Knockdown of lncRNA HOXA-AS3 Suppresses the Progression of Atherosclerosis via Sponging miR-455-5p.
Atherosclerosis can lead to multiple cardiovascular diseases, especially myocardial infarction. Long noncoding RNAs (lncRNAs) are involved in multiple diseases, including atherosclerosis. LncRNA HOXA-AS3 was found to be notably upregulated in atherosclerosis. However, the biological function of HOXA-AS3 during the occurrence and development of atherosclerosis remains unclear. Human vascular endothelial cells (HUVECs) were treated with oxidized low-density lipoprotein (oxLDL) to mimic atherosclerosis in vitro. Gene and protein expressions in HUVECs were detected by RT-qPCR and Western blot, respectively. Cell proliferation was tested by CCK-8 and Ki67 staining. Cell apoptosis and cycle were measured by flow cytometry. Additionally, the correlation between HOXA-AS3 and miR-455-5p was confirmed by dual luciferase report assay and RNA pull-down. Finally, in vivo model of atherosclerosis was established to confirm the function of HOXA-AS3 during the development of atherosclerosis in vivo. LncRNA HOXA-AS3 was upregulated in oxLDL-treated HUVECs. In addition, oxLDL-induced growth inhibition of HUVECs was significantly reversed by knockdown of HOXA-AS3. Consistently, oxLDL notably induced G1 arrest in HUVECs, while this phenomenon was greatly reversed by HOXA-AS3 siRNA. Furthermore, downregulation of HOXA-AS3 notably inhibited the progression of atherosclerosis through mediation of miR-455-5p/p27 Kip1 axis. Besides, silencing of HOXA-AS3 notably relieved the symptom of atherosclerosis in vivo. Downregulation of HOXA-AS3 significantly suppressed the progression of atherosclerosis via regulating miR-455-5p/p27 Kip1 axis. Thus, HOXA-AS3 might serve as a potential target for the treatment of atherosclerosis.


Expert curation of the human and mouse olfactory receptor gene repertoires identifies conserved coding regions split across two exons.
Olfactory receptor (OR) genes are the largest multi-gene family in the mammalian genome, with 874 in human and 1483 loci in mouse (including pseudogenes). The expansion of the OR gene repertoire has occurred through numerous duplication events followed by diversification, resulting in a large number of highly similar paralogous genes. These characteristics have made the annotation of the complete OR gene repertoire a complex task. Most OR genes have been predicted in silico and are typically annotated as intronless coding sequences. Here we have developed an expert curation pipeline to analyse and annotate every OR gene in the human and mouse reference genomes. By combining evidence from structural features, evolutionary conservation and experimental data, we have unified the annotation of these gene families, and have systematically determined the protein-coding potential of each locus. We have defined the non-coding regions of many OR genes, enabling us to generate full-length transcript models. We found that 13 human and 41 mouse OR loci have coding sequences that are split across two exons. These split OR genes are conserved across mammals, and are expressed at the same level as protein-coding OR genes with an intronless coding region. Our findings challenge the long-standing and widespread notion that the coding region of a vertebrate OR gene is contained within a single exon. This work provides the most comprehensive curation effort of the human and mouse OR gene repertoires to date. The complete annotation has been integrated into the GENCODE reference gene set, for immediate availability to the research community.


Photochemotherapy of psoriasis using methoxsalen and sunlight. A controlled study.
Fifty-one patients with psoriasis were treated with oral methoxsalen and sunlight exposure. Twelve of these patients received either methoxsalen or placebo prior to whole-body exposure. The remainder were treated with methoxsalen and sunlight to one side of the body and sunlight alone to the other. The conventional dose of methoxsalen (0.6 mg/kg) was compared with a low dose (0.3 mg/kg). Oral methoxsalen when used in the higher dose followed by sun exposure is an effective treatment for psoriasis. Accurate ultraviolet dosimetry is essential to avoid phototoxic burns. The advantages and disadvantages of solar photochemotherapy are discussed.


Influence of T cell specificity on the heterogeneity and disease-causing capability of antibody against the acetylcholine receptor.
Adoptive secondary anti-acetylcholine receptor (AChR) antibody responses were examined in rats to evaluate the influence of helper T cell specificity on the nature and disease-causing potential of antibody produced. Mixtures of B cells reactive with the intact AChR plus T cells reactive with purified AChR subunits (alpha, beta, gamma, delta) were transferred and antigen-challenged in immunologically naive recipient rats; the serum anti-AChR antibody produced was assessed by radioimmunoassay for differences in titers and by isoelectric focusing for differences in clonal heterogeneity as a function of the subunit specificity of T cells transferred. In addition, rats receiving different sources of AChR or AChR subunit-reactive T cells were examined for AChR-dependent muscle dysfunction. The results indicated a clear reduction in anti-AChR antibody concentrations and clonal heterogeneity in recipient rats receiving T cells of specificities restricted to individual subunits. However, except for a clear relationship between serum anti-AChR antibody concentration and disease induction, no particular AChR subunit-reactive helper T cell specificity appeared to preferentially cause muscle dysfunction. We conclude that if such relationships exists, T cells with specificities more restricted than those described here will have to be used.


Management of carcinoma of the bladder.
Carcinoma of the bladder (CaB) is a common tumor of the genitourinary tract. In the United States in 1997, CaB was second in frequency of occurrence and third in mortality among genitourinary tumors. This tumor has a well-documented history of environmental and industrial causative factors. The strongest etiologic risk factors include the use of tobacco, which is thought to be responsible for half of the CaB diagnosed in men in the United States, and some arylamines. In the past 30 years, there has been major improvement in the survival of patients with this disease. Multiple factors were responsible for this accomplishment and they include: 1) better understanding of the natural history of CaB, 2) development of immunohistochemical analysis helpful in defining prognostic factors, 3) improved imaging and nonimaging diagnostic modalities helpful in making earlier diagnosis and better defining the true anatomical extent of the tumor, 4) development of more effective therapy for carcinoma in situ, 5) major improvement in surgical techniques resulting in better treatment outcomes, and 6) the wide use of adjuvant chemotherapy. Major stress has been placed on the quality of life of patients treated for CaB. Quality of life was improved by optimizing surgical, radiation, and medical treatment techniques. The two most important factors producing this quality-of-life improvement include: 1) the use of organ-preserving therapy in properly selected patients that involves the use of a multimodality therapeutic approach with transurethral resection, radiation therapy, and chemotherapy; and 2) the ability to treat selected men and women with radical cystectomy followed by orthotopic reconstruction that allows patients nearly physiologic voiding. Current research efforts are directed toward better patient selection for appropriate therapy which is expected to increase patient survival and improve quality of life. Of particular importance in the selection of this optimal therapy in patients with CaB is a wide application in the clinical practice of important recent advances in molecular genetics.


Differential clinical outcomes associated with hypoglycemia and hyperglycemia in acute myocardial infarction.
In patients with acute myocardial infarction (AMI), hyperglycemia predicts death, but the prognostic significance of hypoglycemia is controversial. We evaluated the prognostic significance of hypoglycemia and hyperglycemia in 30 536 AMI patients in a post hoc analysis of 2 large trials of glucose-insulin-potassium therapy in AMI. Glucose levels on admission and at 6 and 24 hours after admission, as well as 30-day mortality, were documented. In separate multivariable Cox models for admission and postadmission glucose, we compared the prognostic value of hypoglycemia (< or =70 mg/dL) and hyperglycemia (> or =140 mg/dL) with normoglycemia (>70 and <140 mg/dL). Analyses were repeated with hypoglycemia defined as glucose < or =60 mg/dL and in key subgroups based on diabetes or insulin (glucose-insulin-potassium) allocation status. Both high and low percentiles of admission glucose predicted increased 30-day mortality. However, for postadmission glucose, this U-shaped relationship was attenuated so that only high and not low glucose levels remained prognostic. Hyperglycemia (> or =140 mg/dL), both on admission (adjusted hazard ratio 1.43, 95% confidence interval 1.32 to 1.56, P<0.0001) and after admission (adjusted hazard ratio 1.47, 95% confidence interval 1.31 to 1.66, P<0.0001), predicted death compared with normoglycemia. In contrast, hypoglycemia (glucose < or =70 mg/dL) on admission was not prognostic (adjusted hazard ratio 1.16, 95% confidence interval 0.84 to 1.62, P=0.37), nor was postadmission hypoglycemia (adjusted hazard ratio 0.96, 95% confidence interval 0.72 to 1.26, P=0.75). Exploratory analyses that redefined hypoglycemia as glucose < or =60 mg/dL showed consistent results, as did analyses restricted to diabetic patients (18% of the study population). Postadmission hypoglycemia was more common in insulin (glucose-insulin-potassium)-treated patients (6.9%) than in untreated patients (3.4%) but did not predict mortality in either subgroup. Both admission and postadmission hyperglycemia predict 30-day death in AMI patients. In contrast, only hypoglycemia on admission predicted death, and this relationship dissipated after admission. These data suggest hypoglycemia may not be a direct mediator of adverse outcomes in AMI patients.


Urinary Orosomucoid A Potential Marker Of Inflammation In Psoriasis.
Background: Psoriasis is one of the most common chronic, life-long dermatologic diseases, which has considerable negative effects on quality of life. Psoriasis is considered as a systemic inflammatory disease, thus acute phase proteins such as C-reactive protein (CRP) and orosomucoid (ORM) have been shown to play a role in its pathophysiology. This study was aimed to compare CRP, serum ORM (se-ORM) and urinary ORM (u-ORM) levels of psoriatic patients to healthy individuals. Methods: 87 psoriatic patients and 41 healthy individuals were enrolled. Simultaneously obtained venous blood and spot urine samples were analysed. High sensitivity CRP and se-ORM levels were determined by routine procedures on automated analyzers. Urinary ORM was measured by a novel automated turbidimetric assay. U-ORM was referred to urinary creatinine (u-ORM/u-CREAT, mg/mmol). Results: Significantly higher hsCRP (p<0.001) and u-ORM/u-CREAT (p=0.001) levels were found among psoriatic patients compared to controls. No significant differences were found between the groups regarding se-ORM levels. HsCRP, se-ORM and u-ORM/u-CREAT levels were significantly higher in patients with severe psoriasis than in mild and moderate cases (p<0.05). Conclusion: As a highly sensitive, easily available biomarker u-ORM shows itself capable of becoming a new inflammatory marker in psoriasis providing clinically useful information on disease severity.


