Left-sided embryonic expression of the BCL-6 corepressor, BCOR, is required for vertebrate laterality determination.
Oculofaciocardiodental (OFCD) syndrome is an X-linked male lethal condition encompassing cardiac septal defects, as well as ocular and dental anomalies. The gene mutated in OFCD syndrome, the BCL-6 corepressor (BCOR), is part of a transcriptional repression complex whose transcriptional targets remain largely unknown. We reviewed cases of OFCD syndrome and identified patients exhibiting defective lateralization including dextrocardia, asplenia and intestinal malrotation, suggesting that BCOR is required in normal laterality determination. To study the function of BCOR, we used morpholino oligonucleotides (MOs) to knockdown expression of xtBcor in Xenopus tropicalis, thus creating an animal model for OFCD syndrome. The resulting tadpoles had cardiac and ocular features characteristic of OFCD syndrome. Reversed cardiac orientation and disorganized gut patterning were seen when MOs were injected into the left side of embryos, demonstrating a left-sided requirement for xtBcor in lateral determination in Xenopus. Ocular defects displayed no left-right bias and included anterior and posterior segment disorders such as microphthalmia and coloboma. Expression of xtPitx2c was shown to be downregulated when xtBcor was depleted. This identifies a pathway in which xtBcor is required for lateral specification, a process intrinsically linked to correct cardiac septal development.


[Influence of the difference in start-up echo on signal intensity in the FIESTA sequence].
The FIESTA sequence is a fast imaging method used for various parts in recent years. A constant flip angle (CFA) or linear flip angle (LFA) are used as the start-up echo in many cases. It is reported from CFA, which is the conventional method, that the T1 value and T2 value influence the speed that reaches steady state. However, there is no such report in LFA. Therefore, we examined the influence of the difference of start-up echo method upon signal intensity. In phantoms other than vegetable oil, the difference was not accepted in the change of speed that reaches steady state and the signal intensity in steady-state transit. In LFA, signal intensity of vegetable oil was clearly lower than CFA. The same result was obtained regardless of on or off resonance. From the result, it was thought that it depended on T2/T1 for the speed that reaches steady state. Moreover, the difference in resonant frequency was considered to greatly influence LFA but not CFA. That is, it was suggested by the difference in start-up echo that the signal intensity of fat changes greatly.


PROTECTIVE ACTION IN IRRADIATION OF AMYLASE SOLUTIONS WITH ULTRAVIOLET LIGHT.
Evidence has been presented which indicates that the protective action of dogs' sera in irradiation of pancreatin solutions with ultraviolet light is the result of a competitive absorption (screening action). A similar effect is found in simple pancreatin solutions for which we may account (at least to a first approximation) on the basis of assumed homogeneous absorption by a strong competitor in the solution for the radiations having inactivating power. These observations are of interest in connection with the theory of what has been called negative catalysis, especially in view of the marked effects of small quantities of the protecting substances.


How do Trends for Behavioral Health Inpatient Care Differ from Medical Inpatient Care in U.S. Community Hospitals?
BACKGROUND: Inpatient care in the United States accounts for one third of the health care expenditures. There exists a well-established trend towards fewer inpatient admissions and shorter lengths of stay for all inpatient care, which can be attributed to cost containment efforts through managed care and advances in treatment technologies. However, different illnesses may not necessarily share the same pattern of change in inpatient care utilization. In particular, mental health and substance abuse (MHSA) care has experienced a particularly dramatic growth of specialized managed behavioral organizations, which could have led to an even faster decline. AIMS OF THE STUDY: This study contrasts the trends of MHSA inpatient care in U.S. community hospitals with medical inpatient care over the years 1988 to 1997. It also analyzes the trends for subgroups of MHSA stays by diagnostic groups, age and primary payer. METHODS: We use the National Inpatient Sample (NIS) from the Health Care Cost and Utilization Project (HCUP) to estimate both number of inpatient discharges per 1,000 population and average length of stay over the years and relate the two indices. Inpatient MHSA stays are categorized into subgroups by age, primary payer of the care, and diagnostic group. We use the Clinical Classification Software (CCS) to distinguish between affective disorders, schizophrenia and related disorders, other psychoses, anxiety and related disorders, pre-adult disorders, and alcohol-, substance- related mental disorders and other mental disorders. Trends of population adjusted discharges and length of stay were tested using a weighted least squares method. RESULTS: Population-adjusted MHSA discharges from community hospitals increased by 8.1% over the study period, whereas discharges for all conditions decreased. Within MHSA discharges, the 20-39 and 40-64 age groups experienced significant increase relative to other age group; the increase was particularly high for affective and psychotic disorders, which are only partially offset by a decrease for other diagnostic groups. Hospitalization for both MHSA and medical conditions displayed trends towards shorter lengths of stay, but with the decline for MHSA stays steeper (40%) than for all stays (21%). The reduction in length of stay not only applied to the privately insured, for which managed behavioral health care had the highest penetration rate, but held for all other payers as well, although the rate of decline is higher for private insurance than for other insurance. Inpatient stays with pre-adult disorders displayed the greatest percentage decline for both population-adjusted discharges and average length of stay. IMPLICATIONS FOR HEALTH CARE PROVISION AND USE: Different pattern of utilization emerged for MHSA inpatient care as compared to hospitalization for all medical care over the years 1988-97. The more rapid decline in length of stay for MHSA stays than for all stays may have been a result of greater incentive for cost containment and therefore more intensive care management, and advances in treatment technology, especially medication. However, the fast decline in length of stay may also have led to repeat hospitalization as a result of premature discharges for patients with affective or psychotic disorders. Some financial incentives, such as case-rates or DRG-type payments to hospitals could have contributed to such adverse effects. Increases in discharges for severe disorders could also be a consequence of shifts from long-term facilities (for which no comparable data are available) to community hospitals, although the largest absolute and relative increases were for affective disorders rather than schizophrenia or other psychoses, the two disease subgroups that make up the majority of the institutionalized patients. International comparisons, assisted by new data, may help disentangle the effect of institutional change and that of development in treatment technology or practice pattern.


[Diffuse and compact chromatin in the cell nuclei from tissues derived from different germ layers].
Chromatin structure of nuclei of histogenetically distinct cells of humans and animals under normal and pathological courses of gestation was studied by the method of optic-structural computer analysis. A constant ratio of compact and diffuse chromatin is detected in nuclei of cells originating from all the germ layers. This ratio can change to a variable degree in cases of pathological gestation.


Microtiter plate adherence assay and receptor analogs for Mycoplasma hyopneumoniae.
A microtiter plate adherence assay for Mycoplasma hyopneumoniae was established by use of purified swine tracheal cilia which contained receptors for the mycoplasmas. M. hyopneumoniae bound specifically to plates coated with solubilized cilia. The binding was dependent on both the concentration of cilia and the number of mycoplasmas. Dextran sulfate, heparin, chondroitin sulfate, laminin, mucin, and fucoidan significantly inhibited the binding of the mycoplasmas. The six inhibitors also disrupted the adherence of the mycoplasmas to intact ciliated cells. Preincubation with either mycoplasmas or cilia indicated that heparin, mucin, fucoidan, and chondroitin sulfate interacted with the adhesive molecules on the surface of the mycoplasmas, while laminin blocked the receptors in cilia. The basis for the inhibition induced by dextran sulfate was unknown. Treatment of cilia with neuraminidase appeared to promote adherence of the mycoplasmas, whereas treatment of cilia with sodium metaperiodate decreased binding. These results indicate that receptors for M. hyopneumoniae in the ciliated epithelium of the respiratory tract of pigs are glycoconjugate in nature.


Primary sclerosing epithelioid fibrosarcoma of the sacrum: a case report and review of the literature.
Sclerosing epithelioid fibrosarcoma is a rare tumour characterised histologically by a predominant population of epithelioid cells arranged in strands and nests, embedded in a fibrotic and hyalinised stroma. It is a low grade tumour with an indolent course. A 48 year old woman presented with a painful swelling over her back for six months. Investigation and biopsy revealed features of sclerosing epithelioid fibrosarcoma involving the left half of the sacrum, left sacro-iliac joint, and posterior part of the left ilium. Preoperative radiotherapy and wide location excision of the tumour were followed by metastatic recurrence of the tumour in the lung and scalp six years after initial presentation. The tumour showed typical histology of sclerosing epithelioid fibrosarcoma. The radiological features confirmed its primary location in the sacrum. The patient declined chemotherapy and died of disseminated disease eight years after initial presentation. Review of the literature confirms the fact that sclerosing epithelioid fibrosarcoma, despite its low grade, is a clinicopathologically distinct tumour with full malignant potential, the recurrence, metastasis, and mortality rate being 48%, 60%, and 35%, respectively. Sclerosing epithelioid fibrosarcoma can occur as a primary bone tumour, the clinical behaviour of which is probably similar to its soft tissue counterpart.


Survival forests under test: Impact of the proportional hazards assumption on prognostic and predictive forests for amyotrophic lateral sclerosis survival.
We investigate the effect of the proportional hazards assumption on prognostic and predictive models of the survival time of patients suffering from amyotrophic lateral sclerosis. We theoretically compare the underlying model formulations of several variants of survival forests and implementations thereof, including random forests for survival, conditional inference forests, Ranger, and survival forests with L1 splitting, with two novel variants, namely distributional and transformation survival forests. Theoretical considerations explain the low power of log-rank-based splitting in detecting patterns in non-proportional hazards situations in survival trees and corresponding forests. This limitation can potentially be overcome by the alternative split procedures suggested herein. We empirically investigated this effect using simulation experiments and a re-analysis of the Pooled Resource Open-Access ALS Clinical Trials database of amyotrophic lateral sclerosis survival, giving special emphasis to both prognostic and predictive models.


