The effects of restoring logged tropical forests on avian phylogenetic and functional diversity.
Selective logging is the most prevalent land-use change in the tropics. Despite the resulting degradation of forest structure, selectively logged forests still harbor a substantial amount of biodiversity leading to suggestions that their protection is the next best alternative to conserving primary, old-growth forests. Restoring carbon stocks under Reducing Emissions from Deforestation and Forest Degradation (REDD+) schemes is a potential method for obtaining funding to protect logged forests, via enrichment planting and liberation cutting of vines. This study investigates the impacts of restoring logged forests in Borneo on avian phylogenetic diversity, the total evolutionary history shared across all species within a community, and on functional diversity, with important implications for the protection of evolutionarily unique species and the provision of many ecosystem services. Overall and understorey avifaunal communities were studied using point count and mist netting surveys, respectively. Restoration caused a significant loss in phylogenetic diversity and MPD (mean pairwise distance) leaving an overall bird community of less total evolutionary history and more closely related species compared to unlogged forests, while the understorey bird community had MNTD (mean nearest taxon distance) that returned toward the lower levels found in a primary forest, indicating more closely related species pairs. The overall bird community experienced a significant loss of functional strategies and species with more specialized traits in restored forests compared to that of unlogged forests, which led to functional clustering in the community. Restoration also led to a reduction in functional richness and thus niches occupied in the understorey bird community compared to unlogged forests. While there are additional benefits of restoration for forest regeneration, carbon sequestration, future timber harvests, and potentially reduced threat of forest conversion, this must be weighed against the apparent loss of phylogenetic and functional diversity from unlogged forest levels, making the biodiversity-friendliness of carbon sequestration schemes questionable under future REDD+ agreements. To reduce perverse biodiversity outcomes, it is important to focus restoration only on the most degraded areas or at reduced intensity where breaks between regimes are incorporated.


Pathogenic Variants in ACTRT1 Cause Acephalic Spermatozoa Syndrome.
Acephalic spermatozoa syndrome is a rare type of teratozoospermia, but its pathogenesis is largely unknown. Here, we performed whole-exome sequencing for 34 patients with acephalic spermatozoa syndrome and identified pathogenic variants in the X-linked gene, ACTRT1, in two patients. Sanger sequencing confirmed the pathogenic variants of ACTRT1 in the patients. Both pathogenic variants of ACTRT1 were highly conserved, and in silico analysis revealed that they were deleterious and rare. Actrt1-knockout mice exhibited a similar acephalic spermatozoa phenotype. Therefore, we speculated that mutations in ACTRT1 account for acephalic spermatozoa syndrome. Moreover, the patients in this study conceived their children through artificial insemination. This study provides further insights for clinicians and researchers regarding the genetic etiology and therapeutic strategies for acephalic spermatozoa patients with pathogenic variants in ACTRT1.


Easy or effective? Explaining young adults' and older adults' likelihood of using various strategies to improve their memory.
We examined two factors to explain why young and older adults report using different memory strategies in their everyday lives. Participants rated the likelihood of use, difficulty, and effectiveness of six categories of memory strategies that they could implement in order to improve their general memory performance. Consistent with previous literature, older adults were more likely to report utilizing "use it or lose it" approaches than young adults, whereas young adults reported a greater likelihood of using task-focused approaches such as internal strategies and effort than older adults. We found that both perceived strategy difficulty and perceived strategy effectiveness predicted likelihood of strategy use, but young and older adults differentially weighed these factors. Young adults' likelihood of using different strategies was influenced more by strategy effectiveness than difficulty. Older adults differentially weighed difficulty and effectiveness when considering how likely they were to use various strategies.


Maternal depression symptoms, unhealthy diet and child emotional-behavioural dysregulation.
Maternal depression and unhealthy diet are well-known risk factors for adverse child emotional-behavioural outcomes, but their developmental relationships during the prenatal and postnatal periods are largely uncharted. This study sought to examine the inter-relationships between maternal depression symptoms and unhealthy diet (assessed during pregnancy and postnatal periods) in relation to child emotional-behavioural dysregulation (assessed at the ages of 2, 4 and 7 years). In a large prospective birth cohort of 7814 mother-child pairs, path analysis was used to examine the independent and inter-related associations of maternal depression symptoms and unhealthy diet with child dysregulation. Higher prenatal maternal depression symptoms were prospectively associated with higher unhealthy diet, both during pregnancy and the postnatal period, which, in turn, was associated with higher child dysregulation up to the age of 7 years. In addition, during pregnancy, higher maternal depression symptoms and unhealthy diet were each independently associated with higher child dysregulation up to the age of 7 years. These results were robust to other prenatal, perinatal and postnatal confounders (such as parity and birth complications, poverty, maternal education, etc.). Maternal depression symptoms and unhealthy diet show important developmental associations, but are also independent risk factors for abnormal child development.


A real world evaluation of a treatment for infant colic based on the experience and perceptions of 4004 parents.
Infant colic (IC) is a common condition in young babies seen by primary care health professionals, especially health visitors. Nevertheless, the diagnostic criteria for IC are vague, which has resulted in a lack of clarity in published guidance on its causes and treatment. Credence has been given to alternative therapies, while health professionals are sceptical about the efficacy of over-the-counter treatments. Some 4004 parents of babies considered to have IC participated in this retrospective real world evidence study on the efficacy of a simeticone suspension in the treatment of IC. They were recruited via social media sources and were eligible for inclusion if their baby had received at least one dose of the simeticone suspension. Data were collected via an online questionnaire. The results showed that crying and discomfort-associated behaviour reduced and the babies' sleeping patterns improved following use of the suspension. More than two-thirds (69.7%) of respondents, who either used the suspension on its own or alongside another treatment, reported improvements in the signs of IC within one day. Almost all (93.2%) considered that its use was associated with either complete resolution of IC or had some effect on symptoms.


Optimization of Internally Deleted Dystrophin Constructs.
Duchenne muscular dystrophy (DMD) is a severe, genetic muscle disease caused by the absence of the sarcolemmal protein dystrophin. Gene replacement therapy is considered a potential strategy for the treatment of DMD, aiming to restore the missing protein. Although the elements of the dystrophin molecule have been identified and studies in transgenic mdx mice have explored the importance of a number of these structural domains, the resulting modified dystrophin protein products that have been developed so far are only partially characterized in relation to their structure and function in vivo. To optimize a dystrophin cDNA construct for therapeutic application we designed and produced four human minidystrophins within the packaging capacity of lentiviral vectors. Two novel minidystrophins retained the centrally located neuronal nitric oxide synthase (nNOS)-anchoring domain in order to achieve sarcolemmal nNOS restoration, which is lost in most internally deleted dystrophin constructs. Functionality of the resulting truncated dystrophin proteins was investigated in muscle of adult dystrophin-deficient mdx mice followed by a battery of detailed immunohistochemical and morphometric tests. This initial assessment aimed to determine the overall suitability of various constructs for cloning into lentiviral vectors for ex vivo gene delivery to stem cells for future preclinical studies.


Purification and characterization of Gbetagamma-responsive phosphoinositide 3-kinases from pig platelet cytosol.
A G-protein betagamma subunit (Gbetagamma)-responsive phosphoinositide 3-kinase (PI 3-kinase) was purified approximately 5000-fold from pig platelet cytosol. The enzyme was purified by polyethylene glycol precipitation of the cytosol followed by column chromatography on Q-Sepharose fast flow, gel filtration, heparin-Sepharose, and hydroxyapatite. The major Gbetagamma-responsive PI 3-kinase is distinct from p85 containing PI 3-kinase as the activities can be distinguished chromatographically and immunologically and is related to p110gamma as it cross-reacts with anti-p110gamma-specific antibodies. The p110gamma-related PI 3-kinase cannot be activated by G-protein alphai/o subunits, and it has an apparent native molecular mass of 210 kDa. The p110gamma-related PI 3-kinase phosphorylates phosphatidylinositol (PtdIns), phosphatidylinositol 4-phosphate (PtdIns4P), and phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). The apparent Km values for ATP were found to be 25 microM with PtdIns, 44 microM with PtdIns4P, and 37 microM with PtdIns(4,5)P2 as the substrate. Gbetagamma subunits did not alter the Km of the enzyme for ATP; however, Vmax increased 2-fold with PtdIns as substrate, 3.5-fold with PtdIns4P, and 10-fold with PtdIns(4,5)P2. Under basal conditions the apparent Km values for lipid substrates were 64, 10, and 15 microM for PtdIns, PtdIns4P, and PtdIns(4,5)P2, respectively. In the presence of Gbetagamma subunits the dependence of PI 3-kinase activity on the concentrations of lipid substrates became complex with the highest level of stimulation occurring at high substrate concentration, suggesting that the binding of Gbetagamma and lipid substrate (particularly PtdIns(4,5)P2) may be mutually cooperative. Wortmannin and LY294002 inhibit the Gbetagamma-responsive PI 3-kinase activity with IC50 values of 10 nM and 2 microM, respectively. Unlike the p85 containing PI 3-kinase in platelets, the p110gamma-related PI 3-kinase is not associated with a PtdIns(3,4,5)P3 specific 5-phosphatase. The p85-associated PI 3-kinase was not activated by Gbetagamma alone but could be synergistically activated by Gbetagamma and phosphotyrosyl platelet-derived growth factor receptor peptides. This may represent a form of coincidence detection through which the effects of tyrosine kinase and G-protein-linked receptors might be coordinated.


Inhibition of immunoproteasome subunit low molecular mass polypeptide 7 with ONX-0914 improves hypoxic-ischemic brain damage via PI3K/Akt signaling.
The immunoproteasome subunit low molecular mass polypeptide 7 (LMP7) leads to brain injuries, such as autoimmune neuritis and ischemic stroke, by activating inflammation. However, the roles and mechanisms of LMP7 in hypoxic-ischemic brain damage (HIBD) remain unclear. This study explored these issues in a rat model of HIBD. Pathology was evaluated using hematoxylin-eosin staining. LMP7 expression was detected using western blot analysis, reverse transcription-quantitative PCR (RT-qPCR), and immunohistochemical staining. The presence of proinflammatory cytokines, including tumor necrosis factor-a, interleukin-6, and interleukin-1β, was tested using ELISA and RT-qPCR. Behavioral performance was evaluated using a short-term neurological function score and the Morris water maze test. Compared to those in the Sham group, the HIBD group exhibited obvious upregulated LMP7 and pro-inflammatory cytokine levels. HIBD rats exhibited severe pathological and behavioral damage. LMP7 inhibition with ONX-0914 reduced proinflammatory cytokine expression, attenuated pathological damage, and enhanced behavioral performance of rats with HIBD. Inhibition of phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling with LY29400 increased LMP7 expression and abolished the protective effects of ONX-0914 in HIBD rats. Our findings indicate that LMP7 aggravates brain injury by triggering inflammatory responses in HIBD rats. LMP7 inhibition with ONX-0914 exerts protective effects on HIBD rats, possibly via PI3K/Akt signaling.


