Alprazolam attenuates the behavioral effects of d-amphetamine in humans.
The results of preclinical behavioral pharmacology studies suggest that gamma-aminobutyric acidA (GABAA) receptor modulators attenuate the behavioral effects of commonly abused stimulants such as amphetamines and cocaine under a variety of behavioral arrangements including drug discrimination and self-administration. In the present experiment, 6 healthy humans learned to discriminate 15-mg oral D-amphetamine. After acquiring the discrimination (ie, . > or = 80% correct responding on 4 consecutive days), the effects of a range of doses of D-amphetamine (0, 2.5, 5, 10, and 15 mg), alone and following pretreatment with alprazolam (0 and 0.5 mg), a GABAA receptor modulator, were assessed. D-Amphetamine alone functioned as a discriminative stimulus and produced stimulant-like self-reported drug effects (eg, increased scores on a Stimulant-Sensitive Adjective-Rating Scale). These effects were generally a function of dose. Alprazolam alone did not occasion D-amphetamine-like discriminative stimulus effects, nor did it increase ratings of sedation or impair performance. Alprazolam pretreatment significantly attenuated the discriminative stimulus effects of D-amphetamine, and some of the self-reported drug effects. Future human laboratory experiments should compare the behavioral effects of D-amphetamine alone and following pretreatment with alprazolam using other behavioral arrangements such as drug self-administration. Future laboratory experiments with humans should also determine if benzodiazepines with lower abuse potential (eg, oxazepam) might also attenuate the behavioral effects of D-amphetamine.


Peripheral blood and intestinal lymphocyte sub-populations in Crohn's disease.
Immunofluorescent technques were utilized to study the nature and distribution of cells forming the inflammatory infiltrate in Crohn's disease. Tissue from resected ileum (one patient) or colon (one patient) when compared with corresponding control tissues contained increased numbers of B and T lymphocytes. B-cells of IgG class predominated in the mucosal lamina propria, whereas T-cells were prominent in the deeper layers of inflamed bowel. Inflammatory cells bearing Fc receptors were also present in these tissues. Decreased peripheral blood T-cell numbers returned to normal after resection of the involved bowel in the two patients studied. Impaired cellular immunity in Crohn's disease may thus result from T-cell sequestration in or loss from involved segments of intestine.


Microsurgical Neurovascular Anatomy of the Brain: The Anterior Circulation (Part I).
Introduction Treatment of cranial neurovascular pathology requires a detailed understanding of the brain, head, and neck vasculature. This study aims at a comprehensive overview of the microsurgical anatomy of the anterior cerebral circulation. Methods Five formalin-fixed adult cadaveric heads were used. Common carotid arteries, vertebral arteries, and internal jugular veins were injected with colored latex (red for arteries and blue for veins). The heads were dissected under a surgical microscope with magnifications ranging between 3× to 40× focusing on the anterior circulation. A synoptic approach was used to describe in detail the segments, branches, perforating arteries, veins, and vascular territories of the cerebral arteries and veins. Results The anterior arterial circulation of the brain is provided by the internal carotid artery (ICA), anterior cerebral artery (ACA), middle cerebral artery (MCA), anterior communicating artery (ACoA), and perforating arteries. Perforating arteries of the anterior circulation arise from the ICA, ACA, MCA, ACoA, and posterior communicating artery (PCoA). The distal segments and collateral branches of the ICA, ACA, and MCA give the arterial supply to the largest part of the forebrain, whereas perforating arteries of the anterior circulation are related to the striatum, thalamus, and basal ganglia. The ACoA is the core functional anastomosis between the left and right ICA systems. The external carotid artery provides the vascular supply to the region of the face, head, and neck, and most of the meninges. The internal jugular venous system is composed of the internal and external jugular veins, which constitutes the outflow of the cerebral and facial venous system, respectively. Conclusion Thorough knowledge of the topographic, cisternal, and functional anatomy of the anterior circulation of the brain is critical for surgery of the supratentorial lesions.


Phase-separated composite films for liquid crystal displays
A method of preparing liquid crystal devices by phase separation of liquid crystal from its solution in a prepolymer, which results in adjacent layers of liquid crystal and polymer, is described. Liquid crystals in these phase-separated composite films exhibit electro-optical properties not observed in devices prepared by conventional methods, polymer dispersion, or polymer-stabilization methods. Devices incorporating ferroelectric liquid crystals have gray scale and switch 100 times faster at low fields than conventional surface-stabilized devices. This method makes it possible to prepare devices with liquid crystal film thickness comparable to optical wavelengths.


Polymorphism of the rat liver mitochondrial aldehyde dehydrogenase cDNA.
In humans, a deficiency in mitochondrial aldehyde dehydrogenase (Class 2 ALDH) activity due to a single base-pair exchange in its structural gene serves as a deterrent to excessive alcohol consumption. Differences in Class 2 ALDH isozyme patterns on isoelectric focusing gels have been observed in the selectively bred, alcohol-preferring (P) and alcohol-nonpreferring (NP) lines of rats. To determine whether the differences are the result of sequence variation in the structural gene, we sequenced the cDNAs for Class 2 ALDH from P and NP rats. A synonymous exchange was seen in the codon for amino acid 473 in both lines, when compared with published sequences. Additionally, when the cDNA from P rats was used as reference, a substitution (G for A) was identified in the cDNA of NP rats which changes amino acid 67 from Gln (CAG codon; ALDH2Q allele) to Arg (CGG codon; ALDH2R allele). The Arg for Gln substitution makes the enzyme more basic and could account for the different electrophoretic mobilities. To determine whether the polymorphism was associated with drinking behavior, we genotyped the ALDH2 locus by amplifying rat genomic DNA encompassing the nucleotide exchange followed by probing with allele-specific oligonucleotides. There are highly significant differences in the frequencies of the two alleles in the P and NP rat lines. The frequency of the ALDH2R allele is 63% in the NP line and only 18% in the P line, whereas the frequency of the ALDH2Q allele is 82% in the P line and 37% in the NP line.


JAK/STAT Activation: A General Mechanism for Bone Development, Homeostasis, and Regeneration.
The Janus kinase (JAK) signal transducer and activator of transcription (STAT) signaling pathway serves as an important downstream mediator for a variety of cytokines, hormones, and growth factors. Emerging evidence suggests JAK/STAT signaling pathway plays an important role in bone development, metabolism, and healing. In this light, pro-inflammatory cytokines are now clearly implicated in these processes as they can perturb normal bone remodeling through their action on osteoclasts and osteoblasts at both intra- and extra-articular skeletal sites. Here, we summarize the role of JAK/STAT pathway on development, homeostasis, and regeneration based on skeletal phenotype of individual JAK and STAT gene knockout models and selective inhibition of components of the JAK/STAT signaling including influences of JAK inhibition in osteoclasts, osteoblasts, and osteocytes.


Magnaporthe grisea interactions with the model grass Brachypodium distachyon closely resemble those with rice (Oryza sativa).
SUMMARY Germplasm of Brachypodium distachyon was inoculated with Magnaporthe grisea using either rice- (Guy11) or grass-adapted (FAG1.1.1, PA19w-06, PA31v-01) host-limited forms of the fungus, and interactions with varying degrees of susceptibility and resistance were identified. Ecotype ABR5 was resistant to each M. grisea strain whereas ABR1 was susceptible to all but P31vi-01. Mendelian segregation in ABR1 x ABR5 crosses suggested that a single dominant resistance gene conferred resistance to Guy11. Microscopic analyses revealed that the aetiology of Guy11 fungal development and disease progression in ABR1 closely resembled that of rice infections. In ABR5, Guy11 pathogenesis was first suppressed at 48 h post-inoculation, at the secondary hyphal formation stage and was coincident with cytoplasmic granulation. Resistance to strains PA31v-01 and FAG1.1.1 was associated with a localized cell death with little callose deposition. 3,3-Diaminobenzidine staining indicated the elicitation of cell death in B. distachyon was preceded by oxidative stress in the interacting epidermal cells and the underlying mesophyll cells. Northern blot hybridization using probes for barley genes (PR1, PR5 and PAL) indicated that each was more rapidly expressed in ABR5 challenged with Guy11 although the B. distachyon defence genes BD1 and BD8 were more quickly induced in ABR1. Such data show that B. distachyon is an appropriate host for functional genomic investigations into M. grisea pathology and plant responses.


Escape to Alcatraz: evolutionary history of slender salamanders (Batrachoseps) on the islands of San Francisco Bay.
Island populations are excellent model systems for studies of phenotypic, ecological and molecular evolution. In this study, molecular markers of mitochondrial and nuclear derivation were used to investigate the evolution, structure and origin of populations of the California slender salamander (Batrachoseps attenuatus) inhabiting the six major islands of San Francisco Bay, formed following the rising of sea level around 9,000 years ago. There was a high degree of congruence in the results of analyses of nucleotide and allozyme data, both of which strongly support the hypothesis that, for the majority of the islands, salamanders are descended from hilltop populations that became isolated with the formation of the Bay ca. 9,000 years ago. There are two exceptions (Alcatraz and Yerba Buena) where the evidence suggests that salamander populations are wholly or in part, the result of anthropogenic introductions.Comparison of the molecular data and the interpretations drawn therefrom with an earlier morphological study of many of the same salamander populations show some of the same evolutionary trends. In spite of marked differences between the evolutionary rates of the two kinds of molecular markers, both indicate distinctive and similar patterns of population structure for B. attenuatus in the San Francisco Bay Area and its islands. With the two noted exceptions, it is clear that most island populations were established prior to the 9,000 years since the formation of the Bay. Results of coalescence-based analyses suggest that for most island populations the mtDNA lineages from which they were derived date from the Pleistocene.It can be said that, based on observed values of genetic diversity, the last 9,000 years of evolution on these islands have been characterized by relative stability, with the occasional extinction of some haplotypes or alleles that were formerly shared between island and mainland populations but overall maintaining high levels of variation (with the exception of Alcatraz). In contrast, there is some evidence for rapid morphological changes between populations in some islands and their closest mainland counterparts. This pattern of rapid morphological divergence (e. g., resulting from founder effects) is similar to that observed in other studies about recent colonization of island habitats.


