, and maximum bits-per-position. A ROC analysis shows that this model more accurately classifies amino acid pairs (edges in the alignment path graph) according to the likelihood of appearance in structural alignments than the robustness score alone. We investigated various trimming protocols for removing incorrect edges from the optimal sequence alignment; the most effective protocol is to remove matches from the semi-global optimal alignment that are outside the boundaries of the local alignment, although trimming according to the model-generated probabilities achieves a similar level of improvement. The model can also be used to generate novel alignments by using the probabilities in lieu of a scoring matrix. These alignments are typically better than the optimal sequence alignment, and include novel correct structural edges. We find that the probA alignments sample a larger variety of alignments than the Zuker set, which more frequently results in alignments that are closer to the structural alignments, but that using the probA alignments as input to the regression model does not increase performance. The pool of suboptimal pairwise protein sequence alignments substantially overlaps structure-based alignments for pairs with statistically significant similarity, and a regression model based on information contained in this alignment pool improves the accuracy of pairwise alignments with respect to structure-based alignments.


Patterns of nucleotide diversity at photoperiod related genes in Norway spruce [Picea abies (L.) Karst].
The ability of plants to track seasonal changes is largely dependent on genes assigned to the photoperiod pathway, and variation in those genes is thereby important for adaptation to local day length conditions. Extensive physiological data in several temperate conifer species suggest that populations are adapted to local light conditions, but data on the genes underlying this adaptation are more limited. Here we present nucleotide diversity data from 19 genes putatively involved in photoperiodic response in Norway spruce (Picea abies). Based on similarity to model plants the genes were grouped into three categories according to their presumed position in the photoperiod pathway: photoreceptors, circadian clock genes, and downstream targets. An HKA (Hudson, Kreitman and Aquade) test showed a significant excess of diversity at photoreceptor genes, but no departure from neutrality at circadian genes and downstream targets. Departures from neutrality were also tested with Tajima's D and Fay and Wu's H statistics under three demographic scenarios: the standard neutral model, a population expansion model, and a more complex population split model. Only one gene, the circadian clock gene PaPRR3 with a highly positive Tajima's D value, deviates significantly from all tested demographic scenarios. As the PaPRR3 gene harbours multiple non-synonymous variants it appears as an excellent candidate gene for control of photoperiod response in Norway spruce.


Brain glutamate in medication-free depressed patients: a proton MRS study at 7 Tesla.
The possible role of glutamate in the pathophysiology and treatment of depression is of intense current interest. Proton magnetic resonance spectroscopy (MRS) enables the detection of glutamate in the living human brain and meta-analyses of previous MRS studies in depressed patients have suggested that glutamate levels are decreased in anterior brain regions. Nevertheless, at conventional magnetic field strengths [1.5-3 Tesla (T)], it is difficult to separate glutamate from its metabolite and precursor, glutamine, with the two often being measured together as Glx. In contrast, MRS at 7 T allows clear spectral resolution of glutamate and glutamine. We studied 55 un-medicated depressed patients and 50 healthy controls who underwent MRS scanning at 7 T with voxels placed in anterior cingulate cortex, occipital cortex and putamen (PUT). Neurometabolites were calculated using the unsuppressed water signal as a reference. Compared with controls, depressed patients showed no significant difference in glutamate in any of the three voxels studied; however, glutamine concentrations in the patients were elevated by about 12% in the PUT (p < 0.001). The increase in glutamine in PUT is of interest in view of the postulated role of the basal ganglia in the neuropsychology of depression and is consistent with elevated activity in the descending cortical glutamatergic innervation to the PUT. The basal ganglia have rarely been the subject of MRS investigations in depressed patients and further MRS studies of these structures in depression are warranted.


The Cost of Providing District-Level Surgery in Malawi.
Three district hospitals in Malawi that provide essential surgery, which for many patients can be lifesaving or prevent disability, formed the setting of this costing study. All resources used at district hospitals for the delivery of surgery were identified and quantified. The hospital departments were divided into three categories of cost centres-the final cost centre, intermediate and ancillary cost centres. All costs of human resources, buildings, equipment, medical and non-medical supplies and utilities were quantified and allocated to surgery through step-down accounting. The total cost of surgery, including post-operative care, ranged from US$ 329,000 per year to more than twice that amount at one of the hospitals. At two hospitals, it represented 16-17% of the total cost of running the hospital. The main cost drivers of surgery were transport and inpatient services, including catering. The cost of a C-section ranged from $ 164 to 638 that of a hernia repair from $ 137 to 598. Evacuations from uterus were cheapest mainly because of the shorter duration of patient stay. Low bed occupancy rates and utilisation rates of the operating theatres suggest overcapacity but may also indicate a potential to scale up surgery. This may be achieved by adding surgical staff, although there may be rate-limiting steps, such as demand for surgery in the community or capacity to provide anaesthesia. If a scale-up of surgery cannot be realised, hospital managers may be forced to reduce the number of beds, reorganise wards and/or reallocate staff to achieve better economies of scale.