Effects of mixing on fed-batch fermentation of L-ornithine.
The effects of mixing on L-ornithine fermentation were studied using an L-arginine auxotrophic mutant of Brevibacterium ketoglutamicum ATCC 21092. Three different modes of fed-batch culture using two different impeller types were studied in a 7 l fermentor. The first two modes of fed-batch culture were carried out in a fermentor equipped with six-flat-blade disk-turbine impellers with top and bottom feeding. The third mode of fed batch culture was carried out using pitched-six-flat-blade disk-turbine impellers with top feeding. The titre of L-ornithine increased up to 1.8 fold with bottom-feeding or when the pitched-six-flat-blade disk-turbine impellers were used compared to when the six-flat-blade disk-turbine impellers with top-feeding were used. It was observed that the mixing time of the limiting nutrients varied significantly depending on both the direction of feeding and the impeller type. Since the profiles of the specific rates of CO2 evolution, oxygen and glucose uptakes were very similar for the three culture modes, it could be reasonably assumed that the microorganism exhibited similar growth rates for each mode used. However, different amino acid producing activities were observed in the three culture modes. From these results it is concluded that the productivity of L-ornithine fermentation is significantly improved by shortening the mixing time of the limiting nutrient in the fermentor.


Feature amplified voting algorithm for functional analysis of protein superfamily.
Identifying the regions associated with protein function is a singularly important task in the post-genomic era. Biological studies often identify functional enzyme residues by amino acid sequences, particularly when related structural information is unavailable. In some cases of protein superfamilies, functional residues are difficult to detect by current alignment tools or evolutionary strategies when phylogenetic relationships do not parallel their protein functions. The solution proposed in this study is Feature Amplified Voting Algorithm with Three-profile alignment (FAVAT). The core concept of FAVAT is to reveal the desired features of a target enzyme or protein by voting on three different property groups aligned by three-profile alignment method. Functional residues of a target protein can then be retrieved by FAVAT analysis. In this study, the amidohydrolase superfamily was an interesting case for verifying the proposed approach because it contains divergent enzymes and proteins. The FAVAT was used to identify critical residues of mammalian imidase, a member of the amidohydrolase superfamily. Members of this superfamily were first classified by their functional properties and sources of original organisms. After FAVAT analysis, candidate residues were identified and compared to a bacterial hydantoinase in which the crystal structure (1GKQ) has been fully elucidated. One modified lysine, three histidines and one aspartate were found to participate in the coordination of metal ions in the active site. The FAVAT analysis also redressed the misrecognition of metal coordinator Asp57 by the multiple sequence alignment (MSA) method. Several other amino acid residues known to be related to the function or structure of mammalian imidase were also identified. The FAVAT is shown to predict functionally important amino acids in amidohydrolase superfamily. This strategy effectively identifies functionally important residues by analyzing the discrepancy between the sequence and functional properties of related proteins in a superfamily, and it should be applicable to other protein families.


Short-Time Wind Speed Forecast Using Artificial Learning-Based Algorithms.
The need for an efficient power source for operating the modern industry has been rapidly increasing in the past years. Therefore, the latest renewable power sources are difficult to be predicted. The generated power is highly dependent on fluctuated factors (such as wind bearing, pressure, wind speed, and humidity of surrounding atmosphere). Thus, accurate forecasting methods are of paramount importance to be developed and employed in practice. In this paper, a case study of a wind harvesting farm is investigated in terms of wind speed collected data. For data like the wind speed that are hard to be predicted, a well built and tested forecasting algorithm must be provided. To accomplish this goal, four neural network-based algorithms: artificial neural network (ANN), convolutional neural network (CNN), long short-term memory (LSTM), and a hybrid model convolutional LSTM (ConvLSTM) that combines LSTM with CNN, and one support vector machine (SVM) model are investigated, evaluated, and compared using different statistical and time indicators to assure that the final model meets the goal that is built for. Results show that even though SVM delivered the most accurate predictions, ConvLSTM was chosen due to its less computational efforts as well as high prediction accuracy.


Ethanol inhibits nonadrenergic, noncholinergic neurotransmission in the anococcygeus muscle of the rat.
The anococcygeus muscle of the rat is innervated by both excitatory adrenergic and inhibitory nonadrenergic, noncholinergic (NANC) neurons. The transmitter released from NANC neurons appears to be nitric oxide or a related molecule. In vitro, acute administration of ethanol inhibited, in a dose-dependent manner, NANC-induced relaxation of anococcygeus muscle obtained from ethanol-naive animals. Two days of in vivo ethanol administration resulted in an increase in the maximal relaxation induced by stimulation of NANC neurons and in a significant shift to the right of the acute ethanol dose-response curve for inhibition of NANC relaxation. The sensitivity of the anococcygeus muscle to relaxation induced by the nitric oxide donors, acidified sodium nitrite or sodium nitroprusside, was not altered significantly by acute in vitro or chronic ethanol treatment 2 days in vivo. These data suggest that acutely administered in vitro ethanol inhibits the production of nitric oxide induced by stimulation of NANC neurons. Data further suggest that 2 days of ethanol administration in vivo produce an enhanced responsiveness of the NANC neurons to transmural stimulation and that this enhanced responsiveness accounts for the tolerance to the inhibition induced by the acutely administered ethanol in vitro.


Card9-dependent IL-1β regulates IL-22 production from group 3 innate lymphoid cells and promotes colitis-associated cancer.
Inflammatory bowel diseases (IBD) are key risk factors for the development of colorectal cancer, but the mechanisms that link intestinal inflammation with carcinogenesis are insufficiently understood. Card9 is a myeloid cell-specific signaling protein that regulates inflammatory responses downstream of various pattern recognition receptors and which cooperates with the inflammasomes for IL-1β production. Because polymorphisms in Card9 were recurrently associated with human IBD, we investigated the function of Card9 in a colitis-associated cancer (CAC) model. Card9-/- mice develop smaller, less proliferative and less dysplastic tumors compared to their littermates and in the regenerating mucosa we detected dramatically impaired IL-1β generation and defective IL-1β controlled IL-22 production from group 3 innate lymphoid cells. Consistent with the key role of immune-derived IL-22 in activating STAT3 signaling during normal and pathological intestinal epithelial cell (IEC) proliferation, Card9-/- mice also exhibit impaired tumor cell intrinsic STAT3 activation. Our results imply a Card9-controlled, ILC3-mediated mechanism regulating healthy and malignant IEC proliferation and demonstrates a role of Card9-mediated innate immunity in inflammation-associated carcinogenesis.


Serum acetaminophen concentrations after acute overdose are not altered by opioid co-ingestion.
Serum acetaminophen concentrations are of critical importance in determining the need for acetylcysteine therapy after acute acetaminophen overdose. Limited data suggest opioid co-ingestion might alter acetaminophen pharmacokinetics. The present study was designed to examine serum acetaminophen concentrations after acute overdose, and to compare between patients that co-ingested an opioid and those that did not. A prospective study of consecutive patients that presented to hospital within 16 hr of acute acetaminophen overdose. Equivalent 4-hr acetaminophen concentrations were calculated using the serum acetaminophen concentration at a fixed interval 3 to 16 hr after ingestion. Groups were compared using Mann Whitney tests. There were 990 patients; 295 (29.8%) had co-ingested an opioid, and 695 had not. The median (interquartile range) stated dose was 10 g (6-16 g) vs. 10 g (7-16 g) respectively (P = 0.94), interval between ingestion and acetaminophen determination was 4.5 hr (4.0-6.0 hr) vs. 4.5 hr (4.0-5.5 hr) respectively (P = 0.41), and serum acetaminophen concentration was 56 mg/l (24-105 mg/l) va. 60 mg/l (23-129 mg/l) respectively (P = 0.25). A positive relationship was noted between stated dose and equivalent 4-hr serum acetaminophen concentration, but did not differ between groups. The acetaminophen dose-concentration relationship was similar in patients that did and did not co-ingest an opioid. Therefore, early serum acetaminophen concentrations can be used to determine the extent of drug exposure, irrespective of whether an opioid has been co-ingested.


QOL and Survival Comparisons by Race in Oncology Clinical Trials.
Significant efforts have been made to increase access and accrual to clinical trials for minority cancer patients (MP). This meta-analysis looked for differences in survival and baseline quality of life (QOL) between MP and non-minority cancer patients (NMP). Baseline QOL and overall survival times from 47 clinical trials (6513 patients) conducted at Mayo Clinic Cancer Center/North Central Cancer Treatment Group were utilized. Assessments included Uniscale, Linear Analogue Self Assessment, Symptom Distress Scale (SDS), Profile of Mood States and Functional Assessment of Cancer Therapy - General, each transformed into a 0-100 scale with higher scores indicating better outcomes. This transformation involves subtracting the lowest possible value from the assessment, dividing by the range of the scale (the maximum minus the minimum), and multiplying by 100. Analyses included Fisher's Exact tests, linear regression, Kaplan-Meier curves, and Cox proportional hazards models. Eight percent of patients self-reported as MP (0.45% American Indian/Alaskan Native, 0.7% Asian, 5% Black/African American, 1.5% Hispanic, 0.1% Native Hawaiian and 0.3% Other). MP had no meaningful deficits relative to non-MP in overall QOL but were slightly worse on FACT-G total score, physical, social/family, functional, and SDS nausea severity. MP with lung, neurological or GI cancers had significantly worse mean scores in nausea (58 vs. 69), sleep problems (34 vs. 54); emotional (53 vs. 74); and social/family (60 vs. 67), respectively. Regression models confirmed these results. After adjusting for disease site, there were no significant differences in survival. MP on these clinical trials indicated small deficits in physical, social, and emotional subscales at baseline compared to NMP. Within cancer sites, MP experienced large deficits for selected QOL domains that bear further attention.


Pharmacoepidemiological perspectives on the suspected teratogenic effects of benzodiazepines.
Abnormalities (dysmorphism, mental retardation etc) were reported (The Lancet 1987; i: 108-9) in children of mothers using high doses of benzodiazepines regularly during pregnancy in the area of Sweden with the highest use of benzodiazepines (Gothenburg). This signal was investigated in Sweden by use of available drug data bases, and in the USA by use of computerized health care data in Medicaid, including drugs and diagnoses. Neither the Swedish survey, nor the preliminary analysis of the pediatric profiles in the US-Medicaid population supported the occurrence of drug-associated abnormalities as described in The Lancet. Also, no significant findings were seen in a survey in Czechoslovakia on behavioural changes in children, whose mothers used diazepam during the second part of their pregnancy. Although available pharmacoepidemiology data do not confirm the hypothesis, this review points to existing geographic differences in use of benzodiazepines during pregnancy (frequency of chronic use and dosage level) and their potential clinical consequences. (Fig. 1, Ref. 25).