Failure to find intercellular protoplasmic continuity in Griffithsia globulifera.
A method was devised for estimtaing the electrical resistance between the cytoplasm of adjacent cells of the red marine alga Griffithsia globulifera. A very high resistance was found, which argues strongly against the existence of protoplasmic continuity in this species.


Cold-Induced Brown Adipose Tissue Activity Alters Plasma Fatty Acids and Improves Glucose Metabolism in Men.
Mounting evidence suggests beneficial effects of brown adipose tissue (BAT) activation on glucose and lipid metabolism in humans. It is unclear whether cold-induced BAT activation affects not only insulin sensitivity but also insulin secretion. Likewise, the role in clearing circulating fatty acids (FAs) has not been fully explored. Exploring the effects of cold-induced BAT activation on insulin sensitivity and secretion, as well as on plasma FA profiles. Fifteen healthy men participated in a cross-balanced repeated within-subject study with two experimental conditions. Subjects were exposed to thermoneutrality (22°C) and to moderate cold (18.06°C, shivering excluded) by use of a water-perfused whole body suit. Cold-induced BAT activation was quantified by [18F]-fluorodeoxyglucose positron emission tomography-computed tomography in a subset of volunteers. A Botnia clamp procedure was applied to determine pancreatic first phase insulin response (FPIR) and insulin sensitivity. Hormones and metabolites, including 26 specific plasma FAs, were sampled throughout the experiment. Cold exposure induced BAT activity. Plasma noradrenaline and dopamine concentrations increased in response to cold. Peripheral glucose uptake and insulin sensitivity significantly improved by ∼20%, whereas FPIR remained stable. Lignoceric acid (C24:0) concentrations increased, whereas levels of eicosanoic acid (C20:1n9), nervonic acid (C24:1n9), and behenic acid (C22:0) decreased. Cold-exposure induces sympathetic nervous system activity and BAT metabolism in humans, resulting in improved glucose metabolism without affecting pancreatic insulin secretion. In addition, BAT activation is associated with altered circulating concentrations of distinct FAs. These data support the concept that human BAT metabolism significantly contributes to whole body glucose and lipid utilization in a coordinated manner.


Off-balance-sheet financing can generate capital for strategic development.
To manage their real estate portfolios effectively and obtain funding for strategic development, IDSs should consider adopting off-balance-sheet financing strategies, such as sale-and-leaseback transactions, synthetic leases, and joint-venture arrangements. Under these approaches, real estate assets are moved off of the organization's balance sheet via a partial or complete transfer of ownership to a third-party entity. The organization typically retains a satisfactory degree of control over the assets as lessee in sale-and-leaseback and synthetic-lease arrangements, or limited or minority partner in a joint venture, while freeing up cash to use for other strategic purposes.


Dermographism and atopy in patients with Behçet's disease.
Dermographism is the appearance of whealing and erythema within minutes in a site where skin has been exposed to pressure or mechanical irritation. In our clinical observations, dermographism seems to be frequent in patients with Behçet's disease. Since the prevalence of allergic responses is reportedly increased in vasculitic syndromes, we aimed to assess dermographism and atopy in a group of Behçet's patients. The study group comprised 30 consecutive patients with Behçet's disease. The study was carried out in two parts: elicited dermographism and atopy tests. In the first part, dermographism was investigated in the study group (Behçet's patients) and 230 healthy controls. In the second part, the study group, 30 healthy controls and 17 patients with allergic bronchial asthma were evaluated for specific and nonspecific atopy. Dermographism was found to be increased in patients with Behçet's disease. Peripheral blood eosinophil count, serum total IgE and nasal eosinophil scores were similar in patients with Behçet's disease and healthy controls. Although blood eosinophil count and serum total IgE levels were higher in allergic bronchial asthma patients than in Behçet's patients, the difference was significant only in the former. Skin prick test was positive in three of the patients with Behçet's disease and in six healthy controls. The difference was statistically insignificant (p > 0.05). None of the Behçet's disease patients had pathergy or a pathergy-like reaction at the site of the skin prick test after 48 h. In conclusion, our results confirm the general impression that dermographism is common in patients suffering from Behçet's disease.


Trabecular bone of precocials at birth; Are they prepared to run for the wolf(f)?
Bone is a dynamic tissue adapting to loading according to "Wolff's law of bone adaptation." During very early life, however, such a mechanism may not be adequate enough to adapt to the dramatic change in environmental challenges in precocial species. Their neonates are required to stand and walk within hours after birth, in contrast to altricial animals that have much more time to adapt from the intrauterine environment to the outside world. In this study, trabecular bone parameters of the talus and sagittal ridge of the tibia from stillborn but full-term precocials (calves and foals) were analyzed by micro-CT imaging in order to identify possible anticipatory mechanisms to loading. Calculated average bone volume fraction in the Shetland pony (49-74%) was significantly higher compared to Warmblood foals (28-51%). Bovine trabecular bone was characterized by a low average bone volume fraction (22-28%), however, more directional anisotropy was found. It is concluded that anticipatory strategies in skeletal development exist in precocial species, which differ per species and are most likely related to anatomical differences in joint geometry and related loading patterns. The underlying regulatory mechanisms are still unknown, but they may be based on a genetic blueprint for the development of bone. More knowledge, both about a possible blueprint and its regulation, will be helpful in understanding developmental bone and joint diseases. J. Morphol. 277:948-956, 2016. © 2016 Wiley Periodicals, Inc.


Protective vaccination of ferrets against canine distemper with recombinant pox virus vaccines expressing the H or F genes of rinderpest virus.
To investigate the ability of rinderpest virus (RPV) antigens, expressed in pox virus vectors, to protect against canine distemper virus (CDV) infection in ferrets. Ferrets (Mustela putorius; n = 27) with no previous exposure to CDV. Ferrets were inoculated intradermally with recombinant vaccinia viruses expressing the H gene of RPV, the F gene of RPV, the H and F genes of RPV, or fowlpox virus recombinant expressing both genes. Two ferrets were vaccinated s.c. with CDV vaccine as positive controls, and 1 group was left unvaccinated as a negative control. Blood was obtained from ferrets biweekly; antibody titer to RPV was detected by ELISA, and CDV antibody titer was measured by serum neutralization testing and ELISA. Partial protection was seen in all groups, with vRVFH vaccination being the most protective (60%). A single inoculation with a vaccinia virus expressing the H and F genes of RPV was able to protect 60% of the vaccinated ferrets challenge exposed with a high dose of CDV. These results indicate the ability of RPV antigens expressed by vaccinia virus to protect ferrets against a related morbillivirus. Further, they document the safety and efficacy of a recombinant vaccinia virus vaccine for ferrets. Such vaccines may be useful given the susceptibility of ferrets to CDV and the problem of maternal antibody interfering with vaccination of young animals.


Obliterative airway disease after heterotopic tracheal xenotransplantation: pathogenesis and prevention using new immunosuppressive agents.
The purpose of this study was to investigate whether obliterative bronchiolitis might occur after xenogenic pulmonary transplantation. A model for obliterative airway disease (OAD) after tracheal allograft transplantation in the rat undergoes tracheal obliteration with histologic features characteristic of obliterative bronchiolitis in human lung transplant recipients. Using this model, the pathogenesis of OAD and its prevention with immunosuppressive drugs was studied in rat recipients of hamster tracheal grafts. Tracheae from 30 hamsters (xenografts) or 23 Brown-Norway rats (allografts) were implanted and wrapped in the greater omentum of untreated Lewis rats. The grafts were removed on day 1, 3, 7, 14, 21, or 28 after transplantation and stained with hematoxylin and eosin and Masson's trichrome and by immunohistochemistry and immunofluorescence (IFL) techniques. In addition, 25 recipients were treated with cyclosporine (CsA, 10 mg/kg p.o.), leflunomide (LFM, 20 mg/kg p.o.), or rapamycin (RPM, 6 mg/kg i.p.) for 14 or 21 days (5 animals per treatment group). Visual and morphometric analyses were used to evaluate the extent of airway obliteration, luminal coverage by respiratory or flattened cuboidal epithelium, and extent and density of peritracheal cellular inflammation. In all xenografts, a neutrophilic infiltration of the mucosa and submucosa was observed from day 1 until day 14 and was associated with complete loss of tracheal epithelium by day 14. A marked peritracheal mononuclear cellular infiltrate mixed with plasma cells and eosinophils was seen on days 7 and 14. Both the extent of peritracheal inflammation and the density of the mononuclear cell infiltrate were significantly increased in xenograft tracheae when compared with the allografts. Tracheal obliteration began on day 14 and reached a maximum of 43% on day 21 with evidence of intraluminal fibrosis. In contrast to IFL of allografts, IFL of xenografts demonstrated marked deposition of rat immunoglobulin in the peritracheal tissue on days 7 and 14. The effects of treatment with immunosuppressive drugs on tracheal graft narrowing and protection of respiratory epithelium were as follows: After 14 days of treatment, the percentage of tracheal graft narrowing was 12%, 23%, and 19% in the no treatment, CsA, and LFM groups, respectively; the percentage of respiratory epithelium at 14 days was 0%, 21%, and 95%. After 21 days of treatment, the percentage of tracheal graft narrowing was 43%, 49%, 12%, and 5% for the no treatment, CsA, LFM, and RPM groups, respectively; the percentage of respiratory epithelium at 21 days was 0%, 39%, 86%, and 0%. Using computerized morphometry, the extent and densities of the peritracheal cellular infiltrates were significantly reduced in LFM- and CsA-treated groups when compared with untreated xenograft controls. LFM and RPM, but not CsA, significantly reduced the degree of luminal obliteration compared with no treatment (P<0.05). LFM and, to a lesser extent, CsA were able to prevent the loss of normal respiratory epithelium. Analysis by IFL revealed a marked decrease in rat immunoglobulin deposition in xenografts from LFM- and RPM-treated groups compared with xenografts from CsA-treated or untreated rats. (1) OAD occurs not only after tracheal allotransplantation but also after xenotransplantation. (2) Subepithelial infiltration of neutrophils and the appearance of plasma cells and eosinophils in the peritracheal infiltrates distinguished the histology of rejected xenografts from allografts. (3) Antibody deposition was detected by IFL only in xenografts. (4) Treatment with LFM or RPM significantly decreased the severity of luminal obliteration. Importantly, LFM also prevented the loss of respiratory epithelium.