3-T contrast-enhanced MR angiography in evaluation of suspected intracranial aneurysm: comparison with MDCT angiography.
The purpose of this study was to prospectively evaluate a high-spatial-resolution contrast-enhanced 3-T MR angiography protocol for detection and characterization of intracranial aneurysms and to compare the results with those of MDCT angiography. Forty-one patients with suspected intracranial aneurysm underwent high-spatial-resolution 3D contrast-enhanced MR angiography and CT angiography (CTA). With a generalized autocalibrating partially parallel acquisition algorithm with an acceleration factor of 4 at 3 T, contrast-enhanced MR angiographic images were acquired over 20 seconds with a spatial-resolution of 0.7 x 0.7 x 0.8 mm. CTA images were acquired with a spatial resolution of 0.35 x 0.35 x 0.8 mm on a 16-MDCT scanner in 17 seconds. The images from the two studies were evaluated independently by two neuroradiologists for image quality, presence of aneurysm, and characterization of aneurysm. The dimensions of the aneurysm were measured independently with both techniques. A total of 25 aneurysms were identified with both contrast-enhanced MR angiography and CTA. A comparative analysis of detection and depiction of aneurysms showed excellent interobserver agreement for both contrast-enhanced MR angiography (kappa = 0.81) and CTA (kappa = 0.91) images. There was significant correlation between the techniques for both qualitative assessment of aneurysm depiction (rho = 0.92; 95% CI, 0.88-0.95) and quantitative dimensional measurement of aneurysm size (r = 0.94; 95% CI, 0.92-0.97). Contrast-enhanced MR angiography at 3 T is reliable for evaluation and characterization of intracranial aneurysms. The results are comparable with those of MDCTA.


Polyethyleneimine is a potent systemic adjuvant for glycoprotein antigens.
Polyethyleneimine (PEI) is an organic polycation used extensively as a gene and DNA vaccine delivery reagent. Although the DNA targeting activity of PEI is well documented, its immune activating activity is not. We recently reported that PEI has robust mucosal adjuvanticity when administered intranasally with glycoprotein antigens. Here, we show that PEI has strong immune activating activity after systemic delivery. PEI administered subcutaneously with viral glycoprotein (HIV-1 gp140) enhanced antigen-specific serum IgG production in the context of mixed Th1/Th2-type immunity. PEI elicited higher titers of both antigen binding and neutralizing antibodies than alum in mice and rabbits and induced an increased proportion of antibodies reactive with native antigen. In an intraperitoneal model, PEI recruited neutrophils followed by monocytes to the site of administration and enhanced antigen uptake by antigen-presenting cells. The Th bias was modulated by PEI activation of the Nlrp3 inflammasome; however its global adjuvanticity was unchanged in Nlrp3-deficient mice. When coformulated with CpG oligodeoxynucleotides, PEI adjuvant potency was synergistically increased and biased toward a Th1-type immune profile. Taken together, these data support the use of PEI as a versatile systemic adjuvant platform with particular utility for induction of secondary structure-reactive antibodies against glycoprotein antigens.


"AMPE" Exercise Programme Has Positive Effects on Anthropometric and Physiological Parameters of School Children: A Pilot Study.
Projection of the effectiveness of house-hold physical activity may be a vital tool to improve active lifestyle. Although ampe is a common house-hold recreational physical activity among all population groups especially school children in Ghana, no empirical evidence of its effects on the anthropometric and physiological parameters of the children. This pilot study examined the effect of ampe exercise programme on the anthropometric and physiological parameters of school children. Purposive and stratified sampling techniques were applied to recruit 78 school children (ages of 9 to 12, mean age of 10.65±0.94 years). The participants attended 40 minutes of ampe exercise program three times per week, for four weeks consecutively. Body mass index, waist circumference, hip circumference, waist-to-hip ratio; % body fat, diastolic blood pressure, systolic blood pressure and heart rate were measured prepost training. Ampe exercise programme produced positive effects on all parameters. Body weight (0.31%) and body mass index (0.58%) decreased significantly (P<0.05). Systolic blood pressure (3.15%), diastolic blood pressure (1.92%) and heart rate (2.13) significantly improved (P<0.05). CONCLUSION: Ampe exercise programme is effective as paediatric obesity house-hold intervention to provide the impetus for active lifestyles of school children.


Virgibacillus phasianinus sp. nov., a halophilic bacterium isolated from faeces of a Swinhoe's pheasant, Lophura swinhoii.
A rod-shaped, Gram-stain-positive, motile and aerobic bacterium, designated LM2416T, was isolated from faeces of Lophuras winhoii living in Seoul Grand Park, Gyeonggi-do, Republic of Korea. Phylogenetic analyses based on 16S rRNA gene sequences indicated that strain LM2416T belonged to the genus Virgibacillus, sharing high 16S rRNA gene sequence similarities to Virgibacillus necropolis LMG 19488T (99.0 %), Virgibacillus carmonensis LMG 20964T (98.4 %), Virgibacillus arcticus Hal 1T (98.3 %) and Virgibacillus flavescens S1-20T (97.9 %). The isolate grew at 10-30 °C, pH 6-7 and 0-20 % (w/v) NaCl. Optimal growth was observed at 30 °C, pH 6-7 and 10 % (w/v) NaCl. The major fatty acid was anteiso-C15 : 0. Polar lipids were composed of phosphatidylglycerol, diphosphatidylglycerol, three unknown phospholipids and two unknown aminophospholipids. The main menaquinone was MK-7. Strain LM2416T had alanine, lysine, glutamic acid, glycine and aspartic acid as cell-wall amino acids and ribose as a cell-wall sugar. The whole genome sequences of strain LM2416T and V. necropolis KCTC 3820T were sequenced by PacBio RS II sequencing. The genome sequence-based G+C content of strain LM2416T was 39.5 mol%. The orthologous average nucleotide identity value, showing genetic relatedness between strain LM2416T and V. necropolis KCTC 3820T, was 78.3 %. Based on the phylogenetic, biochemical, chemotaxonomic and genotypic data presented in this study, strain LM2416T is considered to represent a novel species of the genus Virgibacillus, for which the name Virgibacillus phasianinus is proposed. The type strain is LM2416T (=KCTC 33927T=JCM 32144T).