Seminal plasma microRNAs: potential biomarkers for spermatogenesis status.
MicroRNAs (miRNAs) are small non-coding RNAs (18-25 nt), playing important regulatory roles via interaction with cellular messenger RNAs. The altered expression of miRNAs in specific tissues has been associated with diseases such as cancer and diabetes. We examined the presence of two selected miRNAs (miR-19b and let-7a) in human seminal plasma from fertile men and idiopathic infertile patients with oligozoospermia and non-obstructive azoospermia (NOA) using quantitative real-time PCR. We detected miRNAs in the seminal plasma of humans. The levels of miRNAs in the seminal plasma were reproducible in repeat samples from the same individuals. In addition, we examined the expression patterns of two selected miRNAs in 96 idiopathic infertile males (48 oligozoospermia and 48 NOA) and 48 fertile controls. Another 48 individuals of each group were used for verification. Our data showed that the expression levels of these two miRNAs in the seminal plasma significantly increased in idiopathic infertile males with NOA compared with fertile controls, whereas the expression levels were similar between idiopathic infertile males with oligozoospermia and fertile controls. In conclusion our results indicate that the expression of miR-19b and let-7a in the seminal plasma are reproducible and stable. Aberrant over-expression levels of miR-19b and let-7a may be an indicator of spermatogenic failure.


Unfolding Mechanisms and Conformational Stability of the Dimeric Endophilin N-BAR Domain.
Endophilin, which is a member of the Bin-amphiphysin-Rvs (BAR) domain protein superfamily, contains a homodimeric N-BAR domain of a characteristic crescent shape. The N-BAR domain comprises a six-helix bundle and is known to sense and generate membrane curvature. Here, we characterize aspects of the unfolding mechanism of the endophilin A1 N-BAR domain during thermal denaturation and examine factors that influence the thermal stability of this domain. Far-UV circular dichroism (CD) spectroscopy was applied to monitor changes in the secondary structure above room temperature. The protein's conformational changes were further characterized through Foerster resonance energy transfer and cross-linking experiments at varying temperatures. Our results indicate that thermal unfolding of the endophilin N-BAR is (minimally) a two-step process, with a dimeric intermediate that displays partial helicity loss. Furthermore, a thermal shift assay and temperature-dependent CD were applied to compare the unfolding processes of several truncated versions of endophilin. The melting temperature of the N-BAR domain decreased when we deleted either the N-terminal H0 helix or the unstructured linker of endophilin. This result suggests that these intrinsically disordered domains may play a role in structurally stabilizing the functional N-BAR domain in vivo. Finally, we show that single-site mutations can also compromise endophilin's thermal stability.


Cardiovascular actions of lead and relationship to hypertension: a review.
Chronic and acute lead poisoning cause overt, clinical symptoms of cardiac and vascular damage with potentially lethal consequences. Morphological, biochemical, and functional derangements of the heart have all been described in patients following exposure to excessive lead levels. Disturbances in cardiac electrical and mechanical activity and postmortem evidence of morphological and biochemical derangements of the myocardium have all been reported following excessive exposure to lead in humans. In addition, signs of vascular degeneration, abnormal vascular smooth muscle function, and altered vessel compliance have been described in humans chronically and acutely exposed to toxic lead levels. Similar cardiovascular complications have been detected following excessive lead exposure in experimental animals. Myocarditis, electrocardiographic disturbances, heightened catecholamine arrhythmogenicity, altered myocardial contractile responsiveness to inotropic stimulation, degenerative structural and biochemical changes affecting the musculature of the heart and vasculature, hypertension, hypercholesterolemia, atherosclerosis, and increased vascular reactivity to alpha-adrenergic agonists have been among the reported cardiovascular disturbances linked to lead poisoning. Less certain are the cardiovascular effects of subclinical lead poisoning. Although controversial, chronic low-level lead exposure has been linked to hypertension and other cardiovascular disturbances in both clinical and experimental studies. In general, it can be concluded that lead over a wide range of exposure intensities can induce significant changes in the function of the cardiovascular system. Evidence points to the involvement of multiple sites of action. Cardiac and vascular sites, as well as sites within the central nervous system, have all been implicated in the sequelae of cardiovascular effects. The exact pathogenic mechanisms that underlie the actions of lead in the cardiovascular system, however, have yet to be elucidated definitively.(ABSTRACT TRUNCATED AT 250 WORDS)


Aging without Medicare? Evidence from New York City.
Medicare and Social Security often are assumed to provide universal coverage for the population age 65 and older. Evidence from New York City raises doubts. Data from the Statewide Planning and Research Cooperative System, the Centers for Medicare and Medicaid Services, the Social Security Administration, and the U.S. Bureau of the Census provide evidence that 16% to 20% of New York City residents age 65 and older lack such coverage. Noncoverage is not unique to this city, but it may be particularly common there. Noncoverage is pronounced in, but not limited to, certain immigrant groups. Because the population share covered by Medicare increases with age and most hospitalizations not covered by Medicare are paid by Medicaid, Medicaid gradually may be replacing Medicare as the payer for hospitalizations for a substantial share of the 65+ population in New York City.


Transition into adult care: factors associated with level of preparedness among adolescents living with HIV in Cambodia.
Preparing adolescents for transition into adult care and supporting their acquisition of self-health care management skills is a critical determinant of their post-transition HIV care outcomes. However, there is a scarcity of research on effective transition strategies. This study explores factors associated with adolescent preparedness for transition into adult care in Cambodia. In August 2016, a cross-sectional study was conducted among 223 adolescents living with HIV aged 15-17, randomly selected from 11 antiretroviral therapy clinics, utilizing a structured questionnaire. The level of preparedness was determined using a pre-existing scale, and adolescents were categorized as having a high- or low level of preparedness for transition. Bivariate and multivariate analyses were conducted. Of 223 adolescents, 55.2% were male, and their mean age was 15.8 years. Overall, 53.3% had a high level of preparedness for transition. As part of the transition protocol, 2.7% had completed a transfer form, 24.7% had a transition case manager, 29.6% had been counselled about the transition, and 19.7% had visited an adult ART clinic. In multivariate analysis, a higher level of preparedness for transition was independently associated with older age (AOR 2.44, 95% CI 1.34-4.46; p = 0.004), family having received social support for their health (AOR 5.32, 95% CI 1.97-14.36; p = 0.001), knowing the kind of treatment they received (ART) (AOR 12.67, 95% CI 2.91-15.19; p = 0.001), trust in friends or family for HIV treatment (AOR 7.82, 95% CI 1.13-8.89; p = 0.008), receiving counseling on transition (AOR 3.17, 95% CI 1.15-8.76; p = 0.03), having a 'Case Manager' identified to support them during the preparation process for transition (AOR 3.89, 95% CI 1.08-13.96; p = 0.04), and satisfaction with preparation process for transition in general (AOR 0.35, 95% CI 0.03-0.87; p = 0.01). A range of individual, social and health system and services factors may determine successful transition preparedness among adolescents in Cambodia. Strengthening implementation of age-appropriate and individualized case management transition at all sites, while creating supportive family, peer, and healthcare environments for adolescent transition is required.


Unintentional ingestion of brimonidine antiglaucoma drops: a case report and review of the literature.
A previously healthy, 1-year 7-month-old boy was brought to the emergency department after having unintentionally ingested topical brimonidine antiglaucoma drops. He was pale and lethargic and had brief periods of apnea and bradycardia. Activated charcoal was administered, and supportive measures were initiated, achieving complete resolution of the symptoms 4 hours after admission. Brimonidine poisoning is very rare, and a high index of suspicion is necessary to identify its signs and symptoms in the pediatric emergency department. To our knowledge, only 1 case of brimonidine poisoning after oral ingestion of this topical drug has been previously reported in the literature.


Are We Missing the Opportunity to Measure Muscle Mass on Computed Tomography Thorax?
Hand grip strength (HGS) and fat free mass index (FFMI) are important indicators of skeletal muscle mass and correlate with prognosis in patients with respiratory diseases. It is also possible to estimate muscle mass by measuring muscle density and volume on cross sectional imaging. We reviewed all patients of the All Wales Cystic Fibrosis Centre who had a computed tomography thorax as part of routine clinical care between 2013 and 2017. By multiplying the volume and average Hounsfield units of the paraspinal muscles at T4 and T12 levels we were able to estimate the patients skeletal muscle mass. This was compared with their FFMI, HGS and forced expiratory volume in 1 second. Measurements of muscle mass at T4 and T12 showed significant correlation with HGS and FFMI, and T12 also showed significant correlation with forced expiratory volume in 1 second. This method may provide further prognostic information for patient with cystic fibrosis, particularly where equipment for HGS and FFMI assessments are lacking.


Acid phosphatase activity in the rat neurohypophysis during increased levels of gonadothrophic hormones, in diabetes insipidus (Bratteboro strain) and after water loading.
The acid phos phatase activity of the rat neurohypophysis was measured during increased gonadotrophic hormone levels, in diabetes insipidus (DI) (Brattleboro strain) and after water loading, i.e. conditions that interfere with the function of the hypothalamo-neurohypophyseal system (HNS). In addition determination of tissue protein, lipid and DNA and of water metabolism were performed. Neurohypophyseal acid phosphatase activity expressed on a dry weight basis increased under all conditions. For gonadectomized females, Brattleboro rats and water loaded males an increased water metabolism was observed. The increased acid phosphatase activity is interpreted as being related to disposal of release residues during stimulation of the HNS (increased gonadotrophic hormone levels and DI) and to disposal of neurosecretory material during inhibition (water loading).


Parallel and distributed encoding of speech across human auditory cortex.
Speech perception is thought to rely on a cortical feedforward serial transformation of acoustic into linguistic representations. Using intracranial recordings across the entire human auditory cortex, electrocortical stimulation, and surgical ablation, we show that cortical processing across areas is not consistent with a serial hierarchical organization. Instead, response latency and receptive field analyses demonstrate parallel and distinct information processing in the primary and nonprimary auditory cortices. This functional dissociation was also observed where stimulation of the primary auditory cortex evokes auditory hallucination but does not distort or interfere with speech perception. Opposite effects were observed during stimulation of nonprimary cortex in superior temporal gyrus. Ablation of the primary auditory cortex does not affect speech perception. These results establish a distributed functional organization of parallel information processing throughout the human auditory cortex and demonstrate an essential independent role for nonprimary auditory cortex in speech processing.