The incidence and severity of burn injuries following Project Burn Prevention.
Project Burn Prevention, an educational program about burn safety, was implemented in the Greater Boston area from October 1977 through May 1978. The program consisted of three components: a media campaign, a school-initiated intervention, and a community-initiated intervention. Estimates of burn incidence and severity of injury because of scald, flame, electrical or contact burns, or smoke inhalation were made on all patients coming to target- or comparison-area hospitals for a four-year period before the program, the eight months during the program, and the 12 months after the program. Analysis of burn incidence during and after the interventions showed that the school-initiated intervention did not reduce the incidence or severity of burn injuries. The community-initiated intervention may have brought about a moderate, temporary reduction in the rate of burn injuries, although the increase in burn incidence observed for the media campaign of educational messages broadcast to the Greater Boston area suggests that the more plausible explanation for this effect is random variation in burn incidence.


Characterisation of tumoral markers correlated with ErbB2 (HER2/Neu) overexpression and metastasis in breast cancer.
The receptor tyrosine kinase ErbB2 (HER2/neu) is overexpressed in ˜30% of breast cancers and is associated with poor prognosis and an increased likelihood of metastasis. Clinical treatments such as trastuzumab are effective in less than 35% of women diagnosed as ErbB2-positive, highlighting the necessity of searching for novel targets and alternative therapies. Herein, a proteomic screening strategy combining quantitative-based gel electrophoresis and MS was used to compare the protein expression of 48 normal human breast and tumour tissues differing in ErbB2 expression and lymph node status. The aim was to identify proteins associated with the aggressive phenotype of ErbB2-positive breast cancer which could be potential biomarkers of the disease as well as therapy targets. In total, 177 protein isoforms (107 gene products) differentially expressed between tissue groups were identified. Immunohistochemical staining of a tissue-microarray was used for validation of selected protein candidates. We found that expression of HSP90α, laminin and GSTP1 significantly correlated with ErbB2 expression, while others such as AGR2, NM23H1 and Annexin 2 were overexpressed in greater than 40% of tumours. Finally, knocking-down the expression by RNA interference of three candidates, AGR2, Transgelin2 and NM23H1 resulted in an enhanced invasive capacity of MDA-MB435 cells. These data support the involvement of these targets in tumour progression and identify them as novel biomarkers of the disease.


Female dispersal and male kinship-based association in southern hairy-nosed wombats (Lasiorhinus latifrons).
Generalizations about sociobiology require investigations of species with diverse ecological roles and phylogenetic affiliations. The southern hairy-nosed wombat (Lasiorhinus latifrons) is valuable here, in that it is a marsupial of semi-arid habitat, and one of the largest burrowing herbivores (commonly attaining 26 kg). Its sociobiology is poorly understood because the species is nocturnal, shy, and difficult to observe or capture nondisruptively. To investigate aspects of the species' sociobiology in continuous habitat, we applied high-intensity, temporally replicated, noninvasive sampling and genotyping of hairs to identify individuals and their sex. Spatial relatedness (kinship) structure was estimated, and related to patterns of burrow-use. To understand the association of kinship with burrow/warren-sharing and preferential colocation between wombats, > 100 genetically 'tagged' individuals at Brookfield Conservation Park (Murraylands, South Australia) were 'tracked' through multiple seasons between 1999 and 2001. Dispersal was female-biased, and may be performed by females after breeding. Conversely, males were philopatric. Male kin relationships were characterized by preferential burrow- and warren-sharing among closely related males, often in associations lasting for years. In contrast, females under-associated with their close female relatives and did not form matrilineal groupings with potential for favourable kin interactions. This fundamental departure from the predominant mammalian pattern raises questions about the origins and maintenance of the system, which is now known from all three species of wombat. The present study provides starting points to address those questions by adding to our knowledge of longitudinal spatiotemporal associations and habitat use of a marsupial with the unusual system of female-biased dispersal, and by outlining robust methodologies.


Effect of Erlotinib Plus Bevacizumab vs Erlotinib Alone on Progression-Free Survival in Patients With Advanced EGFR-Mutant Non-Small Cell Lung Cancer: A Phase 2 Randomized Clinical Trial.
Erlotinib is a standard first-line therapy for patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). Median progression-free survival (PFS) with erlotinib is approximately 10 months. To determine whether adding bevacizumab to erlotinib treatment results in superior progression-free survival compared with erlotinib alone. This phase 2 randomized clinical trial compared erlotinib plus bevacizumab with erlotinib alone in EGFR-mutant NSCLC. The trial was conducted in 17 US academic and community medical centers among 88 patients with EGFR exon 19 deletion or exon 21 L858R mutation based on local testing and stage 4 NSCLC who were eligible for bevacizumab. Patients were enrolled between November 2, 2012, and August 22, 2016, and followed up for a median (range) of 33 (0.7-62.5) months. Data were analyzed on August 28, 2018, and included data from November 2, 2012, to August 20, 2018. Patients were randomized with equal allocation to 150 mg of oral erlotinib daily alone or with 15 mg/kg of intravenous bevacizumab every 3 weeks. Study therapy continued until disease progression, unacceptable adverse event, or withdrawal of consent. The primary outcome was PFS as assessed by the investigator; secondary outcomes were objective response rate (ORR), adverse events, and overall survival (OS). Analysis was designed to detect a hazard ratio (HR) of 0.667 for PFS (an improvement from a median PFS of 10 to 15 months). Among 88 patients enrolled, the median (range) age was 63 (31-84) years; 62 patients (70%) were female; 75 (85%) were white, 8 (9%) were African American, 3 (3%) were Asian, and for 2 (2%), data on race were not available. Forty-eight patients (55%) were never smokers, 45 patients (51%) were of Eastern Cooperative Oncology Group performance status 1, and 59 patients (67%) had EGFR exon 19 deletion. Compared with erlotinib, the combination did not result in a significant difference in PFS (HR, 0.81; 95% CI, 0.50-1.31; P = .39; median PFS 17.9 [combination] and 13.5 months [erlotinib]), ORR (81% vs 83%; P = .81), and OS (HR, 1.41; 95% CI, 0.71-2.81; P = .33; median OS, 32.4 months [combination] and 50.6 months [erlotinib]). Adverse events of grade 3 or higher observed in 5 or more patients in the combination and erlotinib arms were skin eruption in 11 (26%) vs 7 (16%) patients, diarrhea in 4 (9%) vs 6 (13%) patients, hypertension in 17 (40%) vs 9 (20%) patients, and proteinuria in 5 (12%) vs 0 (0%) patients. Erlotinib plus bevacizumab compared with erlotinib did not result in a significant improvement in PFS in EGFR-mutant NSCLC. ClinicalTrials.gov identifier: NCT01532089.


Satiating capacity and post-prandial relationships between appetite parameters and gut-peptide concentrations with solid and liquefied carbohydrate.
Differences in satiating capacity of liquid and solid meals are unclear. Investigating appetite parameters, physiological measurements and within-subject relationships after consumption of a single macronutrient, subject-specific carbohydrate meal in liquefied versus solid form, controlled for energy density, weight and volume. In a cross-over design, ten male subjects (age = 21.1±3.9 y, BMI = 22.4±1.2 kg/m(2)) consumed a solid (CS, whole peaches +750 ml water) and liquefied carbohydrate (CL, peach blended in 500 ml water +250 ml water) lunch. Appetite profiles, insulin-, glucose- and ghrelin concentrations were measured over three hours. Post-prandial relationships between appetite and blood parameters were calculated using subject-specific regression analyses. Fullness ratings were higher in the CL (85±5 mm) compared to the CS condition (73±8 mm) at 20 min (p<0.03). Glucose concentrations peaked 20 to 30 min after the start of the lunch in the CL condition, and 30 to 40 min after start of the CS condition. Correspondingly, insulin concentrations were peaked at 20-30 min in the CL condition, and at 30-40 min in the CS condition. AUC or condition x time interactions were not different comparing the CL and the CS condition. Insulin was significantly higher in the CS compared to the CL condition 40 min after the start of the lunch (p<0.05). Fullness scores were significantly related to insulin concentrations but not to glucose concentrations; desire to eat scores were significantly associated with ghrelin concentrations in both, the CL and the CS condition. The relationship between fullness scores and glucose concentrations was not statistically significant. Liquefied and solid carbohydrate meals do not differ in satiating capacity, supported by appetite profile and relevant blood parameters. Postprandially, fullness and desire to eat were associated with respectively insulin and ghrelin concentrations.


Patient satisfaction and discussion of smoking cessation during clinical visits.
To learn whether patients who smoke and who receive smoking cessation information during medical office visits were less likely to be satisfied with the smoking cessation help they received than patients who smoke but who did not receive such information. A total of 3703 current cigarette smokers were identified by a mailing in November 1998 to 163,596 members of 2 Minnesota health plans, and 2714 (77.3%) responses to a 44-item questionnaire were available for analysis. Using hierarchical analysis to control confounding variables, we assessed the relationship between patient-reported smoking cessation support actions at the last physician visit and satisfaction "with the help received from your doctor about quitting smoking." Smokers were very satisfied (12.0%), satisfied (25.3%), neutral (48.6%), and dissatisfied or very dissatisfied (13.5%) with physician help. After controlling for other characteristics, the 1898 patients who reported that they had been asked about tobacco use or advised to quit during the latest visit had 10 percentage point greater satisfaction ratings and 5 percentage point less dissatisfaction than those not reporting such discussions (P<.001). Smokers reporting no interest in quitting at the time of the latest visit also demonstrated greater satisfaction in association with these actions. Smoking cessation interventions during physician visits were associated with increased patient satisfaction with their care among those who smoke. This information should reduce concerns of physicians or nurses about providing tobacco cessation assistance to patients during office visits.


Reye's syndrome in Johannesburg. Epidemiology and clinical presentation.
The aetiology of Reye's syndrome is uncertain. Factors such as environment (urban or rural), socioeconomic conditions and race seem to influence the variation in incidence. These factors, as well as clinical presentation, were studied in the Johannesburg area over a 5-year period. The preceding illness differed from that in the other reports. The pattern of presentation among the White population has changed.


Comparative genomics.
The genomes from three mammals (human, mouse, and rat), two worms, and several yeasts have been sequenced, and more genomes will be completed in the near future for comparison with those of the major model organisms. Scientists have used various methods to align and compare the sequenced genomes to address critical issues in genome function and evolution. This review covers some of the major new insights about gene content, gene regulation, and the fraction of mammalian genomes that are under purifying selection and presumed functional. We review the evolutionary processes that shape genomes, with particular attention to variation in rates within genomes and along different lineages. Internet resources for accessing and analyzing the treasure trove of sequence alignments and annotations are reviewed, and we discuss critical problems to address in new bioinformatic developments in comparative genomics.