Sources of the neurotoxin quinolinic acid in the brain of HIV-1-infected patients and retrovirus-infected macaques.
This study investigated the sources of quinolinic acid, a neurotoxic tryptophan-kynurenine pathway metabolite, in the brain and blood of HIV-infected patients and retrovirus-infected macaques. In brain, quinolinic acid concentrations in HIV-infected patients were elevated by > 300-fold to concentrations that exceeded cerebrospinal fluid (CSF) by 8.9-fold. There were no significant correlations between elevated serum quinolinic acid levels with those in CSF and brain parenchyma. Because nonretrovirus-induced encephalitis confounds the interpretation of human postmortem data, rhesus macaques infected with retrovirus were used to examine the mechanisms of increased quinolinic acid accumulations and determine the relationships of quinolinic acid to encephalitits and systemic responses. The largest kynurenine pathway responses in brain were associated with encephalitis and were independent of systemic responses. CSF quinolinic acid levels were also elevated in all infected macaques, but particularly those with retrovirus-induced encephalitis. In contrast to the brain changes, there was no difference in any systemic measure between macaques with encephalitis vs. those without. Direct measures of the amount of quinolinic acid in brain derived from blood in a macaque with encephalitis showed that almost all quinolinic acid (>98%) was synthesized locally within the brain. These results demonstrate a role for induction of indoleamine-2,3dioxygenase in accelerating the local formation of quinolinic acid within the brain tissue, particularly in areas of encephalitis, rather than entry of quinolinic acid into the brain from the meninges or blood. Strategies to reduce QUIN production, targeted at intracerebral sites, are potential approaches to therapy.


The spectrum of neuropsychiatric abnormalities associated with electrical status epilepticus in sleep.
Electrical status epilepticus in sleep (ESES) is an electrographic pattern consisting of an almost continuous presence of spike-wave discharges in slow wave sleep. ESES is frequently encountered in pediatric syndromes associated with epilepsy or cognitive and language dysfunction. It can be present in various evolutionary stages of a spectrum of diseases, the prototypes of which are the 'continuous spikes and waves during slow wave sleep' syndrome (CSWS), the Landau-Kleffner syndrome (LKS), as well as in patients initially presenting as benign childhood epilepsy with centrotemporal spikes (BECTS). The purpose of this article is to review the literature data on the semiology, electrographic findings, prognosis, therapeutic options, as well as the current theories on the pathophysiology of these disorders. The frequent overlap of CSWS, LKS, and BECTS urges an increased level of awareness for the occasional transition from benign conditions such as BECTS to more devastating syndromes such as LKS and CSWS. Identification of atypical signs and symptoms, such as high discharge rates, prolonged duration of ESES, neuropsychiatric and cognitive dysfunction, lack of responsiveness to medications, and pre-existing neurologic conditions is of paramount importance in order to initiate the appropriate diagnostic measures. Prolonged and if needed repetitive sleep electroencephalographs (EEGs) are warranted for proper diagnosis.


Roll aftereffects: influence of tilt and inter-stimulus interval.
A theme in sensory perception is that exposure to a stimulus causes perception of subsequent stimuli to be shifted in the opposite direction. Such phenomenon is known as aftereffect and has been extensively described in the visual system as well as recently described for the vestibular system during translation. It is known from aviation studies that after a maneuver in roll, pilots can experience a false perception of roll in the opposite direction. The magnitude and duration of this effect as well as the potential influence of the gravity vector have not previously been defined. In the current paper this roll aftereffect (RAE) is examined in response to whole-body roll about an earth-horizontal axis in eight healthy human subjects. The peak velocity of a 0.5-s-duration roll was varied based on previous responses to find the point where subjects perceived no motion. Without a preceding stimulus, the starting position (upright, 9° left, or 9° right) did not influence roll perception. The RAE was measured in a completely dark room using an adapting (first interval) stimulus consisting of 9° of roll over 1.5 s (peak velocity, 12°/s), delivered 0.5, 3, or 6 s prior to test (second interval) stimulus. A significant RAE was seen in all subjects. Half a second after the adapting stimulus, a test stimulus had to be on average 1.5 ± 0.4°/s in the opposite direction to be perceived as stationary. When the subject remained upright after the adapting stimulus, the RAE diminished with time, although it remained significantly larger at 3 and 6 s when the subject remained tilted after the adapting stimulus. These data demonstrate that roll perception can be influenced by small preceding stimuli and tilt causes a persistence of the RAE.