The incidence of erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis. A population-based study with particular reference to reactions caused by drugs among outpatients.
We carried out a study to estimate the incidence of erythema multiforme (EM), Stevens Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN) requiring hospitalization and to determine which drug therapies were associated with these reactions. We reviewed the clinical records of all patients who were hospitalized with these discharge diagnoses at Group Health Cooperative (GHC) of Puget Sound, Seattle, Wash, from 1972 through 1986. During this 14-year period, an average of about 260,000 persons, with demographic characteristics similar to those of the general population, received their care from GHC, and there were about 25,000 admissions to hospitals per year at the GHC hospitals. Based on International Classification of Diseases-Adapted coding, a total of 61 suspect cases of EM, SJS, or TEN were identified from the computerized hospital discharge file. Based on record review and the application of a uniform set of diagnostic criteria, a total of 37 patients (61%) were classified as having EM, SJS, or TEN. Of these, 16 cases (43%) were attributed to drugs administered to these patients prior to hospitalization. The overall incidence of hospitalization for EM, SJS, or TEN due to all causes was 4.2 per 10(6) person-years. The incidence of TEN alone due to all causes was 0.5 per 10(6) person-years. The incidence of EM, SJS, or TEN associated with drug use were 7.0, 1.8, and 9.0 per 10(6) person-years, respectively, for persons younger than 20 years of age, 20 to 64 years of age, and 65 years of age and older. Drug therapies with reaction rates in excess of 1 per 100,000 exposed individuals include phenobarbital (20 per 100,000), nitrofurantoin (7 per 100,000), sulfamethoxazole and trimethoprim, and ampicillin (both 3 per 100,000), and amoxicillin (2 per 100,000). Overall, our data suggest that cases of EM, SJS, and TEN sufficiently severe to require hospitalization are infrequent among outpatients using well-established drug therapies. A continuing challenge is the evaluation of these severe cutaneous reactions that are associated with newly marketed or less frequently prescribed drug therapies.


Combined Activity of DCL2 and DCL3 Is Crucial in the Defense against Potato Spindle Tuber Viroid.
Viroids are self replicating non-coding RNAs capable of infecting a wide range of plant hosts. They do not encode any proteins, thus the mechanism by which they escape plant defenses remains unclear. RNAi silencing is a major defense mechanism against virus infections, with the four DCL proteins being principal components of the pathway. We have used Nicotiana benthamiana as a model to study Potato spindle tuber viroid infection. This viroid is a member of the Pospiviroidae family and replicates in the nucleus via an asymmetric rolling circle mechanism. We have created knock-down plants for all four DCL genes and their combinations. Previously, we showed that DCL4 has a positive effect on PSTVd infectivity since viroid levels drop when DCL4 is suppressed. Here, we show that PSTVd levels remain decreased throughout infection in DCL4 knockdown plants, and that simultaneous knockdown of DCL1, DCL2 or DCL3 together with DCL4 cannot reverse this effect. Through infection of plants suppressed for multiple DCLs we further show that a combined suppression of DCL2 and DCL3 has a major effect in succumbing plant antiviral defense. Based on our results, we further suggest that Pospoviroids may have evolved to be primarily processed by DCL4 as it seems to be a DCL protein with less detrimental effects on viroid infectivity. These findings pave the way to delineate the complexity of the relationship between viroids and plant RNA silencing response.


Investigation of the effect of black walnut extract on in vitro ion transport and structure of equine colonic mucosa.
To examine the secretory response (in the presence and absence of prostaglandin inhibition) in vitro and structural alterations of colonic mucosa in horses after intragastric administration of black walnut extract (BWE). 14 adult horses. Seven horses were administered BWE intragastrically and monitored for 11 hours. Tissue samples were obtained from the right ventral, left ventral, and right dorsal colons (RVC, LVC, and RDC, respectively) of the 7 BWE-treated and 7 control horses. Tissue samples were examined via light microscopy, and the extent of hemorrhage, edema, and granulocytic cellular infiltration (neutrophils and eosinophils) was graded. Colonic mucosal segments were incubated with or without flunixin meglumine (FLM) for 240 minutes; spontaneous electrical potential difference and short-circuit current (Isc) were recorded and used to calculate mucosal resistance. Colonic tissues from BWE-treated horses (with or without FLM exposure) had an overall greater Isc during the 240-minute incubation period, compared with tissues from control horses. The resistance pattern in RVC, LVC, and RDC samples (with or without FLM exposure) from BWE-treated horses was decreased overall, compared with control tissues (with or without FLM exposure). Histologically, colonic mucosal tissues from BWE-treated horses had more severe inflammation (involving primarily eosinophils), edema, and hemorrhage, compared with tissue from control horses. In horses, BWE administration appears to cause an inflammatory response in colonic mucosal epithelium that results in mucosal barrier compromise as indicated by decreased mucosal resistance with presumed concomitant electrogenic chloride secretory response, which is not associated with prostaglandin mediation.


Differences in detection of alcohol use in a prenatal population (on a Northern Plains Indian Reservation) using various methods of ascertainment.
Although Fetal Alcohol Syndrome (FAS) rates have been reported to be higher in American Indian populations, no screening tool has been validated for alcohol use in American Indian women. The objectives of this study were to compare the detection of prenatal alcohol use by a self-administered questionnaire to detection by clinical interview; and to ascertain whether the screening tool would increase detection of pregnant women who are abusing alcohol. The hospital records of the women were reviewed for any history of alcohol-related illnesses or injuries to compare with results obtained from the questionnaire. Seventy women attending their first prenatal clinic visit on a reservation were screened for alcohol use. There was a wide range in detection of prenatal alcohol use (20%-71% of the sample detected) depending on the method used. There was a large variation in sensitivities (7%-93%) of the individual questions in identifying patients detected as "high risk" by the clinicians. The T-ACE screening questions significantly increased detection of alcohol use compared to detection by the clinicians (p = 0.04 Fisher's exact test). Due to the large variation between different methods of detection, it is recommended that screening tools that increase detection of alcohol use should be combined with methods of higher specificity such as using questions about quantity and frequency of alcohol intake, medical chart review and clinical interview. We also found that various interpretations of the screening questions by the patients highlighted the need to tailor the wording of individual questions to the particular patient population.


Cost-effectiveness analysis of a randomized study of depression treatment options in primary care suggests stepped-care treatment may have economic benefits.
The stepped-care pathway (SCP) model has previously been found to be clinically effective for depressive disorder in some studies, but not all. Several groups have suggested that a stepped-care approach is the most appropriate in primary care. There is relatively little information, however, regarding which specific stepped-care pathway may be best. This analysis aimed to determine cost-effectiveness of a stepped-care pathway for depression in adults in primary care versus standard care (SC), treatment-as-usual (TAU), and online cognitive behavioural therapy (CBT). We conducted a randomized trial with 1400 participants and 12-week follow-up to assess the impact of the four treatment options on health-related quality of life and depression severity. Costs for the groups were calculated on the basis of physician, outpatient, and inpatient services using administrative data. We then calculated the incremental cost-effectiveness ratios using this information. Cost-effectiveness acceptability curves and incremental cost-effectiveness scatterplots were created using Monte Carlo simulation with 10,000 replications. A subgroup analysis was conducted for participants who screened as depressed at baseline. For all participants, TAU was the most expensive followed by CBT, SC, and SCP. QALYs were highest in SCP, followed by SC, CBT, and TAU. In the depressed subgroup, TAU was still the most expensive, followed by SC, SCP, and CBT, while QALYs were still highest in SCP, followed by SC, CBT, and TAU. The cost-effectiveness acceptability curves suggested that SCP had a higher probability for cost-effectiveness than the other three alternatives in all participants. In the depressed subgroup, CBT was associated with the highest probability of cost-effectiveness for a willingness-to-pay cut-off of less than approximately $50,000, while SCP was the highest at a cut-off higher than $50,000. There is considerable uncertainty around the cost-effectiveness estimates. Our analysis showed that even where there are no clinically significant differences in health outcomes between treatment approaches, there may be economic benefit from implementing the stepped-care model. While more work is required to identify the most clinically effective versions of a stepped-care pathway, our findings suggest that the care pathway may have potential to improve health care system value. NCT01975207 . The trial was prospectively registered on 4 November 2013.


Assessing Variations in Sexual Orientation- and Gender Identity-Related U.S. State Laws for Sexual and Gender Minority Health Research and Action, 1996-2016.
Purpose: We developed a multiyear database of sexual orientation- and gender identity-related U.S. state laws to advance sexual and gender minority (SGM) health research and practice and assessed variability in U.S. state laws from 1996 through 2016 across all U.S. states and D.C. Methods: Between 2014 and 2016, a multidisciplinary group of SGM health researchers and legal experts used secondary and primary legal sources and policy surveillance methods to systematically develop a state-level legal database of 30 sexual orientation- and gender identity-related U.S. state laws in 9 legal domains from 1996 through 2016. We calculated descriptive statistics and created maps to observe the distribution of these laws over both time and space. Results: Although progress has occurred in some domains, such as same-sex marriage, adoption, and employment discrimination, significant challenges to SGM rights remain, especially with regard to HIV criminalization, transgender rights, and discrimination in health care settings. Further, notable variation exists in the presence of protective lesbian, gay, bisexual, transgender, queer (LGBTQ) state laws across U.S. states and D.C. Conclusion: Efforts to repeal harmful U.S. state laws are needed, as are new laws, policies, regulations, practices, and norms that advance social justice and health equity for all SGM people.


Common Medications and Intracerebral Hemorrhage: The ARIC Study.
Background Antiplatelets, anticoagulants, and statins are commonly prescribed for various indications. The associations between these medications and the risk of intracerebral hemorrhage (ICH) and cerebral microbleeds (CMBs) are unclear. Methods and Results We performed a retrospective study of the ARIC (Atherosclerosis Risk in Communities) study cohort, recruited from 4 US communities in 1987 to 1989 with follow-up. In 2011 to 2013, a subset (N=1942) underwent brain magnetic resonance imaging with CMB evaluation. Time-varying and any antiplatelet, anticoagulant, or statin use was evaluated at subsequent study visits in participants not on each medication at baseline. To determine the hazard of ICH and odds of CMB by medication use, logistic and Cox proportional hazard models were built, respectively, adjusting for the propensity to take the medication, concomitant use of other medications, and cognitive, genetic, and radiographic data. Of 15 719 individuals during up to 20 years of follow-up, 130 participants experienced an ICH. The adjusted hazard of ICH was significantly lower among participants taking an antiplatelet at the most recent study visit before ICH versus nonusers (hazard ratio [HR], 0.53; 95% CI, 0.30-0.92). Statin users had a significantly lower hazard of an ICH compared with nonusers (adjusted HR, 0.13; 95% CI, 0.05-0.34). There was no association of CMB and antiplatelet, anticoagulant, or statin use in adjusted models. Conclusions In this US community-based study, antiplatelet and statin use were associated with lower ICH hazard, whereas no association was noted between CMBs and antiplatelets, anticoagulants, and statins. Further study is needed to understand the differential roles of these medications in cerebral microhemorrhages and macrohemorrhages.