Disease activity and joint damage progression in early rheumatoid arthritis: relation to IgG, IgA, and IgM rheumatoid factor.
The clinical and biochemical correlations with joint damage progression over two years in a consecutive group of 68 patients with rheumatoid arthritis with disease duration of less than two years are reported. Joint damage was assessed with Larsen's severity scale and a measure of change in progression rate constructed. Initial haemoglobin concentration, Ritchie index, and Waaler-Rose titre in combination accounted for one third of the variance in joint damage progression. Rheumatoid factor (RF) concentrations were followed with enzyme linked immunosorbent assays (ELISAs) for IgG RF, IgA RF, and IgM RF. The RF concentrations, except IgG RF, decreased with time; significant correlations between RFs and disease activity were few and barely clinically useful. After two years IgG RF correlated significantly with a radiological score if early non-erosive changes were omitted. All RFs tended to correlate better with this radiological score at all three observation points. Analyses of the change in progression rate indicated a time delay between development of radiographic changes and increase of IgG RF. These results suggest an indirect relation between RFs and joint damage. Clinical and biochemical improvements in early RA occur despite joint damage progression, and conventional markers have insufficient predictive value.


Computational models for the combination of advice and individual learning.
Decision making often takes place in social environments where other actors influence individuals' decisions. The present article examines how advice affects individual learning. Five social learning models combining advice and individual learning-four based on reinforcement learning and one on Bayesian learning-and one individual learning model are tested against each other. In two experiments, some participants received good or bad advice prior to a repeated multioption choice task. Receivers of advice adhered to the advice, so that good advice improved performance. The social learning models described the observed learning processes better than the individual learning model. Of the models tested, the best social learning model assumes that outcomes from recommended options are more positively evaluated than outcomes from nonrecommended options. This model correctly predicted that receivers first adhere to advice, then explore other options, and finally return to the recommended option. The model also predicted accurately that good advice has a stronger impact on learning than bad advice. One-time advice can have a long-lasting influence on learning by changing the subjective evaluation of outcomes of recommended options.


Secretory microRNA-29 expression in gingival crevicular fluid during orthodontic tooth movement.
Secretory microRNAs (miRNAs) have been used increasingly as biomarkers for cancers, autoimmune diseases and inflammatory diseases. They are reported as being freely circulated or encapsulated in microvesicles such as exosomes. This study was performed to elucidate the presence of miRNAs with exosomes in human gingival crevicular fluid (GCF), and the expression profile of miRNA-29 during orthodontic tooth movement. Four healthy volunteer and fifteen orthodontic patients were enrolled in the study. Secretory miRNA in GCF was collected and analyzed using a bioanalyzer, realtime PCR and Western blot analysis. The expression profile of secretory miR-29 family in GCF was analyzed during the course of canine retraction for 6 weeks. The results demonstrated the presence of miRNAs in the GCF. After series of ultracentrifugation and RT-PCR array, exosome-depleted fractions and pellets were isolated and we found that secretory miRNAs were detected in both the exosome-associated fraction and the exosome-depleted supernatant fraction; however, the concentration of miRNAs was higher in the exosome-associated fraction than in the exosome-depleted fraction suggesting a close association between the secretory miRNAs and exosomes in GCF. We also demonstrated the increased expression profiles of miR-29 family during six weeks of orthodontic tooth movement in humans. Secretory miRNAs are present in GCF and secretory miRNA-29 family expression profiles increase during the tooth movement in humans. Secretory miRNA-29 in GCF could serve as potential biomarkers for periodontal remodeling.


Management of gastroenteritis in children under five years.
This article explores the causes and management of gastroenteritis in children under five years. It considers in particular national guidance from the National Institute for Health and Care Excellence. The importance of identifying and assessing dehydration is discussed, as well as its systematic management, carer education and infection prevention. Promoting carer competence, confidence and self-management is emphasised.


The development of an assessment and intervention falls guide for older hospitalized adults with cardiac conditions.
Older patients with chronic cardiac conditions are more vulnerable to falls and injuries. Cardiovascular conditions, prevalent in older people, are also the frequent cause of potentially harmful fall injuries among this group. The need to identify the fall risk-related factors that cluster with arrhythmia and syncope is relevant as it will potentially reduce patients' risk for falls and fall injuries. The paper describes the process taken to design, develop and implement a practice-change initiative that specifically focuses on cardiac-related falls and injuries. A review of best practice guidelines, related studies and patients' profiles from chart audits were utilized to obtain evidence-based information to develop this assessment and intervention falls guide. Prior to the development of this guide, the charts of six patients were reviewed to assess specific data including age, history of falls, type of injury, cognitive function and underlying medical conditions. The developed Assessment and intervention falls guide was utilized with seven patients in the Cardiology Unit who were admitted with diagnosis of syncope and atrial fibrillation to assess their risk for falls. The project demonstrated an evidence-informed process that was used to design and implement this assessment tool and a change in nursing practice. It also provided information about the prevalence of cardiac-related risk fall factors that were utilized in the development of this Assessment and Intervention Falls Guide for elderly people.


Transcriptome Dynamics of Brassica juncea Leaves in Response to Omnivorous Beet Armyworm (Spodoptera exigua, Hübner).
Cruciferous plants manufacture glucosinolates (GSLs) as special and important defense compounds against insects. However, how insect feeding induces glucosinolates in Brassica to mediate insect resistance, and how plants regulate the strength of anti-insect defense response during insect feeding, remains unclear. Here, mustard (Brassica juncea), a widely cultivated Brassica plant, and beet armyworm (Spodoptera exigua), an economically important polyphagous pest of many crops, were used to analyze the changes in GSLs and transcriptome of Brassica during insect feeding, thereby revealing the plant-insect interaction in Brassica plants. The results showed that the content of GSLs began to significantly increase after 48 h of herbivory by S. exigua, with sinigrin as the main component. Transcriptome analysis showed that a total of 8940 DEGs were identified in mustard challenged with beet armyworm larvae. The functional enrichment results revealed that the pathways related to the biosynthesis of glucosinolate and jasmonic acid were significantly enriched by upregulated DEGs, suggesting that mustard might provide a defense against herbivory by inducing JA biosynthesis and then promoting GSL accumulation. Surprisingly, genes regulating JA catabolism and inactivation were also activated, and both JA signaling repressors (JAZs and JAMs) and activators (MYCs and NACs) were upregulated during herbivory. Taken together, our results indicate that the accumulation of GSLs regulated by JA signaling, and the regulation of active and inactive JA compound conversion, as well as the activation of JA signaling repressors and activators, collectively control the anti-insect defense response and avoid over-stunted growth in mustard during insect feeding.


Participation of lower-to-middle wage workers in a study of Chronic Disease Self-Management Program (CDSMP) effectiveness: Implications for reducing chronic disease burden among racial and ethnic minority populations.
Although the Chronic Disease Self-Management Program (CDSMP) improves chronic disease outcomes, little is known about CDSMP participation in populations less than 65 years of age. We explore study and CDSMP participation rates by demographic characteristics with younger (40-64 years old), lower-to-middle wage workers with chronic disease in a randomized clinical trial (RCT) conducted in North Carolina. Descriptive statistics and regression models were used to examine associations between demographic, chronic disease burden, and employment variables, and time-dependent study enrollment and intervention participation outcomes that ranged from initiating consent (n = 1,067) to CDSMP completion (n = 41). Overall, participation among non-Whites was disproportionately higher (43%-59%) than that of Whites (42%-57%) relative to the age-matched racial composition of North Carolina (31% non-White and 69% White). Among participants randomized to the CDSMP, racial and ethnic minorities had the highest rates of participation. There were no significant demographic, chronic disease burden, or employment predictors among the participation outcomes examined, although this may have been due to the limited number of CDSMP workshop participation observations. Extending the CDSMP to lower-to-middle wage workers may be particularly effective in reaching racial and ethnic minority populations, who complete the program to a greater extent than their White, non-Hispanic counterparts.


Structural and histological characterization of oviductal magnum and lectin-binding patterns in Gallus domesticus.
Although chicken oviduct is a useful model and target tissue for reproductive biology and transgenesis, little is known because of the highly specific hormonal regulation and the lack of fundamental researches, including lectin-binding activities and glycobiology. Because lectin is attached to secreted glycoproteins, we hypothesized that lectin could be bound to secretory egg-white proteins, and played a crucial role in the generation of egg-white protein in the oviduct. Hence, the purpose of this study was to investigate the structural, histological and lectin-binding characteristics of the chicken oviductal magnum from juvenile and adult hens. The oviductal magnums from juvenile and adult hens were prepared for ultrastructural analysis, qRT-PCR and immunostaining. Immunohistochemistry of anti-ovalbumin, anti-ESR1 and anti-PGR, and mRNA expression of egg-white genes and steroid hormone receptor genes were evaluated. Lectin histochemical staining was also conducted in juvenile and adult oviductal magnum tissues. The ultrastructural analysis showed that ciliated cells were rarely developed on luminal surface in juvenile magnum, but not tubular gland cells. In adult magnum, two types of epithelium and three types of tubular gland cells were observed. qRT-PCR analysis showed that egg-white genes were highly expressed in adult oviduct compared with the juvenile. However, mRNA expressions of ESR1 and PGR were considerably higher in juvenile oviduct than adult (P < 0.05). The immunohistochemical analysis showed that anti-ovalbumin antibody was detected in adult oviduct not in juvenile, unlikely anti-ESR1 and anti-PGR antibodies that were stained in both oviducts. In histological analysis, Toluidine blue was stained in juvenile and adult oviductal epithelia, and adult tubular glands located in the outer layer of oviductal magnum. In contrast, PAS was positive only in adult oviductal tubular gland. Lectins were selectively bound to oviductal epithelium, stroma, and tubular gland cells. Particularly, lectin-ConA and WGA were bound to electron-dense secretory granules in tubular gland. The observation of ultrastructural analysis, mRNA expression, immunohistochemistry and lectin staining showed structural and physiological characterization of juvenile and adult oviductal magnum. Consequently, oviduct study could be helped to in vitro culture of chicken oviductal cells, to develop epithelial or tubular gland cell-specific markers, and to understand female reproductive biology and endocrinology.