Confocal microscopic features of scarring alopecia: preliminary report.
Lichen planopilaris (LPP) and discoid lupus erythematosus (DLE) are the most common causes of lymphocytic primary cicatricial alopecia. The management of scarring alopecia can be difficult. The combination of clinical, dermoscopy and reflectance confocal microscopy (RCM), a noninvasive, high-resolution imaging technique, examinations have already been demonstrated to be useful for choosing the correct biopsy site in patients with inflammatory skin disease and obtaining microscopic diagnostic criteria. We evaluated the usefulness in practice of RCM for the identification of criteria for LPP and DLE involving the scalp and their management during therapeutic follow-up. Seven white patients with a previously established histological diagnosis of DLE (three) and LPP (four), were included in the study. RCM criteria for primary scarring alopecia were selected: epidermal disarray, spongiosis, exocytosis of inflammatory cells in the epidermis, interface dermatitis, peri- and intra-adnexal infiltration of inflammatory cells, dilated vessels in the dermis, dermal infiltration of inflammatory cells and melanophages and dermal sclerosis. All patients were followed up using RCM during the treatment. During follow-up the RCM evolution of the epidermal, junctional and dermal inflammation were evaluated. A series of RCM features of scalp LPP and DLE were identified that show correlation with the histopathological evaluation. During the treatment follow-up of the cases RCM was shown to be sensitive for the identification of therapeutic response. In our preliminary study the effective usefulness of RCM for the diagnosis of scarring alopecia and follow-up seemed to be evident. Moreover, RCM seems to be also promising for differential diagnosis between the different entities.


Higher serum tenascin-C levels reflect the severity of heart failure, left ventricular dysfunction and remodeling in patients with dilated cardiomyopathy.
Tenascin-C (TN-C), an extracellular matrix glycoprotein, is specifically expressed at high levels during embryonic development, but not in the adult heart. TN-C reappears at sites of inflammatory tissue remodeling or wound healing under various pathologic conditions, such as acute myocardial infarction, acute myocarditis, and some cases of cardiomyopathy. Therefore, the expression of TN-C might be useful for detecting the clinical characteristics of, and ventricular remodeling in, dilated cardiomyopathy (DCM). Circulating serum TN-C levels in 107 patients with DCM were measured using an ELISA kit. Clinical data were also assessed by Pearson's or Spearman's correlation analysis to estimate correlations between variables. Serum TN-C levels in DCM patients were higher than those in normal controls (p<0.001). TNC levels showed a significantly positive correlation with New York Heart Association functional class (p<0.001), B-type natriuretic peptide level (p<0.001), cardiothoracic ratio on chest X-ray (p<0.01), left ventricular end-diastolic diameter (p<0.05) and left ventricular end-systolic diameter (p<0.01), and a significantly negative correlation with left ventricular ejection fraction (p<0.01). The findings suggest that increased serum TN-C levels indicate the severity of heart failure, left ventricular dysfunction and remodeling in patients with DCM.


The scope of upper limb surgery for tetraplegics: Role of tendon transfers and Universal Cuff.
The aim of this study was to evaluate the role of tendon transfers and universal cuff in restoring hand function in tetraplegic patients. Twenty-one upper limbs on 12 tetraplegic patients (9 males and 3 females); mean age: 42.2 years (range 22-58 years) with a spinal cord injury at or distal to C6, were included in this study. Key pinch was restored using Brachioradialis to Flexor Pollicis Longus transfer and hook using Pronator Teres to Flexor Digitorum Profundus transfer. The gains achieved were measured objectively at six months and at final follow up, the average follow up being 26 months. The functional outcome was assessed using the Modified Lamb and Chan score. Average value was 1.67 kg for key pinch and 2.58 kg for hook grip at final follow up. The Modified Lamb and Chan score revealed good to fair outcome in 75% of patients. Complications resulted from stretching of transfer and mal-tensioning and were salvaged by the use of a 'Universal Cuff'. Surgery should be routinely offered to tetraplegic patients with deficient hand function in whom no recovery is expected after six months following spinal cord injury. Universal Cuff is a good salvage method for patients who refuse re-surgery. Level IV, Therapeutic study.


Prediction of the Contribution Ratio of a Target Metabolic Enzyme to Clearance from Chemical Structure Information.
The contribution ratio of metabolic enzymes such as cytochrome P450 to in vivo clearance (fraction metabolized: fm) is a pharmacokinetic index that is particularly important for the quantitative evaluation of drug-drug interactions. Since obtaining experimental in vivo fm values is challenging, those derived from in vitro experiments have often been used alternatively. This study aimed to explore the possibility of constructing machine learning models for predicting in vivo fm using chemical structure information alone. We collected in vivo fm values and chemical structures of 319 compounds from a public database with careful manual curation and constructed predictive models using several machine learning methods. The results showed that in vivo fm values can be obtained from structural information alone with a performance comparable to that based on in vitro experimental values and that the prediction accuracy for the compounds involved in CYP induction or inhibition is significantly higher than that by using in vitro values. Our new approach to predicting in vivo fm values in the early stages of drug discovery should help improve the efficiency of the drug optimization process.


Measuring physical activity-related environmental factors: reliability and predictive validity of the European environmental questionnaire ALPHA.
A questionnaire to assess physical activity related environmental factors in the European population (a 49-item and an 11-item version) was created as part of the framework of the EU-funded project "Instruments for Assessing Levels of PHysical Activity and fitness (ALPHA)". This paper reports on the development and assessment of the questionnaire's test-retest stability, predictive validity, and applicability to European adults. The first pilot test was conducted in Belgium, France and the UK. In total 190 adults completed both forms of the ALPHA questionnaire twice with a one-week interval. Physical activity was concurrently measured (i) by administration of the long version of the International Physical Activity Questionnaire (IPAQ) by interview and (ii) by accelerometry (Actigraph device). After adaptations, the second field test took place in Belgium, the UK and Austria; 166 adults completed the adapted questionnaire at two time points, with minimum one-week interval. In both field studies intraclass correlation coefficients (ICC) and proportion of agreement were computed to assess the stability of the two test scores. Predictive validity was examined in the first field test by correlating the results of the questionnaires with physical activity data from accelerometry and long IPAQ-last 7 days. The reliability scores of the ALPHA questionnaire were moderate-to good in the first field testing (ICC range 0.66 - 0.86) and good in the second field testing (ICC range 0.71 - 0.87). The proportion of agreement for the ALPHA short increased significantly from the first (range 50 - 83%) to the second field testing (range 85 - 95%). Environmental scales from both versions of the ALPHA questionnaire were significantly associated with self-reported minutes of transport-related walking, and objectively measured low intensity physical activity levels, particularly in women. Both versions were easily administered with an average completion time of six minutes for the 49-item version and less than two minutes for the short version. The ALPHA questionnaire is an instrument to measure environmental perceptions in relation to physical activity. It appears to have good reliability and predictive validity. The questionnaire is now available to other researchers to investigate its usefulness and applicability across Europe.


Hypertrophic cardiomyopathy: etiology, diagnosis, and treatment.
Hypertrophic cardiomyopathy (HCM) is a disease characterized by primary hypertrophy of the left (and sometimes right) ventricle. The clinical manifestations of the disease are dyspnea, angina, and a continuum encompassing lightheadedness, presyncope, syncope, and sudden death. Although HCM is often caused by an identifiable mutation in a gene coding for a sarcomeric protein and inherited in an autosomal-dominant pattern, many patients do not have any relatives in whom the disease is manifest. The prevalence of HCM is estimated to be 0.2%, with nearly 600,000 Americans affected. This limited exposure of clinicians to HCM understandably accounts for the uncertainty that prevails regarding this disease and its management.


Activation of p38mapk, MKK3, and MKK4 by TNF-alpha in mouse bone marrow-derived macrophages.
TNF-alpha regulates the expression of many proinflammatory and profibrogenic gene products in macrophages, and hence plays a vital role in controlling the inflammatory response. We have shown previously that exposure of macrophages to TNF-alpha stimulates the activation of members of the mitogen-activated protein kinase (MAPK) family. In this study, we have investigated the mechanism of activation of the p38mapk by TNF-alpha in mouse bone marrow-derived macrophages. Exposure to TNF-alpha resulted in the activation of p38mapk, as measured by 1) the trans-phosphorylation of recombinant activating transcription factor-2 substrate by immunoprecipitated p38mapk and 2) specific tyrosine phosphorylation of immunoprecipitated p38mapk. In addition, selective ligation of the TNF-alpha receptor CD120a (p55) with human TNF-alpha was sufficient to induce p38mapk activation. Using an in vitro kinase assay with recombinant kinase-inactive p38mapk as substrate in the presence of [gamma-32P]ATP, the upstream kinases MKK3 (mitogen-activated protein kinase kinase 3) and MKK4 were found to be activated in response to TNF-alpha. These findings suggest that TNF-alpha transiently phosphorylates and activates the three members of the MAPK family, namely p42(mapk/erk2), p46 c-Jun amino-terminal kinase/stress-activated protein kinase (JNK/SAPK), and p38mapk following cross-linking of CD120a (p55), and that MKK3 and MKK4 are capable of phosphorylating p38mapk.


When familiar is not better: 12-month-old infants respond to talk about absent objects.
Three experiments that demonstrate a novel constraint on infants' language skills are described. Across the experiments it is shown that as babies near their 1st birthday, their ability to respond to talk about an absent object is influenced by a referent's spatiotemporal history: familiarizing infants with an object in 1 or several nontest locations before the study interferes with their ability to respond to talk about the object when it is out of view. Familiarity with an object may not always strengthen infants' object representations and therefore facilitate their ability to appropriately react to the mention of absent objects. On the contrary, early in development, irrelevant information about prior location may be bound to representations of familiar objects and thus interfere with infants' ability to respond to talk about absent things.


Laparoscopic partial versus radical nephrectomy for localized renal cell carcinoma over 4 cm.
To compare the long-term clinical and oncologic outcomes of laparoscopic partial nephrectomy (LPN) and laparoscopic radical nephrectomy (LRN) in patients with renal cell carcinoma (RCC) > 4 cm. We retrospectively reviewed the records of all patients who underwent LPN or LRN in our department from January 2012 to December 2017. Of the 151 patients who met the study selection criteria, 54 received LPN, and 97 received LRN. After propensity-score matching, 51 matched pairs were further analyzed. Data on patients' surgical data, complications, histologic data, renal function, and survival outcomes were collected and analyzed. Compared with the LRN group, the LPN group had a longer operative time (135 min vs. 102.5 min, p = 0.001), larger intraoperative bleeding (150 ml vs. 50 ml, p < 0.001), and required longer stays in hospital (8 days vs. 6 days, p < 0.001); however, the level of ECT-GFR was superior at 3, 6, and 12 months (all p < 0.001). Similarly, a greater number of LRN patients developed CKD compared with LPN until postoperative 12 months (58.8% vs. 19.6%, p < 0.001). In patients with preoperative CKD, LPN may delay the progression of the CKD stage and even improve it when compared to LRN treatment. There were no significant differences between the two groups for OS, CSS, MFS, and PFS (p = 0.06, p = 0.30, p = 0.90, p = 0.31, respectively). The surgical method may not be a risk factor for long-term survival prognosis. LPN preserves renal function better than LRN and has the potential value of significantly reducing the risk of postoperative CKD, but the long-term survival prognosis of patients is comparable.