Categorising major cardiovascular disease hospitalisations from routinely collected data.
Objectives and importance of the study: Routine hospital administrative data provide an important source of information about cardiovascular disease (CVD) for health statistics reporting, health services and research. How such conditions are classified and grouped has implications for the use and interpretation of these data. International Classification of Diseases (ICD) diagnosis codes from hospital data collections are often used to classify CVD, but there is little published evidence on the most appropriate ways to use these codes to categorise CVD in a way that maximises the usefulness of hospital data for reporting and research. In particular, ICD codes under 'Diseases of the circulatory system' (I00-I99) are often grouped together into a general CVD category. However, this category is heterogeneous and combines common severe atherosclerotic and thrombotic CVDs (such as myocardial infarction and pulmonary embolism) with common, less severe and pathologically dissimilar conditions (such as varicose veins and haemorrhoids). In addition, hospital data collections contain a range of data fields, including those relating to primary and additional diagnoses and those relating to procedures. All of these have the potential to contribute valuable information on CVD. This paper proposes a pragmatic approach to using ICD diagnosis codes and procedure codes to capture major atherosclerotic and arteriovenous thromboembolic and related CVD. We reviewed the ICD diagnosis codes and procedure codes and developed an algorithm for classifying and categorising major CVD diagnoses. This approach was then applied to linked hospitalisation data from individuals participating in the 45 and Up Study, a cohort study of 267 153 New South Wales residents aged 45 and over, to investigate the implications of the proposed approach for quantifying CVD. Large differences were observed in the numbers of events in grouped CVD outcomes, depending on the methods used. In cases where the reporting and research interest relates to incident disease, it may be appropriate to prioritise specific disease categories and pathological homogeneity.


Mapping DNA quantity into electrophoretic mobility through quantum dot nanotethers for high-resolution genetic and epigenetic analysis.
Newly discovered nanoparticle properties have driven the development of novel applications and uses. We report a new observation where the electrophoretic mobility of a quantum dot/DNA nanoassembly can be precisely modulated by the degree of surface DNA conjugation. By using streptavidin-coated quantum dots (QDs) as nanotethers to gather biotin-labeled DNA into electrophoretic nanoassemblies, the QD surface charge is modulated and transformed into electrophoretic mobility shifts using standard agarose gel electrophoresis. Typical fluorescent assays quantify based on relative intensity. However, this phenomenon uses a novel approach that accurately maps DNA quantity into shifts in relative band position. This property was applied in a QD-enabled nanoassay called quantum dot electrophoretic mobility shift assay (QEMSA) that enables accurate quantification of DNA targets down to 1.1-fold (9%) changes in quantity, beyond what is achievable in qPCR. In addition to these experimental findings, an analytical model is presented to explain this behavior. Finally, QEMSA was applied to both genetic and epigenetic analysis of cancer. First, it was used to analyze copy number variation (CNV) of the RSF1/HBXAP gene, where conventional approaches for CNV analysis based on comparative genomic hybridization (CGH), microarrays, and qPCR are unable to reliably differentiate less than 2-fold changes in copy number. Then, QEMSA was used for DNA methylation analysis of the p16/CDK2A tumor suppressor gene, where its ability to detect subtle changes in methylation was shown to be superior to that of qPCR.


Can general practitioners counsel?
It has been suggested that general practitioners are in a prime position to counsel patients presenting with psychosocial problems. While many doctors use counselling skills in their consultations few have received training in counselling and the difference between the use of counselling skills and the process of counselling is not always understood. This paper examines the differences between counselling and counselling skills and compares the role of doctors and counsellors. It is concluded that there is a need for trained counsellors to work alongside general practitioners and that this is of benefit to patients and all members of the primary care team.


The Ruby UCSC API: accessing the UCSC genome database using Ruby.
The University of California, Santa Cruz (UCSC) genome database is among the most used sources of genomic annotation in human and other organisms. The database offers an excellent web-based graphical user interface (the UCSC genome browser) and several means for programmatic queries. A simple application programming interface (API) in a scripting language aimed at the biologist was however not yet available. Here, we present the Ruby UCSC API, a library to access the UCSC genome database using Ruby. The API is designed as a BioRuby plug-in and built on the ActiveRecord 3 framework for the object-relational mapping, making writing SQL statements unnecessary. The current version of the API supports databases of all organisms in the UCSC genome database including human, mammals, vertebrates, deuterostomes, insects, nematodes, and yeast.The API uses the bin index-if available-when querying for genomic intervals. The API also supports genomic sequence queries using locally downloaded *.2bit files that are not stored in the official MySQL database. The API is implemented in pure Ruby and is therefore available in different environments and with different Ruby interpreters (including JRuby). Assisted by the straightforward object-oriented design of Ruby and ActiveRecord, the Ruby UCSC API will facilitate biologists to query the UCSC genome database programmatically. The API is available through the RubyGem system. Source code and documentation are available at https://github.com/misshie/bioruby-ucsc-api/ under the Ruby license. Feedback and help is provided via the website at http://rubyucscapi.userecho.com/.


Gill epithelial cell nuclear virus disease is prevalent and widespread in Mya arenaria clams of Chesapeake Bay, USA.
Several historic investigations have reported intranuclear virus infections of Mya arenaria soft-shell clams from the Atlantic coast of North America, but their descriptive details are limited. Among numerous multi-clam samples of Chesapeake Bay M. arenaria that were analyzed histopathologically during clam population surveys from 2000-2009, virus replication apparently caused extreme hypertrophy among the infected nuclei of gill epithelial cells. Infected cells were often abundant within the gill epithelia of affected clams, where their nuclear abnormalities suggested compromised genetic controls of critical cellular physiological functions. Infection prevalences were generally elevated, reaching 90% in 25% of samples. A grand mean prevalence of 67% resulted for all (69) M. arenaria samples of the decadal investigation, which included 1934 individual clams. Infected nuclei of gill epithelial cells were microscopically conspicuous by their extreme hypertrophic diameters of 10 µm or more and their prominent DNA-inclusion bodies. Cells with abnormal, hypertrophic nuclei were often abundant in the epithelia of M. arenaria gills. Transmission electron microscopy revealed abundant, replicating, icosahedral viral particles of 65-85 nm diameter within such hypertrophic nuclei. Viruses frequently occurred in paracrystalline nuclear arrays, showed granular internal contents, and had radial structures that suggested capsid surface ornamentation. Normal heterochromatin of infected nuclei appeared emarginated by dense central masses of replicating virions. Large, electron-dense DNA inclusion bodies routinely occurred at the internal margins of virus-infected nuclei. These may be virus replication centers based on their ultrastructural features and close proximity to replicated viral particles.


Aggressive infantile myofibromatosis with intestinal involvement.
Infantile myofibromatosis (IM) is the most common cause of multiple fibrous tumors in infancy. Multicentric disease can be associated with life-threatening visceral lesions. Germline gain-of-function mutations in PDGFRB have been identified as the most common molecular defect in familial IM. We here describe an infant with PDGFRB-driven IM with multiple tumors at different sites, including intestinal polyposis with hematochezia, necessitating temporary chemotherapy. PDGFRB-driven IM is clinically challenging due to its fluctuating course and multiple organ involvement in the first years of life. Early molecular genetic analysis is necessary to consider tyrosine kinase inhibitor treatment in case of aggressive visceral lesions.


The relevance of selenium to immunity, cancer, and infectious/inflammatory diseases.
Selenium is an essential trace element involved in several key metabolic activities via selenoproteins, enzymes that are essential to protect against oxidative damage and to regulate immune function. Selenium also may have other health benefits unrelated to its enzymatic functions. It may provide important health benefits to people whose oxidative stress loads are high, such as those with inflammatory or infectious diseases like rheumatoid arthritis or human immunodeficiency virus/acquired immunodeficiency syndrome, or who are at high risk for cancers, particularly prostate cancer. Some studies have generated compelling evidence that selenium is beneficial, either alone or in conjunction with other micronutrients. Additional data from large clinical trials that provide the highest level of evidence will be key to determining the benefits accrued at various selenium intake levels. When the strength of the evidence becomes sufficient, clinical health professionals will need to use dietary and clinical assessment methods to ensure that people at increased risk for cancer or inflammatory and infectious diseases can be appropriately advised about selenium intake.


Wnt inhibitor XAV939 suppresses the viability of small cell lung cancer NCI-H446 cells and induces apoptosis.
Small cell lung cancer (SCLC) is the most aggressive type of lung cancer due to a fast tumor doubling time and early hematogenous spread. Advances in the treatment of non-small cell lung cancer using targeted therapies having been made, but no targeted drugs for SCLC have been approved. The Wnt signaling pathway is associated with tumor progression and metastasis; therefore, the inhibition of Wnt/β-catenin signaling is a strategy for anticancer drugs. Tankyrase 1 (TNKS1) is overexpressed in a number of types of cancer and XAV939 is a small molecule inhibitor of TNKS1 which may inhibit tumor growth. The present study aimed to investigate the potential molecular mechanisms underlying XAV939-induced suppression of the viability of SCLC cells. MTT assays were used to determine the viability-inhibition rate of cells and to identify the drug concentration which optimally inhibited cell viability. Flow cytometry was used to determine whether XAV939 induced apoptosis of SCLC cells, and to analyze the effect of the drug on the cell cycle. The results of the present study identified that XAV939 inhibited the viability of NCI-H446 cells in a dose-dependent manner, but cisplatin inhibited NCI-H446 cell viability in a time- and dose-dependent manner. The combination of XAV939 and cisplatin exhibited a slightly more pronounced inhibition of cell viability at an increased dose of XAV939. In addition, XAV939 markedly induced cell apoptosis of the SCLC cell line H446 by increasing the proportion of cells in the G0/G1 phase, leading to inhibition of the cell cycle. The results of the present study indicated that XAV939 inhibited the viability of the NCI-H446 SCLC cell line by inducing cell apoptosis through the Wnt signaling pathway. Therefore, XAV939 may be useful for the treatment of SCLC.