Contribution of mortality from cardiovascular disease to overall mortality.
The most significant chronic non-infectious diseases (CVD) are cardiovascular diseases (CVD), oncological, chronic respiratory diseases, diabetes, which together account for 59% of 57 million deaths each year in the world and constitute 46% of the global burden of the disease. To study the contribution of cardiovascular diseases to the overall mortality of the population of the Poltava region. For the study, the mortality data of the population of Ukraine and the Poltava region for 2005-2015 were used. Sources of data on the natural movement of the population were forms of state statistical reporting and official data on calculations for primary data of statistical offices. The calculation of intensive death rates by the method of direct standardization according to the world standard (Standard "World"), approved by WHO [19] was carried out. For the analysis of time trends, the JoinPoint software, the Regression Program Statistical Methodology and Applications Branch, the Surveillance Research Program (Electronic Resourse) / National Cancer Institute, was used to analyze population-based piece-wise time trends, as well as the MS EXCEL 2010 office suite. It was shown the increase in the overall mortality of the population of the Poltava region and Ukraine as a whole. In the structure of the causes of death, the first place is occupied by diseases of the cardiovascular system, and in the structure of the Diseases of the blood supply systems, the greatest part is occupied by ischemic heart disease. An increase in mortality and mortality from acute myocardial infarction was noted. The contribution of diseases of the cardiovascular system plays a leading role among all causes of mortality in the Poltava region and in Ukraine as a whole. There is an increase in overall mortality and in particular from acute myocardial infarction. A significant difference between mortality rates, both general and from myocardial infarction, in Ukraine and the Poltava region was not revealed (p> 0.05).


Stoichiometry and pharmacology of two human alpha4beta2 nicotinic receptor types.
The alpha4beta2 nicotinic acetylcholine receptor (nAChR) is the most abundant nAChR subtype in the brain, where it forms the high-affinity binding site for nicotine. The alpha4beta2 nAChR belongs to a gene family of ligand-gated ion channels that also includes muscle nAChRs, GABAA receptors, and glycine receptors and that assembles into pentameric structures. alpha4 and beta2 nAChR subunits expressed heterologously in Xenopus laevis oocytes assemble into a mixture of high- and low-affinity functional receptors, giving rise to biphasic ACh concentration-response curves (Zwart and Vijverberg, 1998; Buisson and Bertrand, 2001; Houlihan et al., 2001). High- and low-affinity alpha4beta2 nAChRs differ significantly in their functional and pharmacological properties (Zwart and Vijverberg, 1998; Buisson and Bertrand, 2001; Houlihan et al., 2001; Nelson et al., 2003) and result from the assembly of alpha4 and beta2 subunits into two distinct stoichiometric arrangements: (alpha4)2(beta2)3(high-affinity subtype) and (alpha4)3(beta2)2 (low-affinity subtype) (Nelson et al., 2003). In this study we have examined the functional and pharmacological properties of high- and low-affinity alpha4beta2 receptors using two-electrode voltage clamp procedures on Xenopus oocytes transfected with high (1:10) or low (10:1) ratios of alpha4/beta2 cDNAs, which yield high (1:10)- or low (10:1)- affinity receptors with monophasic ACh concentration- response curves. Furthermore, to determine the stoichiometry of high- and low-affinity receptors expressed heterologously by Xenopus oocytes, we have determined the stoichiometry of high- and low-affinity alpha4beta2 receptors by mutating a highly conserved hydrophobic residue in the middle (position 9') of the pore-lining domain, which increases agonist potency in a manner that allows predictions on subunit composition (Cooper et al., 1991; Revah et al., 1991; Labarca et al., 1995; Boorman et al., 2000).


Matrix metalloproteinase-1 and tissue inhibitor of metalloproteinases-1 levels in severely obese patients: what is the effect of weight loss?
There is increased evidence that circulating levels of matrix metalloproteinases and their tissue inhibitors are altered in obesity and may be implicated in its pathogenesis. This study aimed to compare the serum concentrations of pro-matrix metalloproteinase-1 (pro-MMP-1) and tissue inhibitor of metalloproteinases-1 (TIMP-1) in severely obese patients with or without metabolic syndrome, and to investigate the potential effect of weight loss on their circulating levels. A total of 102 severely obese subjects were included in our study. Of these, 61 had no other features of metabolic syndrome, while the rest were 41 age- and sex-matched subjects with severe obesity and metabolic syndrome according to the NCEP-ATP criteria. Fourty-two age and sex-matched healthy lean individuals were used as controls. Severely obese subjects had higher circulating levels of TIMP-1 than the lean ones (120.6 ± 50.6 vs. 89.0 ± 35.2 ng/ml) and obese patients with metabolic syndrome had higher TIMP-1 levels than their metabolically healthy counterparts (134.8 ± 38.4 vs. 111.0 ± 55.62 ng/ml). A positive association was also found between TIMP-1 levels and various anthropometric and metabolic parameters in the obese subjects. Moreover, weight loss of more than 5% resulted in a significant reduction of the TIMP-1 levels in obese subjects, irrespective of the presence or not of metabolic syndrome. No significant differences in pro-MMP-1 concentrations were found between the obese (2.8 ± 2.4 ng/ml) and lean individuals (2.8 ± 0.8 ng/ml). In conclusion, we demonstrated that increased TIMP-1 serum levels are found in severely obese patients and particularly in these with metabolic syndrome, while weight loss of more than 5% resulted in reduction of TIMP-1 levels.


Invited Commentary: The Framingham Offspring Study-A Pioneering Investigation Into Familial Aggregation of Cardiovascular Risk.
Launched in 1948, the Framingham Heart Study was a seminal prospective cohort study of 5,209 adult residents of Framingham, Massachusetts, that was designed to uncover the determinants and natural history of coronary heart disease. Data from this original cohort established the cardiac threat posed by high blood pressure, high cholesterol, smoking, obesity, physical inactivity, diabetes, and other factors. In the late 1960s, investigators conceived the innovative idea of assembling a second cohort that comprised the adult children of the original study population (and these children's spouses). From 1971 to 1975, a total of 5,124 individuals were recruited to form the Offspring Cohort. Studying successive generations in this fashion provided an efficient method for examining secular trends in cardiovascular disease and its risk factors, as well as an opportunity to assess familial aggregation of risk without the threat of recall bias. In a paper published in the September 1979 issue of the Journal, then study director William Kannel et al. (Am J Epidemiol. 1979;110(3):281-290) described the sampling design of the Offspring Study and presented selected baseline characteristics of the cohort. The scientific questions addressed by this research provided the impetus for a decades-long effort-still in full force today both within the Framingham Study itself and in the broader cardiovascular epidemiologic community-to quantify the independent and synergistic effects of genetic, lifestyle, and other environmental factors on cardiovascular outcomes.


Mass reconstitution of neutral cephalothin sodium using tandem sequence filling.
A procedure is described for reconstituting and packaging neutral cephalothin sodium in large numbers of underfilled minibags for i.v. bolus administration. A special rack to hold six 20-g Keflin vials was designed for the procedure which employs an automatic pipetting device in a laminar air flow hood. A reconstitution deck and needle holder are used in the admixing stage. The minibags are frozen and later thawed prior to dispensing. The average labor and material cost (excluding drug and minibag) ranges from $0.195 to $0.124 per minibag depending on batch size. The 20-g neutral cephalothin sodium vial improves speed of reconstitution and does not require transfer into an intermediate container during the packaging cycle.


[Research advance of gene therapy for peripheral arterial disease using hepatocyte growth factor].
To introduce the studies on gene therapy for peripheral arterial disease (PAD) using plasmid DNA encoding human hepatocyte growth factor(HGF) gene. Recent articles including preclinical and clinical studies were reviewed. Intramuscular injection of human HGF plasmid DNA into rat, rabbit, dog and diabetic hindlimb ischemic models, resulted in a significant increase in capillary density, blood flow and blood pressure. but no influence on tumor growth in mice. A clinical trial was performed in ischemic limbs of 6 critical limb ischemic patients, the result showed that no side effect caused by gene transfer was detected in all 6 patients. The pain scale and long diameter of ischemic ulcers were reduced. Intramuscular injection of naked HGF plasmid DNA could be a safe and potential treatment for PAD.


Usefulness of the Prenatal Echocardiogram in Fetuses With Isolated Transposition of the Great Arteries to Predict the Need for Balloon Atrial Septostomy.
The outcome of the arterial switch operation for transposition of the great arteries (TGA) is excellent, but there is still associated preoperative mortality. Hypoxemia due to inadequate mixing of the pulmonary and systemic circulations may be implicated. Prediction of early hypoxemia by prenatal echocardiographic criteria has proved difficult. We aimed to identify prenatal echocardiographic features that may predict the need for emergency balloon atrial septostomy (BAS) in isolated TGA. Third trimester fetal echocardiograms of the last 40 cases of isolated TGA were reviewed without knowledge of the postnatal outcome. Measurements of the arterial valves, arterial duct, total septal length (TSL), and foramen ovale (FO) length were made, in addition to a subjective assessment of the atrial septum. The first postnatal echocardiogram and charts were reviewed. Comparison with 40 gestation-matched control fetuses was performed. The FO length in normal fetuses was not significantly different from those with TGA who did not require an emergency BAS but was significantly smaller in fetuses with TGA who required an emergency BAS (p = 0.01). An emergency BAS was required in 12 of 40 cases. All 3 cases with limited movement of the atrial septum required emergency BAS. A hypermobile atrial septum was observed in 10 cases and was not associated with emergency BAS (p = 0.8). The FO:TSL was significantly smaller in those who required an emergency BAS with good predictive value (area under the receiver operating characteristics curve: 0.80). The sensitivity for FO:TSL <0.5 was 99%. There was no significant difference in arterial duct, pulmonary valve, or branch pulmonary artery diameters between those cases requiring emergency BAS and those who did not. In conclusion, the likelihood of an emergency BAS is increased by FO:TSL <0.5 and a fixed appearance of the flap valve. Hypermobile and/or aneurysmal atrial septum did not indicate inadequate postnatal mixing in our group.