Expression analysis of cyclooxygenase-2 in patients suffering from esophageal squamous cell carcinoma.
Esophageal squamous cell carcinoma (ESCC) is one of the aggressive malignancies and mechanisms underlying its pathogenesis remain unclear. Cyclooxygenase-2 (COX-2) enzyme system plays a crucial role in many gastrointestinal malignancies and is an important regulator of cell growth, proliferation, apoptosis, differentiation and transformation. More precise outcome of COX-2 in ESCC is less investigated. In this study we investigated the risk factors of ESCC and expression of COX-2 in Carcinoma in situ (CIS) and ESCC compared to normal esophageal mucosa. ESCC relationship to clinico-pathological parameters using immunohistochemistry was also part of this investigation. Current study was conducted in the Institute of Basic Medical Sciences, Khyber Medical University, Peshawar, Pakistan. A total of 69 diagnosed patients of ESCC, both Pakistanis and Afghans were enrolled. Various risk factors associated with ESCC were recorded. Mean age at the time of diagnosis was 55 years. Out of 69 patients of ESCC 46 (67%) were users of dipping tobacco (Naswar). Expression of COX-2 was determined in normal esophageal mucosa, CIS and invasive ESCC using Immunohistochemistry (IHC). Differences of mean were computed using ANOVA followed by applying Post Hoc test. Patients were categorized as positive with high expression or negative with low to nil expression. ANOVA showed large differences in expression of COX-2 in normal healthy mucosa compared with CIS and ESCC with the mean difference of -9.529 and -7.370 respectively, p-value being <.05 at 95% confidence interval (CI). No significant difference was noticed in the expression of COX-2 in CIS compared with ESCC with p-value >.05 at 95% CI. Our complete cohort (23-85 years) showed statistically significant difference in the expression of COX-2 gene in ESCC and CIS tissue samples compared with normal healthy mucosa. Results of this study indicate that over-expression of COX-2 is positively associated with ESCC.


N-terminal domains in mouse and human 5-hydroxytryptamine3A receptors confer partial agonist and antagonist properties to benzylidene analogs of anabaseine.
The present study tested the hypothesis that mouse and human 5-hydroxytryptamine3A (5-HT3A) receptors may be differentially modulated by benzylidene analogs of anabaseine (BA) and that these analogs may be useful in assessing residues involved in receptor gating. Mouse and human wild-type and mouse and human chimeric 5-HT3A receptors expressed in Xenopus oocytes were evaluated with the two-electrode voltage clamp technique. Our previous studies demonstrated that 3-(2,4-dimethoxybenzylidene)-anabaseine (DMXBA) is an antagonist at the mouse wild-type 5-HT3A receptor, but that its metabolites 3-(2-hydroxy, 4-methoxybenzylidene)-anabaseine (2-OHMBA), 3-(2-methoxy, 4-hydroxybenzylidene)-anabaseine (4-OHMBA), and 3-(2,4-dihydroxybenzylidene)-anabaseine (2,4-DiOHBA) are partial agonists (J Pharmacol Exp Ther, 299: 1112-1117, 2001). In the human wild-type (HWT) 5-HT3A receptor, none of the BA compounds possessed partial agonist activity. BA compounds antagonized 1.5 microM 5-HT-mediated (EC50) responses in the HWT 5-HT3A receptor with a rank order of potency (IC50 in muM) of 2-OHMBA (1.5 +/- 0.1) > DMXBA (3.1 +/- 0.2) > 4-OHMBA (7.4 +/- 0.5) > 2,4-DiOHBA (12.8 +/- 0.7). In mouse receptor chimeras containing N-terminal human receptor orthologs, 2-OHMBA inhibited 5-HT-mediated (EC50) currents with IC50 values of 2.0 +/- 0.08 and 3.0 +/- 0.13 microM, respectively. In human receptor chimeras containing N-terminal mouse receptor orthologs, 2-OHMBA displayed partial agonist activities with EC50 values of 1.3 +/- 0.15 and 5.0 +/- 0.4 microM; efficacies were 43 and 57%, respectively. Thus, amino acids present in the distal one-third of the N terminus of mouse and human 5-HT3A receptors are necessary and sufficient to confer partial agonist or antagonist properties of 2-OHMBA.