Characterization of Nonlinear Ultrasonic Diffuse Energy Imaging.
Nonlinear ultrasonic diffuse energy imaging is a highly sensitive method for the measurement of elastic nonlinearity. While the underlying principles that govern the technique are understood, the precise behavior and sensitivity have not previously been quantified. This paper presents experimental, theoretical, and numerical modeling studies undertaken to characterize nonlinear diffuse energy imaging. The influence of incoherent noise, elastic nonlinearity, and instrumentation error are quantified. This paper enables the prediction of spatial sensitivity, aperture, and amplitude dependence of the measurement, all of which moves the technique toward industrial viability. Furthermore, while previous studies have focused on the detection of closed cracks, the ultimate aim for nonlinear ultrasonic imaging in application to material testing is the detection of damage precursors, which requires a sensitivity to weak classical nonlinearity. This paper identifies the experimental requirements necessary for this to be achieved, greatly expanding the potential applicability of nonlinear ultrasonic array imaging.


Increased cytochrome P450 17alpha-hydroxylase promoter function in theca cells isolated from patients with polycystic ovary syndrome involves nuclear factor-1.
Cytochrome P450 17alpha-hydroxylase (CYP17) gene expression and androgen biosynthesis are persistently elevated in theca cells isolated from ovaries of women with polycystic ovary syndrome (PCOS). We previously reported that -235 to -109 bp of the CYP17 promoter confers increased CYP17 promoter function in PCOS theca cells. In this report, additional deletion and mutational analyses of the CYP17 promoter were performed to identify the sequences that contribute to increased CYP17 promoter function in PCOS theca cells. Results of these analyses established that augmented promoter function in PCOS theca cells results from preferentially increased basal regulation conferred by sequences between -188 and -147 bp of the CYP17 promoter. Scanning mutant analysis demonstrated that mutations within a 16-bp sequence, spanning -174 to -158 bp of the promoter, ablated increased basal CYP17 promoter function in PCOS theca cells. EMSA analysis demonstrated that the NF-1 family member, NF-1C, bound this sequence. Cotransfection of several NF-1C isoforms expressed in normal and PCOS cells repressed CYP17 promoter function. NF-1C protein and DNA binding were reduced in PCOS theca cell nuclear extracts, as compared with normal. Another NF-1C site between -102 and -90 bp of the promoter was also identified. However, mutation of this site had no effect on differential promoter function in PCOS theca cells. These studies demonstrate that 1) augmented CYP17 promoter function in PCOS theca cells results from increased basal regulation, and 2) diminished NF-1C-dependent repression may be one mechanism underlying increased basal CYP17 promoter activity and altered gene expression in PCOS theca cells.


Insights Into Subspecies Discrimination Potentiality From Bacteria MALDI-TOF Mass Spectra by Using Data Mining and Diversity Studies.
Bacterial identification at subspecies level is critical in clinical care and epidemiological investigations due to the different epidemic potentialities of a species. For this purpose, matrix-assisted laser desorption ionization - time-of-flight mass spectrometry (MALDI-TOF MS) has been proposed in place of molecular genotyping, but with some result discrepancies. The aim of this work is to methodically mine the expression diversities of MALDI-TOF bacterial species spectra and their possible latent organization in order to evaluate their subspecies specific expression. Peak expression diversities of MALDI-TOF spectra coming from routine identifications have been analyzed using Hill numbers, rarefaction curves, and peak clustering. Some size effect critical thresholds were estimated using change point analyses. We included 167,528 spectra corresponding to 405 species. Species spectra diversities have a broad size-dependent variability, which may be influenced by the kind of sampling. Peak organization is characterized by the presence of a main cluster made of the most frequently co-occurring peaks and around 20 secondary clusters grouping less frequently co-occurring peaks. The 35 most represented species in our sample are distributed in two groups depending on the focusing of their protein synthesis activity on the main cluster or not. Our results may advocate some analogy with genomics studies of bacteria, with a main species-related cluster of co-occurring peaks and several secondary clusters, which may host peaks able to discriminate bacterial subgroups. This systematic study of the expression diversities of MALDI-TOF spectra shows that latent organization of co-occurring peaks supports subspecies discrimination and may explain why studies on MALDI-TOF-based typing exhibit some result divergences.


The similarity of DNA sequences remaining bound to scaffold upon nuclease treatment of interphase nuclei and metaphase chromosomes.
The fragments of DNA attached to protein skeleton of interphase nuclei or metaphase chromosomes were obtained. Both the method involving restriction endonuclease treatment/1,2/and a novel procedure based on mild staphylococcal nuclease digestion were used. In the latter case, DNA fragments remaining bound to nuclei or chromosomes are not enriched in satellite but only in abundant middle repetitive DNA. The shorter the fragments of attached DNA, the higher the content of middle repetitive DNA in the fraction. It has a slightly higher density in a CsCl gradient comparing to the main DNA. The yield of attached DNA, its distribution in a CsCl density gradient, and its renaturation properties are essentially the same for interphase and metaphase chromosomes. The average size of DNA loops was found to be equal to approximately 60 kb for both metaphase chromosomes and interphase nuclei. The conclusion has been drawn that the bulk of attachment sites of DNP fibrils to axial chromosomal structures remains unchanged during the cell cycle.


Perovskite Quantum Wells Formation Mechanism for Stable Efficient Perovskite Photovoltaics-A Real-Time Phase-Transition Study.
The combination of a bulk 3D perovskite layer and a reduced dimensional perovskite layer (perovskite quantum wells (PQWs)) is demonstrated to enhance the performance of perovskite solar cells (PSCs) significantly in terms of stability and efficiency. This perovskite hierarchy has attracted intensive research interest; however, the in-depth formation mechanism of perovskite quantum wells on top of a 3D perovskite layer is not clearly understood and is therefore the focus of this study. Along with ex situ morphology and photophysical characterization, the time-resolved grazing-incidence wide-angle X-ray scattering (TS-GIWAXS) technique performed in this study provides real-time insights on the phase-transition during the organic cation (HTAB ligand molecule) coating and PQWs/3D architecture formation process. A strikingly strong ionic reaction between the 3D perovskite and the long-chain organic cation leads to the quick formation of an ordered intermediate phase within only a few seconds. The optimal PQWs/3D architecture is achieved by controlling the HTAB casting, which is assisted by time-of-flight SIMS characterization. By controlling the second ionic reaction during the long-chain cation coating process, along with the fluorinated poly(triarylamine) (PTAA) as a hole-transport layer, the perovskite solar cells demonstrate efficiencies exceeding 22% along with drastically improved device stability.


Physiological factors characterizing heat-vulnerable older adults: A narrative review.
More frequent and intense periods of extreme heat (heatwaves) represent the most direct challenge to human health posed by climate change. Older adults are particularly vulnerable, especially those with common age-associated chronic health conditions (e.g., cardiovascular disease, hypertension, obesity, type 2 diabetes, chronic kidney disease). In parallel, the global population is aging and age-associated disease rates are on the rise. Impairments in the physiological responses tasked with maintaining homeostasis during heat exposure have long been thought to contribute to increased risk of health disorders in older adults during heatwaves. As such, a comprehensive overview of the provisional links between age-related physiological dysfunction and elevated risk of heat-related injury in older adults would be of great value to healthcare officials and policy makers concerned with protecting heat-vulnerable sectors of the population from the adverse health impacts of heatwaves. In this narrative review, we therefore summarize our current understanding of the physiological mechanisms by which aging impairs the regulation of body temperature, hemodynamic stability and hydration status. We then examine how these impairments may contribute to acute pathophysiological events common during heatwaves (e.g., heatstroke, major adverse cardiovascular events, acute kidney injury) and discuss how age-associated chronic health conditions may exacerbate those impairments. Finally, we briefly consider the importance of physiological research in the development of climate-health programs aimed at protecting heat-vulnerable individuals.


Severe acanthamoeba keratitis after overnight orthokeratology.
To document a clinical case of Acanthamoeba keratitis associated with orthokeratology overnight lens wear that resulted in severe, permanent vision loss. Case report. At the age of 11 years, a boy received a spectacle correction for the following refractive error: -3.25 -0.50 x090 in the right eye and -3.50 -0.25 x 040 in the left eye. Alternative wear of daily-wear, disposable, soft contact lenses and rigid gas-permeable lenses was used for athletic activities to the age of 16 years. Between the ages of 16 and 19 years, the patient wore Boston Equalens 2c27 (type Percision Corneal Molding - 51) lenses with a base curve of 9.25, power of +2.50 diopters (D), and diameter of 10.6 mm in the right eye and a base curve of 9.15, power of +3.00 D, and diameter of 10.6 mm in the left eye for overnight orthokeratology wear. A corneal ulcer in the left eye was noted on November 13, 2004 (age of 19 years) and confirmed as Acanthamoeba infection by confocal microscopy on February 15, 2005, when triple topical therapy (Brolene, polyhexamethylbiguanide, and chlorhexidene) was initiated. Vision deteriorated to light perception with accurate projection by cessation of therapy on March 28, 2006. Additional complications included secondary angle-closure glaucoma, treated with an Ahmed tube shunt on April 12, 2005, and a mature cataract. The important message conveyed by this case was the finding that for several years, unknown to his eye care physicians, the patient cleaned his lenses with the Boston Cleaning System, as instructed, but followed this step with a routine rinse with tap water and storage in tap water in his lens case, which was not replaced or cleaned. The tragic loss of vision in this case probably could have been prevented by focused attention to lens hygiene by the patient, parents, and practitioner. Such heightened scrutiny is critically important in orthokeratology rigid lens wear, especially in children, independent of the lens polymer or fitting algorithm used.