Prediction of Milk/Plasma Concentration Ratios of Drugs and Environmental Pollutants Using In Silico Tools: Classification and Regression Based QSARs and Pharmacophore Mapping.
A large set of 185 compounds with diverse molecular structures and different mechanisms of therapeutic actions was used to develop and validate statistically significant classification and regression based QSTR models for predicting partitioning of drugs/chemicals into breast milk. Pharmacophore mapping was also carried out which showed four important features required for lower risk of secretion into milk: (i) hydrophobic group (HYD), (ii) ring aromatic group (RA), (iii) negative ionizable (NegIon) and (iv) hydrogen bond donor (HBA). QSTR and pharmacophore models were rigorously validated internally as well as externally to check the possibilities of any chance correlation and judge the predictive potential of the models. Pharmacological distribution diagrams (PDDs) were used for the classification model as a visualizing technique for the identification and selection of chemicals with lower partitioning into milk. Our in silico models enable to identify the essential structural attributes and quantify the prime molecular pre-requisites which were chiefly responsible for secretion into milk. The developed models were also implemented to screen milk/plasma partitioning potential for a huge number DrugBank database (http://www.drugbank.ca/) compounds.


Colorectal cancer causes alteration of thyroid hormone profile in newly diagnosed patients.
Subcellular alteration of thyroid hormones (THs) signaling is proposed in many types of cancers. Some studies show deiodinase type 3, as an oncofetal protein, re-expresses in some cancer types. Therefore, we aimed to investigate the product of this enzyme, reverse triiodothyronine (rT3) in serum of newly diagnosed colorectal cancer (CRC) patients. In this cross-sectional study, blood from 38 laboratory-confirmed cases was taken, and serum levels of rT3, total T3 (triiodothyronine), total T4 (thyroxine), free T3, free T4, and thyroid-stimulating hormone (TSH) were detected by using an enzyme-linked immunosorbent assay. The results illustrated that rT3 and free T3 levels increased in patients with early stages of colorectal cancer, despite normal levels of total T3, total T4, free T4, and TSH. The elevation of rT3 in CRC patients can probably be due to the re-expression of deiodinase type 3 in CRC. Further research is needed to study the role of intracellular THs modulation in CRC and its impact on CRC treatment.


Effects of antineoplastics, antibiotics and antidiabetics on acetaldehyde metabolism after alcohol ingestion.
The main purpose of this study was to evaluate the inhibitory effects of 5-fluorouracil antineoplastics, cephem antibiotics containing the methyltetrazolylthiol (MTT) group and antidiabetics on aldehyde dehydrogenase (ALDH) activity in vivo and in vitro. In in vivo experiments, rats were given a 100 mg/kg dose of drugs (10 mg/kg for glibenclamide) orally or intraperitoneally. When each drug was administered singly immediately after an oral administration of 1.5 g/kg ethanol, only carmofur, an antineoplastic, produced marked increases in blood acetaldehyde concentrations. This action was also noted when ethanol was ingested 15 h after administration. The remaining drugs did not increase blood acetaldehyde concentrations. When rats were treated with carmofur at 12 h intervals for 3 consecutive days and were given 1.5 g/kg ethanol after the final treatment, blood acetaldehyde concentrations were elevated more significantly than with a single administration of carmofur. Furthermore, daily administration of cephem antibiotics containing the MTT group, latamoxef, cefamandole, cefoperazone and cefbuperazone, significantly increased blood acetaldehyde concentrations. Daily administration of sulfonylurea antidiabetics, chlorpropamide and acetohexamide, slightly increased blood acetaldehyde concentrations. Drugs causing increases in blood acetaldehyde concentrations when administration was combined with ethanol ingestion also inhibited ALDH activity in vitro. The results of the in vitro experiments roughly correlated with those of the in vivo experiments. The inhibitory effects of drugs on ALDH activity were in the following order: carmofur >> cephem antibiotics containing the MTT group > sulfonylurea antidiabetics.


Latex agglutination test for staphylococcal toxic shock syndrome toxin 1.
A reversed passive latex agglutination method, in which latex particles were sensitized with specific anti-toxic shock syndrome toxin-1 (TSST-1) immunoglobulin, was found to be a simple and sensitive method for the detection of TSST-1 production by Staphylococcus aureus strains. The minimum amount of TSST-1 detectable was approximately 1.0 ng/ml. Of 41 S. aureus isolates from toxic shock syndrome patients and controls, 23 were positive for TSST-1 production, whereas only 20 strains were positive for TSST-1 production by an Ouchterlony immunodiffusion method. The reversed passive latex agglutination method was used to examine S. aureus strains isolated in Japan from staphylococcal infections, feces from healthy individuals, food from poisoning outbreaks, and market food.


NFAT5/TonEBP mutant mice define osmotic stress as a critical feature of the lymphoid microenvironment.
Osmotic stress responses are critical not only to the survival of unicellular organisms but also to the normal function of the mammalian kidney. However, the extent to which cells outside the kidney rely on osmotic stress responses in vivo remains unknown. Nuclear factor of activated T cells 5 (NFAT5)/tonicity enhancer binding protein (TonEBP), the only known osmosensitive mammalian transcription factor, is expressed most abundantly in the thymus and is induced upon lymphocyte activation. Here we report that NFAT5/TonEBP is not only essential for normal cell proliferation under hyperosmotic conditions but also necessary for optimal adaptive immunity. Targeted deletion of exons 6 and 7 of the Nfat5 gene, which encode a critical region of the DNA-binding domain, gave rise to a complete loss of function in the homozygous state and a partial loss of function in the heterozygous state. Complete loss of function resulted in late gestational lethality. Furthermore, hypertonicity-induced NFAT5/TonEBP transcriptional activity and hsp70.1 promoter function were completely eliminated, and cell proliferation under hyperosmotic culture conditions was markedly impaired. Partial loss of NFAT5/TonEBP function resulted in lymphoid hypocellularity and impaired antigen-specific antibody responses in viable heterozygous animals. In addition, lymphocyte proliferation ex vivo was reduced under hypertonic, but not isotonic, culture conditions. Direct measurement of tissue osmolality further revealed lymphoid tissues to be hyperosmolar. These results indicate that lymphocyte-mediated immunity is contingent on adaptation to physiologic osmotic stress, thus providing insight into the lymphoid microenvironment and the importance of the NFAT5/TonEBP osmotic stress response pathway in vivo.


[Accidental mortality and compensation payment in school activities among elementary, middle and high school students in Seoul over twenty years (1988-2007)].
The purpose of this study was to identify accidental mortality during school activities of students in elementary, middle or high school in Seoul and consequent compensation payment. Fifty-eight students died due to accidents during the period 1988 through 2007. Data were obtained from the Seoul School Safety and Insurance Association, and Seoul Metropolitan Office of Education. Chi-square, t test, and ANCOVA were used in the data analysis. Among students, 75.9% were male and 37.9% were high school students. Accidental mortality was 1.61 per one million students (2.33 for male, and 0.82 for female students, and 0.93, 2.13 and 2.31 for elementary, middle and high school students, respectively). Mortality caused by drowning and falls per one million student was 0.85 and 0.74 for male, and 0.23 and 0.35 for female students. After age, year and cause were adjusted using ANCOVA, the mean compensation payment was 40,615 thousand won for male, and 62,000 thousands for female students. Highest compensation payment was 127,137 thousand for cerebral concussion after age, gender, year and cause were adjusted. To decrease student accidental mortality, especially drowning and falls, development of efficient safety-enforcing education is essential to prevent injuries and avoid preventable compensation costs.


Optimization of surface acoustic wave-based rate sensors.
The optimization of an surface acoustic wave (SAW)-based rate sensor incorporating metallic dot arrays was performed by using the approach of partial-wave analysis in layered media. The optimal sensor chip designs, including the material choice of piezoelectric crystals and metallic dots, dot thickness, and sensor operation frequency were determined theoretically. The theoretical predictions were confirmed experimentally by using the developed SAW sensor composed of differential delay line-oscillators and a metallic dot array deposited along the acoustic wave propagation path of the SAW delay lines. A significant improvement in sensor sensitivity was achieved in the case of 128° YX LiNbO₃, and a thicker Au dot array, and low operation frequency were used to structure the sensor.


Effects of male rape on psychological functioning.
Since the 1970s there has been a wealth of literature on the effects of rape on women. However, the study of the effects of male rape is still in its infancy. The aim of this study was investigate the psychological functioning of 40 British male rape survivors, and compare their level of functioning with that of a matched control group. Participants, recruited through national advertising in the British press, completed a series of questionnaires, measuring psychological functioning, assumptions about the world, self-esteem, and (survivors only) PTSD-related intrusion and avoidance. The male rape group had much poorer psychological functioning than the controls, lower self-worth, and lower self-esteem. Most survivors reported high levels of intrusive thoughts and avoidance in relation to the assault. Logistic regression showed that lack of treatment after the assault predicted suicide attempts. Results are discussed in relation to treatment issues for male rape survivors.


Assessment of Toxicity Risk of Selected Insecticides Used in Pistachio Ecosystem on Two Egg Parasitoids (Hymenoptera: Scelionidae) of Stink Bugs (Hemiptera: Pentatomidae).
Psix saccharicola (Mani) and Trissolcus semistriatus (Nees) are the most abundant eggs parasitoids of the stink bug, Acrosternum arabicum Wagner, in pistachio orchards and have the potential to contribute to their suppression. However, treatment of orchards with broad-spectrum insecticides may greatly reduce populations of these beneficial natural enemies. Therefore, we conducted risk assessments and evaluated sublethal impacts of two insecticides routinely used in pistachio orchards: the organophosphate fenitrothion and a formulated mixture of the neonicotinoid thiamethoxam and the pyrethroid lambda-cyhalothrin on parasitism success, emergence and sex ratio of P. saccharicola and T. semistriatus. Based on the values of their risk quotients (RQ), which are derived from toxicity data, the two insecticide products would be classified as slightly-to-moderately toxic although an alternative metric, the safety factor (SF), showed them to be highly risky. Assessments of sublethal effects on adult wasps showed that insecticide exposure significantly reduced their ability to successfully parasitize stink bug eggs, and exposure of adult females reduced the emergence, survival, and proportion of females of their progeny, which could disrupt biological control for an extended period of time. Analysis of the decreased emergence and parasitism for P. saccharicola and T. semistriatus in accordance with the standards of the International Organization for Biological Control (IOBC) indicate that fenitrothion is slightly harmful to both parasitoid species whereas the mixture of thiamethoxam + lambda-cyhalothrin is moderately harmful. These findings will be useful for integrating insecticides and egg parasitoids into a comprehensive integrated pest management program for managing stink bugs populations in pistachio orchards.


New Middle Pleistocene human remains from northern Italy.
The description of several teeth and a fragment of mandible found in the Visogliano rock-shelter (Northern Italy) is presented in this paper. The teeth have been analysed from a morphological and metrical point of view and compared with other specimens of Homo erectus, archaic Homo sapiens and Homo neanderthalensis. The MD and BL diameters and the peculiar dental features are archaic and support the antiquity of the specimens. Microwear analysis of Visogliano teeth show various dietary strategies adopted by the individuals of the same site.