Glycemic index, glycemic load, and risk of coronary heart disease: a pan-European cohort study.
High carbohydrate intake raises blood triglycerides, glucose, and insulin; reduces HDLs; and may increase risk of coronary heart disease (CHD). Epidemiological studies indicate that high dietary glycemic index (GI) and glycemic load (GL) are associated with increased CHD risk. The aim of this study was to determine whether dietary GI, GL, and available carbohydrates are associated with CHD risk in both sexes. This large prospective study-the European Prospective Investigation into Cancer and Nutrition-consisted of 338,325 participants who completed a dietary questionnaire. HRs with 95% CIs for a CHD event, in relation to intake of GI, GL, and carbohydrates, were estimated using covariate-adjusted Cox proportional hazard models. After 12.8 y (median), 6378 participants had experienced a CHD event. High GL was associated with greater CHD risk [HR 1.16 (95% CI: 1.02, 1.31) highest vs. lowest quintile, p-trend 0.035; HR 1.18 (95% CI: 1.07, 1.29) per 50 g/day of GL intake]. The association between GL and CHD risk was evident in subjects with BMI (in kg/m2) ≥25 [HR: 1.22 (95% CI: 1.11, 1.35) per 50 g/d] but not in those with BMI <25 [HR: 1.09 (95% CI: 0.98, 1.22) per 50 g/d) (P-interaction = 0.022). The GL-CHD association did not differ between men [HR: 1.19 (95% CI: 1.08, 1.30) per 50 g/d] and women [HR: 1.22 (95% CI: 1.07, 1.40) per 50 g/d] (test for interaction not significant). GI was associated with CHD risk only in the continuous model [HR: 1.04 (95% CI: 1.00, 1.08) per 5 units/d]. High available carbohydrate was associated with greater CHD risk [HR: 1.11 (95% CI: 1.03, 1.18) per 50 g/d]. High sugar intake was associated with greater CHD risk [HR: 1.09 (95% CI: 1.02, 1.17) per 50 g/d]. This large pan-European study provides robust additional support for the hypothesis that a diet that induces a high glucose response is associated with greater CHD risk.


Determination and modeling of kinetics of cancer cell killing by doxorubicin and doxorubicin encapsulated in targeted liposomes.
Various mathematical approaches have been devised to relate the cytotoxic effect of drugs in cell culture to the drug concentration added to the cell culture medium. Such approaches can satisfactorily account for drug response when the drugs are free in solution, but the approach becomes problematic when the drug is delivered in a drug delivery system, such as a liposome. To address this problem, we have developed a simple model that assumes that the cytotoxic potency of a drug is a function of the intracellular drug level in a critical compartment. Upon exposure to drug, cell death commences after a lag time, and the cell kill rate is dependent on the amount of drug in the critical intracellular compartment. The computed number of cells in culture, at any time after exposure to the drug, takes into account the cell proliferation rate, the cell kill rate, the average intracellular drug concentration, and a lag time for cell killing. We have applied this model to compare the cytotoxic effect of doxorubicin (DOX), or DOX encapsulated in a liposome that is targeted to CD44 on B16F10 melanoma cells in culture. CD44 is the surface receptor that binds to hyaluronan and is overexpressed on various cancer cells, including B16F10. We have shown previously that the drug encapsulated in hyaluronan-targeted liposomes was more potent than was the free drug. The model required the determination of the cell-associated DOX after the cells were incubated with various concentrations of the free or the encapsulated drug for 3 h, and the quantification of cell number at various times after exposure to the drug. The uptake of encapsulated drug was greater than that of the free drug, and the ratio of cell association of encapsulated:free drug was 1.3 at 0.5 micro g/ml and increased to 3.3 at 20 micro g/ml DOX. The results demonstrate that the enhanced potency of the encapsulated drug could stem from its enhanced uptake. However, in certain cases, where larger amounts of the free drug were added, such that the intracellular amounts of drug exceeded those obtained from the encapsulated drug, the numbers of viable cells were still significantly smaller for the encapsulated drug. This finding demonstrates that for given amounts of intracellular DOX, the encapsulated form was more efficient in killing B16F10 cells than the free drug. The outcome was expressed in the kinetic model as a 5-6-fold larger rate constant of cell killing potency for the encapsulated drug versus the free drug. The model provides a quantitative framework for comparing the cytotoxic effect in cultured cells when applying the drug in the free form or in a delivery system.


Simulation of monoclonal antibody pharmacokinetics in humans using a minimal physiologically based model.
Compared to small chemical molecules, monoclonal antibodies and Fc-containing derivatives (mAbs) have unique pharmacokinetic behaviour characterised by relatively poor cellular permeability, minimal renal filtration, binding to FcRn, target-mediated drug disposition, and disposition via lymph. A minimal physiologically based pharmacokinetic (PBPK) model to describe the pharmacokinetics of mAbs in humans was developed. Within the model, the body is divided into three physiological compartments; plasma, a single tissue compartment and lymph. The tissue compartment is further sub-divided into vascular, endothelial and interstitial spaces. The model simultaneously describes the levels of endogenous IgG and exogenous mAbs in each compartment and sub-compartment and, in particular, considers the competition of these two species for FcRn binding in the endothelial space. A Monte-Carlo sampling approach is used to simulate the concentrations of endogenous IgG and mAb in a human population. Existing targeted-mediated drug disposition (TMDD) models are coupled with the minimal PBPK model to provide a general platform for simulating the pharmacokinetics of therapeutic antibodies using primarily pre-clinical data inputs. The feasibility of utilising pre-clinical data to parameterise the model and to simulate the pharmacokinetics of adalimumab and an anti-ALK1 antibody (PF-03446962) in a population of individuals was investigated and results were compared to published clinical data.


Spectral radiative-transfer modeling with minimized computation time by use of a neural-network technique.
A new approach based on a neural-network technique for reduction in the computation time of radiative-transfer models is presented. This approach gives high spectral resolution without significant loss of accuracy. A rigorous radiative-transfer model is used to calculate radiation values at a few selected wavelengths, and a neural-network algorithm replenishes them to a complete spectrum with radiation values at a high spectral resolution. This method is used for the UV and visible spectral ranges. The results document the ability of a neural network to learn this specific task. More than 20,000 UV-index values for all kinds of atmosphere are calculated by both the rigorous radiative-transfer model alone and the model in combination with the neural-network algorithm. The agreement between both approaches is generally of the order of ?1%; the computation time is reduced by a factor of more than 20. The new algorithm can be used for all kinds of high-quality radiative-transfer model to speed up computation time.