Seasonal changes in haematology, lymphocyte transferrin receptors and intracellular iron in Ironman triathletes and untrained men.
We investigated whether 12 months of chronic endurance training would affect haematology, CD4(+) lymphocyte transferrin receptor (CD71) expression, CD4(+) intracellular iron and the incidence of upper respiratory tract illnesses (URTI) in Ironman triathletes compared with untrained men. Resting venous blood samples were taken from 15 Ironman triathletes (TR 30 ± 5 year) and 12 untrained men (UT 30 ± 6 year) every 4 weeks for 12 months. Erythrocyte, leukocyte and platelet concentration, haematocrit, haemoglobin (Hb) and mean corpuscular haemoglobin (MCHC) were measured with a full blood count. CD4(+) lymphocytes were analysed for changes in transferrin receptor (CD71) expression (CD4(+)CD71(+)), and intracellular iron (Fe(3+)), by flow cytometry. The TR group had significantly lower Hb, MCHC, and platelets for 10, 9 and 11 months, respectively; lower CD4(+)CD71(+) (3 months) and Fe(3+) (1 month), respectively; higher CD4(+)CD71(+) (1 month); a higher lymphocyte count for 4 months. There were no between-group differences in other variables. In both groups haematology and lymphocytes increased during spring, early summer and winter and decreased during late summer/late winter, with an inverse relationship between CD4(+)CD71(+) and Fe(3+). The TR group reported significantly fewer URTI than the UT. Low Hb and MCHC suggest an iron deficiency which may affect triathlete performance. Monthly changes in lymphocytes, CD4(+)CD71(+) and Fe(3+) suggested that spring, summer and late autumn are associated with CD4(+) proliferation. There may be seasonal relationships between haematology and lymphocyte function, independent of endurance training, possibly affecting performance but not the incidence of URTI.


The effect of income growth and inequality on health inequality: Theory and empirical evidence from the European Panel.
Governments of EU countries have declared that they would like to couple income growth with reductions in social inequalities in income and health. We show that, theoretically, both aims can be reconciled only under very specific conditions concerning the type of growth and the income responsiveness of health. We investigate whether these conditions were met in Europe in the 1990s using panel data from the European Community Household Panel. We demonstrate that (i) in most countries, the income elasticity of health was positive and increases with income, and (ii) that income growth was not pro-rich in most EU countries, resulting in small or negligible reductions in income inequality. The combination of both findings explains the modest increases we observe in income-related health inequality in the majority of countries.


Expanding the limits of catalysts with low-valent main-group elements for the hydroboration of aldehydes and ketones using [L†Sn(ii)][OTf] (L† = aminotroponate; OTf = triflate).
A triflatostannylene [L†Sn(ii)][OTf] (2) is reported here as an efficient catalyst with low-valent main-group element for the hydroboration of aldehydes and ketones (L† = aminotroponate). Using 0.025-0.25 mol% of compound 2, hydroboration of various aldehydes and ketones is accomplished in 0.13-1.25 h at room temperature; the aliphatic aldehydes show an impressive TOF of around 30 000 h-1. DFT calculations are performed to explore the mechanistic aspects of this reaction suggesting that the reaction proceeds via a stepwise pathway with hydridostannylene [L†Sn(ii)H] (2a) as the active catalyst and the H atom transfer from the Sn-H bond to the carbonyl carbon being the rate determining step.


Differential distribution of cobalt, chromium, and nickel between whole blood, plasma and urine in patients after metal-on-metal (MoM) hip arthroplasty.
Evidence shows that raised cobalt (Co), chromium (Cr), and nickel (Ni) whole blood concentrations correlate with poor device outcome in patients following metal-on-metal (MoM) hip arthroplasty. To understand the local and systemic pathological effects of these raised metal concentrations it is important to define their distribution between whole blood, plasma, and urine. The metals were measured by Inductively Coupled Plasma Mass Spectrometry (ICPMS). Two hundred and five plasma, 199 whole blood, and 24 sets of urine samples were analyzed from 202 patients with Co-Cr alloy MoM hip prostheses implanted between 8 months to 12 years (mean 6.0 years) prior to analysis. Plasma Co (median 39.1 nmol/L) showed significantly positive 1:1 correlation with whole blood Co (median 45.9 nmol/L; R(2) = 0.98, p < 0.001, slope = 1.0). Plasma Cr (median 53.8 nmol/L) and whole blood Cr (median 40.3 nmol/L) were also correlated; however, concentrations were significantly higher in plasma indicating relatively little blood cell uptake (R(2) = 0.96, p < 0.001, slope = 1.6). Urinary Co was up to threefold higher than Cr (median 334.0 vs. 97.3 nmol/L respectively). Nickel concentrations in whole blood, plasma, and urine were low relative to Co and Cr. The analysis shows fundamental differences in the physiological handling of these metals: Co is distributed approximately equally between blood cells and plasma, whereas Cr is mainly in plasma, despite which, Cr had far less renal excretion than Co.


Revision of species delineation in the genus Ectothiorhodospira.
When the type strains and other strains of the six currently defined species of the genus Ectothiorhodospira were examined by DNA-DNA reassociation and RFLP of 16S/23S rDNA (ribotype), only four genospecies could be found. The possibility of defining taxonomically meaningful species corresponding to these four genospecies was investigated by combining DNA relatedness and ribotype data with other genotypic and phenotypic characters already described in the literature, an approach known as polyphasic taxonomy. Following this comparison, the type strain and another strain of Ectothiorhodospira vacuolata were found to be very similar to the type strain of Ectothiorhodospira shaposhnikovii and have been transferred to this latter species. Also, the type strain of Ectothiorhodospira marismortui and another previously unidentified strain were found to be very similar to the type strain of Ectothiorhodospira mobilis and have been transferred to this latter species. Due to the limited degree of reciprocal DNA relatedness, strains belonging either to Ectothiorhodospira marina or to Ectothiorhodospira haloalkaliphila are still considered as belonging to separate species, even though they show a remarkable phenotypic similarity. This revision has led to the delineation of only four species in the genus Ectothiorhodospira, namely E. mobilis, E. shaposhnikovii, E. marina and E. haloalkaliphila. E. vacuolata is recognized as a junior synonym of E. shaposhnikovii and E. marismortui as a junior synonym of E. mobilis.


Self-reported prevalence of chronic diseases and their relation to selected sociodemographic variables: a study in INDEPTH Asian sites, 2005.
Lack of reliable population-based data, especially morbidity data, is a barrier to preventing and controlling chronic diseases in developing countries. We report the self-reported prevalences of major chronic diseases in Southeast Asia and examine their relation to selected sociodemographic variables in adults. Data are from a 2005 cross-site study of 8 sites in 5 Asian countries that surveyed 18,484 people aged 25-64 years. Respondents were asked whether they had been told by a health care worker that they had any of 7 chronic health conditions: joint problems, stroke, heart disease, diabetes, pulmonary disease, hypertension, or cancer. Information about participants' sex, age, and educational level was also obtained. We found that 22.7% of men and 31.6% of women reported having at least 1 of the chronic health conditions of interest, and 5.1% of men and 9.2% of women reported having 2 or more chronic conditions. Multivariate regression analyses showed that women had more chronic conditions than men, the prevalence of chronic conditions increased with age, and people with the least education were more likely to have chronic conditions. Chronic conditions are commonly reported among adults in Asian countries. Disparities in the prevalence of chronic conditions by sex and education are evident.


A multilevel mHealth intervention boosts adherence to hydroxyurea in individuals with sickle cell disease.
Hydroxyurea reduces sickle cell disease (SCD) complications, but medication adherence is low. We tested 2 mobile health (mHealth) interventions targeting determinants of low adherence among patients (InCharge Health) and low prescribing among providers (HU Toolbox) in a multi-center, non-randomized trial of individuals with SCD ages 15-45. We compared the percentage of days covered (PDC), labs, healthcare utilization, and self-reported pain over 24 weeks of intervention and 12 weeks post-study with a 24-week preintervention interval. We enrolled 293 patients (51% male; median age 27.5 years, 86.8% HbSS/HbSβ0-thalassemia). The mean change in PDC among 235 evaluable subjects increased (39.7% to 56.0%; P < 0.001) and sustained (39.7% to 51.4%, P < 0.001). Mean HbF increased (10.95% to 12.78%; P = 0.03). Self-reported pain frequency reduced (3.54 to 3.35 events/year; P = 0.041). InCharge Health was used ≥1 day by 199 of 235 participants (84.7% implementation; median usage: 17% study days; IQR: 4.8-45.8%). For individuals with ≥1 baseline admission for pain, admissions per 24 weeks declined from baseline through 24 weeks (1.97 to 1.48 events/patient, P = 0.0045) and weeks 25-36 (1.25 events/patient, P = 0.0015). PDC increased with app use (P < 0.001), with the greatest effect in those with private insurance (P = 0.0078), older subjects (P = 0.033), and those with lower pain interference (P = 0.0012). Of the 89 providers (49 hematologists, 36 advanced care providers, 4 unreported), only 11.2% used HU Toolbox ≥1/month on average. This use did not affect change in PDC. Tailoring mHealth solutions to address barriers to hydroxyurea adherence can potentially improve adherence and provide clinical benefits. A definitive randomized study is warranted. This trial was registered at www.clinicaltrials.gov as #NCT04080167.