Discovery of four recessive developmental disorders using probabilistic genotype and phenotype matching among 4,125 families.
Discovery of most autosomal recessive disease-associated genes has involved analysis of large, often consanguineous multiplex families or small cohorts of unrelated individuals with a well-defined clinical condition. Discovery of new dominant causes of rare, genetically heterogeneous developmental disorders has been revolutionized by exome analysis of large cohorts of phenotypically diverse parent-offspring trios. Here we analyzed 4,125 families with diverse, rare and genetically heterogeneous developmental disorders and identified four new autosomal recessive disorders. These four disorders were identified by integrating Mendelian filtering (selecting probands with rare, biallelic and putatively damaging variants in the same gene) with statistical assessments of (i) the likelihood of sampling the observed genotypes from the general population and (ii) the phenotypic similarity of patients with recessive variants in the same candidate gene. This new paradigm promises to catalyze the discovery of novel recessive disorders, especially those with less consistent or nonspecific clinical presentations and those caused predominantly by compound heterozygous genotypes.


Influence of Ocular Residual Astigmatism and Target-Induced Astigmatism on the Efficacy of the Implantation of a Toric Implantable Collamer Lens With Central Hole for Myopic Astigmatism Correction.
To investigate the effects of ocular residual astigmatism (ORA) and target-induced astigmatism (TIA) on the efficacy of toric implantable collamer lens (TICL) with central hole for myopic astigmatism correction. Retrospective case series. One hundred and eighteen eyes implanted with a TICL (V4c) from 118 patients were included. Subjective refraction and corneal topography were examined preoperatively, at 1 and 12 months postoperatively. The eyes were divided into the low-ORA ( ≤ 0.5 D) and high-ORA (>0.5 D) groups based on vector analysis, and into the low-TIA (≥0.75D and <2 D) and the high-TIA (≥2 D and ≤ 4 D) groups according to preoperative refractive astigmatism. Correction index (CI) and index of success (IOS) were compared between different groups. All surgeries were uneventful, and no complications occurred during follow-up. At 1 and 12 months postoperatively, no significant differences were found in CI or IOS values between the high and low ORA groups, while significantly higher CI and lower IOS were detected in the high-TIA group than in the low-TIA group (P < 0.05). No significant difference was found in CI between 1 and 12 months postoperatively in either group (P > 0.05). However, significantly lower IOS was found at 12 months compared with 1 month postoperatively for each group (P < 0.05). Toric implantable collamer lens (TICL) implantation is effective in correcting myopic astigmatism and is more effective in eyes with high TIA, while ORA has a minor effect.


Prevalence of Diarrheagenic Escherichia coli in Foods and Fecal Specimens Obtained from Cattle, Pigs, Chickens, Asymptomatic Carriers, and Patients in Osaka and Hyogo, Japan.
The source and routes of diarrheagenic Escherichia coli (DEC) remain poorly understood. To investigate the involvement of domestic animals in the dissemination of DEC, the prevalence of DEC in foods and fecal specimens from cattle, pigs, chickens, healthy carriers, and patients in Osaka and Hyogo, Japan was investigated using a multiplex real-time Polymerase Chain Reaction assay. The most abundant virulence genes were astA and eae, which had a prevalence 46.8% and 27.4%, respectively. Additionally, stx1 (26.6%) and stx2 (45.9%) were prevalent in cattle feces, while est (8.5%) and elt (7.6%) were prevalent in pig feces. afaB was the second-most prevalent gene in patients and healthy carriers, and it had detection rates of 5.1% and 8.1%, respectively. In contrast, afaB was not detected in animal feces or foods, except for three porcine fecal samples. The aggR gene was more prevalent in humans than in foods or animal feces. Both Shiga toxin-producing E. coli and atypical enteropathogenic E. coli carried by cattle may be sources for diarrheal diseases in humans. Pigs may be a source for human enterotoxigenic E. coli infections, whereas humans are expected to be the reservoir for diffusely adhering E. coli, enteroaggregative E. coli, and enteroinvasive E. coli.


Comparison of environmental and isolate Sulfobacillus genomes reveals diverse carbon, sulfur, nitrogen, and hydrogen metabolisms.
Bacteria of the genus Sulfobacillus are found worldwide as members of microbial communities that accelerate sulfide mineral dissolution in acid mine drainage environments (AMD), acid-rock drainage environments (ARD), as well as in industrial bioleaching operations. Despite their frequent identification in these environments, their role in biogeochemical cycling is poorly understood. Here we report draft genomes of five species of the Sulfobacillus genus (AMDSBA1-5) reconstructed by cultivation-independent sequencing of biofilms sampled from the Richmond Mine (Iron Mountain, CA). Three of these species (AMDSBA2, AMDSBA3, and AMDSBA4) have no cultured representatives while AMDSBA1 is a strain of S. benefaciens, and AMDSBA5 a strain of S. thermosulfidooxidans. We analyzed the diversity of energy conservation and central carbon metabolisms for these genomes and previously published Sulfobacillus genomes. Pathways of sulfur oxidation vary considerably across the genus, including the number and type of subunits of putative heterodisulfide reductase complexes likely involved in sulfur oxidation. The number and type of nickel-iron hydrogenase proteins varied across the genus, as does the presence of different central carbon pathways. Only the AMDSBA3 genome encodes a dissimilatory nitrate reducatase and only the AMDSBA5 and S. thermosulfidooxidans genomes encode assimilatory nitrate reductases. Within the genus, AMDSBA4 is unusual in that its electron transport chain includes a cytochrome bc type complex, a unique cytochrome c oxidase, and two distinct succinate dehydrogenase complexes. Overall, the results significantly expand our understanding of carbon, sulfur, nitrogen, and hydrogen metabolism within the Sulfobacillus genus.


Changes in Habitat Structure May Explain Decrease in Reintroduced Mohor Gazelle Population in the Guembeul Fauna Reserve, Senegal.
Reintroduction is a widespread method for saving populations of endangered species from extinction. In spite of recent reviews, it is difficult to reach general conclusions about its value as a conservation tool, as authors are reluctant to publish unsuccessful results. The Mohor gazelle is a North African gazelle, extinct in the wild. Eight individuals were reintroduced in Senegal in 1984. The population grew progressively, albeit slowly, during the first 20 years after release, but then declined dramatically, until the population in 2009 was estimated at no more than 13-15 individuals. This study attempts to determine the likelihood of gazelle-habitat relationships to explain why the size of the gazelle population has diminished. Our results show that the Mohor gazelle in Guembeul is found in open habitats with less developed canopy where the grass is shorter, suggesting the possibility that changes in habitat structure have taken place during the time the gazelles have been in the Reserve, reducing the amount of suitable habitat. Reintroduction design usually concentrates on short-term factors that may affect survival of the released animals and their descendants (short-term achievement), while the key factors for assessing its success may be those that affect the long-term evolution of the population.


Methods to calibrate the absolute receive sensitivity of single-element, focused transducers.
Absolute pressure measurements of acoustic emissions by single-element, focused passive cavitation detectors would be facilitated by improved wideband receive calibration techniques. Here, calibration methods were developed to characterize the absolute, frequency-dependent receive sensitivity of a spherically focused, single-element transducer using pulse-echo and pitch-catch techniques. Validation of these calibration methods on a focused receiver were made by generating a pulse from a small diameter source at the focus of the transducer and comparing the absolute pressure measured by a calibrated hydrophone to that of the focused transducer using the receive sensitivities determined here.


Gender differences in cardiovascular risk factors and risk perception among individuals with diabetes.
The purpose of this study was to examine gender-based differences in cardiovascular risk factors and risk perception among individuals with diabetes. The sample consisted of patients with an established history of diabetes who were enrolled in a telemedicine trial to reduce cardiovascular disease (CVD) risk. All subjects had a 10% or greater risk on the Framingham risk index. Assessments included blood pressure, A1C, lipid profile, medication history, and knowledge and risk perception surveys. Data were available for 211 individuals with type 2 diabetes (88 men and 123 women). The women and men did not differ in age, body mass index, or Framingham risk. Only 37.4% of women and 40.9% of men were at an A1C target of <7%. Total cholesterol levels were significantly higher among women, and fewer women were at low-density lipoprotein or blood pressure targets. Knowledge of CVD was similar between the 2 sexes. However, women perceived their risk for CVD to be significantly higher than did men. Less favorable cardiovascular risk profiles are observed among women with diabetes as compared with their male counterparts. Multifaceted approaches to both diabetes management and education are needed to target CVD risk reduction among individuals with diabetes.


Tetradecylselenoacetic acid, a PPAR ligand with antioxidant, antiinflammatory, and hypolipidemic properties.
Antioxidants protect against oxidative stress and inflammation, which, in combination with hyperlipidemia, are important mediators of atherogenesis. Here we present a selenium-substituted fatty acid, tetradecylselenoacetic acid (TSA), which is hypothesized to have antioxidant, antiinflammatory, and hypolipidemic properties. We show that TSA exerts antioxidant properties by delaying the onset of oxidation of human low density lipoprotein (LDL), by reducing the uptake of oxidized LDL in murine macrophages, and by increasing the mRNA level of superoxide dismutase in rat liver. TSA also showed antiinflammatory effects by suppressing the release of interleukin (IL)-2 and -4, and by increasing the release of IL-10 in human blood leukocytes. In addition, TSA decreased the plasma triacylglycerol level and increased the mitochondrial fatty acid beta-oxidation in rat liver. In pigs, TSA seemed to reduce coronary artery intimal thickening after percutaneous coronary intervention. In HepG2 cells TSA activated all peroxisome proliferator-activated receptors (PPARs) in a dose-dependent manner. Our data suggest that TSA exert potent antioxidant, antiinflammatory, and hypolipidemic properties, potentially involving PPAR-related mechanisms. Based on these effects, it is tempting to hypothesize that TSA could be an interesting antiatherogenic approach to atherosclerotic disorders.


An outbreak of botulism in waterfowl and fly larvae in New York State.
In October 1982 the death of approximately 1,500 wild ducks, mostly mallards (Anas platyrhynchos), and about 100 shore birds including greater yellowlegs (Tringa melanoleuca) was observed in the New York State Oak Orchard Wildlife Management Area. The lack of gross pathology, the signs exhibited by the moribund ducks, and the ecologic conditions indicated possible botulinal intoxication. Clostridium botulinum toxin type C was demonstrated in duck serum (approximately 5 X 10(4) mouse intraperitoneal LD50 of toxin per ml of serum) and in an extract from fly larvae (Lucilia spp.) taken from the same area (approximately 1 X 10(6) mouse intraperitoneal LD50 of toxin per gram of larvae).