How to Relax in Stressful Situations: A Smart Stress Reduction System.
Stress is an inescapable element of the modern age. Instances of untreated stress may lead to a reduction in the individual's health, well-being and socio-economic situation. Stress management application development for wearable smart devices is a growing market. The use of wearable smart devices and biofeedback for individualized real-life stress reduction interventions has received less attention. By using our unobtrusive automatic stress detection system for use with consumer-grade smart bands, we first detected stress levels. When a high stress level is detected, our system suggests the most appropriate relaxation method by analyzing the physical activity-based contextual information. In more restricted contexts, physical activity is lower and mobile relaxation methods might be more appropriate, whereas in free contexts traditional methods might be useful. We further compared traditional and mobile relaxation methods by using our stress level detection system during an eight day EU project training event involving 15 early stage researchers (mean age 28; gender 9 Male, 6 Female). Participants' daily stress levels were monitored and a range of traditional and mobile stress management techniques was applied. On day eight, participants were exposed to a 'stressful' event by being required to give an oral presentation. Insights about the success of both traditional and mobile relaxation methods by using the physiological signals and collected self-reports were provided.


Assessment of the behaviour and welfare of laying hens on free-range units.
The aims of this study were twofold: to develop and test an animal-based protocol for the assessment of the physical and emotional elements of the welfare of laying hens on free-range units and to investigate the effects of different approaches to housing and management on the welfare of the birds. The protocol was tested on 25 free-range units for laying hens, each of which was visited on four occasions by one of five trained observers; further information about husbandry, health and productivity was gathered from interviews with the farmers. Measures of the birds' attitude included arousal, noise, flight distance and response to a novel object, measures of their activity included feather pecking, aggression and use of range, and measures of their physical welfare included mortality, body condition and egg quality. Increased arousal was associated with increased flight distance, greater reluctance to approach a novel object and higher levels of feather pecking and feather loss, but the correlation between pecking and feather loss was low. The birds maintained body condition throughout the period of lay. Neither body condition, feather pecking nor feather loss was affected by the extent of beak trimming. Estimated losses (deaths and culls) ranged from 1.8 to 21.4 per cent (median 6.95 per cent). Few birds showed signs of ill health, limb lesions or red mite infestation. No feature of building design had a significant effect on mortality, but there were consistent differences in the birds' attitude, behaviour and performance attributable to the type of floor and the presence or absence of perches, which suggested that the welfare of the hens was inferior when they were housed on plastic floors with no perches.


The maximal sniff in the assessment of diaphragm function in man.
We studied diaphragm function in a total of 64 normal subjects, who had no past or present respiratory or neuromuscular impairment. We measured transdiaphragmatic pressure (Pdi) during maximal sniffs and compared these values with Pdi during maximal static inspiratory efforts (PImax.). The range of Pdi during maximal sniffs (82-204 cm H2O) had better defined lower limits than Pdi during PImax. (16-164 cm H2O) and a higher mean value: mean +/- SD for maximal sniffs was 137 +/- 28 cm H2O and for PImax. was 90 +/- 37 cm H2O. The reproducibility of sniff Pdi was assessed in eight randomly chosen subjects over 3 days: the mean coefficient of variation was 7.2%. By comparison the coefficient of variation of Pdi during PImax. was 13.0% in seven subjects. The maximal sniff is a spontaneous manoeuvre, easily performed, repeatable without tiring, and reproducible. Its measurement provides a more reliable quantitative method for assessment of diaphragm strength, which has potential in clinical practice.


Radiolabeled probes targeting tyrosine-kinase receptors for personalized medicine.
Receptor tyrosine kinases (RTK) are transmembrane receptors regulating cellular proliferation, differentiation, apoptosis, motility and recruitment of the vasculature. Aberrant expression and/or function of RTK have been detected in many malignant tumors and are considered to be a part of the transformed phenotype. The action of several classes of anti-cancer drugs is based on specific recognition of RTK. Monoclonal antibodies target extracellular binding domains, while tyrosine kinase inhibitors (TKI) bind to intracellular kinase domains to suppress RTK signaling. The issues regarding the efficient use of RTK targeting are the inter- and intra-patient heterogeneity of RTK expression and the changes of expression levels during the course of disease and in response to therapy. Radionuclide molecular imaging of RTK expression may aid in selecting patients who would benefit from RTK-targeting therapy and in identifying non-responders. Therefore, the therapy would be more personalized. Currently, radiolabeled proteins (monoclonal antibodies and their fragments, natural peptides ligands to RTK and de novo selected affinity proteins) and TKI and their analogues are under development for the visualization of RTK. In this review, we discuss the advantages and disadvantages of these approaches.