Association of asthma with extra-respiratory symptoms in schoolchildren: two cross-sectional studies 6 years apart.
Epidemiological information on symptoms affecting extra-respiratory organs and apparatuses in asthmatic children is scarce. The aim of this study therefore was to evaluate, at a population level, if and what extra-respiratory symptoms are associated with asthma. Two questionnaire-based, cross-sectional surveys were carried out on 1,262 students (651 males; mean age 9.57 years, age-range 6-14 years) in 1992 and on 1,210 students (639 males; mean age 9.02 years, age-range 6-14 years) in 1998, from two elementary and two junior high schools in Rome, Italy. Questionnaires included queries about asthma and its risk factors and extra-respiratory symptoms (headache, restlessness, sleep disturbances, urticaria, itching, and abdominal pain). Of responders, 11.9% (279/2,342) had a history of asthma. After adjustment for gender, family history of atopic disease, low birth weight, early respiratory problems, and damp house, asthma was significantly associated with recurrent abdominal pain (odds ratio [OR] 1.90; 95% confidence interval [CI]: 1.04, 3.16), itching (OR 3.15; 95% CI: 1.75, 5.68), and urticaria (OR 2.52; 95% CI: 1.02, 6.20). Asthma was reported by 10.2% (201/1,962) of children unaffected by this triad, by 20.1% (56/279; OR 2.20) with one of the symptoms, and by 31.6% (12/38; OR 4.04) with two or more symptoms. An emerging characteristic of pediatric asthma in our setting appears to be its association with certain extra-respiratory symptoms (abdominal pain, itching, and urticaria). A global, internistic approach to asthmatic children is increasingly required both in the clinical setting and in future epidemiological studies.


Alcohol septal ablation for hypertrophic obstructive cardiomyopathy.
Since its original description in 1994, alcohol septal ablation (ASA) has emerged as a minimally invasive modality for treatment of hypertrophic obstructive cardiomyopathy compared to surgical myomectomy. This catheter-based intervention relies on the injection of absolute alcohol into the septal perforator to induce a controlled infarction of the hypertrophied septum and consequently abolish the dynamic outflow obstruction. This gradient reduction has been correlated with a significant clinical improvement in the patient's symptomatology and with left ventricular remodeling. The procedure has been refined throughout the years, especially with the introduction of myocardial contrast echocardiography for localization of the area at risk of infarction and the reduction in the amount of alcohol used. Major complications of ASA are uncommon in large referral centers but conduction system disturbances has been the most commonly reported complications of ASA with 10% of patients necessitating permanent pacemaker implantation for complete heart block. ASA has not been compared to the gold standard surgical myomectomy in a randomized prospective study. We review the clinical aspects of this procedure and provide some historical background.


Organochlorine residues in three bat species from four localities in Maryland and West Virginia, 1973.
In 1973, 119 bats of three species were collected from four localities in Maryland and West Virginia. The collection included 43 big brown bats (Eptesicus fuscus), 43 little brown brown bats (Myotis lucifugus), and 33 eastern pipistrelles (Pipistrellus subflavus). The bats were collected from Round Top Mountain, Washington Co., Md.; Trout Cave, Pendleton Co., W. Va.; Montpelier Barn, Prince Georges Co., Md. Residues of sigmaDDT were highest in carcasses of bats from Round Top Mountain, which is surrounded by apple orchards. Bats from Trout Cave had the lowest residues, a circumstance which probably reflects the absence of agriculture and industry in the area. A polychlorinated biphenyl (PCB) and oxychlordane were highest at Montpelier Barn. Sources of the PCB are unknown, but chlordane is used against termites and in gardening at nearby housing developments. Residues in bats from North East Methodist Church were low except for dieldrin. Among species, little brown bats usually had the highest residue concentrations in their carcasses, whereas big brown bats had the lowest. When DDE in carcass fat of all species was above 60-90 ppm, it became measurable in brain tissue. Above 60-90 ppm, DDE levels in brains rose with increasing levels in carcass lipids. Residues of the PCB tended to respond similarly. Residue levels in brains were greatest in little brown bats; the maximum level of the PCB, 7.9 Ppm, was more than twice that of DDE.


Implications of genomic instability in the diagnosis and treatment of breast cancer.
Tumorigenesis is a multistep process resulting from DNA mutations observed at the DNA sequence and chromosome level as well as epigenetic changes, which affect expression of oncogenes and tumor suppressor genes. Breast cancer is a very heterogeneous disease that manifests in various histological and clinical types. Defects in the biological action of the genome driven by various alterations, such as point mutations and chromosomal rearrangements, lead to the collapse of genome integrity, uncontrolled cell proliferation and failure in apoptotic cell death. Detailed profiling of breast cancer-associated genomic alterations is indispensable for the design of individualized anticancer therapy, by suggesting diagnostic and prognostic criteria as well as the outcome of applied treatment. Among various directions of cancer research, identification of genomic alterations in breast cancer and their translation into clinical applications is at the forefront.


François Magendie (1783-1855) and his contributions to the foundations of neuroscience and neurosurgery.
François Magendie lived during a tumultuous period in French history. Although this early medical pioneer made significant contributions to the fields of neuroanatomy, physiology, and pharmacology, little information is found in the non-French literature regarding this significant person in history. Based on this review, one could also consider this trained surgeon as an early pioneer of neurosurgery. For example, he is known to have used Galvanic current to treat various neuralgias, described a technique for extracting cerebrospinal fluid and quantitated and described its characteristics in normal and pathological specimens, and elucidated the functions of the the cranial nerves using vivisection. Additionally, he accurately described the functions of the dorsal and ventral rootlets using vivisection, and realized that the exposed meninges were susceptible to painful stimuli. Our current knowledge is based on the early contributions of scientists such as François Magendie.


Primary fourth ventricular meningioma: case report and review of the literature.
Primary fourth ventricle meningiomas are extremely rare, and they are defined as meningiomas arising from the choroid plexus and lying strictly within the fourth ventricle. In this report we present a 61-year-old man with progressive worsening vertigo and gait disturbance, and new onset of diplopia. Neurological examination revealed bilateral abducens nerve paralysis, horizontal nystagmus, and gait disturbance with truncal ataxia. Neuroimaging revealed a mass lesion in the fourth ventricle with brain stem compression, and obstructive hydrocephalus. The patient was operated in the prone position with suboccipital craniotomy and splitting the lower vermis. Total resection of the tumor was achieved with no intra- or post-operative complications. Histopathologic examination revealed fibroblastic type meningioma (WHO grade I).


Collapsing glomerulopathy.
Collapsing glomerulopathy is a morphologic variant of focal segmental glomerulosclerosis (FSGS) characterized by segmental and global collapse of the glomerular capillaries, marked hypertrophy and hyperplasia of podocytes, and severe tubulointerstitial disease. The cause of this disorder is unknown, but nearly identical pathologic findings are present in idiopathic collapsing glomerulopathy and human immunodeficiency virus (HIV)-associated nephropathy, and collapsing glomerulopathy has been associated with parvovirus B19 infection and treatment with pamidronate. The pathogenesis of collapsing glomerulopathy involves visceral epithelial cell injury leading to cell cycle dysregulation and a proliferative phenotype. Clinically, collapsing glomerulopathy is characterized by black racial predominance, a high incidence of nephrotic syndrome, and rapidly progressive renal failure. Collapsing glomerulopathy also may recur after renal transplantation or present de novo, often leading to loss of the allograft. The optimal treatment for collapsing glomerulopathy is unknown. Treatments may include steroids or cyclosporine in addition to aggressive blood pressure control, angiotensin converting enzyme inhibitors and/or angiotensin II receptor blockers, and lipid lowering agents. The role of other immunosuppressive agents such as mycophenolate mofetil in the treatment of collapsing FSGS remains to be defined. Prospective clinical trials are needed to define optimal therapy of this aggressive form of FSGS.


[The ways of transmission of liver cell cytoplasma components to differential erythroblasts in erythropoiesis].
Intercellular interactions consisting of cytoplasmatic bridges and net-like ductal structures were revealed while electron-microscopic investigation in erythropoietic foci of hepar of mammals and amphibians. Hepatic microenvironment cells may influence the erythroblasts via the vascular net of the blood-producing foci and via the cytoplasm of interspaced cells of microenvironment of another kind. The presence of such morphologic structures makes possible to suppose the possibility of transit of ribosomes, protein molecules, lipids and other components of the microenvironmental cells cytoplasm into differentiating erythroblasts. Significant acceleration of maturing process of the red blood cells in erythropoietic foci was promoted by entrance of the cytoplasm components of the microenvironmental cells into erythroblasts.


Non-Native Site-Selective Enzyme Catalysis.
The ability to site-selectively modify equivalent functional groups in a molecule has the potential to streamline syntheses and increase product yields by lowering step counts. Enzymes catalyze site-selective transformations throughout primary and secondary metabolism, but leveraging this capability for non-native substrates and reactions requires a detailed understanding of the potential and limitations of enzyme catalysis and how these bounds can be extended by protein engineering. In this review, we discuss representative examples of site-selective enzyme catalysis involving functional group manipulation and C-H bond functionalization. We include illustrative examples of native catalysis, but our focus is on cases involving non-native substrates and reactions often using engineered enzymes. We then discuss the use of these enzymes for chemoenzymatic transformations and target-oriented synthesis and conclude with a survey of tools and techniques that could expand the scope of non-native site-selective enzyme catalysis.


Methylene unit calibration for analysis of organic acids by gas--liquid chromatography/mass spectrometry.
We describe a method for automatic computation of "methylene unit" retention-time indices in real time on a computer-controlled gas chromatograph/mass spectrometer system. The calculation is based on the exponential relationship between the methylene unit values of hydrocarbon reference standards and the oven temperature at their elution. Using this mathematical relationship, we calculated calibration factors, which eliminates the need to include a set of methylene unit reference standards with each run and simplifies and speeds identification of unknown peaks in chromatograms. Long-term stability and good precision of the calibration factors were observed during the six-month period of study.


Planning continuing nursing education: an interview with Ronald M. Cervero. Interview by Donna L Waddell.
This article reports an interview with Ronald M. Cervero, scholar in the field of continuing professional education and co-author with Arthur L. Wilson of Planning Responsibly for Adult Education: A Guide for Negotiating Power and Interests (1994). The substance of the interview elucidates the role of the manager of the continuing nursing educational experience. He discusses the concepts of negotiation, power, interests, and responsibility and how they impact the planning of continuing nursing education.