A Detailed Comparative Analysis of Anterior Versus Posterior Approach to Lenke 5C Curves.
Prospective cohort study. To prospectively compare radiographic, perioperative, and functional outcomes between anterior spinal instrumentation and fusion (ASIF) and posterior spinal instrumentation and fusion (PSIF) in Lenke 5C curves. Historically, ASIF has been the treatment of choice for treatment of thoracolumbar adolescent idiopathic scoliosis. More recently, PSIF has gained popularity for its ease, versatility, and amount of correction achieved. Current literature lacks a prospective comparative analysis between these two approaches to better aid treating surgeons in decision making when treating Lenke 5C curves. A prospective, longitudinal multicenter adolescent idiopathic scoliosis database was used to identify 161 consecutive patients with Lenke 5C curves treated by ASIF with a dual rod system, or PSIF with a pedicle screw-rod construct. Pre- and 2-year postoperative radiographic data, Scoliosis Research Society outcome scores, and perioperative comparisons were made between the two approaches. A total of 69 patients were treated with ASIF and 92 patients with PSIF. Curve extent, magnitude, stable, and end vertebrae distribution before surgery were similar between the two groups. At 2-year follow-up, there were no significant differences in percentage correction of the main curve (ASIF: 59.1%, PSIF: 59.6%), C7 decompensation (ASIF: -0.6 ± 1.2, PSIF: -0.3 ± 1.4 cm), length of hospital stay (ASIF: 5.6 days, PSIF: 5.7 days), postoperative day conversion to oral pain medication (ASIF: 3.2 days, PSIF: 3.2 days), and SRS outcome scores (P = 0.560) between the two groups. The number of levels fused was significantly lower in ASIF group (ASIF: 4.7, PSIF: 6.3; P < 0.001), but PSIF resulted in significantly less disc angulation below lowest instrumented vertebrae (ASIF: 3.4°, PSIF: 1.7°; P = 0.011), greater lumbar lordosis (P < 0.001), and greater % correction of lumbar prominence (P = 0.017). The amount of correction achieved was similar between ASIF and PSIF. ASIF resulted in shorter fusions (average 1.6 levels) compared with PSIF. This was at the expense of increased disc angulation below the lowest instrumented vertebrae, less lumbar lordosis, and a lower % correction of the lumbar prominence than PSIF. 2.


Coxa vara infantum, hip growth disturbances, etiopathogenesis, and long-term results of treatment.
The literature concerning coxa vara infantum (CVI) contains only a few long-term follow-up reports of the treatment. This study was performed to define the clinical and roentgenographic features of coxa vara infantum (CVI) in children and skeletally mature patients. Special attention was given in follow-up evaluations to the growth and impairment of the hip joint (acetabulum, femoral head, and neck) before and after operative treatment in different age groups. Because in difficult cases the results of subtrochanteric osteotomy have not been satisfactory and have led to recurrences, the use of overcorrecting of the neck-shaft angle value into valgus position has been adopted. To gain further insight into etiopathogenesis of CVI, histologic investigations were carried out. These investigations revealed growth and endochondral ossification disorders. Similar changes found in the growth zone of the iliac bone seem to indicate that the ossification disturbances are multifocal. Expansion of the fibrous connective and calluslike tissues is evidence of the overload syndrome in CVI.


The role of sexually explicit material in the sexual development of same-sex-attracted Black adolescent males.
Sexually explicit material (SEM) (including Internet, video, and print) may play a key role in the lives of Black same-sex sexually active youth by providing the only information to learn about sexual development. There is limited school- and/or family-based sex education to serve as models for sexual behaviors for Black youth. We describe the role SEM plays in the sexual development of a sample of Black same-sex attracted (SSA) young adolescent males ages 15-19. Adolescents recruited from clinics, social networking sites, and through snowball sampling were invited to participate in a 90-min, semi-structured qualitative interview. Most participants described using SEM prior to their first same-sex sexual experience. Participants described using SEM primarily for sexual development, including learning about sexual organs and function, the mechanics of same-gender sex, and to negotiate one's sexual identity. Secondary functions were to determine readiness for sex; to learn about sexual performance, including understanding sexual roles and responsibilities (e.g., "top" or "bottom"); to introduce sexual performance scripts; and to develop models for how sex should feel (e.g., pleasure and pain). Youth also described engaging in sexual behaviors (including condom non-use and/or swallowing ejaculate) that were modeled on SEM. Comprehensive sexuality education programs should be designed to address the unmet needs of young, Black SSA men, with explicit focus on sexual roles and behaviors that may be inaccurately portrayed and/or involve sexual risk-taking (such as unprotected anal intercourse and swallowing ejaculate) in SEM. This work also calls for development of Internet-based HIV/STI prevention strategies targeting young Black SSA men who may be accessing SEM.


Left subclavian artery trauma: in situ vs. rib interspace mobilization for primary anastomosis.
Fifteen autopsy dissections were performed to evaluate the anatomic relationships of the left subclavian artery and primary arterial anastomosis following trauma. The vessel was transected just beyond the origin of the thyrocervical trunk, and the maximal excisable overlapping segment was determined in situ and through the first and second interspaces. By passing the mobilized left axillary artery through the first intercostal space, up to 7.5 cm of a subclavian arterial segment could be resected and primary arterial repair accomplished. The use of the first interspace to gain additional length in primary repair of the left subclavian artery is suggested as an alternative to grafting.


Effect of milk supplementation on the status of micronutrients among rural school children aged 5-19 years in a tribal predominating district of India.
In the tribal state of Jharkhand, there have been very few studies on micronutrient deficiency and how it is addressed among school children. This study was conceived and undertaken to assess the effect of milk supplementation on the micronutrient status of school children. A comparative observational study was conducted among school children of a tribal district in India during 2017-2018. Two groups of schools/clusters were randomly selected, one with milk supplementation and the other without supplementation. A total of 318 children from the two groups of schools were recruited for biochemical analysis of certain micronutrients, such as calcium, vitamin D, vitamin B12 and iron (haemoglobin level), using cluster random sampling. Data were analysed using SPSS V.20.0 software, and multiple logistic regression analysis was done to determine the predictors of serum calcium and vitamin B12 level among school children. Almost all children from both groups had vitamin D deficiency. A higher risk of lower serum vitamin B12 level (OR 2.59, 95% CI 1.61 to 4.16) and calcium level (OR 3.36, 95% CI 1.74 to 6.49) was observed in children of the control group. The difference in the proportion of anaemia in the two study groups was found to be statistically insignificant. Milk consumption was found to be the only significant predictor of normal vitamin B12 and calcium level in the present study. In this study, it was concluded that milk consumption may help in improving the calcium and vitamin B12 status of school children of a tribal state, whereas it does not have any significant effect on vitamin D level.


Age-related susceptibility of mice to ocular challenge with Pseudomonas aeruginosa exotoxin A.
We studied the responses of mice to ocular challenge with purified exotoxin A from Pseudomonas aeruginosa in 5-, 10-, 16-, 21-, and 30-day-old animals. In the absence of trauma, injection of 3 to 6 microgram of exotoxin per mouse beneath the fused eyelids of 5-day-old Swiss-Webster mice resulted in death of all animals within 24 h. Administration of 1.5, 0.75, and 0.375 microgram of exotoxin per mouse resulted in 24-h mortality rates of 50, 22, and 20%, respectively. Additional deaths were recorded throughout the next 4 days. Similar lethality results were obtained with 10-day-old animals that received equivalent amounts of exotoxin beneath the fused eyelid and in these experiments, the 72-h 50% lethal dose was 0.49 microgram of exotoxin per mouse. Mice that were 16 and 21 days old, whose eyelids were open, each received from 0.375 to 15 microgram of exotoxin topically applied to the surface of a wounded cornea. Cataracts were observed within 1 week in both groups, and none of the animals that received the higher concentrations of toxin died. Young adult (30-day-old) animals also received from 1.8 to 15 microgram of exotoxin topically on the surfaces of wounded corneas. Corneal swelling and slight opacity were observed at 24 h and within 1 month; 80% of these mice had cataracts of the ocular lens.


Proteolysis of isolated mitochondria by myocardial lysosomal enzymes.
1. Solubilized mitochondria and lysosomal fractions were obtained from guinea-pig heart by differential centrifugation and selective membrane disruption. 2. Mitochondria incubated at 37 degrees C in the presence of lysosomal enzymes underwent proteolysis. The rate of protein degradation was inversely dependent on pH. 3. The use of proteinase inhibitors showed that at low pH the major enzyme involved in mitochondrial digestion was cathepsin D. 4. At neutral pH carboxyl proteinases were still active, but thiol proteinases accounted for most of the protein breakdown. 5. The role of lysosomal enzymes as mediators of mitochondrial damage in ischaemic myocardium is discussed.


Methylprednisolone and gentamicin effects on hepatosplanchnic blood flow and carbohydrate metabolism in endotoxemic Yucatan miniature pigs.
Conjoint therapy of a glucocorticoid and aminoglycoside antibiotic have been recommended for septic shock. These studies examined the hemodynamic and metabolic effects of methylprednisolone sodium succinate (MPSS) with and without gentamicin sulfate in a nonanesthetized model of nonseptic endotoxemia in Yucatan miniature pigs. Methylprednisolone sodium succinate alone had no effect on endotoxin-induced systemic hypotension. Endotoxemic pigs treated with MPSS in combination with gentamicin sulfate had lower mean arterial pressures than did MPSS-treated and nontreated endotoxemic pigs. Methylprednisolone sodium succinate alone and with gentamicin sulfate improved portal and hepatic venous blood flows moderately. Net hepatic lactate extraction, glucose production, and whole body [6-3H]glucose-derived rates of glucose appearance were also improved, but [6-3H]glucose-derived rates of glucose disappearance and blood lactate concentrations were increased, leading to no improvement in plasma glucose concentration. Pancreatic insulin secretion was higher in treated groups, which may have contributed to greater glucose utilization rates. Hepatic oxygen extraction efficiency was not affected by treatment, but increased in all groups to maintain hepatic oxygenation at base-line values. Although a calcium-antagonistic activity of gentamicin has been reported to synergize with endotoxin, thereby adversely affecting cardiovascular function, such effects did not complicate the metabolic response to steroid in the present studies.


[Water and intestinal parasitic diseases].
The paper presents data on the rates of Lamblia cyst dissemination of surface water sources in foreign countries, the Russian Federation, Moscow, and the Moscow Region. It shows a role of drinking water in the spread of intestinal parasitic diseases. In accordance with parasitological parameters, specific data on improvement of methodological control of water quality are presented. The dosages of ultraviolet radiation are given in relation to water decontamination of parasitic disease germs.