Facial nerve neuroma.
Facial nerve neuromas are uncommon, slow-growing neoplasms that may occur anywhere along the course of the facial nerve from the brainstem to the facial muscles. The signs and symptoms are characteristic and vary with the anatomic site of origin. Surgery should not be attempted until a complete and thorough diagnostic examination has been completed. The surgeon should be prepared to perform a middle-cranial fossa or translabyrinthine approach in all cases, and must expect to do a nerve graft. The results of 37 patients treated by the author reveal that, under optimal conditions, patients who have had a facial nerve graft, can be expected to regain an average of 80% facial nerve strength in almost every case. All patients who have had a facial nerve graft will have some degree of synkinesis. No graft was required in 3 patients, and a hypoglossal facial anastomosis was used for one. Facial function was completely normal in 2 patients, 16 had 80-90% return, 5 patients had 50-80% return, 4 had 20-50% return, one had no recovery at all and 9 recent patients have not reached the time for their expected recovery. Early diagnosis, prompt surgical removal and VII-VII Nerve graft for facial paralysis of ten or fewer years duration offers patients the best opportunity to avoid a permanent facial palsy.


vir genes influence conjugal transfer of the Ti plasmid of Agrobacterium tumefaciens.
Mutation of the genes virA, virB, virC, and virG of the Agrobacterium tumefaciens octopine-type Ti plasmid pTiR10 was found to cause a 100- to 10,000-fold decrease in the frequency of conjugal transfer of this plasmid between Agrobacterium cells. This effect was not absolute, however, in that it occurred only during early times (18 to 24 h) of induction of the conjugal transfer apparatus by octopine. Induction of these mutant Agrobacterium strains by octopine for longer periods (48 to 72 h) resulted in a normal conjugal transfer frequency. The effect of these vir gene mutations upon conjugation could be restored by the introduction of cosmids harboring wild-type copies of the corresponding disrupted vir genes into the mutant Agrobacterium strains. In addition, transfer of the self-mobilizable plasmid pPH1JI was not impaired in any of the mutant Agrobacterium strains tested. The effect of vir gene function on the conjugal transfer of the Ti plasmid suggests that a relationship may exist between the processes that control the transfer of the T-DNA from Agrobacterium to plant cells and the conjugal transfer of the Ti plasmid between bacterial cells.


Work-Related Human T-lymphotropic Virus 1 and 2 (HTLV-1/2) Infection: A Systematic Review.
Human T-lymphotropic virus 1 and 2 (HTLV-1/2) belong to the delta group of retroviruses which may cause a life-long infection in humans, HTLV-1 leading to adult T-cell leukemia/lymphoma and other diseases. Different transmission modes have been described, such as breastfeeding, and, as for other blood-borne pathogens, unsafe sexual activity, intravenous drug usage, and blood transfusion and transplantation. The present systematic review was conducted to identify all peer-reviewed studies concerning the work-related infection by HTLV-1/2. A literature search was conducted from January to May 2021, according to the PRISMA methodology, selecting 29 studies: seven related to health care workers (HCWs), five to non-HCWs, and 17 to sex workers (SWs). The findings showed no clear evidence as to the possibility of HTLV-1/2 occupational transmission in HCWs, according to the limited number and quality of the papers. Moreover, non-HCWs showed a higher prevalence in jobs consistent with a lower socioeconomic status or that could represent a familial cluster, and an increased risk of zoonotic transmission from STLV-1-infected non-human primates has been observed in African hunters. Finally, a general increase of HTLV-1 infection was observed in SWs, whereas only one paper described an increased prevalence for HTLV-2, supporting the urgent need for prevention and control measures, including screening, diagnosis, and treatment of HTLV-1/2, to be offered routinely as part of a comprehensive approach to decrease the impact of sexually transmitted diseases in SWs.


Optimising sample preparation for FTIR-based microplastic analysis in wastewater and sludge samples: multiple digestions.
The lack of standardised methodologies in microplastic research has been addressed in recent years as it hampers the comparison of results across studies. The quantification of microplastics in the environment is key to the assessment of the potential eco-toxicological impacts that this new category of emerging pollutants could have on terrestrial and aquatic species. Therefore, the need for protocols that are robust, simple and reliable together with their standardisation are of crucial importance. This study has focused on removal of organic matter with Fenton reagent from wastewater and sludge samples. This step of analysis was optimised by implementing a multi-digestion treatment on these samples that have high concentration of complex mixtures of organic matter, which interfere with microplastic enumeration. Moreover, this study targeted the detection of microplastics in the sub-hundred-micron size range due to the potential higher risks associated with smaller-sized particles and the limited data available from previous wastewater research. To show the validity of the method, triplicate samples of raw sewage, final effluent and sludge were independently spiked with two different sizes and types of microplastic polymers. Due to the various analytical stages required for the isolation of microplastics, time is a limiting factor in sample processing. The sequential digestion with Fenton reagent represents an inexpensive and time-efficient procedure for wastewater research providing effective degradation of organic material. These advantages over other currently available methods mean the method is suitable for analysis of large numbers of samples allowing robust monitoring data sets to be generated.


Noninvasive Testing for Diagnosis of Stable Coronary Artery Disease in the Elderly.
Efficient diagnostic approaches to detect coronary artery disease (CAD) in elderly patients are necessary to ensure optimal and timely treatment. The population of suspected CAD patients older than 70 years is especially vulnerable and constantly growing. Finding the optimal diagnostic approach is challenging due to certain features of this population, such as high prevalence of comorbidities, existing contraindications to exercise tests or cognitive decline, which hinders correct assessment of the patient's situation. Moreover, some symptoms of CAD can have variable significance in the elderly compared to younger adult groups. In this review, we present current recommendations of the United States (US) and European cardiologists' associations and discuss their applicability for diagnostics in the elderly population. Exercise electrocardiogram (ECG) and exercise stress echocardiography (SE) tests are not feasible for a substantial proportion of elderly patients. Coronary computed tomography angiography (CTA) appears to be an attractive alternative for such patients, but is not universally applicable; for instance, it is problematic in patients with significant calcification of the vessels. Moreover, more studies are needed to compare the results delivered by CTA to those of other diagnostic methods. Future efforts should be focused on comparative studies to better understand the limits and advantages of different diagnostic methods and their combinations. It is possible that some of the currently used diagnostic criteria could be improved to better accommodate the needs of the elderly population.


White blood cell mitochondrial DNA copy number is decreased in rheumatoid arthritis and linked with risk factors. A twin study.
Low mitochondrial DNA copy number (mtDNA CN) has been associated with e.g. cancer, cardiovascular and autoimmune diseases. We aimed to study a potential association between mtDNA CN and rheumatoid arthritis (RA). The relative quantity of mitochondrial DNA compared to nuclear DNA was measured in peripheral white blood cells from 149 RA affected twin pairs and 1321 non-affected twin pairs. Multiple regression analysis including RA discordant twin pairs was performed in order to separate specific effects of RA and familial RA predisposition using non-RA affected twin pairs as reference group. In addition, we performed a twin pair level analysis including only RA discordant twin pairs evaluating the effect of cell type, auto antibodies and RA genetic risk factors. Both the RA twins and their non-affected co-twins had significantly lower mtDNA CN than non-affected twins (-28.7 and -23.1 mtDNA CN, respectively). Adjusting for cell count attenuated these differences (-23.1 mtDNA CN and -20.1 mtDNA CN respectively). Within RA discordant twin pairs PTPN22(T) positive RA twins had a significantly lower amount than their co-twins (-16.3 mtDNA CN). PTPN22(T) had no effect among twins from non-affected twin pairs. MtDNA CN is significantly lower in persons with established RA and in predisposed non-affected RA co-twins suggesting that mitochondrial variation may be involved in the RA disease pathways. Our results also suggest that the RA associated genetic risk factor, PTPN22(T), further decreases the mtDNA CN, but only in carriers with established RA.


Adrenal corticoids in hamsters: role in circadian timing.
The 24-h patterns of circulating cortisol and corticosterone were determined in male hamsters housed under a 14:10 light-dark cycle. Corticoid levels varied significantly over the 24-h sampling period with peak levels of both hormones occurring near the onset of the daily dark phase. The ratio of cortisol to corticosterone changed dramatically during the day. Corticosterone levels were significantly higher than cortisol during the early part of the light phase; however, cortisol levels became significantly higher than corticosterone when both hormones began their daily rise. To examine whether the circadian rhythm of cortisol secretion could be involved in the physiological control of hamster circadian organization, cortisol was infused at approximately physiological levels into adrenalectomized hamsters either continuously or in a 24-h rhythm. No significant differences were observed in the timing of circadian wheel-running rhythms in hamsters housed in LD 16:8, LD 14:10, or LL when cortisol was infused continuously, in a 24-h rhythm that mimicked the cortisol rhythm of intact hamsters, or in a 24-h rhythm several hours out of phase with the rhythm of intact hamsters. Provision of cortisol in a 24-h rhythm appeared to promote the survival of adrenalectomized hamsters since hamsters receiving a 24-h pattern of cortisol survived the experimental protocol significantly longer than those receiving the same dose of cortisol continuously.


Trans-species polymorphism in humans and the great apes is generally maintained by balancing selection that modulates the host immune response.
Known examples of ancient identical-by-descent genetic variants being shared between evolutionarily related species, known as trans-species polymorphisms (TSPs), result from counterbalancing selective forces acting on target genes to confer resistance against infectious agents. To date, putative TSPs between humans and other primate species have been identified for the highly polymorphic major histocompatibility complex (MHC), the histo-blood ABO group, two antiviral genes (ZC3HAV1 and TRIM5), an autoimmunity-related gene LAD1 and several non-coding genomic segments with a putative regulatory role. Although the number of well-characterized TSPs under long-term balancing selection is still very small, these examples are connected by a common thread, namely that they involve genes with key roles in the immune system and, in heterozygosity, appear to confer genetic resistance to pathogens. Here, we review known cases of shared polymorphism that appear to be under long-term balancing selection in humans and the great apes. Although the specific selective agent(s) responsible are still unknown, these TSPs may nevertheless be seen as constituting important adaptive events that have occurred during the evolution of the primate immune system.