A review of methods for achieving upper limb movement following spinal cord injury through hybrid muscle stimulation and robotic assistance.
Individuals with tetraplegia, typically attributed to spinal cord injuries (SCI) at the cervical level, experience significant health care costs and loss of independence due to their limited reaching and grasping capabilities. Neuromuscular electrical stimulation (NMES) is a promising intervention to restore arm and hand function because it activates a person's own paralyzed muscles; however, NMES sometimes lacks the accuracy and repeatability necessary to position the limb for functional tasks, and repeated muscle stimulation can lead to fatigue. Robotic devices have the potential to restore function when used as assistive devices to supplement or replace limited or lost function of the upper limb following SCI. Unfortunately, most robotic solutions are bulky or require significant power to operate, limiting their applicability to restore functional independence in a home environment. Combining NMES and robotic support systems into a single hybrid neuroprosthesis is compelling, since the robotic device can supplement the action of the muscles and improve repeatability and accuracy. Research groups have begun to explore applications of movement assistance for individuals with spinal cord injury using these technologies in concert. In this review, we present the state of the art in hybrid NMES-orthotic systems for upper limb movement restoration following spinal cord injury, and suggest areas for emphasis necessary to move the field forward. Currently, NMES-robotic systems use either surface or implanted electrodes to stimulate muscles, with rigid robotic supports holding the limb against gravity, or providing assistance in reaching movements. Usability of such systems outside of the lab or clinic is limited due to the complexity of both the mechanical components, stimulation systems, and human-machine interfaces. Assessment of system and participant performance is not reported in a standardized way. Future directions should address wearability through improvements in component technologies and user interfaces. Further, increased integration of the control action between NMES and robotic subsystems to reanimate the limb should be pursued. Standardized reporting of system performance and expanded clinical assessments of these systems are also needed. All of these advancements are critical to facilitate translation from lab to home.


Effects of feeding methylthio butyric Acid isopropyl ester on postpartum performance and metabolism in dairy cows.
The present experiment aimed to evaluate the effect of HMBi on the production performance and metabolism in dairy cows. Thirty multiparous Holstein dairy cows under similar conditions were randomly assigned to three dietary treatments; i) Control, a basal diet; ii) T1, a basal diet plus HMBi (0 g prepartum and 18 g postpartum); and iii) T2, a basal diet plus HMBi (10 g prepartum and 18 g postpartum). Treatments were initiated 21 d before expected calving and continued through 91 d postpartum. HMBi was top-dressed onto the total mixed ration of each cow. Treatments did not affect dry matter intake, plasma urea nitrogen, peak milk yield, days to peak milk yield, nonesterified fatty acid, glutamate pyruvate transaminase, glutamic oxalaetic transaminase, milk fat content, milk protein content, milk lactose content, and milk solid non-fat content. The milk composition yields were increased by the HMBi-supplemented treatment. The T1 and T2 treatments increased the yields of 4% fat-corrected milk yield, milk fat, milk protein, and milk lactose compared with the control. Although there was no difference in the milk composition of the control and T2-treated cows, the T2-treated cows exhibited higher milk fat yield (increased by 74 g/d), lower milk urea nitrogen (reduced by 3.41%), and plasma β-hydroxy butyrate than the control cows. The results indicate that HMBi supplementation to diet has beneficial effects, and that there is no difference between supplementation at prepartum and starting only at parturition.


Aldosterone induces oxidative stress, oxidative DNA damage and NF-κB-activation in kidney tubule cells.
An increase of the mineralocorticoid aldosterone is induced by a stimulated renin-angiotensin system in a subgroup of hypertensive patients. Epidemiological studies find higher cancer mortality in hypertensive patients and an increased risk to develop kidney cancer. This work investigated the involvement of oxidants in the genotoxicity of aldosterone and on a potential activation of transcription factor nuclear factor-κB (NF-κB) in kidney tubule cells. Aldosterone, at concentrations as low as 1 nM caused a significant increase of DNA damage, as assessed by comet assay and micronucleus frequency test. Aldosterone also led to a dose-dependent activation of NF-κB. Time courses of DNA damage and NF-κB-activation showed that these effects already occurred after 5 and 3 min of aldosterone exposure, respectively, suggesting non-genomic events of the hormone. Antioxidants prevented aldosterone-induced DNA damage and NF-κB-activation, indicating the involvement of oxidants. In fact, aldosterone caused an increase in intracellular oxidant levels, and in particular of superoxide anions. As a consequence, increased levels of the oxidized DNA modification 7,8-dihydro-8-oxo-guanine were observed in aldosterone-treated kidney cells. Aldosterone-induced DNA damage and NF-κB-activation was dependent on the involvement of the mineralocorticoid receptor. The induction of oxidant-mediated genotoxic effects, and of a long-term activation of the potentially oncogenic cell signal NF-κB by aldosterone could contribute to the increased kidney cancer incidence in hypertensive patients.


Arrhythmogenic effect of hypercapnia in ducks anesthetized with halothane.
To determine effects of hypercapnia on arrhythmias in ducks anesthetized with halothane. 12 ducks, 6 to 8 months old, weighing 1.1 to 1.6 kg. Each duck was anesthetized with a 1.5% mixture of halothane in oxygen, and anesthetic depth was stabilized during a 20-minute period. We added CO2 to the inspired oxygen to produce CO2 partial pressures of 40, 60, and 80 mm Hg in the inspired gas mixture.The CO2 partial pressure was increased in a stepwise manner. When arrhythmias were not evident during inhalation of the gas mixture at a specific CO2 partial pressure, the CO2 partial pressure was maintained for 10 minutes before a sample was collected for blood gas analysis. When arrhythmias were detected, a sample for blood gas analysis was collected after the CO2 partial pressure was maintained for at least 2 minutes, and CO2 inhalation then was terminated. During the stabilization period, PaCO2 (mean +/- SD) was 33 +/- 5 mm Hg,and arrhythmias were not detected. In 6 ducks, arrhythmias such as unifocal and multifocal premature ventricular contractions developed during inhalation of CO2. Mean PaCO2 at which arrhythmias developed was 67 +/- 12 mm Hg. In 5 of 6 ducks with arrhythmias, the arrhythmias disappeared after CO2 inhalation was terminated. Analysis of data from this study indicated that hypercapnia can lead to arrhythmias in ducks during halothane-induced anesthesia. Thus, ventilatory support to maintain normocapnia is important for managing ducks anesthetized with halothane.


Sustainability of coral reefs are affected by ecological light pollution in the Gulf of Aqaba/Eilat.
As human populations grow and lighting technologies improve, artificial light gradually alters natural cycles of light and dark that have been consistent over long periods of geological and evolutionary time. While considerable ecological implications of artificial light have been identified in both terrestrial and aquatic habitats, knowledge about the physiological and molecular effects of light pollution is vague. To determine if ecological light pollution (ELP) impacts coral biological processes, we characterized the transcriptome of the coral Acropora eurystoma under two different light regimes: control conditions and treatment with light at night. Here we show that corals exposed to ELP have approximately 25 times more differentially expressed genes that regulate cell cycle, cell proliferation, cell growth, protein synthesis and display changes in photo physiology. The finding of this work confirms that ELP acts as a chronic disturbance that may impact the future of coral reefs.


Full-body skin examinations and the female veteran: prevalence and perspective.
To determine the frequency of full-body skin examinations (FBSEs) among female veterans and to determine whether patient risk factors for skin cancer alter the frequency of screening. Subjects were also queried as to attitudes about FBSE. Questionnaires pertaining to whether patients underwent regular FBSE, their opinions and attitudes about this screening test, and their risks for developing skin cancer. A primary health care clinic for female veterans at a Veterans Affairs medical center. A convenience sample of 245 patients awaiting clinic appointments. Of those asked to participate, 201 agreed, for a participation rate of 82%. Patient report of undergoing FBSE, attitudes regarding FBSE, and risk factors for cutaneous malignancy. Eighteen percent of all respondents reported undergoing regular FBSE by their primary care provider, whereas 9 (45%) of the 20 with a history of skin cancer reported undergoing FBSE. Fifteen percent of subjects reported embarrassment with FBSE. Seventy-nine percent reported that their primary care provider would be considered thorough by performing FBSE, and 69% would like their primary care provider to perform FBSE regularly. We found that 16% of subjects would refuse the examination if the primary care provider were of the opposite sex, whereas 38% would not refuse but be less willing to be examined. Female veterans report a low incidence of FBSE, although those with a personal history of skin cancer are more likely to undergo screening. Despite embarrassment expressed about a sex difference between the patient and examiner, female veterans have a strong preference to undergo FBSE.


Anteromedial Surface Plating for Midshaft Fracture Humerus Through an Anterolateral Approach - A Better Option than Anterolateral Plating.
Osteosynthesis by plate fixation of humeral shaft fractures as a gold standard for fracture fixation has been proven beyond doubt. However, during conventional anterolateral plating Radial nerve injury may occur which can be avoided by applying plate on the medial flat surface. The aim of this study was to evaluate the results of application of plate on the flat medial surface of humerus rather than the conventional anterolateral surface. This study was conducted between Oct 2010 to Dec 2015. One-hundred-fifty fracture shafts of the humerus were treated with the anteromedial plating through the anterolateral approach. One-hundred-fifty patients with a fracture shaft of the humerus were treated with anteromedial plating. Twenty were female (mean ±SD,28 years±4.5) and 130 were male (mean ± SD, 38 years±5.6). One hundred and forty-eight out of 150 (98.6%) patients achieved union at 12 months. Two of three patients developed a superficial infection, both of which were treated successfully by antibiotics and one developed a deep infection, which was treated by wound debridement, prolonged antibiotics with the removal of the plate and subsequently by delayed plating and bone grafting. In the present study, we applied plate on the anteromedial flat surface of humerus using the anterolateral approach. It is an easier and quicker fixation as compared to anterolateral plating because later involved much more dissection than a medial application of the plate and this application of plate on a medial flat surface, does not required Radial nerve exposure and palsy post-operatively. The significant improvement in elbow flexion without brachialis dissection is also a potential benefit of this approach. Based on our results, we recommend the application of an anteromedial plate for treatment of midshaft fractures humerus.