Crush head injuries in infants and young children neurologic and neuropsychologic sequelae.
Neurologic and neuropsychologic sequelae of crush head injury, which is produced by static forces occurring when the head is stationary and pinned against a rigid structure, were studied prospectively in a series of eight children ranging in age from 13 to 32 months. Hospital course, computed tomographic findings, and neurologic and developmental outcomes were examined. All children sustained pronounced cerebral trauma characterized by multiple fractures throughout the calvaria, extra-axial hemorrhages, and parenchymal contusions. Cranial nerve injuries were noted in three and hemiparesis in two of the cases. Two months after the injury, 63% of the children displayed deficits in either IQ or motor functioning. One year after the injury, five of the six children reevaluated had a good recovery. Motor scores were significantly lower than cognitive scores at baseline and showed the greatest degree of improvement over time. Neuropsychologic outcome after brain injury produced by static loading of the head is more favorable than from traumatic brain injury associated with dynamic loading.


Morphine use in cancer care: A survey of attitudes and perceptions in general practice patients.
Morphine is widely prescribed for patients with cancer, although a number of attitudes have been cited as barriers to its use, including fear, addiction and associations with death. The aim of this study was to explore the nature of these beliefs, and assess the extent to which these attitudes exist in a general practice patient population that may require morphine in the future. A 30-item survey was distributed through general practices in Victoria, Australia. Of the 379 questionnaires distributed, 290 were collected (76.5%). Participants were predominantly neutral on questions regarding the effect of morphine on the duration of life. Morphine was seen to be prescribed responsibly (73.5%), even while most perceived its potential for addiction (69.7%). Participants with experience of morphine use had more negative perceptions regarding its efficacy. Conversations regarding morphine use should include a discussion about the beliefs and experiences of the individual, many of which may reinforce the utility of morphine.


A method for efficient execution of bioinformatics workflows.
Efficient execution of data-intensive workflows has been playing an important role in bioinformatics as the amount of data has been rapidly increasing. The execution of such workflows must take into account the volume and pattern of communication. When orchestrating data-centric workflows, a centralized workflow engine can become a bottleneck to performance. To cope with the bottleneck, a hybrid approach with choreography for data management of workflows is proposed. However, when a workflow includes many repetitive operations, the approach might not gain good performance because of the overheads of its additional mechanism. This paper presents and evaluates an improvement of the hybrid approach for managing a large amount of data. The performance of the proposed method is demonstrated by measuring execution times of example workflows.


Spatiotemporal filtering of high harmonics in solids.
We study the macroscopic spatial and temporal properties of harmonic radiation generated by a model solid in the interaction with an intense, focused laser beam. We show that different temporal contributions to the harmonic yield can be separated in the spatial domain because they lead to radiation with different divergences, similar to what is observed in gas-phase harmonic generation. We show that applying a spatial filter in the far field results in a temporal separation of the two contributions upon refocusing, which yields spatially collimated harmonics, a spectrum with well-resolved peaks, and a subcycle time profile of the harmonic radiation with only one burst per half-cycle.


Why Do Children Who Solve False Belief Tasks Begin to Find True Belief Control Tasks Difficult? A Test of Pragmatic Performance Factors in Theory of Mind Tasks.
The litmus test for the development of a metarepresentational Theory of Mind is the false belief (FB) task in which children have to represent how another agent misrepresents the world. Children typically start mastering this task around age four. Recently, however, a puzzling finding has emerged: Once children master the FB task, they begin to fail true belief (TB) control tasks. Pragmatic accounts assume that the TB task is pragmatically confusing because it poses a trivial academic test question about a rational agent's perspective; and we do not normally engage in such discourse about subjective mental perspectives unless there is at least the possibility of error or deviance. The lack of such an obvious possibility in the TB task implicates that there might be some hidden perspective difference and thus makes the task confusing. In the present study, we test the pragmatic account by administering to 3- to 6-year-olds (N = 88) TB and FB tasks and structurally analogous true and false sign (TS/FS) tasks. The belief and sign tasks are matched in terms of representational and metarepresentational complexity; the crucial difference is that TS tasks do not implicate an alternative non-mental perspective and should thus be less pragmatically confusing than TB tasks. The results show parallel and correlated development in FB and FS tasks, replicate the puzzling performance pattern in TB tasks, but show no trace of this in TS tasks. Taken together, these results speak in favor of the pragmatic performance account.


Revisiting the GroEL-GroES reaction cycle via the symmetric intermediate implied by novel aspects of the GroEL(D398A) mutant.
The Escherichia coli chaperonin GroEL is a double-ring chaperone that assists in protein folding with the aid of GroES and ATP. It is believed that GroEL alternates the folding-active rings and that the substrate protein (and GroES) can bind to the open trans-ring only after ATP in the cis-ring is hydrolyzed. However, we found that a substrate protein prebound to the trans-ring remained bound during the first ATP cycle, and this substrate was assisted by GroEL-GroES when the second cycle began. Moreover, a slow ATP-hydrolyzing GroEL mutant (D398A) in the ATP-bound form bound a substrate protein and GroES to the trans-ring. The apparent discrepancy with the results from an earlier study (Rye, H. S., Roseman, A. M., Chen, S., Furtak, K., Fenton, W. A., Saibil, H. R., and Horwich, A. L. (1999) Cell 97, 325-338) can be explained by the previously unnoticed fact that the ATP-bound form of the D398A mutant exists as a symmetric 1:2 GroEL-GroES complex (the "football"-shaped complex) and that the substrate protein (and GroES) in the medium is incorporated into the complex only after the slow turnover. In light of these results, the current model of the GroEL-GroES reaction cycle via the asymmetric 1:1 GroEL-GroES complex deserves reexamination.


Transcranial direct-current stimulation combined with attention increases cortical excitability and improves motor learning in healthy volunteers.
Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that has the potential to induce motor cortical plasticity in humans. It is well known that motor cortical plasticity plays an essential role in motor learning and recovery in patients with stroke and neurodegenerative disorders. However, it remains unclear how cognitive function influences motor cortical plasticity induced by tDCS. The present study aimed to investigate whether anodal tDCS combined with attention to a target muscle could enhance motor cortical plasticity and improve motor learning in healthy individuals. Thirty-three healthy volunteers were assigned to two experiments. In experiment 1, there were three interventional conditions: 1) anodal tDCS was applied while participants paid attention to the first dorsal interosseous (FDI) muscle, 2) anodal tDCS was applied while participants paid attention to the sound, and 3) anodal tDCS was applied without the participants paying attention to the FDI muscle or the sound. Anodal tDCS (2 mA, 10 min) was applied over the primary motor cortex (M1). Changes in motor evoked potentials (MEPs), short-interval intracortical inhibition (SICI), and intracortical facilitation (ICF) were assessed before and immediately after (0 min), and then 10 min, 30 min, and 60 min after each intervention. In experiment 2, we investigated whether the combination of anodal tDCS and attention to the abductor pollicis brevis (APB) muscle could facilitate the learning of a ballistic thumb movement. Anodal tDCS increased cortical excitability in all conditions immediately after the stimulation. Significant increases in MEPs and significant decreases in SICI were observed for at least 60 min after anodal tDCS, but only when participants paid attention to the FDI muscle. In contrast, no significant changes in ICF were observed in any condition. In experiment 2, the combination of tDCS and attention to the APB muscle significantly enhanced the acquisition of a ballistic thumb movement. The higher performance was still observed 7 days after the stimulation. This study shows that anodal tDCS over M1 in conjunction with attention to the target muscle enhances motor cortex plasticity and improves motor learning in healthy adults. These findings suggest that a combination of attention and tDCS may be an effective strategy to promote rehabilitation training in patients with stroke and neurodegenerative disorders. Retrospectively registered (UMIN000036848).


Biofeedback improves activities of the lower limb after stroke: a systematic review.
Is biofeedback during the practice of lower limb activities after stroke effective in improving performance of those activities, and are any benefits maintained after intervention ceases? Systematic review with meta-analysis of randomised trials. People who have had a stroke. Biofeedback during practice of sitting, standing up, standing, or walking. Continuous measures of activity congruent with the activity trained. 22 trials met the inclusion criteria and 19 contained data suitable for analysis. Effect sizes were calculated as standardised mean differences because different outcome measures were used. Since inclusion of all trials produced substantial statistical heterogeneity, only trials with a PEDro score >4 (11 trials) were included in the final analysis (mean PEDro score 5.7). In the short-term, biofeedback improved lower limb activities compared with usual therapy/placebo (SMD=0.49, 95% CI 0.22 to 0.75). Lower limb activities were still improved compared with usual therapy/placebo 1 to 5 months after the cessation of intervention (SMD=0.41, 95% CI 0.06 to 0.75). Augmenting feedback through the use of biofeedback is superior to usual therapy/placebo at improving lower limb activities in people following stroke. Furthermore, these benefits are largely maintained in the longer term. Given that many biofeedback machines are relatively inexpensive, biofeedback could be utilised more widely in clinical practice.


Perception of a single-session pre-in vitro fertilisation counselling service and attitudes towards support group: a survey of patients in Singapore.
This study aimed to investigate patients' evaluation of a compulsory pre-in vitro fertilisation (IVF) counselling session in Singapore and determine their attitudes towards attending a support group during IVF treatment. 464 patients due to undergo their first IVF treatment were recruited at the Clinic for Human Reproduction, National University Hospital, Singapore. Prior to IVF treatment, all patients attended a counselling session conducted by a clinical psychologist trained in infertility counselling. The Depression Anxiety Stress Scales 21 was used to measure patients' psychological symptoms of depression, anxiety and stress. A feedback form was administered after the session to determine their evaluation of the session and interest in attending a support group. After the pre-IVF counselling session, 90.9% of patients reported that the session was useful, with over 80% of participants reporting that the session had helped them to better prepare for the IVF treatment, enhanced their coping and enabled them to better communicate their needs to their spouse. Overall, 64.1% of patients expressed interest in attending a support group, with male patients showing more interest. Financial resources and the level of psychological symptoms experienced were found to influence patients' motivation to attend a support group. The single pre-IVF counselling session was well received and found to be useful by patients. Hence, it is recommended that IVF counselling be made an essential part of the holistic care given to patients undergoing IVF, particularly those who experience higher levels of distressing psychological symptoms.