Transglutaminase activity in equine strongyles and its potential role in growth and development.
Transglutaminases (E.C. 188.8.131.52) are a family of Ca(2+)-dependent enzymes that stabilize protein structure by catalyzing the formation of isopeptide bonds. A novel form of transglutaminase has been identified and characterized that seem to play an important role in growth, development, and molting in adult and larval stages of filarial nematodes. The aim of this study was to identify the ubiquitous nature of this enzyme in other nematodes and to measure its significance to larval growth, molting, and development. For this purpose, equine Strongylus spp. were used. Activity of this enzyme was identified in extracts of larvae and adults of Strongylus vulgaris, S. edentatus, Parascaris equorum and Cylicocyclus insigne. The significance of transglutaminase in the early growth and development of Strongylus vulgaris, S. edentatus and S. equinus was tested by adding specific inhibitors, monodansylcadaverine (MDC) or cystamine (CS), to in vitro cultures of third (L3) and fourth stage larvae (L4). The viability, molting and growth of these nematode species were affected by both inhibitors. Cystamine promoted abnormal development of Strongylus edentatus L3, resulting in an aberrant expansion of the anterior end. Addition of these inhibitors to cultures of L4 also reduced growth of the three species. The results indicated that transglutaminase is present in a wide array of nematode parasites and may be important in growth and development of their larval stages.


Pediatric antiphospholipid syndrome: clinical and immunologic features of 121 patients in an international registry.
The purpose of this study was to obtain data on the association of antiphospholipid antibodies with clinical manifestations in childhood and to enable future studies to determine the impact of treatment and long-term outcome of pediatric antiphospholipid syndrome. A European registry extended internationally of pediatric patients with antiphospholipid syndrome was established as a collaborative project of the European Antiphospholipid Antibodies Forum and Lupus Working Group of the Pediatric Rheumatology European Society. To be eligible for enrollment the patient must meet the preliminary criteria for the classification of pediatric antiphospholipid syndrome and the onset of antiphospholipid syndrome must have occurred before the patient's 18th birthday. As of December 1, 2007, there were 121 confirmed antiphospholipid syndrome cases registered from 14 countries. Fifty-six patients were male, and 65 were female, with a mean age at the onset of antiphospholipid syndrome of 10.7 years. Sixty (49.5%) patients had underlying autoimmune disease. Venous thrombosis occurred in 72 (60%), arterial thrombosis in 39 (32%), small-vessel thrombosis in 7 (6%), and mixed arterial and venous thrombosis in 3 (2%). Associated nonthrombotic clinical manifestations included hematologic manifestations (38%), skin disorders (18%), and nonthrombotic neurologic manifestations (16%). Laboratory investigations revealed positive anticardiolipin antibodies in 81% of the patients, anti-beta(2)-glycoprotein I antibodies in 67%, and lupus anticoagulant in 72%. Comparisons between different subgroups revealed that patients with primary antiphospholipid syndrome were younger and had a higher frequency of arterial thrombotic events, whereas patients with antiphospholipid syndrome associated with underlying autoimmune disease were older and had a higher frequency of venous thrombotic events associated with hematologic and skin manifestations. Clinical and laboratory characterization of patients with pediatric antiphospholipid syndrome implies some important differences between antiphospholipid syndrome in pediatric and adult populations. Comparisons between children with primary antiphospholipid syndrome and antiphospholipid syndrome associated with autoimmune disease have revealed certain differences that suggest 2 distinct subgroups.


Brain Tumor Diagnosis Using Machine Learning, Convolutional Neural Networks, Capsule Neural Networks and Vision Transformers, Applied to MRI: A Survey.
Management of brain tumors is based on clinical and radiological information with presumed grade dictating treatment. Hence, a non-invasive assessment of tumor grade is of paramount importance to choose the best treatment plan. Convolutional Neural Networks (CNNs) represent one of the effective Deep Learning (DL)-based techniques that have been used for brain tumor diagnosis. However, they are unable to handle input modifications effectively. Capsule neural networks (CapsNets) are a novel type of machine learning (ML) architecture that was recently developed to address the drawbacks of CNNs. CapsNets are resistant to rotations and affine translations, which is beneficial when processing medical imaging datasets. Moreover, Vision Transformers (ViT)-based solutions have been very recently proposed to address the issue of long-range dependency in CNNs. This survey provides a comprehensive overview of brain tumor classification and segmentation techniques, with a focus on ML-based, CNN-based, CapsNet-based, and ViT-based techniques. The survey highlights the fundamental contributions of recent studies and the performance of state-of-the-art techniques. Moreover, we present an in-depth discussion of crucial issues and open challenges. We also identify some key limitations and promising future research directions. We envisage that this survey shall serve as a good springboard for further study.


Oral health impact, dental caries, and oral health behaviors among the National Cadets Corps in South India.
The aim of the present study was to assess the oral health impact and to evaluate the association between socioeconomic status, oral health behaviors, dental caries experience, and oral health impacts among children enrolled in the National Cadets Corps. A cross-sectional survey was conducted among 389 male cadets aged between 13 and 15 years. Sociodemographic and oral health behavior-related information was collected using a self-administered questionnaire. The Child-Oral Impacts on Daily Performances (OIDP) Index was used to assess the oral impacts. The cadets were clinically examined for caries experience using decayed, missing, filled tooth index. A total of 359 children completed all stages of the survey. The mean age of the children was 13.96 ± 0.6 years. Fifty-five percent of the participants experienced at least one impact in the last 3 months. The mean OIDP score for the population was 12.13 ± 5.85. The most prevalent impact was difficulty in eating (37%), and the least affected daily performance was social contact (17%). Dental attendance and caries experience were significant predictors of oral impacts. The present study revealed that oral health had a significant impact on quality of life. Caries experience and past dental visits were associated with oral health-related quality of life among this study population.