Predictors of lymphocyte count recovery after dimethyl fumarate-induced lymphopenia in people with multiple sclerosis.
Dimethyl fumarate (DMF) is an oral drug approved for Relapsing Multiple Sclerosis (RMS) patients. Grade III lymphopenia is reported in 5-10% DMF-treated patients. Data on lymphocyte count (ALC) recovery after DMF withdrawal following prolonged lymphopenia are still scarce. To characterize ALC recovery and to identify predictors of slower recovery after DMF interruption. Multicenter data from RMS patients who started DMF and developed lymphopenia during treatment were collected. In patients with grade II-III lymphopenia, ALCs were evaluated from DMF withdrawal until reaching lymphocyte counts > 800/mm3. Among 1034 patients who started DMF, we found 198 (19.1%) patients with lymphopenia and 65 patients (6.3%) who discontinued DMF due to persistent grade II-III lymphopenia. Complete data were available for 51 patients. All patients recovered to ALC > 800 cells/mm3 with a median time of 3.4 months. Lower ALCs at DMF suspension (HR 0.98; p = 0.005), longer disease duration (HR 1.29; p = 0.014) and prior exposure to MS treatments (HR 0.03; p = 0.025) were found predictive of delayed ALC recovery. ALC recovery after DMF withdrawal is usually rapid, nevertheless it may require longer time in patients with lower ALC count at DMF interruption, longer disease duration and previous exposure to MS treatments, potentially leading to delayed initiation of a new therapy.


Diagnosis and therapy of coronary artery disease in renal failure, end-stage renal disease, and renal transplant populations.
Even though cardiovascular disease is the leading cause of death in patients with CRF and end-stage renal disease (ESRD), ill-conceived notions have led to therapeutic nihilism as the predominant strategy in the management of cardiovascular disease in these populations. The recent data clearly support the application of proven interventions in the general population, such as angiotensin-converting enzyme inhibitors and statins to patients with CRF and ESRD. The advances in coronary stents and intracoronary irradiation have decreased the restenosis rates in renal failure patients. Coronary artery bypass with internal mammary graft might be the procedure of choice for coronary revascularization in these patients. The role of screening for asymptomatic coronary disease is established as a pretransplant procedure, but it is unclear whether this will be applicable to all patients with ESRD. Future studies need to focus on unraveling the mechanisms by which uremia leads to increased cardiovascular events to design optimal therapies targeted toward these mechanisms and improve cardiovascular outcomes.


Medical imaging.
There is now a wide choice of medical imaging to show both focal and diffuse pathologies in various organs. Conventional radiology with plain films, fluoroscopy and contrast medium have many advantages, being readily available with low-cost apparatus and a familiarity that almost leads to contempt. The use of plain films in chest disease and in trauma does not need emphasizing, yet there are still too many occasions when the answer obtainable from a plain radiograph has not been available. The film may have been mislaid, or the examination was not requested, or the radiograph had been misinterpreted. The converse is also quite common. Examinations are performed that add nothing to patient management, such as skull films when CT will in any case be requested or views of the internal auditory meatus and heal pad thickness in acromegaly, to quote some examples. Other issues are more complicated. Should the patient who clinically has gall-bladder disease have more than a plain film that shows gall-stones? If the answer is yes, then why request a plain film if sonography will in any case be required to 'exclude' other pathologies especially of the liver or pancreas? But then should cholecystography, CT or scintigraphy be added for confirmation? Quite clearly there will be individual circumstances to indicate further imaging after sonography but in the vast majority of patients little or no extra information will be added. Statistics on accuracy and specificity will, in the case of gall-bladder pathology, vary widely if adenomyomatosis is considered by some to be a cause of symptoms or if sonographic examinations 'after fatty meals' are performed. The arguments for or against routine contrast urography rather than sonography are similar but the possibility of contrast reactions and the need to limit ionizing radiation must be borne in mind. These diagnostic strategies are also being influenced by their cost and availability; purely pragmatic considerations are not infrequently the overriding factor. Non-invasive methods will be preferred, particularly sonography as it is far more acceptable by not being claustrophobic and totally free of any known untoward effects. There is another quite different but unrelated aspect. The imaging methods, apart from limited exceptions, cannot characterize tissues as benign or malignant, granulomatous or neoplastic; cytology or histology usually provides the answer. Sonography is most commonly used to locate the needle tip correctly for percutaneous sampling of tissues. Frequently sonography with fine needle aspiration cytology or biopsy is the least expensive, safest and most direct route to a definitive diagnosis. Abscesses can be similarly diagnosed but with needles or catheters through which the pus can be drained. The versatility and mobility of sonography has spawned other uses, particularly for the very ill and immobile, for the intensive therapy units and for the operating theatre, as well in endosonography. The appointment of more skilled sonographers to the National Health Service could make a substantial contribution to cost-effective management of hospital services. Just when contrast agents and angiography have become safe and are performed rapidly, they are being supplanted by scanning methods. They are now mainly used for interventional procedures or of pre-operative 'road maps' and may be required even less in the future as MRI angiography and Doppler techniques progress. MRI will almost certainly extent its role beyond the central nervous system (CNS) should the equipment become more freely available, especially to orthopaedics. Until then plain films, sonography or CT will have to suffice. Even in the CNS there are conditions where CT is more diagnostic, as in showing calculations in cerebral cysticercosis. Then, too, in most cases CT produces results comparable to MRI apart from areas close to bone, structures at the base of the brain, in the posterior fossa and in the spinal cord. Scintigraphy for pulmonary infarcts and bone metastases and in renal disease in children plays a prominent role and its scope has increased with new equipment and radionuclides. Radio-immunoscintigraphy in particular is likely to expand greatly not only in tumour diagnosis but also in metabolic and infective conditions. Whether the therapeutic implications will be realized is more problematic. The value of MRS and NM for metabolic studies in clinical practice is equally problematical, although the data from cerebral activity are extremely interesting. While scanning has replaced many radiographic examinations, endoscopy has had a similar effect on barium meals and to a lesser extent on barium enemas. The combined visual/sonographic endoscope is likely to accelerate this process. There is no doubt that over the last 2 decades medical imaging has changed the diagnostic process, but its influence on the outcome of disease other than infections is less certain and probably indefinable. Data concerning the comparative efficacy in terms of patient outcome for each of the imaging techniques would be of considerable interest and a great help in determining diagnostic strategies.


Creating change: building the capacity of the medical workforce in Aboriginal health.
This paper provides an overview of the long-term strategies that have been in place at the University of Western Australia, which aim to build the capacity and preparedness of the health-care workforce in Aboriginal health. In 1996, the Centre for Aboriginal Medical and Dental Health was established within the Faculty of Medicine, Dentistry and Health Sciences to implement a comprehensive approach to Aboriginal health. The initial focus was on developing recruitment and retention strategies that meaningfully address the significant under-representation of Aboriginal and Torres Strait Islander people in the medical and broader health professions. At the same time, the Centre developed, implemented and evaluated a comprehensive vertically and horizontally integrated Aboriginal health curriculum initially in the Medicine course and subsequently in the Podiatry and Nursing courses within the faculty. The priority has been to ensure that all graduates will be better prepared to work effectively and safely with Aboriginal and Torres Strait Islander people and communities. Without effective alternative entry processes access to tertiary health courses and health careers would not have been an option for the majority of Aboriginal and Torres Strait Islander students and graduates. This paper reflects on the partnerships, structures and approaches that have enabled the achievements to date and on the challenges that confront not only initial implementation but also sustaining the gains already made.


Visible Blue Light Therapy: Molecular Mechanisms and Therapeutic Opportunities.
Visible light is absorbed by photoacceptors in pigmented and non-pigmented mammalian cells, activating signaling cascades and downstream mechanisms that lead to the modulation of cellular processes. Most studies have investigated the molecular mechanisms and therapeutic applications of UV and the red to near infrared regions of the visible spectrum. Considerably less effort has been dedicated to the blue, UV-free part of the spectrum. In this review, we discuss the current advances in the understanding of the molecular photoacceptors, signaling mechanisms, and corresponding therapeutic opportunities of blue light photoreception in non-visual mammalian cells in the context of inflammatory skin conditions. The literature was scanned for peer-reviewed articles focusing on the molecular mechanisms, cellular effects, and therapeutic applications of blue light. At a molecular level, blue light is absorbed by flavins, porphyrins, nitrosated proteins, and opsins; inducing the generation of ROS, nitric oxide release, and the activation of G protein coupled signaling. Limited and contrasting results have been reported on the cellular effects of blue light induced signaling. Some investigations describe a regulation of proliferation and differentiation or a modulation of inflammatory parameters; others show growth inhibition and apoptosis. Regardless of the elusive underlying mechanism, clinical studies show that blue light is beneficial in the treatment of inflammatory skin conditions. To strengthen the use of blue light for therapeutic purposes, further in depth studies are clearly needed with regard to its underlying molecular and cellular mechanisms, and their translation into clinical applications.


On the behaviour of evolution strategies optimising cigar functions.
This paper studies the performance of multi-recombinative evolution strategies using isotropically distributed mutations with cumulative step length adaptation when applied to optimising cigar functions. Cigar functions are convex-quadratic objective functions that are characterised by the presence of only two distinct eigenvalues of their Hessian, the smaller one of which occurs with multiplicity one. A simplified model of the strategy's behaviour is developed. Using it, expressions that approximately describe the stationary state that is attained when the mutation strength is adapted are derived. The performance achieved by cumulative step length adaptation is compared with that obtained when using optimally adapted step lengths.


Clinical and VEMPS Characteristics of Benign Recurrent Vertigo With Cochlear Symptoms and Migraine.
Objectives: To explore the clinical manifestations and vestibular-evoked myogenic potential (VEMP) characteristics in patients diagnosed with benign recurrent vertigo (BRV) accompanied by cochlear symptoms or migraine history. Methods: A total of 34 patients were diagnosed with BRV (57 ears) and 30 healthy volunteers (60 ears) were recruited. They were divided into 4 groups: Group A consisted of 17 patients diagnosed as BRV with cochlear symptoms (21 ears), Group B consisted of 11 patients diagnosed as BRV with migraine history (22 ears), and Group C consisted of 7 patients with BRV without cochlear symptoms and migraine history (14 ears). Group D, as a Normal control (NC) group, consisted of 30 healthy volunteers without a history of migraine and cochlear symptoms. Detailed consultations and VEMP testing were performed separately. The VEMPs elicitation rate, amplitude ratio at different frequencies and amplitude statistics were compared and analyzed among the 4 groups. Results: The amplitudes of cervical vestibular evoked myogenic potential (cVEMP) have significant differences between Groups D and A, and Group C, under 500 Hz (PAD = .017, PBD = .052, PCD = .044), but the amplitudes of cVEMP have significant differences between Groups D and A, and Group B under 1000 Hz, respectively (PAD = .008, PBD = .020, PCD = .119). The amplitudes of ocular vestibular evoked myogenic potential (oVEMP) have significant differences between Groups D and A, and Group B, under 500 Hz, respectively (PAD = .029, PBD = .005, PCD = .198). oVEMP amplitudes significantly differ between Groups D and A under 1000 Hz (PAD = .049, PBD = .079, PCD = .103). The statistical difference was absent in elicit rates of cVEMP and oVEMP between the NC and experimental groups (cVEMP: PAD = .525, PBD = .917, PCD = .374; oVEMP: PAD = .678, PBD = .523, PCD = .427). Moreover, there is no significant difference between the NC group and experimental groups among VEMPs and VEMP frequency amplitude ratio (P > .05). Conclusion: VEMPs could be a diagnostic indicator for BRV patients with cochlear symptoms. The pathogenesis of BRV may be related to damage to the otolithic apparatus.