Glycosylation of n-pentenyl glycosides using bromodiethylsulfonium salt as an activator: interception of the glycosyl intermediate by chloride ion transfer.
Utilization of n-pentenyl glycosides (NPGs) in modern carbohydrate synthesis may be hindered by their sluggish activation, which results from reversible halogenation and cyclization processes. Bromodiethylsulfonium bromopentachloroantimonate (BDSB) has been previously shown to be a powerful brominating agent for the cation-π polyene cyclization of less reactive and electron-poor polyenes. This study demonstrates the activation of NPGs using BDSB as a powerful brominating agent. BDSB effectively activates the terminal olefins of NPGs and the reaction proceeds through 5-exo-tet cyclization, offering a rapid and mild approach for glycosylation with a wide range of glycosyl donors, including n-pentenyl mannoside, n-pentenyl galactoside, and n-pentenyl glucoside. The success of this approach derives from the chloride ion transfer from the nonnucleophilic SbCl5Br anion to the glycosyl intermediate, which disrupts the equilibrium and produces a glycosyl chloride intermediate that is smoothly converted to 22 coupling products, with yields ranging from moderate to excellent (49-100%). The β-selective glycosylation is accomplished when employing NPGs equipped with a neighboring participating group. The practicality of the BDSB-activated glycosylation is demonstrated by a gram-scale synthesis. This study showcases BDSB as a potent activator for NPG glycosylation through the interception of a glycosyl intermediate that diminishes the equilibration during halogenation and 5-exo-tet cyclization.


Associations Between ADHD Medication Use in Pregnancy and Severe Malformations Based on Prenatal and Postnatal Diagnoses: A Danish Registry-Based Study.
Attention-deficit/hyperactivity disorder (ADHD) medications are increasingly used in pregnancy. Studies on the pregnancy safety of these medications that are restricted to live births may underestimate severe teratogenic effects that cause fetal demise or termination of pregnancy. The present study addresses this limitation by including data from both prenatal and postnatal diagnoses of major malformations. A nationwide registry-based study was conducted of 364,012 singleton pregnancies in Denmark from November 1, 2007, to February 1, 2014. Exposures to ADHD medication were obtained from redeemed prescriptions from the Danish Health Services Prescription Database. Outcome data included prenatally diagnosed malformations from the Danish Fetal Medicine Database and postnatally diagnosed malformations from the Danish National Patient Registry. The primary outcome was major malformations overall, and secondary outcomes were malformations of the central nervous system and cardiac malformations. The comparison group was pregnancies with no redeemed prescriptions for ADHD medication. We defined severe cardiac malformations (SCM) as concurrent diagnoses of a cardiac malformation with miscarriage, termination, stillbirth, postnatal death, or cardiac surgery within 1 year of birth. The prevalence of first-trimester exposure to ADHD medication increased during the study period from 0.05% in 2008 to 0.27% in 2013, with the majority (473/569) of the exposures being to methylphenidate. There were 5.1% malformations overall and 2.1% cardiac malformations among the exposed compared to 4.6% and 1.0%, respectively, among the unexposed. For methylphenidate, the adjusted prevalence ratios (PRs) were 1.04 (95% confidence interval [CI], 0.70-1.55) for malformations overall and 1.65 (95% CI, 0.89-3.05) for any cardiac malformations (number needed to harm [NNH] = 92), with septum defects in 10 out of 12 cases. The PR for ventricular septal defect was 2.74 (95% CI, 1.03-7.28) and for SCM, 2.59 (95% CI, 0.98-6.90). Exposure to methylphenidate was not associated with an increased risk of malformations overall in data that included information from both prenatal and postnatal diagnoses of major malformations. There was an increased risk of cardiac malformations with NNH of 92 based on 12 cases among the exposed. More data are needed on other types of ADHD medication.


Rhizobium japonicum mutants that are hypersensitive to repression of H2 uptake by oxygen.
The synthesis of an H2 oxidation system in free-living Rhizobium japonicum wild-type strain SR is repressed by oxygen. Maximal H2 uptake rates were obtained in strain SR after derepression in 11 microM or less dissolved oxygen. Oxygen levels above 45 microM completely repressed H2 uptake in strain SR. Five R. japonicum mutant strains that are hypersensitive to repression or H2 oxidation by oxygen were derived from strain SR. The mutants were obtained by screening H2 uptake-negative mutants that retained the ability to oxidize H2 as bacteroids from soybean nodules. As bacteroids, the five mutant strains were capable of H2 oxidation rates comparable to that of the wild type. The mutants did not take up H2 when derepressed in 22 microM dissolved oxygen, whereas strain SR had substantial activity at this oxygen concentration. The O2 repression of H2 uptake in both the wild-type and two mutant strains, SR174 and SR200, was rapid and was similar to the effect of inhibiting synthesis of H2 uptake system components with rifampin. None of the mutant strains was able to oxidize H2 when the artificial electron acceptors methylene blue or phenazine methosulfate were provided. The mutant strains were not sensitive to killing by oxygen, they took up O2 at rates similar to strain SR, and they did not produce an H2 uptake system that was oxygen labile. Cyclic AMP levels were comparable in strain SR and the five mutant strains after subjection of the cultures to the derepression conditions.


[Effective of surgical decortication on cardio-cardiac reflexes in cats].
The cardio-cardiac reflexes were studied in unanesthetized curarized cats before and after surgical decortication. The data obtained showed three varieties of the cortical adaptation: the inhibition of the reflexes, their facilitation, and the effects of regulatory "silence". Under normal condition the cortical function seems to exert modulating influences on the cardio-cardiac reflexes by way of the afferent vagal nucleus.


The effect of radiation and cytotoxic platinum compounds on the growth of normal and tumour bladder explant cultures.
Using an explant tissue culture model developed by this group for use with human surgical and biopsy specimens, data are presented showing the response of normal and tumor bladder urothelium to radiation in combination with cis- and carboplatin. Cellular response is measured after two weeks in culture as a reduction in the extent of outgrowth from the explant. The outgrowth has been shown to be growing and to be epithelial. Results showed that when either drug or radiation is used singly, the tumour is resistant to treatment while the normal cells are severely affected. However, appropriate combinations of either drug with radiation reverse the unfavourable therapeutic ratio and result in higher tumour cell kill. The model may be useful for investigating mechanisms of radiation/chemotherapy action at the cellular level and, if integrated into appropriate clinical trials, may serve as an easy-to-use in vitro test for optimising single agent or combination therapy regimens.


[Effects of ginkgo biloba extraction on contraction capacity of diaphragm from type 2 diabetic rats].
To investigate the effects of Ginkgo biloba extract (GbE) on the activities of energy metabolism enzymes and contraction capacity of diaphragm from type 2 diabetic rats. Forty SD male rats were randomly divided into normal control group (n=10) and model group (n=30). Type 2 diabetes models were induced by feeding with high-sucrose-high-fat diet and intraperitoneal injecting 25 mg/kg streptozotocin. 20 successful models were rearranged to two groups: diabetic group and GbE treatment group, 10 rats in each. Then the saline and 8 mg/(kg x d) of GbE were respectively intraperitoneal injected, once a day continuously for 8 weeks. Then diaphragm contractility was assessed using Peak twitch tension (Pt), Maximum tetanic tension (P0) and fatigue index (FI) in vitro diaphragm strip preparations. Cytochrome oxidase (CCO), lactate dehydrogenase (LDH) and succinate dehydrogenase (SDH) in diaphragm were detected and the varieties of diaphragm ultrastructure were observed. Compared with control group, Pt, P0 and FI in diabetic group decreased significantly (P < 0.01); the activity of CCO, LDH and SDH in the tissues was more obviously reduced than those in control group (P < 0.01). The ultrastructure in diabetic group under electron microscope indicated that diaphragm mitochondrions swelled and degenerated. The above changes were inhibited by GbE. GbE can enhance contraction capacity of diaphragm from type 2 diabetic rats by increasing the aerobic oxidation capacity, glycolytic capacity and the function of respiratory chain.


Educational attainment, deprivation-affluence and self reported health in Britain: a cross sectional study.
The level of material deprivation or affluence is strongly and independently correlated with all cause mortality at an area level, but educational attainment, after controlling for deprivation-affluence, remains strongly associated with coronary and infant mortality. This study investigated whether these relations hold at an individual level with self reported morbidity. Analysis of the cross sectional associations of self reported longstanding illness and "not good" or "fairly good" self assessed health with individual educational attainment in seven levels, adjusting for deprivation measures (economic status of head of household, car ownership, housing tenure, overcrowding). The 1993 General Household Survey, a random sample of households in Great Britain. 11,634 subjects aged 22 to 69. After adjusting for household deprivation, lower educational attainment was significantly associated with longstanding illness in men (odds ratio 1.05 per education category, 95% CI 1.02 to 1.08), but not in women (odds ratio 1.01, 95% CI 0.98 to 1.04). The associations with "not good" or "fairly good" self assessed health were stronger and significant in both men and women (men 1.13, 95% CI 1.10 to 1.17; women 1.10, 95% CI 1.07 to 1.14). The findings were little changed by allowing for people in poor health becoming economically inactive. The associations of self reported health with deprivation-affluence are stronger than with educational attainment. However, educational attainment is associated with self assessed health in adulthood, independently of deprivation-affluence. Longstanding illness may be associated with educational attainment in men only. Educational attainment may be a marker for childhood socioeconomic circumstances, its association with health may result from occupational characteristics, or education may influence the propensity to follow health education advice.


Plasma iron, C-reactive protein, albumin, and plasma fibrinogen concentrations in dogs with systemic inflammatory response syndrome.
To investigate the diagnostic and prognostic value over time of plasma iron compared with the inflammatory markers albumin, C-reactive protein (CRP), and fibrinogen in dogs with systemic inflammatory response syndrome (SIRS). Prospective observational study of sequentially enrolled dogs. ICU of a veterinary teaching hospital. One hundred and sixteen client-owned dogs: 54 dogs with SIRS or sepsis, 42 with focal inflammation, and 20 clinically healthy dogs. Blood samples were obtained on admission in all study groups, and then on alternate days until discharge or death in both inflammation groups. On admission, dogs with SIRS had significantly lower plasma iron (65 ± 5.8 μg/dL, P = 0.001) concentrations than dogs with focal inflammation (89.5 ± 6.2 μg/dL, P = 0.001). Plasma iron, albumin, and CRP effectively discriminated the SIRS/sepsis group from those presenting with focal inflammation with areas under the curve for the receiver operating curves of 0.679, 0.834, and 0.704, respectively. The admission values for these variables did not discriminate survivors from nonsurvivors within the SIRS/sepsis group. However, the magnitude of increase in iron concentration and the decrease in CRP concentration from admission to hospital discharge was higher in survivors than in nonsurvivors within the SIRS/septic group (22.8 vs. 2.51 μg/dL, respectively, P = 0.021 for iron; -67.1 vs. -4.1 mg/L, respectively, P = 0.002 for CRP), resulting in iron and CRP concentrations at hospital discharge for survivors similar to those in the focal inflammation group. Hypoferremia is a sensitive marker of systemic inflammation in dogs. In this study, the increase in iron concentrations during the hospitalization period of SIRS/septic dogs was associated with a better prognosis, suggesting that plasma iron in combination with CRP and albumin concentrations might be used to monitor dogs with inflammatory disease processes.