[Amiodarone keratopathy. Prospective longitudinal study].
In order to investigate the frequency of corneal micro-deposits of amiodarone and its relationship to age, sex, dose and treatment duration, we studied one-hundred-fifty consecutive patients from 1982 to 1986. The average age was 33.8 +/- 17.5 years for eighty woman and seventy men. The mean weekly dose was of 1.1 +/- 0.3 g and the duration was 23.7 +/- 15.3 months. A complete eye examination was performed in all cases. The corneal micro-deposits were classified in three levels according to their density. In one-hundred-fourteen cases there were corneal micro-deposits; sixty-nine had grade I, thirty grade II and fifteen grade III. None had visual disturbances. There was only a direct statistical correlation between age and micro-deposit levels. Nine cases had also deposits of pigment in the lens. Two cases presented atypical keratopathy which by their involution after withdrawal of the drug was considered to be amiodarone-related. Fifteen cases presented chronic blepharitis, and ten, chronic non-secreting conjunctivitis. Therefore, age is a determinant factor for corneal accumulation of amiodarone micro-deposits.


MiR-183 overexpression inhibits tumorigenesis and enhances DDP-induced cytotoxicity by targeting MTA1 in nasopharyngeal carcinoma.
MicroRNA 183 (miR-183) was identified to be downregulated in nasopharyngeal carcinoma spheroids and served as a tumor suppressor in nasopharyngeal carcinoma. However, the regulatory mechanism of miR-183 and its role in cisplatin (DDP) resistance in nasopharyngeal carcinoma cells are still unclear. The expression of miR-183 and metastasis-associated protein 1 at messenger RNA and protein levels in nasopharyngeal carcinoma tissues and cells was evaluated using quantitative reverse transcription real-time polymerase chain reaction and western blotting, respectively. CNE1 and CNE2 cells were transfected with miR-183 mimic, miR-183 inhibitor, pcDNA-metastasis-associated protein 1, or respective controls. The effects of miR-183 and metastasis-associated protein 1 overexpression on cell proliferation, invasion, and DDP-induced apoptosis were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, Transwell invasion assay, and flow cytometry analysis, respectively. Luciferase reporter assay was performed to explore whether miR-183 directly targeted metastasis-associated protein 1. Xenograft tumor experiment was applied to confirm the biological function of miR-183 in vivo. MiR-183 was downregulated in nasopharyngeal carcinoma tissues and cells and negatively correlated with metastasis-associated protein 1 expression. Ectopic expression of miR-183 markedly suppressed cell proliferation and invasion and strikingly enhanced DDP-induced apoptosis in nasopharyngeal carcinoma cells, whereas metastasis-associated protein 1 overexpression partially reversed these effects. Luciferase reporter assay demonstrated that metastasis-associated protein 1 was a direct target of miR-183. MiR-183 negatively regulated the expression of metastasis-associated protein 1 at both the messenger RNA and protein levels. Xenograft tumor experiment indicated that miR-183 overexpression repressed tumor growth and improved DDP-induced cytotoxicity in nasopharyngeal carcinoma cells in vivo. MiR-183 overexpression inhibited tumorigenesis and enhanced DDP-induced cytotoxicity by targeting metastasis-associated protein 1 in nasopharyngeal carcinoma, contributing to the development of novel therapeutic approaches for the treatment of clinical nasopharyngeal carcinoma patients.


Toll-like receptor 4 signaling in ventilator-induced diaphragm atrophy.
Mechanical ventilation induces diaphragm muscle atrophy, which plays a key role in difficult weaning from mechanical ventilation. The signaling pathways involved in ventilator-induced diaphragm atrophy are poorly understood. The current study investigated the role of Toll-like receptor 4 signaling in the development of ventilator-induced diaphragm atrophy. Unventilated animals were selected for control: wild-type (n = 6) and Toll-like receptor 4 deficient mice (n = 6). Mechanical ventilation (8 h): wild-type (n = 8) and Toll-like receptor 4 deficient (n = 7) mice.Myosin heavy chain content, proinflammatory cytokines, proteolytic activity of the ubiquitin-proteasome pathway, caspase-3 activity, and autophagy were measured in the diaphragm. Mechanical ventilation reduced myosin content by approximately 50% in diaphragms of wild-type mice (P less than 0.05). In contrast, ventilation of Toll-like receptor 4 deficient mice did not significantly affect diaphragm myosin content. Likewise, mechanical ventilation significantly increased interleukin-6 and keratinocyte-derived chemokine in the diaphragm of wild-type mice, but not in ventilated Toll-like receptor 4 deficient mice. Mechanical ventilation increased diaphragmatic muscle atrophy factor box transcription in both wild-type and Toll-like receptor 4 deficient mice. Other components of the ubiquitin-proteasome pathway and caspase-3 activity were not affected by ventilation of either wild-type mice or Toll-like receptor 4 deficient mice. Mechanical ventilation induced autophagy in diaphragms of ventilated wild-type mice, but not Toll-like receptor 4 deficient mice. Toll-like receptor 4 signaling plays an important role in the development of ventilator-induced diaphragm atrophy, most likely through increased expression of cytokines and activation of lysosomal autophagy.


[Possible effects of infusion pumps on the registration of cardiotocograms (author's transl)].
Artifacts in cardiotachographic tracings caused by infusion pumps have been recorded and are presented. Registration of the artifacts occurs in ultrasonic or abdominal EKG-tracings when the fetal signals are weak or absent. The cause of these misregistrations which can lead to faulty interpretations are an interference of the infusion pump through the general circuit. Interference from the infusion pump is registered when grounding is insufficient or when the infusion pump is in close proximity to the abdominal electrode. In the abdominal EKG technique the instruments have to be in closer proximity than in the ultrasonic technique.


In vivo prenylation of rat proteins: modification of proteins with penta- and hexaprenyl groups.
In vivo protein prenylation was studied in newborn rats by repeated injections of [3H]mevalonate. The highest level of protein-bound mevalonate metabolites was found in the kidney, but incorporation was observed in all organs studied. After fluorography of SDS-polyacrylamide gel electrophoresis-separated polypeptides, labeling was found in the 21- to 28-kDa molecular mass region and, after prolonged exposure of the film, additional bands at both higher and lower molecular masses could be detected. Protein prenylation in the kidney increased during the first 5 days after birth, whereas that in the liver reached a maximum on the fourth day. After methyliodide treatment of the prenylated proteins, farnesol, geranylgeraniol, and two larger isoprenoids, pentaprenol and hexaprenol, were released. In the liver, the ratio of protein-bound geranylgeraniol to farnesol increased from 2 to 4.5 during the first 5 days after birth. Upon subfractionation of the kidney, the highest level of labeling was found in mitochondria and microsomes. When the mitochondria were subfractionated into outer membranes, intermembrane space and an inner membrane/matrix fraction, the labeling pattern of prenylated polypeptides differed in all fractions. The results demonstrate that in vivo labeling of rats can be performed to study the extent, type, and distribution of protein prenylation.


Atheromatous extracranial carotid arteries: CT evaluation correlated with arteriography and pathologic examination.
Dynamic, rapid sequence, axial computed tomography (CT) was employed to evaluate the extracranial common and internal carotid arteries in 17 patients with clinical histories suggesting recent or remote ischemia in the territory supplied by the internal carotid artery. The CT findings were correlated with arteriographic observations and with gross and histologic evaluations of endarterectomy specimens. Areas of arterial wall thickening were evaluated on CT scans with regard to both degree of thickening and radiographic density (attenuation). The degree of vessel wall thickening secondary to atheromatous plaque demonstrated on CT scans corresponded closely to the severity of luminal compromise seen on arteriograms. Isodense or mildly hypodense focal mural thickening noted on CT scans of seven endarterectomy specimens proved to be primarily fibrotic (simple) atheromatous plaque on gross and histologic examination. Areas of markedly lucent focal mural thickening on CT scans of 11 specimens all demonstrated varying amounts of subintimal hemorrhage within loosely arranged and rather acellular (complex) atheromatous plaques on pathologic examination. While arteriography provides information regarding the status of the arterial lumen, CT offers the potential of accurate characterization of pathologic changes in the wall of the extracranial carotid arteries in patients with symptoms of cerebral ischemia.


Reduced synovial membrane macrophage numbers, ELAM-1 expression, and lining layer hyperplasia in psoriatic arthritis as compared with rheumatoid arthritis.
To define the immunohistologic features of the synovial membrane (SM) of patients with psoriatic arthritis (PA) and to compare them with those of an age- and disease-duration-matched population of patients with rheumatoid arthritis (RA). Synovial membrane needle biopsy was performed on 15 PA patients with knee involvement (8 had asymmetric oligoarthritis and 7 had symmetric polyarthritis) and on 15 RA controls. Specimens were stained with monoclonal antibodies against T cells (CD3, CD8, CD4, CD45RO), B cells (CD20), macrophages (Mac387, CD14), and cells bearing class II antigens (DAKO-DR). Vascular endothelium was examined using a polyclonal antibody to Factor VIII-related antigen, and adhesion molecule expression was examined using antibodies 1.3B6, 6.5B5, and 1.4C3, which identify endothelial leukocyte adhesion molecule 1 (ELAM-1), intercellular adhesion molecule 1 (ICAM-1), and vascular cell adhesion molecule 1 (VCAM-1), respectively. There was significantly less lining layer hyperplasia, fewer macrophages, and a greater number of blood vessels in PA SM than in RA SM: ELAM-1 expression was less intense in PA than in RA SM, while there was no difference in expression of ICAM-1 and VCAM-1. Numbers of B cells, T cells, and T cell subsets (predominantly CD4, CD45RO T cells) were similar in both groups of patients. Our findings demonstrate important differences in the immunohistologic features of PA and RA SM: The PA SM is more vascular, ELAM-1 expression is less intense, and fewer macrophages invade the stroma and migrate to the lining layer than in RA SM: However, the lymphocytic infiltrate in the SM of both groups is similar.


Bone marrow-derived Gr1+ cells can generate a metastasis-resistant microenvironment via induced secretion of thrombospondin-1.
Metastatic tumors have been shown to establish permissive microenvironments for metastases via recruitment of bone marrow-derived cells. Here, we show that metastasis-incompetent tumors are also capable of generating such microenvironments. However, in these situations, the otherwise prometastatic Gr1(+) myeloid cells create a metastasis-refractory microenvironment via the induction of thrombospondin-1 (Tsp-1) by tumor-secreted prosaposin. Bone marrow-specific genetic deletion of Tsp-1 abolished the inhibition of metastasis, which was restored by bone marrow transplant from Tsp-1(+) donors. We also developed a 5-amino acid peptide from prosaposin as a pharmacologic inducer of Tsp-1 in Gr1(+) bone marrow cells, which dramatically suppressed metastasis. These results provide mechanistic insights into why certain tumors are deficient in metastatic potential and implicate recruited Gr1(+) myeloid cells as the main source of Tsp-1. The results underscore the plasticity of Gr1(+) cells, which, depending on the context, promote or inhibit metastasis, and suggest that the peptide could be a potential therapeutic agent against metastatic cancer. The mechanisms of metastasis suppression are poorly understood. Here, we have identified a novel mechanism whereby metastasis-incompetent tumors generate metastasis-suppressive microenvironments in distant organs by inducing Tsp-1 expression in the bone marrow–derived Gr1+myeloid cells. A 5-amino acid peptide with Tsp-1–inducing activity was identified as a therapeutic agent against metastatic cancer.