Superposition fringes as a measuring tool in optical testing.
Superposition fringes are suitable for making highly accurate measurements of the thicknesses of air layers. A combination of a multiple beam interferometer (Fabry-Perot) and a two-beam interferometer is discussed. In this case the contrast degradation is small. Two possible applications are discussed to some extent: the first deals with the adjustment of air gaps between lenses or other optical elements, and the second is a special spherical Fizeau interferometer. This interferometer makes possible surface testing of spheres with the help of interference colors or rings as is usual with the proof glass method, with radius differences of several centimeters. The latter application seems especially promising.


Elimination of cancer stem-like "side population" cells in hepatoma cell lines by chinese herbal mixture "tien-hsien liquid".
There are increasing pieces of evidence suggesting that the recurrence of cancer may result from a small subpopulation of cancer stem cells, which are resistant to the conventional chemotherapy and radiotherapy. We investigated the effects of Chinese herbal mixture Tien-Hsien Liquid (THL) on the cancer stem-like side population (SP) cells isolated from human hepatoma cells. After sorting and subsequent culture, the SP cells from Huh7 hepatoma cells appear to have higher clonogenicity and mRNA expressions of stemness genes such as SMO, ABCG2, CD133, β-catenin, and Oct-4 than those of non-SP cells. At dose of 2 mg/mL, THL reduced the proportion of SP cells in HepG2, Hep3B, and Huh7 cells from 1.33% to 0.49%, 1.55% to 0.43%, and 1.69% to 0.27%, respectively. The viability and colony formation of Huh7 SP cells were effectively suppressed by THL dose-dependently, accompanied with the inhibition of stemness genes, e.g., ABCG2, CD133, and SMO. The tumorigenicity of THL-treated Huh7 SP cells in NOD/SCID mice was also diminished. Moreover, combination with THL could synergize the effect of doxorubicin against Huh7 SP cells. Our data indicate that THL may act as a cancer stem cell targeting therapeutics and be regarded as complementary and integrative medicine in the treatment of hepatoma.


Functional genomics of lipid metabolism in the oleaginous yeast Rhodosporidium toruloides.
The basidiomycete yeast Rhodosporidium toruloides (also known as Rhodotorula toruloides) accumulates high concentrations of lipids and carotenoids from diverse carbon sources. It has great potential as a model for the cellular biology of lipid droplets and for sustainable chemical production. We developed a method for high-throughput genetics (RB-TDNAseq), using sequence-barcoded Agrobacterium tumefaciens T-DNA insertions. We identified 1,337 putative essential genes with low T-DNA insertion rates. We functionally profiled genes required for fatty acid catabolism and lipid accumulation, validating results with 35 targeted deletion strains. We identified a high-confidence set of 150 genes affecting lipid accumulation, including genes with predicted function in signaling cascades, gene expression, protein modification and vesicular trafficking, autophagy, amino acid synthesis and tRNA modification, and genes of unknown function. These results greatly advance our understanding of lipid metabolism in this oleaginous species and demonstrate a general approach for barcoded mutagenesis that should enable functional genomics in diverse fungi.


A multinational, multidisciplinary consensus for the diagnosis and management of spinal cord compression among patients with mucopolysaccharidosis VI.
Cervical cord compression is a sequela of mucopolysaccharidosis VI, a rare lysosomal storage disorder, and has devastating consequences. An international panel of orthopedic surgeons, neurosurgeons, anesthesiologists, neuroradiologists, metabolic pediatricians, and geneticists pooled their clinical expertise to codify recommendations for diagnosing, monitoring, and managing cervical cord compression; for surgical intervention criteria; and for best airway management practices during imaging or anesthesia. The recommendations offer ideal best practices but also attempt to recognize the worldwide spectrum of resource availability. Functional assessments and clinical neurological examinations remain the cornerstone for identification of early signs of myelopathy, but magnetic resonance imaging is the gold standard for identification of cervical cord compression. Difficult airways of MPS VI patients complicate the anesthetic and, thus, the surgical management of cervical cord compression. All patients with MPS VI require expert airway management during any surgical procedure. Neurophysiological monitoring of the MPS VI patient during complex spine or head and neck surgery is considered standard practice but should also be considered for other procedures performed with the patient under general anesthesia, depending on the length and type of the procedure. Surgical interventions may include cervical decompression, stabilization, or both. Specific techniques vary widely among surgeons. The onset, presentation, and rate of progression of cervical cord compression vary among patients with MPS VI. The availability of medical resources, the expertise and experience of members of the treatment team, and the standard treatment practices vary among centers of expertise. Referral to specialized, experienced MPS treatment centers should be considered for high-risk patients and those requiring complex procedures. Therefore, the key to optimal patient care is to implement best practices through meaningful communication among treatment team members at each center and among MPS VI specialists worldwide.