Genetics and visual attention: selective deficits in healthy adult carriers of the epsilon 4 allele of the apolipoprotein E gene.
The epsilon4 allele of the apolipoprotein E (APOE) gene is associated with altered brain physiology in healthy adults before old age, but concomitant deficits in cognition on standardized tests of cognitive function have not been consistently demonstrated. We hypothesized that sensitive and specific assessment of basic attentional functions that underlie complex cognition would reveal evidence of impairment in otherwise asymptomatic individuals. We found that as early as middle age, nondemented carriers of the varepsilon4 allele of the APOE gene showed deficits when visual attention was spatially directed by cues in tasks of visual discrimination and visual search, in comparison to those without the epsilon4 allele (epsilon2 and epsilon3 carriers). Two component attentional operations were selectively affected: (i) shifting spatial attention following invalid location cues, and (ii) adjusting the spatial scale of attention during visual search. These changes occurred only in the presence of the epsilon4 allele and without decline in other aspects of attention (vigilance), memory, or general cognition. The results show that specific components of visual attention are affected by APOE genotype and that the course of cognitive aging is subject to selective alteration by a genetic trait.


Bullous dermatosis and myeloma. Monoclonal anticytoplasmic antibody activity.
A case of a recurrent bullous eruption in a patient who had myeloma is reported. This eruption was differentiated from pemphigus and bullous pemphigoid by the histological and immunological findings. In addition, antibodies against the cytoplasm of basal cell layer cells in the human epidermis were detected in the patient's serum and in diseased skin. The myelomatous monoclonal protein and the antibody fixed on the cell cytoplasm had an identifical isotypical marker.


Massive bleaching of coral reefs induced by the 2010 ENSO, Puerto Cabello, Venezuela.
El Niño Southern Oscillation (ENSO) has generated global coral massive bleaching. The aim of this work was to evaluate the massive bleaching of coral reefs in Puerto Cabello, Venezuela derived from ENSO 2010. We evaluated the bleaching of reefs at five localities both at three and five meter depth. The coral cover and densities of colonies were estimated. We recorded living coral cover, number and diameter of bleached and non-bleached colonies of each coral species. The colonies were classified according to the proportion of bleached area. Satellite images (Modis Scar) were analyzed for chlorophyll-a concentration and temperature in August, September, October and November from 2008-2010. Precipitation, wind speed and air temperature information was evaluated in meteorological data for 2009 and 2010. A total of 58.3% of colonies, belonging to 11 hexacoral species, were affected and the greatest responses were observed in Colpophyllia natans, Montastraea annularis and Montastraeafaveolata. The most affected localities were closer to the mainland and had a bleached proportion up to 62.73+/-36.55%, with the highest proportion of affected colonies, whereas the farthest locality showed 20.25+/-14.00% bleached and the smallest proportion. The salinity in situ varied between 30 and 33ppm and high levels of turbidity were observed. According to the satellite images, in 2010 the surface water temperature reached 31 degree C in August, September and October, and resulted higher than those registered in 2008 and 2009. Regionally, chlorophyll values were higher in 2010 than in 2008 and 2009. The meteorological data indicated that precipitation in November 2010 was three times higher than in November 2009. Massive coral bleaching occurred due to a three month period of high temperatures followed by one month of intense ENSO-associated precipitation. However, this latter factor was likely the trigger because of the bleaching gradient observed.


Marine litter on the seafloor of the Faial-Pico Passage, Azores Archipelago.
Plastic pollution in the marine environment attracts much attention from both researchers and the general public. Plastic items and other debris are commonly observed everywhere in the ocean, from the surface down to the deep ocean floor. In this study, we analysed 45.2km of video footage, collected during 56 transects surveying the seafloor of the Faial-Pico Passage in order to quantify the abundance of marine litter and its interactions with benthic fauna. The footage was collected by a Remotely Operated Vehicle (ROV) and a manned submersible at depths ranging between 40 and 525m. The mean litter density in the passage was 0.26±0.03 items·100m-1 (±SE) and was significantly higher between 151 and 250m compared to other depth strata. Overall, derelict fishing gear, mostly made of plastic, were the most common objects found on the seafloor, representing 64% of all items. Although we observed few evidence of direct deleterious effects by the litter, interactions with fauna were observed in more than half of the items. This study makes an important contribution in quantifying the abundance of marine litter on the seafloor of the Azores. The location of the Faial-Pico Passage, close to shore, makes it an appropriate site for long-term monitoring of litter on the seafloor and evaluate the efficiency of upcoming public policies aimed at reducing litter input into the oceans.


Metabolic analysis of the increased adventitious rooting mutant of Artemisia annua reveals a role for the plant monoterpene borneol in adventitious root formation.
Adventitious root (AR) formation is a critical process for plant clonal propagation. The role of plant secondary metabolites in AR formation is still poorly understood. Chemical and physical mutagenesis in combination with somatic variation were performed on Artemisia annua in order to obtain a mutant with changes in adventitious rooting and composition of plant secondary metabolites. Metabolic and morphological analyses of the iar (increased adventitious rooting) mutant coupled with in vitro assays were used to elucidate the relationship between plant secondary metabolites and AR formation. The only detected differences between the iar mutant and wild-type were rooting capacity and borneol/camphor content. Consistent with this, treatment with borneol in vitro promoted adventitious rooting in wild-type. The enhanced rooting did not continue upon removal of borneol. The iar mutant displayed no significant differences in AR formation upon treatment with camphor. Together, our results suggest that borneol promotes adventitious rooting whereas camphor has no effect on AR formation.


Image library of biological macromolecules.
An Image Library of Biological Macromolecules is described, which contains image and text files related to structures of biological macromolecules. Currently, the Library has approximately 3000 image files of approximately 300 structures of biological macromolecules whose coordinates are available in the Protein Data Bank and in the Nucleic Acid Database. The entries include all RNA structures, approximately 70 DNA structures, 150 proteins and a few carbohydrates. The Library contains further images of amino acids, of standard and modified nucleotides and of nucleic acid model structures. Each entry consists of an annotation file with bibliographic and sequence information and possibly comments, of a color-coded distance plot and of structure images. Almost all of the images are available both in a mono and in a stereo representation. Standard procedures for generating these images were strictly avoided. Therefore, mixed rendering, coloring and labeling techniques were used extensively. Since May 1995 the Library has a growing division of images in the new Virtual Reality Modeling Language (VRML) format. The Image Library of Biological Macromolecules can be accessed via the World-Wide Web (http://www.imb-jena.de/IMAGE.html). There is a large number of structures determined by experimental and/or modeling techniques which are not intended to be included into the Protein Data Bank or Nucleic Acid Database for some reason. The Image Library could be a repository of these structures and of images of these and other structures of biological macromolecules including structures which are not known at atomic detail. Authors who are willing to make available images or coordinates to the scientific community via the Image Library of Biological Macromolecules are requested to contact the author.


Multimorbidity in a large district hospital: A descriptive cross-sectional study.
There is substantial research documenting the burden of disease globally and in the South African (SA) primary care context. Few studies address the disease profile and its implications in the SA hospital setting. To describe the disease profile in the internal medicine department of a large district hospital, using variables related to comorbidity and patient length of stay. The study included specific exploration into the HIV/tuberculosis (TB) syndemic, the acuity of HIV disease, and lifestyle risk factors. The sample population consisted of all consecutive admissions to the internal medicine department of a large district hospital in the Cape metropole during May 2015. A retrospective folder review and subsequent data analysis were completed. Hypertension, HIV, type 2 diabetes mellitus, TB and cardiac failure were the five most prevalent diseases. Extensive multimorbidity was observed, with 86.0% of patients suffering from two or more diseases concurrently. The average number of comorbidities per patient was 3.4, although no clear relationship between the number of comorbidities and length of stay was found. Of the various diseases, only TB and HIV were associated with above-average length of stay, particularly among co-infected patients and those who had defaulted from or never received antiretroviral (ARV) treatment. Compared with patients currently receiving ARVs, much higher proportions of patients who had defaulted from or never received ARV treatment had CD4+ counts <200 cells/µL. Of the lifestyle risk factors investigated, a history of excessive alcohol use and/or drug use was associated with an increased length of stay. Most patients were discharged home, with 15.7% being referred to other institutions. Chronic conditions, particularly HIV, TB and non-communicable diseases, represented much of the disease profile in the internal medicine department. Of the comorbidities investigated, the greatest contributor to length of stay was HIV/TB co-infection. Factors such as HIV, TB and substance use that increase length of stay cannot be impacted upon by the district hospital staff in isolation. To improve the health of communities, we require partnerships between doctors, community health providers and patients with their families. Multimorbidity was widespread, suggesting the need to include an understanding of multimorbidity, including the patient perspective, in medical education and health system reform.


[Minimally invasive technique treatment of postoperative recurrent bone cysts in juvenile patients].
To study the effect of minimally invasive treatment of postoperative recurrent bone cysts in juvenile patients. From December 1984 to December 2003, 36 cases of postoperative recurrent bone cysts after focal curettage and bone graft included 19 males and 17 females, aging 9-21 years with an average of 15 years. The size of bone cyst ranged from 2.5 cm x 6.0 cm to 3.5 cm x 13.0 cm with an average of 3.0 cm x 8.0 cm. The locations were proximal humerus in 18 cases, humeral shaft in 10 and femoral trochanteric region in 8. The focal curette and bone graft were given once in 23 cases, twice in 10 cases and 3 times in 3 cases. The interval between recurrence and minimally invasive treatment was 5-13 months (6.5 months on average). The posteroanterior and lateral X-ray films were taken to determine the location, range and feature of the focus. Under local anesthesia, 2 canulated needles were used; one was used to aspirate the contents of the cyst, the other was used to inject hydrocortisone acetate. The dose was determined according to the range of the focus. The treatment was repeated every 3. 5-4 months until the focus healed. All patients were followed up from 3 to 18 years with an average of 5 years. The minimally invasive treatment was repeated 3-11 times with an average of 6 times. Twenty-six cases healed completely, 6 cases healed significantly, and 4 cases healed partially. No local or general complications occurred during the treatment. This minimally invasive method for the treatment of postoperative recurrent bone cyst in juvenile patients has following advantages : less pain, easy manipulation, no hospitalization, low cost and definite effect.