Consumption of carbohydrates, amino acids and oxygen across the intestinal circulation in the fetal sheep.
Since large volumes of nutrient rich amniotic fluid are swallowed by the fetus, it has been suggested that intestinal digestion and absorption contribute significantly to fetal nutrition. To see if nutrients are being gained across the intestine, we measured blood flow and intestinal arteriovenous concentration differences of glucose, alpha-amino nitrogen, lactate, fructose and oxygen in eleven third trimester fetal sheep with chronically implanted vascular catheters. We found that in fetal blood circulating through the intestine nutrient concentration decreased significantly with arterio-venous concentration differences for glucose of 0.78 +/- 0.21 (SEM) mg/dl (P < 0.002), for alpha-amino nitrogen of 0.52 +/- 0.15 mg/dl (P < 0.005), for lactate of 0.68 +/- 0.24 mg/dl (P < 0.05) and for oxygen of 1.50 +/- 0.08 ml/dl (P < 0.001). Fructose concentration did not change. Blood flow to the fetal intestine averaged 89.92 +/- 7.16 ml/min and the intestine consumed 0.74 +/- 0.24 mg of glucose, 0.43 +/- 0.17 mg of alpha-amino nitrogen, 0.83 +/- 0.28 mg of lactate and 1.37 +/- 0.14 ml of oxygen per minute. Compared to previously published values for the umbilical uptake of nutrients the fetal intestine metabolizes about 4% of the glucose, 6% of the alpha-amino nitrogen, 13% of the lactate and 6% of the oxygen obtained across the umbilical circulation. Intestinal absorption does not appear to serve as a source of simple nutrients for the rest of the fetus, in fact intestinal metabolism extracts significant amounts of nutrients from fetal blood.


Protein thiolation and reversible protein-protein conjugation. N-Succinimidyl 3-(2-pyridyldithio)propionate, a new heterobifunctional reagent.
A heterobifunctional reagent, N-succinimidyl 3-(2-pyridyldithio)propionate, was synthesized. Its N-hydroxysuccinimide ester group reacts with amino groups and the 2-pyridyl disulphide structure reacts with aliphatic thiols. A new thiolation procedure for proteins is based on this reagent. The procedure involves two steps. First, 2-pyridyl disulphide structures are introduced into the protein by the reaction of some of its amino groups with the N-hydroxysuccinimide ester sie of the reagent. The protein-bound 2-pyridyl disulphide structures are then reduced with dithiothreitol. This reaction can be carried out without concomitant reduction of native disulphide bonds. The technique has been used for the introduction of thiol groups de novo into ribonuclease, gamma-globulin, alpha-amylase and horseradish peroxidase. N-Succinimidyl 3-(2-pyridyldithio)propionate can also be used for the preparation of protein-protein conjugates. This application is based on the fact that protein-2-pyridyl disulphide derivatives (formed from the reaction of non-thiol proteins with the reagent) react with thiol-containing proteins (with native thiols or thiolated by, for example, the method described above) via thiol-disulphide exchange to form disulphide-linked protein-protein conjugates. This conjugation technique has been used for the preparation of an alpha-amylase-urease, a ribonuclease-albumin and a peroxidase-rabbit anti-(human transferrin) antibody conjugate. The disulphide bridges between the protein molecules can easily be split by reduction or by thiol-disulphide exchange. Thus conjugation is reversible. This has been demonstrated by scission of the ribonuclease-albumin and the alpha-amylase-urease conjugate into their components with dithiothreitol. N-Succinimidyl 3-(2-pyridyldithio)propionate has been prepared in crystalline form, in which state (if protected against humidity) it is stable on storage at room temperature (23 degrees C).


A review of research on women's use of violence with male intimate partners.
This article provides a review of research literature on women who use violence with intimate partners. The central purpose is to inform service providers in the military and civilian communities who work with domestically violent women. The major points of this review are as follows: (a) women's violence usually occurs in the context of violence against them by their male partners; (b) in general, women and men perpetrate equivalent levels of physical and psychological aggression, but evidence suggests that men perpetrate sexual abuse, coercive control, and stalking more frequently than women and that women also are much more frequently injured during domestic violence incidents; (c) women and men are equally likely to initiate physical violence in relationships involving less serious "situational couple violence," and in relationships in which serious and very violent "intimate terrorism" occurs, men are much more likely to be perpetrators and women victims; (d) women's physical violence is more likely than men's violence to be motivated by self-defense and fear, whereas men's physical violence is more likely than women's to be driven by control motives; (e) studies of couples in mutually violent relationships find more negative effects for women than for men; and (f) because of the many differences in behaviors and motivations between women's and men's violence, interventions based on male models of partner violence are likely not effective for many women.


High-Field Asymmetric Waveform Ion Mobility Spectrometry: Practical Alternative for Cardiac Proteome Sample Processing.
Heart tissue sample preparation for mass spectrometry (MS) analysis that includes prefractionation reduces the cellular protein dynamic range and increases the relative abundance of nonsarcomeric proteins. We previously described "IN-Sequence" (IN-Seq) where heart tissue lysate is sequentially partitioned into three subcellular fractions to increase the proteome coverage more than a single direct tissue analysis by mass spectrometry. Here, we report an adaptation of the high-field asymmetric ion mobility spectrometry (FAIMS) coupled to mass spectrometry, and the establishment of a simple one step sample preparation coupled with gas-phase fractionation. The FAIMS approach substantially reduces manual sample handling, significantly shortens the MS instrument processing time, and produces unique protein identification and quantification approximating the commonly used IN-Seq method in less time.


[Primary lymphosarcoma of the prostate gland].
Two large tumor nodes of a total weight of about 100 g were removed from the prostate gland of a patient of 28 with the duration of the disease symptoms of approximately 3 1/2 months. Histological diagnosis of polymorphocellular sarcoma was made. On the 19th day postoperation the patient died with phlegmon of the small pelvis tissues in the presence of cachexia. The autopsy revealed a tumor of the prostate gland outgrowing into the soft tissues of the small pelvis without metastases. Histologically it was a diffuse prolymphocytic lymphosarcoma of the prostate gland with small-loop argirophilic reticulum. This neoplasia was combined with multiple glandular gastric polyps.


Transcription-Coupled Repair of DNA Interstrand Crosslinks by UVSSA.
DNA interstrand crosslinks (ICLs) are covalent bonds between opposing strands of the DNA helix which prevent DNA melting and subsequent DNA replication or RNA transcription. Here, we show that UV Stimulated Scaffold Protein A (UVSSA) participates in transcription-coupled repair of ICLs. UVSSA encodes a protein that regulates the activity of RNA polymerase II (Pol II) to facilitate the repair of UV lesions and to relieve transcription stress resulting from MYC activation. We show that UVSSA knockout sensitizes cells to ICL-inducing drugs, that UVSSA is specifically required for transcription-coupled repair of a single ICL in a fluorescence-based reporter assay, and that transcription-coupled repair of ICLs is defective in UVSSA-/- cells. UVSSA localizes to chromatin upon ICL damage, and interacts with transcribing Pol II, CSA, CSB, and TFIIH. The UVSSA-TFIIH interaction facilitates ICL repair. Finally, UVSSA expression positively correlates with ICL chemotherapy resistance in cancer cell lines. Our data strongly suggest that transcription-coupled ICL repair (TCICR) is a bona fide ICL repair mechanism that contributes to crosslinker drug resistance independently of replication-coupled ICL repair.


Clinical, demographic, and laboratory characteristics of children with nephrolithiasis.
While the incidence of pediatric kidney stones appears to be increasing, little is known about the demographic, clinical, laboratory, imaging, and management variables in this patient population. We sought to describe various characteristics of our stone-forming pediatric population. To that end, we retrospectively reviewed the charts of pediatric patients with nephrolithiasis confirmed by imaging. Data were collected on multiple variables from each patient and analyzed for trends. For body mass index (BMI) controls, data from the general pediatrics population similar to our nephrolithiasis population were used. Data on 155 pediatric nephrolithiasis patients were analyzed. Of the 54 calculi available for analysis, 98 % were calcium based. Low urine volume, elevated supersaturation of calcium phosphate, elevated supersaturation of calcium oxalate, and hypercalciuria were the most commonly identified abnormalities on analysis of 24-h urine collections. Our stone-forming population did not have a higher BMI than our general pediatrics population, making it unlikely that obesity is a risk factor for nephrolithiasis in children. More girls presented with their first stone during adolescence, suggesting a role for reproductive hormones contributing to stone risk, while boys tended to present more commonly at a younger age, though this did not reach statistical significance. These intriguing findings warrant further investigation.


[Autopsies for general practitioners and for clinical specialists; analysis of indications].
To evaluate the reasons for autopsies requested by general practitioners, compared with autopsies requested by clinicians. Retrospective descriptive comparative study. Department of Pathology, Free University Hospital, Amsterdam; Medical Centre Alkmaar; Regional Laboratory Twente, Enschede and Regional Pathology Laboratory, Blaricum. In a series of 303 autopsies requested by general practitioners, the reasons for the autopsy were divided into the following categories: sudden unexpected death, short fatal course of disease, intrauterine and perinatal death, evaluation of a protracted course of disease, non-natural death, and others. Results were compared with two series of 2961 and 1747 autopsies performed for clinicians in a university hospital and a non-university hospital, respectively. General practitioners requested autopsy mainly in cases of sudden unexpected death (48.2%) and short fatal courses of disease (16.5%). For the autopsies requested by clinicians in the university hospital these figures were 6.1% and 15.5%, respectively, in the non-university hospital 9.1% and 18.2%. Owing to the autopsies requested the percentage of cases with unknown or uncertain cause of death was reduced from 67.1% to 14.4%. General practitioners mainly request autopsy when important questions of themselves or of the bereaved need to be answered. Thresholds for autopsy, including financial ones, need to be eliminated to enable general practitioners to request autopsies.