Pediatric Horner syndrome.
The purpose of this study was to define the etiologies of Horner syndrome in the pediatric population. A retrospective review was performed of the medical records of all pediatric Horner syndrome patients (< 18 years old) examined by the pediatric ophthalmology services at two large referral centers. Seventy-three pediatric Horner syndrome patients were identified. Of these, 31 (42%) were congenital, 11 (15%) were acquired without surgical intervention, and 31 (42%) were acquired after a surgical procedure of the thorax, neck, or central nervous system. Of the congenital Horner syndrome patients, a history of delivery with the use of forceps, vacuum extraction, shoulder dystocia, fetal rotation, or postterm delivery was elicited in 16 patients (53%). Concomitant brachial plexus injury was identified in only 3 patients. Two patients had congenital varicella syndrome and 1 patient was diagnosed with neuroblastoma. This patient had a palpable supraclavicular mass and stridor. Diagnosis of the patients with acquired Horner syndrome included neuroblastoma (2), trauma (1), rhabdomyosarcoma (1), brainstem vascular malformation (1), disseminated sclerosis (1), and not determined (5). In children with congenital Horner syndrome, a history of forceful manipulation of the infant during birth may reduce the need for extensive systemic evaluation. Without such history, a decision to proceed with further evaluation is made with consideration of the relative incidence of neuroblastoma by age and the physical findings. All acquired pediatric Horner syndrome patients without a known etiology require thorough evaluation because of the frequent association of serious underlying disease.


Service use and cost by mentally ill chemical abusers: differences by retention in a therapeutic community.
Earlier research estimated the incremental costs and outcomes of a modified therapeutic community (modified TC) for mentally ill chemical abusers (MICAs) relative to a treatment-as-usual (TAU) control group. The present study extended the cost analysis by disaggregating the modified TC group into clients who completed the program (completers) and clients who dropped out (separaters). Bivariate and multivariate analyses were conducted to estimate differences in treatment and other service costs among completers, separaters, and TAU. Subjects were sequentially assigned to the modified TC (n = 171) or TAU (n = 47), and the analysis period covered 12 months post-baseline. Using a standardized instrument to collect resource use and cost data, the estimated weekly cost per client in the modified TC was $554, with completers showing a larger average cost of treatment ($27,595) than separaters ($9,986). The average TAU subject had a much higher cost for other (non-modified TC) services ($29,795) relative to separaters ($22,048) or completers ($1,986). These findings suggest that, from baseline to the 12-month follow-up, the total cost of modified TC treatment and other services for completers may be slightly lower than the total cost for separaters or TAU subjects. Since the modified TC group had better outcomes than the TAU group, and the completers had better outcomes than the separaters, the modified TC program could be an effective mechanism to reduce the costs of service utilization as well as improve clinical outcomes. This detailed investigation into service utilization and cost provides policy-makers and program directors with valuable information regarding potentially cost-effective interventions and further underscores the importance of retention in treatment for this vulnerable population.


Elevated soluble triggering receptor expressed on myeloid cells (sTREM)-1 levels in maternal serum during term and preterm labor.
Infection and inflammation are important mechanisms leading to preterm birth. Soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) belongs to a family of cell surface receptors that seems to play an important role in fine-tuning the immune response. It has been demonstrated that sTREM-1 is involved in bacterial infection as well as in non-infectious inflammatory conditions. Few studies have investigated serum sTREM-1 expression during preterm labor. Therefore, the purpose of this study was to assess sTREM-1 concentrations in maternal serum during term and preterm labor. This case control study included 176 singleton pregnancies in the following groups: patients in (1) preterm labor, delivered before 34 weeks (PTB) (n = 52); (2) GA matched controls, not in labor, matched for gestational age (GA) with the PTB group (n = 52); (3) at term in labor (n = 40) and (4) at term not in labor (n = 32). sTREM-1 concentrations were determined by enzyme-linked immunoassay. sTREM-1 was detected in all serum samples. Median sTREM-1 concentrations were significantly higher in women with PTB vs. GA matched controls (367 pg/ml, interquartile range (IQR) 304-483 vs. 273 pg/ml, IQR 208-334; P<0.001) and in women at term in labor vs. at term not in labor (300 pg/ml, IQR 239-353 vs. 228 pg/ml, IQR 174-285; P<0.001). Women with PTB had significantly higher levels of sTREM-1 compared to women at term in labor (P = 0.004). Multiple regression analysis, with groups recoded as three key covariates (labor, preterm and rupture of the membranes), showed significantly higher sTREM-1 concentrations for labor (+30%, P<0.001) and preterm (+15%, P = 0.005) after adjusting for educational level, history of PTB and sample age. sTREM-1 concentrations in maternal serum were elevated during spontaneous term and preterm labor and sTREM-1 levels were significantly higher in preterm labor.


Low torsional barrier challenges in the microwave spectrum of 2,4-dimethylanisole.
Low barriers to internal rotations are especially challenging for both the experimental and theoretical determinations because they result in large tunneling splittings which are hard to assign and in potential functions that can be difficult to model. In the present work, the internal rotations of two methyl groups of 2,4-dimethylanisole were analyzed and modeled using a newly developed computer code, called ntop, adapted for fitting the high-resolution torsion-rotation spectra of molecules with two or more methyl rotors. The spectrum was measured using a pulsed molecular jet Fourier transform microwave spectrometer operating in the frequency range of 2.0-26.5 GHz, revealing internal rotation tunneling quintets with splittings of up to several gigahertz. The V3 potential barriers are 441.139(23) cm-1 and 47.649(30) cm-1 for the o- and p-methyl groups, respectively. Quantum chemical calculations predicted only one conformer with the methoxy group in the anti position related to the neighboring o-methyl group. While the results from geometry optimizations were reliable, ab initio calculations at the MP2 level did not reproduce the low torsional barriers, calling for further experiments on related systems and additional theoretical models.


Multicolor tunable luminescence and paramagnetic properties of NaGdF₄:Tb³⁺/Sm³⁺ multifunctional nanomaterials.
Tb(3+) and/or Sm(3+) doped NaGdF4 luminescent nanomaterials have been successfully synthesized by an SDS-assisted one-step hydrothermal method. The samples were characterized by X-ray diffraction (XRD), field-emission scanning electron microscope (FE-SEM), transmission electron microscope (TEM), X-ray energy dispersive spectrometer (EDS), photoluminescence (PL) spectra and a vibrating sample magnetometer (VSM). The results show that the synthesized samples are all pure β-NaGdF4. The as-prepared Tb(3+) or Sm(3+) doped samples show strong green and yellow emission, originating from the allowed (5)D3→(7)F(J) (J = 5, 4, 3, 2) and (5)D4→(7)F(J) (J = 6, 5, 4, 3) transitions of the Tb(3+) ions and the (4)G(5/2)→(6)H(5/2), (6)H(7/2), (6)H(9/2) transition of the Sm(3+) ions. Based on the excitation wavelengths, multiple (yellowish green, yellow, white) emissions are obtained by Sm(3+) ion co-activated NaGdF4:Tb(3+) phosphors. Moreover, an energy transfer from Tb(3+) to Sm(3+) is observed, which is justified through the luminescence spectra and the fluorescence decay curves. Furthermore, the resonance-type energy transfer from Tb(3+) to Sm(3+) is demonstrated to occur via the dipole-dipole mechanism. In addition, the obtained samples also exhibit paramagnetic properties at room temperature. It is obvious that these multifunctional Tb(3+), Sm(3+) co-doped β-NaGdF4 nanomaterials, with tunable multicolors and intrinsic paramagnetic properties, may have potential application in the fields of full-color displays, biological labels, bioseparation and magnetic resonance imaging.


8-Hydroxyquinoline-based inhibitors of the Rce1 protease disrupt Ras membrane localization in human cells.
Ras converting enzyme 1 (Rce1) is an endoprotease that catalyzes processing of the C-terminus of Ras protein by removing -aaX from the CaaX motif. The activity of Rce1 is crucial for proper localization of Ras to the plasma membrane where it functions. Ras is responsible for transmitting signals related to cell proliferation, cell cycle progression, and apoptosis. The disregulation of these pathways due to constitutively active oncogenic Ras can ultimately lead to cancer. Ras, its effectors and regulators, and the enzymes that are involved in its maturation process are all targets for anti-cancer therapeutics. Key enzymes required for Ras maturation and localization are the farnesyltransferase (FTase), Rce1, and isoprenylcysteine carboxyl methyltransferase (ICMT). Among these proteins, the physiological role of Rce1 in regulating Ras and other CaaX proteins has not been fully explored. Small-molecule inhibitors of Rce1 could be useful as chemical biology tools to understand further the downstream impact of Rce1 on Ras function and serve as potential leads for cancer therapeutics. Structure-activity relationship (SAR) analysis of a previously reported Rce1 inhibitor, NSC1011, has been performed to generate a new library of Rce1 inhibitors. The new inhibitors caused a reduction in Rce1 in vitro activity, exhibited low cell toxicity, and induced mislocalization of EGFP-Ras from the plasma membrane in human colon carcinoma cells giving rise to a phenotype similar to that observed with siRNA knockdowns of Rce1 expression. Several of the new inhibitors were more effective at mislocalizing K-Ras compared to a potent farnesyltransferase inhibitor (FTI), which is significant because of the preponderance of K-Ras mutations in cancer.