Genome Sequence of Bacillus simplex Strain P558, Isolated from a Human Fecal Sample.
Bacillus simplex strain P558 was isolated from a fecal sample of a 25-year-old Saudi male. We sequenced the 5.98-Mb genome of the strain and compared it to that of B. simplex strain 1NLA3E.


Identification of phenylsulfone-substituted quinoxaline (WYE-672) as a tissue selective liver X-receptor (LXR) agonist.
A series of phenyl sulfone substituted quinoxaline were prepared and the lead compound 13 (WYE-672) was shown to be a tissue selective LXR Agonist. Compound 13 demonstrated partial agonism for LXRbeta in kidney HEK-293 cells but did not activate Gal4 LXRbeta fusion proteins in huh-7 liver cells. Although 13 showed potent binding affinity to LXRbeta (IC(50) = 53 nM), it had little binding affinity for LXRalpha (IC(50) > 1.0 microM) and did not recruit any coactivator/corepressor peptides in the LXRalpha multiplex assay. However, compound 13 showed good agonism in THP-1 cells with respect to increasing ABCA1 gene expression and good potency on cholesterol efflux in THP-1 foam cells. In an eight-week lesion study in LDLR -/- mice, compound 13 showed reduction of aortic arch lesion progression and no plasma or hepatic triglyceride increase. These results suggest quinoxaline 13 may have an improved biological profile for potential use as a therapeutic agent.


relA-dependent RNA polymerase activity in Escherichia coli.
Parameters relating to RNA synthesis were measured after a temperature shift from 30 to 42 degrees C, in a relA+ and relA- isogenic pair of Escherichia coli strains containing a temperature-sensitive valyl tRNA synthetase. The following results were obtained: (i) the rRNA chain growth rate increased 2-fold in both strains; (ii) newly synthesized rRNA became unstable in both strains; (iii) the stable RNA gene activity (rRNA and tRNA, measured as stable RNA synthesis rate relative to the total instantaneous rate of RNA synthesis) decreased 1.7-fold in the relA+ strain and increased 1.9-fold in the relA mutant; and (iv) the RNA polymerase activity (measured by the percentage of total RNA polymerase enzyme active in transcription an any instant) decreased from 20 to 3.6% in the relA+ strain and remained unchanged (or increased at most to 22%) in the relA mutant. It is suggested that both rRNA gene activity and the RNA polymerase activity depend on the intracellular concentration of guanosine tetraphosphate, whereas the altered chain elongation rate and stability of rRNA are temperature or amino acid starvation effects, respectively, without involvement of relA function.


Oral Bruton tyrosine kinase inhibitors selectively block atherosclerotic plaque-triggered thrombus formation in humans.
Interaction of von Willebrand factor (VWF) with platelet glycoprotein Ib (GPIb) and interaction of collagen with GPVI are essential for thrombus formation on ruptured or eroded atherosclerotic plaques (atherothrombosis). GPIb and GPVI signal through Bruton tyrosine kinase (Btk), which can be blocked irreversibly by oral application of ibrutinib, an established therapy for chronic lymphocytic leukemia (CLL) with long-term safety. We found that ibrutinib and the novel Btk inhibitors acalabrutinib and ONO/GS-4059 block GPVI-dependent static platelet aggregation in blood exposed to human plaque homogenate and collagen but not to ADP or arachidonic acid. Moreover, Btk inhibitors prevented platelet thrombus formation on human atherosclerotic plaque homogenate and plaque tissue sections from arterially flowing blood, whereas integrin α2β1 and VWF-dependent platelet adhesion to collagen, which is important for physiologic hemostasis, was not affected. This plaque-selective platelet inhibition was also observed in CLL patients taking 450 mg of ibrutinib and in volunteers after much lower and intermittent dosing of the drug. We conclude that Btk inhibitors, by targeting GPIb and GPVI signal transduction, suppress platelet thrombus accretion from flowing blood on atherosclerotic plaque but spare hemostatic platelet function. Btk inhibitors hold promise as the first culprit lesion-focused oral antiplatelet drugs and are effective at low doses.


Adeno-associated virus protects the retinoblastoma family of proteins from adenoviral-induced functional inactivation.
Adeno-associated virus type 2 (AAV) is known to inhibit virally mediated oncogenic transformation. One of the early events of adenovirus (Ad) infection is the functional inactivation of cell cycle regulatory retinoblastoma (RB) family of proteins, which consists of retinoblastoma protein (pRB), p107, and p130. In an effort to understand the molecular basis of anti-oncogenic properties of AAV, we studied the effects of AAV expression on these proteins in cells infected with Ad. Western blot analysis showed that AAV interferes with the adenoviral-induced degradation and hyperphosphorylation of the pRB family of proteins in normal human fibroblasts as well as in HeLa and 293 cell lines. RNase protection assay showed enhanced expression of pocket protein gene by AAV expression. We also demonstrate that Rep proteins, the major AAV regulatory proteins, bind to E1A, the immediate early gene of Ad responsible for hyperphosphorylation and dissociation of pRB-E2F complex. This binding of AAV Rep proteins to E1A leads to decreased association between E1A and pRB leading to protection of pocket proteins from degradation, decreased expression of S phase genes and inhibition of cell cycle progression. These results suggest that the antiproliferative activity of AAV against Ad is mediated, at least in part, by effects of AAV Rep proteins on the Rb family of proteins.


Idiopathic lymphocytoma cutis: a diagnostic dilemma.
Lymphocytoma cutis, also known as cutaneous B cell pseudolymphoma, represents a spectrum of disease that shares similar clinical and histological features and simulates cutaneous lymphoma clinically and histologically. Clinically it is manifested as asymptomatic, indolent, nodular lesions of different sizes varying between 2 and 5 cm, usually solitary, mainly on exposed area of the body like face and neck. The presence of polymorphous cell infiltrates comprising of T and B lymphocytes, plasma cells, oeosinophils, histiocytes and dendritic cells along with lack of atypical lymphocytes after incisional biopsy support diagnosis of pseudolymphoma. Final diagnosis is made on immunohistochemistry.


The ethical justification for inclusion of neonates in pragmatic randomized clinical trials for emergency newborn care.
Research guidelines generally recognize vulnerable populations to include neonates with the aim of enhancing protections from harm. In practice, such guidance results in limiting participation in randomized clinical trials (RCTs). Yet while medical care of neonates should be based on best research evidence to ensure that safe, efficacious treatment or procedures are used, this seldom happens in contemporary practice. The compelling need to generate information on effectiveness and safety of procedures and medications that are already in use during neonatal care has led to increase in calls for pragmatic randomized clinical trials (PCTs). This raises ethical concerns as to whether exclusion of the vulnerable populations from research participations constitutes harm. First, neonates are denied access to both potentially beneficial research outputs and an opportunity to generate data on how interventions or medications perform in diverse clinical settings and inform clinical decision-making. Secondly, risks and harms in PCTs may differ from traditional RCTs, and can be reduced by modifications in study designs. The latter may involve assessment of effectiveness of comparable medication, devices or practices (whose safety data is available), randomization at the group level rather than at the individual level, avoidance of invasive and innovative study procedures, reliance on locally available data on relevant patient outcomes, and employment of procedures that tend to meet the criteria of minimal risk for human subject research. Thirdly, informed consent procedures should be modified from those of traditional RCTs, as neonates in traditional RCTs may be vulnerable to different extents in PCTs. Lastly, regulatory and oversight procedures designed for traditional RCT settings need modification, as they may not be translatable, feasible, appropriate or even ethical to apply in PCTs. The principle of justice, commonly interpreted as preventing an inequitable burden of research, should also allow fair access to potential benefits from PCTs for neonates and other vulnerable populations. Under certain conditions, prospective randomized trials involving neonates should be ethically permissible to allow inclusion of neonates in research. This may require modification of the research design, consent procedures or regulations for research oversight.


Vitamin D resistance in magnesium deficiency.
Four patients with gastrointestinal disorders, and one patient with chronic alcoholism presented with both hypocalcemia and hypomagnesemia. Pharmacological doses of either ergocalciferol or dihydrotachysterol did not correct the hypocalcemia except in one patient who had a minimal rise in serum calcium. Parathormone levels were high in three patients and exogenous parathormone given to the fourth subject failed to elicit a rise in serum calcium, implying impairment of the calcemic response to parathormone. Magnesium repletion simultaneously corrected the hypomagnesemia and hypocalcemia. Balance data suggested that the rise in serum calcium was in part, at least, due to increased mobilization of minerals from bone. While the mechanism remains speculative, it appears that magnesium facilitates the release of calcium from bone in the presence of adequate amounts of vitamin D and parathormone.


Postoperative nausea and vomiting: development of a management protocol.
Postoperative nausea and vomiting (PONV) is still an important and common problem. Despite the introduction of new antiemetic drugs, the management of PONV remains difficult. In this article we describe the development and evaluation of a management protocol for PONV, which consists of a treatment algorithm accompanied by a nursing education program. Implementation of this management protocol has been well-accepted by staff, appears to have reduced delay in patient treatment and improved patient care, and has significantly reduced staff workload. It is planned to use continuous quality improvement techniques to further refine the algorithm and continue assessment of its efficacy and of patient satisfaction.


Evaluation of bleeding disorders. A detailed history and laboratory tests provide clues.
A single, optimal screening laboratory test for hemostasis would evaluate vascular, platelet, coagulation, and fibrinolytic functions. Unfortunately, such a test does not exist. The key factor in determining the presence of a bleeding diathesis is obtaining a detailed patient history. Results of coagulation tests should always be interpreted in the context of such a history. Screening tests include platelet count, PTT, and PT. Subsequent investigations depend on the results of these tests.