Plasticity of sentence processing networks: evidence from a patient with agrammatic variant of primary progressive aphasia (PPA).
This study reports the results of a longitudinal study examining the effects of treatment for sentence processing deficits for a 70-year-old gentleman (DK) with the agrammatic variant of Primary Progressive Aphasia (PPA). On entry into the study, he presented with a 2-year history of impaired verb and sentence processing and concomitant neural atrophy in primarily subcortical regions. Spanning an 18-month period, treatment focused on improving comprehension and production of syntactically complex, passive and object cleft, structures, consecutively. Results, derived from extensive behavioral and neurocognitive testing, showed not only improved ability to comprehend and produce both trained and untrained, less complex, linguistically related structures in offline tasks, but also improved online sentence processing strategies as revealed by partially normalized eye movements in online comprehension (i.e., emergence of thematic prediction and thematic integration) and production (i.e., use of incremental processing) tasks. Changes in neural activation from pre- to post-treatment of both structures also were found, with upregulation of tissue in both the left and right hemispheres, overlapping with regions recruited by neurotypical adults performing the same task. These findings indicate that Treatment of Underlying Forms (TUF) is effective for treatment of patients with the agrammatic variant of PPA (as it is for those with stroke-induced agrammatism), and show that unaffected neural tissue in patients with PPA is malleable and may be recruited to support language, providing evidence of experience-based plasticity in neurodegenerative disease.


Mechanism of proline production by Kurthia catenaforma.
The fate of aspartic acid used for proline fermentation by Kurthia catenaforma was traced by using aspartic acid-U-(14)C. The radioactivities of proline and glutamic acid increased with the disappearance of aspartic acid. After 40 hr, aspartic acid disappeared from the medium and radioactive alpha-ketoglutaric acid was detected. The radioactivity of proline reached 44% of aspartic acid radioactivity at 40 hr. The specific radioactivities of these amino acids and of alpha-ketoglutaric acid supported the notion that proline is produced mainly from aspartic acid via alpha-ketoglutaric acid and glutamic acid. Since the levels of glutamic acid dehydrogenases (EC 220.127.116.11 and EC 22.214.171.124) were low in this organism, it appears that the nitrogen atom of aspartic acid enters proline by the action of aspartate aminotransferase (EC 18.104.22.168). The mechanism of proline production is discussed on the basis of the role of aspartic acid in this fermentation.


Silicon nanomembranes for fingertip electronics.
We describe the use of semiconductor nanomaterials, advanced fabrication methods and unusual device designs for a class of electronics capable of integration onto the inner and outer surfaces of thin, elastomeric sheets in closed-tube geometries, specially formed for mounting on the fingertips. Multifunctional systems of this type allow electrotactile stimulation with electrode arrays multiplexed using silicon nanomembrane (Si NM) diodes, high-sensitivity strain monitoring with Si NM gauges, and tactile sensing with elastomeric capacitors. Analytical calculations and finite element modeling of the mechanics quantitatively capture the key behaviors during fabrication/assembly, mounting and use. The results provide design guidelines that highlight the importance of the NM geometry in achieving the required mechanical properties. This type of technology could be used in applications ranging from human-machine interfaces to 'instrumented' surgical gloves and many others.


A Biomechanical Comparison of Single-Leg Landing and Unplanned Sidestepping.
Unplanned sidestepping and single-leg landing have both been used to screen athletes for injury risk in sport. The aim of this study was to directly compare the lower limb mechanics of three single-leg landing tasks and an unplanned sidestepping task. Thirteen elite female team sport athletes completed a series of non-contact single-leg drop landings, single-leg countermovement jumps, single-leg jump landings and unplanned sidestepping in a randomized counterbalanced design. Three dimensional kinematics (250 Hz) and ground reaction force (2,000 Hz) data with a participant specific lower limb skeletal model were used to calculate and compare hip, knee and ankle joint kinematics, peak joint moments, instantaneous joint power and joint work during the weight acceptance phase of each sporting task (α=0.05). Peak knee joint moments and relevant injury risk thresholds were used to classify each athlete's anterior cruciate ligament injury risk during unplanned sidestepping and single-leg jump landing. Results showed that peak joint moments, power and work were greater during the single-leg jump landing task when compared to the single-leg drop landings and single-leg countermovement jumps tasks. Peak frontal and sagittal plane knee joint moments, knee joint power, as well as hip and knee joint work were greater during unplanned sidestepping when compared to the landing tasks. Peak ankle joint moments, power and work were greater during the landing tasks when compared to unplanned sidestepping. For 4 of the 13 athletes tested, their anterior cruciate ligament injury risk classification changed depending on whether they performed an unplanned sidestepping or single-leg jump landing testing procedure. To summarize, a single-leg jump landing testing procedure places a larger mechanical on the ankle joint when compared to single-leg drop landings, single-leg countermovement jumps and unplanned sidestepping. An unplanned sidestepping testing procedure places a larger mechanical demand on the knee joint when compared to single-leg landing tasks. Both unplanned sidestepping and single-leg jump landing testing procedures are recommended for classifying an athlete's anterior cruciate ligament injury risk in sport.


The Living Planet Index: using species population time series to track trends in biodiversity.
The Living Planet Index was developed to measure the changing state of the world's biodiversity over time. It uses time-series data to calculate average rates of change in a large number of populations of terrestrial, freshwater and marine vertebrate species. The dataset contains about 3000 population time series for over 1100 species. Two methods of calculating the index are outlined: the chain method and a method based on linear modelling of log-transformed data. The dataset is analysed to compare the relative representation of biogeographic realms, ecoregional biomes, threat status and taxonomic groups among species contributing to the index. The two methods show very similar results: terrestrial species declined on average by 25% from 1970 to 2000. Birds and mammals are over-represented in comparison with other vertebrate classes, and temperate species are over-represented compared with tropical species, but there is little difference in representation between threatened and non-threatened species. Some of the problems arising from over-representation are reduced by the way in which the index is calculated. It may be possible to reduce this further by post-stratification and weighting, but new information would first need to be collected for data-poor classes, realms and biomes.


A new acupuncture method for management of irritable bowel syndrome: A randomized double blind clinical trial.
Irritable bowel syndrome (IBS) is gastrointestinal functional disorder which is multifactorial with unknown etiology. There are several modalities for treatment of it. Acupuncture is increasingly used in numerous diseases, also in gastrointestinal disorders like IBS. The purpose of the study was to assess the effects of catgut embedding acupuncture in improving of IBS. A randomized double blind sham control clinical trial was designed. A total of 60 IBS patients assigned to three separated groups. The first group received clofac as drug only group (DO). The second one received catgut embedding acupuncture in special point (AP) and the last group received sham acupuncture (SA). Symptoms, pain, depression and anxiety assessed before and after two weeks at the end of study. There was statistically significant difference between AP and SA and DO in constipation and bloating. Differences that were statistically significant favored acupuncture on pain (F = 6.409, P = 0.003), and depression (F = 6.735, P = 0.002) as the other outcomes. The average (standard deviation (SD)) of weight loss was 2 kg (0.88) in acupuncture group. Our finding showed a significant positive associated between acupuncture and IBS. Catgut embedding acupuncture is a new method which can eliminated IBS symptoms and can use as alternative therapeutic method for improvement of IBS.


Does free fluid on abdominal computed tomographic scan after blunt trauma require laparotomy?
Abdominal computed tomographic (CT) scans are used in the evaluation of blunt trauma. The purpose of this study was to determine if isolated intraperitoneal fluid seen on CT scan necessitates laparotomy. Trauma registry records of patients who underwent abdominal computed tomography from January 1994 through January 1997 were studied. Data were reviewed for age, gender, CT scan interpretation, associated injuries, and operative findings. Abdominal injury was identified in 126 patients. Seventy-eight patients had evidence of solid-organ injury and 17 patients had extraperitoneal injury. Isolated intraperitoneal fluid was identified in 31 patients. All patients with isolated fluid underwent laparotomy; 29 of these procedures (94%) were therapeutic. Bowel injuries occurred in 18 patients and mesenteric injuries in 8 patients. Five patients had intraperitoneal bladder rupture, and undetected solid-organ injuries were found in two patients. Other organs injured included the stomach, pancreas, ovary, and uterus. Exploratory laparotomy was therapeutic in 94% of patients. Isolated intraperitoneal fluid on CT scan after blunt trauma mandates laparotomy.


Binge Alcohol Drinking Alters Synaptic Processing of Executive and Emotional Information in Core Nucleus Accumbens Medium Spiny Neurons.
The nucleus accumbens (NAc) is a forebrain region mediating the positive-reinforcing properties of drugs of abuse, including alcohol. It receives glutamatergic projections from multiple forebrain and limbic regions such as the prefrontal cortex (PFCx) and basolateral amygdala (BLA), respectively. However, it is unknown how NAc medium spiny neurons (MSNs) integrate PFCx and BLA inputs, and how this integration is affected by alcohol exposure. Because progress has been hampered by the inability to independently stimulate different pathways, we implemented a dual wavelength optogenetic approach to selectively and independently stimulate PFCx and BLA NAc inputs within the same brain slice. This approach functionally demonstrates that PFCx and BLA inputs synapse onto the same MSNs where they reciprocally inhibit each other pre-synaptically in a strict time-dependent manner. In alcohol-naïve mice, this temporal gating of BLA-inputs by PFCx afferents is stronger than the reverse, revealing that MSNs prioritize high-order executive processes information from the PFCx. Importantly, binge alcohol drinking alters this reciprocal inhibition by unilaterally strengthening BLA inhibition of PFCx inputs. In line with this observation, we demonstrate that in vivo optogenetic stimulation of the BLA, but not PFCx, blocks binge alcohol drinking escalation in mice. Overall, our results identify NAc MSNs as a key integrator of executive and emotional information and show that this integration is dysregulated during binge alcohol drinking.