N-doped TiO2/Ti3C2-driven self-photocatalytic molecularly imprinted ECL sensor for sensitive and steady detection of dexamethasone.
The conventional luminol-based electrochemiluminescence (ECL) biosensor suffers from hampered signal stability due to the self-decomposition of the H2O2 co-reactant. Here, we propose an N-doped TiO2/Ti3C2 heterojunction driven self-photocatalytic platform for ECL signal amplification and then combine it with molecular imprinting technology for sensitive and steady detection of dexamethasone (DXM). Unlike traditional cases involving specific catalysts or external electron injection, the initial luminescence of luminol in this new system is utilized as the excitation light of N-doped TiO2/Ti3C2 photocatalyst to promote the conversation of dissolved oxygen to H2O2, supplying more co-reactants to improve ECL of luminol in turn. Thanks to the heterojunction and self-photocatalytic cyclic amplification, this molecularly imprinted ECL sensor exhibits a wide linear range (1.0 × 10-6-1.0 × 101 μg mL-1) and a low detection limit, as well as excellent anti-interference capability, sensitivity, and stability. This work contributes to more reliable and steady detection of DXM and brings new insights into developing exogenous co-reactant-free self-enhancement ECL models for biosensor applications.


Detection of Additives and Chemical Contaminants in Turmeric Powder Using FT-IR Spectroscopy.
Yellow turmeric (Curcuma longa) is widely used for culinary and medicinal purposes, and as a dietary supplement. Due to the commercial popularity of C. longa, economic adulteration and contamination with botanical additives and chemical substances has increased. This study used FT-IR spectroscopy for identifying and estimating white turmeric (Curcuma zedoaria), and Sudan Red G dye mixed with yellow turmeric powder. Fifty replicates of yellow turmeric-Sudan Red mixed samples (1%, 5%, 10%, 15%, 20%, 25% Sudan Red, w/w) and fifty replicates of yellow turmeric-white turmeric mixed samples (10%, 20%, 30%, 40%, 50% white turmeric, w/w) were prepared. The IR spectra of the pure compounds and mixtures were analyzed. The 748 cm-1 Sudan Red peak and the 1078 cm-1 white turmeric peak were used as spectral fingerprints. A partial least square regression (PLSR) model was developed for each mixture type to estimate adulteration concentrations. The coefficient of determination (R2v) for the Sudan Red mixture model was 0.97 with a root mean square error of prediction (RMSEP) equal to 1.3%. R2v and RMSEP for the white turmeric model were 0.95 and 3.0%, respectively. Our results indicate that the method developed in this study can be used to identify and quantify yellow turmeric powder adulteration.


Perceived burden of care and reported coping strategies and needs for family caregivers of people with mental disorders in Zimbabwe.
Mental health service resources are inadequate in low-income countries, and families are frequently expected to provide care for their relative with a mental disorder. However, research on the consequences of caregiving has been limited in low-income countries, including Zimbabwe. The study explored the perceived impact of mental illness, reported coping strategies and reported needs of the family members of persons diagnosed with bipolar affective disorder or schizophrenia attending a psychiatric hospital in Harare, Zimbabwe. A purposive sample of 31 family members participated in in-depth interviews and focus group discussions using standardised study guides. Participants were also screened for common mental disorders (CMDs) using the 14-item Shona Symptom Questionnaire. Qualitative data were analysed thematically using NVivo 8 qualitative data analysis software. Statistical Package for Social Sciences (SPSS version 16) was used for descriptive quantitative data analysis. Caregivers experienced physical, psychological, emotional, social and financial burdens associated with caregiving. They used both emotion-focused and problem-focused coping strategies, depending on the ill family members' behaviours. Seeking spiritual assistance emerged as their most common way of coping. Twenty-one (68%) of the caregivers were at risk of CMDs (including three participants who were suicidal) and were referred to a psychiatrist for further management. Caregivers required support from healthcare professionals to help them cope better. Caregivers of patients attending psychiatry hospitals in Zimbabwe carry a substantial and frequently unrecognised burden of caring for a family member with a mental disorder. Better support is needed from health professionals and social services to help them cope better. Further research is required to quantitatively measure caregiver burden and evaluate potential interventions in Zimbabwe.


[Analysis on Malaria Situation in Shaanxi Province during 2005-2014].
To analyze the malaria situation in Shaanxi Province during 2005-2014, in the aim of providing reference for improving malaria elimination strategies and measures. Data on malaria control and malaria epidemic reports during 2005-2014 were collected, and analysis was made on prevalence and regional distribution of malaria, species of plasmodium, diagnosis of patients, and sources of imported malaria. Four hundred and fifty three cases of malaria were reported in Shaanxi Province during 2005-2014, consisting of 73 local cases (16.1%) and 380 imported cases (83.9%) of which 141 were falciparum malaria (37.1%, 141/380). Three patients died and they all were imported cases of falciparum malaria. No indigenous infection had been reported since 2011. Most of the cases were laboratory-confirmed(71.5%, 324/453). The falciparum malaria cases accounted for 31.1%(141/453) of all the cases, and they all were imported cases. No cases of quartan malaria and ovale malaria were reported. The 73 indigenous cases distributed in 25 districts (counties) of 7 cities, including 3 cities in South Shaanxi (Shangluo, Hanzhong, Ankang)(61.6%, 45/73) and four cities in Central Shaanxi (Xi′an, Weinan, Xianyang, Baoji) (38.4%, 28/73). The imported cases showed an increasing trend from 24 in 2005 to 59 in 2014. The 380 imported cases were mainly from over 20 countries in Africa (72.6%, 276/380), with top sources of Angola (64 cases), Cameroon (26), Ghana (24), and Equatorial Guinea (23) accounting for 36.0% ( 137/380). The median of interval from onset to diagnosis was 5 d. The cases were mainly reported by clinical medical institutions (87.6%, 397/453), only 7.5% (34/453) were reported by disease control institutions. No indigenous cases have been reported since 2011, but the imported malaria cases show a trend of increase with a major source of Africa.


A silicon neuron.
By combining neurophysiological principles with silicon engineering, we have produced an analog integrated circuit with the functional characteristics of real nerve cells. Because the physics underlying the conductivity of silicon devices and biological membranes is similar, the 'silicon neuron' is able to emulate efficiently the ion currents that cause nerve impulses and control the dynamics of their discharge. It operates in real-time and consumes little power, and many 'neurons' can be fabricated on a single silicon chip. The silicon neuron represents a step towards constructing artificial nervous systems that use more realistic principles of neuronal computation than do existing electronic neuronal networks.


Thiotepa cyclophosphamide followed by granulocyte colony-stimulating factor mobilized allogeneic peripheral blood cells in adults with advanced leukemia.
Thirty-one patients (median age, 44 years) with advanced hematologic malignancies were given thiotepa 15 mg/kg, and cyclophosphamide 120 (n = 14) or 150 (n = 17) mg/kg followed by unfractionated peripheral blood stem cell transplants (PBSCT) from genotypically identical siblings (n = 28) or one antigen mismatched family donor (n = 3). Donors were mobilized with granulocyte colony-stimulating factor 5 to 10 microgram/kg/d for 6 days and underwent two to three leukapheresis on days +5, +6, +7. The median cell yield per donor expressed/kg of recipients body weight was as follows: nucleated cells 13 x 10(8)/kg; CD34+ cells 6 x 10(6)/kg; colony-forming unit-granulocyte macrophage 38 x 10(4)/kg, and CD3+ cells 449 x 10(6)/kg. The diagnoses were chronic myeloid leukemia (n = 4), acute myeloid (n = 9) or lymphoid leukemia (n = 2), acute myelofibrosis (n = 2), multiple myeloma (n = 1), lymphoma (n = 6), chronic lymphocytic leukemia (n = 1) myelodysplasia (n = 6). Twenty-eight patients had advanced disease, 29 patients were first grafts, and 2 were second transplants 3 and 9 years after the first. Neutrophil counts of 0.5 x 10(9)/L and platelet counts of 30 x 10(9)/L platelets were both achieved on day +14 (median). Engraftment could be proven by sex markers or DNA polymorphism in 29 of 31 patients: one had early leukemia relapse and one patient was unevaluable because of early death. Acute graft-versus-host disease (GVHD) was scored as minimal or absent (grade 0 to 1) in 14 patients, moderate (grade II) in 13, and severe (grade III to IV) in four. Causes of death were leukemia (n = 4), acute GVHD (n = 4, with associated cytomegalovirus infections in three), sepsis (n = 1), liver failure (n = 1), multiorgan failure (n = 1), and hemorrhage (n = 1). The actuarial transplant mortality is 29%, the actuarial relapse rate 22%. Nineteen patients survive with a median follow up of 288 days (100-690). The actuarial 2-year survival is 57%. Three patients received PBSCT from family donors mismatched for one class II antigen: all engrafted, one developed grade I aGVHD; one died of leukemia on day +155; two are alive disease free 267 to 290 days postgraft. This study suggests that thiotepa cyclophosphamide followed by unfractionated PBSC allograft may be an alternative form of transplant for adults with advanced leukemia, also in the setting of one antigen mismatched donor. The engraftment is rapid with acceptable GVHD and relatively low transplant-related mortality.


Clinicobiological features and prognostic impact of diffuse large B-cell lymphoma component in the outcome of patients with previously untreated follicular lymphoma.
The co-existence at diagnosis of follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) components (FL/DLBCL) has been considered a transformed lymphoma and accordingly treated although clinicobiological information on these patients is scarce. The aim of this study was to analyze the initial features and outcome of FL/DLBCL patients in the rituximab era. All patients consecutively diagnosed at a single institution with FL/DLBCL (n = 40), as well as those with pure FL (n = 328) or de novo DLBCL (n = 510) as controls. The proportion of the DLBCL component was highly variable (median 50%). In 29 FL/DLBCL cases analyzed, the cell of origin was GCB in 86%, ABC in 10% and unclassifiable in 4%. NOTCH1-2 was mutated in 10% of these cases. The proportion of DLBCL component did not impact on overall survival (OS). Regarding initial characteristics, patients with FL/DLBCL were closer to FL in terms of primary nodal origin, good performance status and advanced stage, whereas the other features were intermediate between FL and DLBCL. FL/DLBCL patients were treated as DLBCL with no further intensification. Complete response and primary refractory rates were 65% and 20%, respectively, with these figures being similar to DLBCL and worse than FL. Progression-free survival and OS were intermediate between FL and DLBCL (5-year OS: 85%, 73% and 63% for FL, FL/DLBCL and DLBCL, respectively). FL/DLBCL histology did not reach independent prognostic value for OS in the multivariate analyses. The outcome of FL/DLBCL patients is not worse than that of de novo DLBCL. These cases should be treated with immunochemotherapy as DLBCL, but intensification with ASCT may not be necessary. The biological insights of FL/DLBCL warrants further genetic and molecular studies.