Pituitary-adrenal function in uncomplicated falciparum malaria.
To investigate pituitary-adrenal function in acute uncomplicated falciparum malaria, we performed an overnight dexamethasone suppression test in 13 Vietnamese adults with acute malaria and 6 healthy controls. After blood samples were taken for serum cortisol and plasma ACTH at 23.00 hours on the admission day, 1 mg dexamethasone was given and further samples were taken at 08.00, 16.00 and 23.00 hours the next day. The patients received conventional antimalarial and supportive treatment. Baseline plasma ACTH concentrations in the patients [3.9 (0.2-41.2) pmol/l] and controls [3.4 (1.1-4.3) pmol/l] were similar (p=0.51), and exhibited a similar fall after dexamethasone to 0.6 (0.2-2.5) and 0.9 (0.7-1.6) pmol/l at 08.00 hours respectively (p<0.03 vs 23.00 hour values). Serum cortisol levels before dexamethasone were higher in the patients than in the controls [456 (102-821) vs 145 (64-183) nmol/l respectively; p=0.007] and the overnight fall was less in the patients [208 (26-340) and 23 (15-46) nmol/l at 08.00 hours respectively; p<0.001 vs 23.00 hour values and between groups]. Between 08.00 and 23.00 hours, plasma ACTH and serum cortisol remained suppressed in the controls. In the patients, the serum cortisol continued to fall progressively towards control values. These data suggest that there is a raised set point for cortisol inhibition of ACTH secretion but normal corticotrophin responsiveness to dexamethasone in uncomplicated malaria. A raised serum cortisol after dexamethasone in the patients might reflect the combination of a prolonged cortisol half-life and the stimulatory effects of cytokines on the adrenal cortex, with a consequent protective effect against complications such as hypoglycemia.


Physicians' knowledge of genetics and genetic tests.
To assess primary care physicians' and psychiatrists' knowledge of genetics and genetic tests and the factors associated with differences in these physicians' knowledge. Questionnaires were mailed in 1991 to 1,795 primary care physicians (family physicians, internists, pediatricians, obstetrician-gynecologists) and psychiatrists who had graduated from medical school between 1950 and 1985 (67.6% of the sample had graduated after 1970) and who were members of professional societies. The questions elicited demographic and practice characteristics as well as knowledge of genetics concepts and facts and awareness of the availability of genetic tests. To validate the questionnaire, 360 medical geneticists and genetic counselors received questionnaires. Statistical analysis involved arc-sine function transformation, t-tests, analyses of variance, F-tests, Tukey's HSD, and stepwise multiple regression. A total of 1,140 (64.8%) of the non-geneticist physicians responded. They correctly answered an average of 73.9%, SD, 13.9%, of the knowledge items, compared with 94.6%, SD, 4.2%, for the genetics professionals (p < .001). The most significant predictors of knowledge were recency of graduation from medical school and practicing in primary care specialties in which exposure to genetics problems is likely. Other significant predictors (from most to least important) were graduation from a U.S. medical school, willingness to adopt a new predictive test before it becomes standard practice, not using pharmaceutical companies as a source of information about new medical practices, and taking a required genetics course in medical school. The results suggest that knowledge of genetics and genetic tests is increasing among physicians, particularly among more recent graduates and physicians who are exposed to genetics problems in their practices, but deficiencies remain. Although a medical school course in genetics may improve knowledge, it is not sufficient. Greater emphasis is needed at all levels of medical education to reduce the chance of physician error as more genetic tests become available.


Clinical and radiological outcome of cast immobilisation versus surgical treatment of acute scaphoid fractures at a mean follow-up of 93 months.
We report the outcome at a mean of 93 months (73 to 110) of 71 patients with an acute fracture of the scaphoid who were randomised to Herbert screw fixation (35) or below-elbow plaster cast immobilisation (36). These 71 patients represent the majority of a randomised series of 88 patients whose short-term outcome has previously been reported. Those patients available for later review were similar in age, gender and hand dominance. There was no statistical difference in symptoms and disability as assessed by the mean Patient Evaluation Measure (p = 0.4), or mean Patient-Rated Wrist Evaluation (p = 0.9), the mean range of movement of the wrist (p = 0.4), mean grip strength (p = 0.8), or mean pinch strength (p = 0.4). Radiographs were available from the final review for 59 patients. Osteoarthritic changes were seen in the scaphotrapezial and radioscaphoid joints in eight (13.5%) and six patients (10.2%), respectively. Three patients had asymptomatic lucency surrounding the screw. One non-operatively treated patient developed nonunion with avascular necrosis. In five patients who were treated non-operatively (16%) there was an abnormal scapholunate angle ( > 60 degrees ), but in four of these patients this finding was asymptomatic. No medium-term difference in function or radiological outcome was identified between the two treatment groups.


Differential regulation of matrix metalloproteinases in varicella zoster virus-infected human brain vascular adventitial fibroblasts.
Upon reactivation, varicella zoster virus (VZV) spreads transaxonally, infects cerebral arteries and causes ischemic or hemorrhagic stroke, as well as aneurysms. The mechanism(s) of VZV-induced aneurysm formation is unknown. However, matrix metalloproteinases (MMPs), which digest extracellular structural proteins in the artery wall, play a role in cerebral and aortic artery aneurysm formation and rupture. Here, we examined the effect of VZV infection on expression of MMP-1, -2, -3, and -9 in primary human brain vascular adventitial fibroblasts (BRAFS). At 6 days post-infection, VZV- and mock-infected BRAFs were analyzed for mRNA levels of MMP-1, -2, -3 and -9 by RT-PCR and for corresponding total intra- and extracellular protein levels by multiplex ELISA. The activity of MMP-1 was also measured in a substrate cleavage assay. Compared to mock-infected BRAFs, MMP-1, MMP-3 and MMP-9 transcripts, cell lysate protein and conditioned supernatant protein were all increased in VZV-infected BRAFs, whereas MMP-2 transcripts, cell lysate protein and conditioned supernatant protein were decreased. MMP-1 from the conditioned supernatant of VZV-infected BRAFs showed increased cleavage activity on an MMP-1-specific substrate compared to mock-infected BRAFs. Differential regulation of MMPs in VZV-infected BRAFs may contribute to aneurysm formation in VZV vasculopathy.


Dry season limnological conditions and basin geology exhibit complex relationships with δ13C and δ15N of carbon sources in four Neotropical floodplains.
Studies in freshwater ecosystems are seeking to improve understanding of carbon flow in food webs and stable isotopes have been influential in this work. However, variation in isotopic values of basal production sources could either be an asset or a hindrance depending on study objectives. We assessed the potential for basin geology and local limnological conditions to predict stable carbon and nitrogen isotope values of six carbon sources at multiple locations in four Neotropical floodplain ecosystems (Paraná, Pantanal, Araguaia, and Amazon). Limnological conditions exhibited greater variation within than among systems. δ15N differed among basins for most carbon sources, but δ13C did not (though high within-basin variability for periphyton, phytoplankton and particulate organic carbon was observed). Although δ13C and δ15N values exhibited significant correlations with some limnological factors within and among basins, those relationships differed among carbon sources. Regression trees for both carbon and nitrogen isotopes for all sources depicted complex and in some cases nested relationships, and only very limited similarity was observed among trees for different carbon sources. Although limnological conditions predicted variation in isotope values of carbon sources, we suggest the resulting models were too complex to enable mathematical corrections of source isotope values among sites based on these parameters. The importance of local conditions in determining variation in source isotope values suggest that isotopes may be useful for examining habitat use, dispersal and patch dynamics within heterogeneous floodplain ecosystems, but spatial variability in isotope values needs to be explicitly considered when testing ecosystem models of carbon flow in these systems.


Perfluorochemical liquids do not stimulate endothelin-1 or nitric oxide production in human blood leukocytes.
The purpose of these studies was to examine if perfluorochemical (PFC) liquids stimulate blood leukocytes to secrete nitric oxide (NO) and/or endothelin-1 (ET-1). As such, NO and ET-1 may modulate broncho- and vascular dilatation and constriction, respectively, and thereby influence the clinical condition of a patient in respiratory distress with persistent pulmonary hypertension. Blood leukocytes in their natural habitat (whole blood) were incubated in the presence of two different perfluorochemicals (perflubron and perfluorodecalin). The overall response in ET-1 or NO (indirectly measured as nitrite/nitrate) production was examined at increasing PFC percentages (wt/vol) of PFC/whole blood. The lowest proportion used, 0.001% (wt/vol), was relevant to serum concentrations of PFC observed in liquid-ventilated individuals, whereas the highest proportion PFC, 50% (wt/vol), would mimic a situation where leukocytes are presented to PFC-filled airways. Plasma levels of freshly drawn blood, similar to levels of incubated (6 h) non-PFC-supplemented cultures, were ET-1 0.59 +/- 0.07 pg/ml (6 h, mean +/- SEM) and NO(-2)/NO(-3) 50 +/- 9 microM (6 h). Perflubron or perfluorodecalin did not induce significant differences in ET-1 or NO(-2)/NO(-3) levels as function of PFC type or dose. In conclusion, PFC liquids do not stimulate production in leukocytes in vitro of substances that may modulate constriction or dilatation in the vascular and respiratory tract systems.


[Operative correction of a urogenital malformation with persistent cloaca].
A case of malformation of the urogenital system with a persistent urogenital sinus and a cloaca is reported. There was unilateral agenesis of the kidney, megaureter and a double ureter with an ureteral orifice into the vagina and the clitoris. There was a double uterus and vagina with an orifice into the terminal gut. The patient had chronic recurrent urinary tract infections which required a colostomy during childhood. The operation largely restored a normal urogenital area and a functional anus.


[Extrahepatic arterial blood supply of hepatocellular carcinoma and interventional treatment].
To study the pattern extrahepatic arteriy supply to hepatocellular carcinoma and catheterization technique for interventional therapy. Routine celiac and superior mesenteric artery angiography was done before transcatheter arterial chemoembolization (TACE) for 78 collateral arterial pathways of 62 hepatocellular carcinoma patients. Super selective catheterization and transcatheter dual arterial chemoembolization (TDACE) to extrahepatic arterial and hepatic arteries were performed. Extrahepatic blood supply was found in 43.1% of hepatocellular carcinoma patients. There was close correlation between extrahepatic arterial blood supply and location of tumor. Success rate of super selective extrahepatic artery catheterization was 71.8% by the combined use of RH, Cobra and SP catheters. Follow-up studies revealed reduction of tumor and complete dense deposition of lipiodol. Ample extrahepatic arterial blood supply is found in hepatocellular carcinoma. Transcatherdual arterial chemoembolization is effective, necessary and feasible for hepatocellular carcinoma with extrahepatic arterial blood supply.


Congenital dyserytropoietic anaemia, type II (HEMPAS) in three siblings.
These siblings of a Czech family aged 21, 19 and 6 years, respectively, with congenital dyserythropoietic anemia, type II, (HEMPAS) are reported. In two elder siblings ferrokinetic studies revealed a rapid plasma 59Fe clearance, markedly decreased erythrocyte incorporation and shortened 51Cr red-cell survival. Direct anti-globulin test was found positive in one of them. Further investigations revealed low values of blood plasma cholesterol, total lipids, beta-lipoproteins, beta-carotine and vitamin E and A as well as low values of the prothrombin complex. Liver biopsy demonstrated siderosis and disseminated intravascular coagulation in the liver in both patients. The possible reasons for these humoral aberrations are discussed.